A Study to Investigate the Efficacy and Safety of ZX008 (... | NCT03355209 | Trialant
NCT03355209
Sponsor
Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.
Status
Completed
Last Update Posted
Jul 3, 2025Actual
Enrollment
296Actual
Phase
Phase 3
Conditions
Lennox Gastaut Syndrome
Interventions
ZX008 0.2 or 0.8 mg/kg/day
Matching Placebo
Countries
United States
Australia
Belgium
Canada
Denmark
France
Germany
Italy
Japan
Mexico
Netherlands
Poland
Spain
Sweden
Protocol Section
Identification Module
NCT ID
NCT03355209
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
ZX008-1601
Secondary IDs
ID
Type
Description
Link
2017-002628-26
EudraCT Number
Brief Title
A Study to Investigate the Efficacy and Safety of ZX008 (Fenfluramine Hydrochloride) as an Adjunctive Therapy in Children and Adults With Lennox-Gastaut Syndrome
Official Title
A Two-Part Study of ZX008 in Children and Adults With Lennox-Gastaut Syndrome (LGS); Part 1: A Randomized, Double-blind, Placebo-controlled Trial of Two Fixed Doses of ZX008 (Fenfluramine Hydrochloride) Oral Solution as Adjunctive Therapy for Seizures in Children and Adults With LGS, Followed by Part 2: An Open-label Extension to Assess Long-Term Safety of ZX008 in Children and Adults With LGS
Acronym
Not provided
Organization
UCB PharmaINDUSTRY
Status Module
Record Verification Date
Jun 2025
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Nov 27, 2017Actual
Primary Completion Date
May 23, 2024Actual
Completion Date
May 23, 2024Actual
First Submitted Date
Jun 19, 2017
First Submission Date that Met QC Criteria
Nov 21, 2017
First Posted Date
Nov 28, 2017Actual
Results Waived
Not provided
Results First Submitted Date
May 2, 2025
Results First Submitted that Met QC Criteria
Jun 16, 2025
Results First Posted Date
Jul 3, 2025Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Jun 16, 2025
Last Update Posted Date
Jul 3, 2025Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.INDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This is a two-part, multicenter, double-blind, parallel-group, placebo controlled study to evaluate the effect of ZX008 when used as adjunctive therapy for the treatment of uncontrolled seizures in children and adults with Lennox-Gastaut syndrome (LGS).
Detailed Description
Not provided
Conditions Module
Conditions
Lennox Gastaut Syndrome
Keywords
LGS
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
296Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
ZX008 0.2 or 0.8 mg/kg/day
Experimental
Part 1: ZX008 is supplied as an oral solution. Subjects will be randomized to receive 1 of 2 doses of ZX008 0.2 mg/kg/day or 0.8 mg/kg/day.
Drug: ZX008 0.2 or 0.8 mg/kg/day
Matching Placebo
Placebo Comparator
Part 1: Matching ZX008 placebo is supplied as an oral solution.
Drug: Matching Placebo
Open-Label
Experimental
Part 2: ZX008 is supplied as an oral solution. Study medication will be administered twice a day (BID) in equally divided doses.
Drug: ZX008 0.2 or 0.8 mg/kg/day
Interventions
Name
Type
Description
Arm Group Labels
Other Names
ZX008 0.2 or 0.8 mg/kg/day
Drug
ZX008 drug product is an oral aqueous solution of fenfluramine hydrochloride. The product is sugar free and is intended to be compatible with a Ketogenic Diet.
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Part 1: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC-confirmed) in the Combined Titration and Maintenance Period (T+M) in the ZX008 0.8 mg/kg/Day Group Compared to the Placebo Group
Percent change in frequency of seizures that result in drops (DSF: drop seizure frequency) per 28 days between the combined Titration and Maintenance (T+M) and Baseline. The percent change from Baseline DSF was calculated as the change in DSF between T+M and Baseline / DSF during Baseline* 100. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops.
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
Part 2: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
An Adverse event (AE) was defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of investigational product, or whether considered related to the investigational product. A TEAE in Part 2 was defined as any AE with an onset on or after the first dose in Part 2. AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2.
From Part 2 Baseline until end of the OLE Period (up to 72 months)
Part 2: Percentage of Participants With Serious TEAEs
A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose: Results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is medically significant.
From Part 2 Baseline until end of the OLE Period (up to 72 months)
Secondary Outcomes
Measure
Description
Time Frame
Part 1: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC-confirmed) in T+M in the ZX008 0.2 mg/kg/Day Group Compared to the Placebo Group
Percent change in frequency of seizures that result in drops (DSF: drop seizure frequency) per 28 days between the combined Titration and Maintenance (T+M) and Baseline. The percent change from Baseline DSF was calculated as the change in DSF between T+M and Baseline / DSF during Baseline* 100. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Key Inclusion Criteria:
Male or non-pregnant, non-lactating female, age 2 to 35 years, inclusive as of the day of the Screening Visit.
Clinical diagnosis of Lennox-Gastaut syndrome, where seizures that result in drops are not completely controlled by current antiepileptic treatments.
Onset of seizures at 11 years of age or younger.
Abnormal cognitive development.
Must be receiving at least 1 concomitant AED and up to 4 concomitant anti-epileptic treatments.
Key Exclusion Criteria:
Etiology of seizures is a degenerative neurological disease.
History of hemiclonic seizures in the first year of life.
Subject only has drop seizures in clusters, where individual seizures cannot be counted reliably.
Pulmonary arterial hypertension.
Current or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction or stroke.
Receiving concomitant therapy with: centrally-acting anorectic agents; monoamineoxidase inhibitors; any centrally-acting compound with clinically appreciable amount of serotonin agonist or antagonist properties, including serotonin reuptake inhibition; atomoxetine, or other centrally-acting noradrenergic agonist; cyproheptadine.
Taking felbamate for less than 1 year prior to screening and/or does not have stable liver function and hematology laboratory tests, and/or the dose has not been stable for at least 60 days prior to the Screening Visit.
Currently receiving an investigational product.
Institutionalized in a general nursing home (ie, in a facility that does not specialize in epilepsy care).
A clinically significant condition, or has had clinically relevant symptoms or a clinically significant illness in the 4 weeks prior to the Screening Visit, other than epilepsy, that would negatively impact study participation, collection of study data, or pose a risk to the subject.
Knupp KG, Scheffer IE, Ceulemans B, Sullivan JE, Nickels KC, Lagae L, Guerrini R, Zuberi SM, Nabbout R, Riney K, Shore S, Agarwal A, Lock M, Farfel GM, Galer BS, Gammaitoni AR, Davis R, Gil-Nagel A. Efficacy and Safety of Fenfluramine for the Treatment of Seizures Associated With Lennox-Gastaut Syndrome: A Randomized Clinical Trial. JAMA Neurol. 2022 Jun 1;79(6):554-564. doi: 10.1001/jamaneurol.2022.0829.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
Plan to Share IPD
Yes
Description
Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.
Types
Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame
Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
Access Criteria
Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.
The Participant Flow refers to the All Enrolled Participants Set for Part 1 and OLE Safety Population for Part 2 of the study. As planned, Part 2 summaries were presented by the participant's Part 1 treatment groups (placebo, ZX008 0.2 mg/kg/day, ZX008 0.8 mg/kg/day).
Recruitment Details
The study started to enroll participants in November 2017 and concluded in May 2024. Cohort A included participants enrolled at sites in North America, Europe, and Australia. Cohort B included participants enrolled at sites in Japan only.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
Periods
Title
Milestones
Reasons Not Completed
Part 1: Double-Blind Period
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Jul 25, 2022
May 1, 2025
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Austria
Submission Tracking
Estimated Results First Submitted Date
Not provided
Condition Browse Module
MeSH Terms
Intervention Browse Module
No data available
No data is available for this block.
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Part 1: Double-Blind ZX008 - (0.2 mg/kg/day or 0.8mg/kg/day) or Placebo and Part 2: Open-Label
Placebo will be administered twice a day (BID) in equally divided doses.
Matching Placebo
Placebo Comparator
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
Part 1: Percentage of Participants Who Achieve a >=50% Reduction From Baseline in the Frequency of Seizures That Result in Drops Comparing the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops. Participants who achieved a >=50% reduction from Baseline in the DSF, ie, a decrease in DSF of at least 50 percentage points per 28 days during Titration and Maintenance Period.
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
Part 1: Percentage of Participants Who Achieve Improvement (Minimally, Much or Very Much Improved) in the CGI-I Scale as Assessed by Principal Investigator Comparing ZX008 0.8 and 0.2 mg/kg/Day Groups Independently Versus Placebo
Clinical Global Impression - Improvement (CGI-I) scale measures improvement in the participant's condition from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved,2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse.
At Day 99 (Visit 12)
Part 1: Percent Change From Baseline in Frequency of All Seizures That Typically Result in Drops in T+M, Whether ESC-confirmed as Drop or Not in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Seizures that typically result in drops included all: generalized tonic-clonic seizures [GTC], secondarily generalized tonic-clonic [SGTC], tonic seizures [TS], atonic seizures [AS], and tonic/atonic seizures [TA], whether confirmed by the ESC or not. Seizures that result in a drop were defined as seizures involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the participant's head hitting a surface or that could have led to a fall or injury, depending on the patient's position at the time of the seizure.
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
Part 1: Percent Change From Baseline in the Frequency of All Countable Motor Seizures in T+M in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Countable motor seizures included: GTC, SGTC, TS, AS, TA, clonic seizures [CS], hemiclonic seizures [HS], and focal seizures [FS] with clearly observable signs.
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
Part 1: Change From Baseline in the Frequency of All Countable Non-motor Seizures in T+M in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Countable non-motor seizures included: focal seizures [FS] without clear observable signs, myoclonic seizures [MS], absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28.
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
Part 1: Percent Change From Baseline in the Frequency of All Countable Seizures (Motor and Non-motor) in T+M in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures.
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
Part 1: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC Confirmed) Between Baseline and the Maintenance Period
The frequency of drop seizures during a given interval was derived from the number and type of events recorded in participant electronic diaries. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops.
During Maintenance Period (12 weeks), compared to Baseline
Part 1: Percent Change From Baseline in the Frequency of Seizures That Typically Result in Drops in the Maintenance Period in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Seizures that typically result in drops included all: GTC, SGTC, TS, AS, and TA, whether confirmed by the ESC or not.
During Maintenance Period (12 weeks), compared to Baseline
Part 1: Percent Change From Baseline in the Frequency of All Countable Motor Seizures in the Maintenance Period in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Countable motor seizures included: GTC, SGTC,TS, AS, TA, CS, HS, and FS with clearly observable signs.
During Maintenance Period (12 weeks), compared to Baseline
Part 1: Change From Baseline in the Frequency of All Countable Non-motor Seizures in the Maintenance Period in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Countable non-motor seizures included: focal seizures [FS] without clear observable signs, myoclonic seizures [MS], absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28.
During Maintenance Period (12 weeks), compared to Baseline
Part 1: Percent Change From Baseline in the Frequency of All Countable Seizures (Motor and Non-motor) in the Maintenance Period in ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures.
During Maintenance Period (12 weeks), compared to Baseline
Part 1: Percent Change From Baseline in Frequency of Countable Seizures That do Not Result in Drops (ESC Confirmed)
Non-drop seizures were defined as any countable seizure types that did not meet the criteria of drop seizures, ie, are classified as CS, HC, FS with or without observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, or other; or are seizures of the following classifications that were approved for each participant as non-drop seizure types by the ESC: GTC, SGTC, TS, AS, or TA.
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <=0% Reduction), or >0, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Result in Drops
The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Typically Results in Drops
Seizures that typically result in drops included all: GTC, SGTC, TS, AS, and TA, whether confirmed by the ESC or not. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Motor Seizures
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Countable Motor Seizures That do Not Result in Drops
Countable motor seizures included: GTC, SGTC; TS, AS, TA, CS, HS, FS with clearly observable signs. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <= 0% Reduction), or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Seizures
Countable motor seizures included: GTC, SGTC; TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Non-motor Seizures
Countable non-motor seizures include: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
Part 1: Change From Baseline in Number of Seizure-free Days During T+M and M Period
A day with no seizures leading to a drop was defined as a day for which electronic (e) diary data were available and no drop seizures were reported. The total number of drop seizure-free days was calculated per 28 days for Baseline and for T+M.
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
Part 1: Duration of Longest Interval (Days) Between Seizures That Result in Drops Comparing the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
The longest interval between seizures leading to drops were obtained from the eDiary entries in Titration and Maintenance Period. The interval was derived as the maximum value of the number of days between consecutive drop seizures.
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
CGI-I scale measures improvement in the participant's condition from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved, 2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse.
At Days 15, 43, 71 and 99
Part 1: Percentage of Participants With TEAEs
Adverse events were defined as any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. A TEAE in Part 1 was defined as any AE that, based on start date information, occurred after the first dose of study drug in Part 1, but not on or after the first dose of study drug in Part 2.
Baseline up to 14 weeks + Taper/Transition (2 weeks)
Part 1: Percentage of Participants With Serious TEAEs
A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose: Results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is medically significant.
Baseline up to 14 weeks + Taper/Transition (2 weeks)
Part 1: Maximum Observed Plasma Concentration of Fenfluramine and Norfenfluramine Determined Directly From the Concentration Time Profile [Cmax] at Steady State
Cmax is the maximum plasma concentration determined directly from the concentration time profile.
At Visit 8 (Day 43) of the Maintenance Period: pre-dose, 1, 2, and 4-6 hours post-dose
Part 1: Minimum Observed Plasma Concentration of Fenfluramine and Norfenfluramine at Steady State Determined Directly From the Concentration-time Profile [Cmin] at Steady State
Cmin is the minimum plasma concentration determined directly from the concentration-time profile.
At Visit 8 (Day 43) of the Maintenance Period: pre-dose, 1, 2, and 4-6 hours post-dose
Part 1: Area Under the Concentration-time Curve of Fenfluramine and Norfenfluramine From Time Zero to Time 24 Hours [AUC0-24hours] at Steady State
AUC0-24 is the area under the concentration-time curve from time 0 to 24 hours.
At Visit 8 (Day 43) of the Maintenance Period: pre-dose, 1, 2, and 4-6 hours post-dose
Part 2: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC Confirmed) in OLE Period
The frequency of drop seizures during a given interval was derived from the number and type of events recorded in participant electronic diaries. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops.
From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Percent Change From Baseline in the Frequency of All Seizures That Typically Result in Drops Between Baseline and the OLE Period Whether ESC Confirmed as Drop or Not
Seizures that typically result in drops included all: generalized tonic-clonic seizures [GTC], secondarily generalized tonic-clonic [SGTC], tonic seizures [TS], atonic seizures [AS], and tonic/atonic seizures [TA], whether confirmed by the ESC or not. Seizures that result in a drop were defined as seizures involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the participant's head hitting a surface or that could have led to a fall or injury, depending on the patient's position at the time of the seizure.
From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Percent Change From Baseline in the Frequency of All Countable Motor Seizures in OLE Period
Countable motor seizures included: GTC, SGTC, TS, AS, TA, clonic seizures [CS], hemiclonic seizures [HS], and focal seizures [FS] with clearly observable signs.
From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Change From Baseline in the Frequency of All Countable Non-motor Seizures in OLE Period
Countable non-motor seizures included: focal seizures [FS] without clear observable signs, myoclonic seizures [MS], absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28.
From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Percent Change From Baseline in the Frequency of All Countable Seizures (ESC Confirmed or Not) in OLE Period
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures.
From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Change From Baseline in the Frequency of All Countable Seizures That Did Not Result in Drops (ESC Confirmed) in OLE Period
Nondrop seizures were defined as any countable seizure types that did not meet the criteria of drop seizures, ie, are classified as CS, HC, FS with or without observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, or other; or are seizures of the following classifications that were approved for each subject as non-drop seizure types by the ESC: GTC, SGTC, TS, AS, or TA. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28.
From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of Seizures That Result in Drops (ESC Confirmed)
The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of Seizures That Typically Result in Drops
Seizures that typically result in drops included all: GTC, SGTC, TS, AS, and TA, whether confirmed by the ESC or not. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Motor Seizures
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Non-motor Seizures
Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Seizures
Countable motor seizures included: GTC, SGTC; TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
From OLE Month 1 to Month12, compared to Baseline (Part 1)
Part 2: Change From Baseline in Number of Seizure-free Days Per 28 Days (ESC Confirmed) in OLE Period
A day with no seizures leading to a drop was defined as a day for which ediary data were available and no drop seizures were reported.
From Part 2 Baseline until end of OLE Period (up to 72 months)
Part 2: Change From Baseline in Duration of Longest Interval Between Seizures That Result in Drops (ESC Confirmed) in OLE Period
The longest interval between seizures leading to drops were obtained from the eDiary entries in OLE Period. The interval was derived as the maximum value of the number of days between consecutive drop seizures.
From Part 2 Baseline until end of the OLE Period (up to 72 months)
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
CGI-I scale measures improvement in the participant's condition from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved,2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse.
At OLE Day 1, OLE Months (M) 1, 2, 3, 6, 9, 12, and Last Assessment (up to 72 months)
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
CGI-I scale measures improvement in the participant's condition from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved,2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse.
At OLE Day 1, OLE Months (M) 1, 2, 3, 6, 9, 12, and Last Assessment (up to 72 months)
Los Angeles
California
90095-1752
United States
Ep0214 101
San Francisco
California
94158
United States
Ep0214 103
Aurora
Colorado
80045
United States
Ep0214 149
Washington D.C.
District of Columbia
20010
United States
Ep0214 115
Gulf Breeze
Florida
32561
United States
Ep0214 104
Miami
Florida
33155
United States
Ep0214 141
Orlando
Florida
32803
United States
Ep0214 121
Orlando
Florida
32819
United States
Ep0214 117
Atlanta
Georgia
30328
United States
Ep0214 110
Chicago
Illinois
60611
United States
Ep0214 140
Bethesda
Maryland
20817
United States
Ep0214 112
Boston
Massachusetts
02114
United States
Ep0214 136
Grand Rapids
Michigan
49503
United States
Ep0214 147
Royal Oak
Michigan
48073
United States
Ep0214 109
Rochester
Minnesota
55905
United States
Ep0214 132
Saint Paul
Minnesota
55102
United States
Ep0214 105
Hackensack
New Jersey
07601
United States
Ep0214 118
Livingston
New Jersey
07039
United States
Ep0214 150
Hartsdale
New York
10530
United States
Ep0214 142
New York
New York
10016
United States
Ep0214 131
Cleveland
Ohio
44106
United States
Ep0214 143
Portland
Oregon
97239
United States
Ep0214 120
Philadelphia
Pennsylvania
19104-4318
United States
Ep0214 139
York
Pennsylvania
17403
United States
Ep0214 146
Dallas
Texas
75235
United States
Ep0214 126
Fort Worth
Texas
76104
United States
Ep0214 145
San Antonio
Texas
78207-3108
United States
Ep0214 106
Salt Lake City
Utah
84113
United States
Ep0214 125
Tacoma
Washington
98405
United States
Ep0214 301
Heidelberg
Australia
Ep0214 302
South Brisbane
Australia
Ep0214 802
Brussels
Belgium
Ep0214 803
Brussels
Belgium
Ep0214 801
Edegem
Belgium
Ep0214 204
Toronto
Canada
Ep0214 201
Vancouver
Canada
Ep0214 701
Dianalund
Denmark
Ep0214 1004
Bordeaux
France
Ep0214 1006
Bron
France
Ep0214 1005
Lille
France
Ep0214 1007
Marseille
France
Ep0214 1001
Paris
France
Ep0214 1002
Paris
France
Ep0214 902
Bielefeld
Germany
Ep0214 906
Freiburg im Breisgau
Germany
Ep0214 905
Jena
Germany
Ep0214 908
Kiel
Germany
Ep0214 903
Radeberg
Germany
Ep0214 901
Vogtareuth
Germany
Ep0214 1211
Bologna
Italy
Ep0214 1201
Florence
Italy
Ep0214 1204
Genova
Italy
Ep0214 1206
Roma
Italy
Ep0214 1208
Roma
Italy
Ep0214 1510
Fukuoka
Japan
Ep0214 1505
Niigata
Japan
Ep0214 1501
Okayama
Japan
Ep0214 1507
Osaka
Japan
Ep0214 1504
Ōmura
Japan
Ep0214 1508
Sapporo
Japan
Ep0214 1506
Shinjuku-ku
Japan
Ep0214 1502
Shizuoka
Japan
Ep0214 1604
Guadalajara
Mexico
Ep0214 1401
Zwolle
Netherlands
Ep0214 1702
Bydgoszcz
Poland
Ep0214 1701
Krakow
Poland
Ep0214 1105
Barcelona
Spain
Ep0214 1107
Barcelona
Spain
Ep0214 1101
Mirasierra
Spain
Ep0214 1102
Pamplona
Spain
Ep0214 502
Gothenburg
Sweden
FG001
Cohort A: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
FG002
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
FG003
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
FG004
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
FG005
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
FG00087 subjects
FG00189 subjects
FG00287 subjects
FG00311 subjects
FG00411 subjects
FG00511 subjects
COMPLETED
Participants who completed visits up to Week 14 or transitioned early to Part 2
FG00086 subjects
FG00183 subjects
FG00281 subjects
FG00311 subjects
FG00410 subjects
FG00511 subjects
NOT COMPLETED
FG0001 subjects
FG0016 subjects
FG0026 subjects
FG0030 subjects
FG0041 subjects
FG0050 subjects
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0014 subjects
FG0024 subjects
FG0030 subjects
FG0041 subjects
FG0050 subjects
Death
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Physician Decision
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Withdrawal by Subject
FG0001 subjects
FG0011 subjects
FG0021 subjects
FG0030 subjects
FG004
Part 2:Open-Label Extension (OLE) Period
Type
Comment
Milestone Data
STARTED
FG00086 subjects
FG00183 subjects
FG00278 subjects
FG00311 subjects
FG00410 subjects
FG00511 subjects
COMPLETED
FG00061 subjects
FG00151 subjects
FG00246 subjects
FG0035 subjects
FG004
NOT COMPLETED
FG00025 subjects
FG00132 subjects
FG00232 subjects
FG0036 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0005 subjects
FG0015 subjects
FG0023 subjects
FG003
Baseline characteristics refers to Safety Population which consisted of all randomized participants who received at least 1 dose of study drug.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
BG001
Cohort A: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
BG002
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
BG003
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
BG004
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
BG005
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
BG006
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00087
BG00189
BG00287
BG00311
BG00411
BG00511
BG006296
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00014.4± 7.71
BG00113.4± 7.79
BG00213.4± 7.28
BG003
Age, Customized
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
2 - < 12 years
BG00032
BG00141
BG002
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00041
BG00143
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
White
BG00071
BG00167
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG00016
BG00121
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Part 1: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC-confirmed) in the Combined Titration and Maintenance Period (T+M) in the ZX008 0.8 mg/kg/Day Group Compared to the Placebo Group
Percent change in frequency of seizures that result in drops (DSF: drop seizure frequency) per 28 days between the combined Titration and Maintenance (T+M) and Baseline. The percent change from Baseline DSF was calculated as the change in DSF between T+M and Baseline / DSF during Baseline* 100. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops.
The Modified Intent-to-Treat (mITT) Population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.
Posted
Median
Full Range
percent change
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
ID
Title
Description
OG000
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG001
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG002
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG003
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG00087
OG00187
OG00211
OG003
Title
Denominators
Categories
Title
Measurements
OG000-7.59(-100.0 to 557.1)
OG001-26.49(-95.2 to 402.1)
OG002-17.89(-97.3 to 61.8)
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Wilcoxon (Mann-Whitney)
0.0008
Median Difference (A-P)
-19.88
2-Sided
95
-31.02
-8.74
Hodges-Lehmann (HL) method
Superiority
Primary
Part 2: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
An Adverse event (AE) was defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of investigational product, or whether considered related to the investigational product. A TEAE in Part 2 was defined as any AE with an onset on or after the first dose in Part 2. AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2.
The OLE Safety Population included all participants who received at least 1 dose of ZX008 during the OLE. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
Posted
Number
percentage of participants
From Part 2 Baseline until end of the OLE Period (up to 72 months)
ID
Title
Description
OG000
Part 2: Cohort A- Overall
All Cohort A participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period.
OG001
Part 2: Cohort B- Overall
Primary
Part 2: Percentage of Participants With Serious TEAEs
A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose: Results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is medically significant.
The OLE Safety Population included all participants who received at least 1 dose of ZX008 during the OLE. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
Posted
Number
percentage of participants
From Part 2 Baseline until end of the OLE Period (up to 72 months)
ID
Title
Description
OG000
Part 2: Cohort A- Overall
All Cohort A participants who continued in Part 2 received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period.
OG001
Part 2: Cohort B- Overall
Secondary
Part 1: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC-confirmed) in T+M in the ZX008 0.2 mg/kg/Day Group Compared to the Placebo Group
Percent change in frequency of seizures that result in drops (DSF: drop seizure frequency) per 28 days between the combined Titration and Maintenance (T+M) and Baseline. The percent change from Baseline DSF was calculated as the change in DSF between T+M and Baseline / DSF during Baseline* 100. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops.
The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.
Posted
Median
Full Range
percent change
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
ID
Title
Description
OG000
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG001
Cohort A: ZX008 0.2 mg/kg/Day
Secondary
Part 1: Percentage of Participants Who Achieve a >=50% Reduction From Baseline in the Frequency of Seizures That Result in Drops Comparing the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops. Participants who achieved a >=50% reduction from Baseline in the DSF, ie, a decrease in DSF of at least 50 percentage points per 28 days during Titration and Maintenance Period.
The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.
Posted
Number
percentage of participants
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
ID
Title
Description
OG000
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG001
Cohort A: ZX008 0.2 mg/kg/Day
Secondary
Part 1: Percentage of Participants Who Achieve Improvement (Minimally, Much or Very Much Improved) in the CGI-I Scale as Assessed by Principal Investigator Comparing ZX008 0.8 and 0.2 mg/kg/Day Groups Independently Versus Placebo
Clinical Global Impression - Improvement (CGI-I) scale measures improvement in the participant's condition from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved,2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse.
The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment.
Posted
Number
percentage of participants
At Day 99 (Visit 12)
ID
Title
Description
OG000
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG001
Secondary
Part 1: Percent Change From Baseline in Frequency of All Seizures That Typically Result in Drops in T+M, Whether ESC-confirmed as Drop or Not in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Seizures that typically result in drops included all: generalized tonic-clonic seizures [GTC], secondarily generalized tonic-clonic [SGTC], tonic seizures [TS], atonic seizures [AS], and tonic/atonic seizures [TA], whether confirmed by the ESC or not. Seizures that result in a drop were defined as seizures involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the participant's head hitting a surface or that could have led to a fall or injury, depending on the patient's position at the time of the seizure.
The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.
Posted
Median
Full Range
percent change
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
ID
Title
Description
OG000
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
Secondary
Part 1: Percent Change From Baseline in the Frequency of All Countable Motor Seizures in T+M in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Countable motor seizures included: GTC, SGTC, TS, AS, TA, clonic seizures [CS], hemiclonic seizures [HS], and focal seizures [FS] with clearly observable signs.
The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.
Posted
Median
Full Range
percent change
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
ID
Title
Description
OG000
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG001
Cohort A: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
Secondary
Part 1: Change From Baseline in the Frequency of All Countable Non-motor Seizures in T+M in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Countable non-motor seizures included: focal seizures [FS] without clear observable signs, myoclonic seizures [MS], absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28.
The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.
Posted
Median
Full Range
seizure frequency per 28 days
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
ID
Title
Description
OG000
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG001
Cohort A: ZX008 0.2 mg/kg/Day
Secondary
Part 1: Percent Change From Baseline in the Frequency of All Countable Seizures (Motor and Non-motor) in T+M in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures.
The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.
Posted
Median
Full Range
percent change
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
ID
Title
Description
OG000
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG001
Cohort A: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
Secondary
Part 1: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC Confirmed) Between Baseline and the Maintenance Period
The frequency of drop seizures during a given interval was derived from the number and type of events recorded in participant electronic diaries. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops.
The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment.
Posted
Median
Full Range
percent change
During Maintenance Period (12 weeks), compared to Baseline
ID
Title
Description
OG000
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG001
Cohort A: ZX008 0.2 mg/kg/Day
Secondary
Part 1: Percent Change From Baseline in the Frequency of Seizures That Typically Result in Drops in the Maintenance Period in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Seizures that typically result in drops included all: GTC, SGTC, TS, AS, and TA, whether confirmed by the ESC or not.
The mITT Population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment.
Posted
Median
Full Range
percent change
During Maintenance Period (12 weeks), compared to Baseline
ID
Title
Description
OG000
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG001
Cohort A: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
Secondary
Part 1: Percent Change From Baseline in the Frequency of All Countable Motor Seizures in the Maintenance Period in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Countable motor seizures included: GTC, SGTC,TS, AS, TA, CS, HS, and FS with clearly observable signs.
The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment.
Posted
Median
Full Range
percent change
During Maintenance Period (12 weeks), compared to Baseline
ID
Title
Description
OG000
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG001
Cohort A: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
Secondary
Part 1: Change From Baseline in the Frequency of All Countable Non-motor Seizures in the Maintenance Period in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Countable non-motor seizures included: focal seizures [FS] without clear observable signs, myoclonic seizures [MS], absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28.
The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment.
Posted
Median
Full Range
seizure frequency per 28 days
During Maintenance Period (12 weeks), compared to Baseline
ID
Title
Description
OG000
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG001
Secondary
Part 1: Percent Change From Baseline in the Frequency of All Countable Seizures (Motor and Non-motor) in the Maintenance Period in ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures.
The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment.
Posted
Median
Full Range
percent change
During Maintenance Period (12 weeks), compared to Baseline
ID
Title
Description
OG000
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG001
Cohort A: ZX008 0.2 mg/kg/Day
Secondary
Part 1: Percent Change From Baseline in Frequency of Countable Seizures That do Not Result in Drops (ESC Confirmed)
Non-drop seizures were defined as any countable seizure types that did not meet the criteria of drop seizures, ie, are classified as CS, HC, FS with or without observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, or other; or are seizures of the following classifications that were approved for each participant as non-drop seizure types by the ESC: GTC, SGTC, TS, AS, or TA.
The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment.
Posted
Median
Full Range
percent change
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
ID
Title
Description
OG000
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG001
Cohort A: ZX008 0.2 mg/kg/Day
Secondary
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <=0% Reduction), or >0, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Result in Drops
The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, Number Analyzed included those participants who were evaluable at specified time point.
Posted
Number
percentage of participants
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
ID
Title
Description
OG000
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
Secondary
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Typically Results in Drops
Seizures that typically result in drops included all: GTC, SGTC, TS, AS, and TA, whether confirmed by the ESC or not. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number analyzed included those participants who were evaluable at specified time point.
Posted
Number
percentage of participants
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
ID
Title
Description
OG000
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
Secondary
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Motor Seizures
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number analyzed included those participants who were evaluable at specified time point.
Posted
Number
percentage of participants
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
ID
Title
Description
OG000
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
Secondary
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Countable Motor Seizures That do Not Result in Drops
Countable motor seizures included: GTC, SGTC; TS, AS, TA, CS, HS, FS with clearly observable signs. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment. Number analyzed included those participants who were evaluable at specified time point.
Posted
Number
percentage of participants
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
ID
Title
Description
OG000
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
Secondary
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <= 0% Reduction), or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Seizures
Countable motor seizures included: GTC, SGTC; TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number analyzed included those participants who were evaluable at specified time point.
Posted
Number
percentage of participants
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
ID
Title
Description
OG000
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
Secondary
Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Non-motor Seizures
Countable non-motor seizures include: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during T+M); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during combined T+M Period and Maintenance Period were reported.
The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment. Number analyzed included those participants who were evaluable at specified time point.
Posted
Number
percentage of participants
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
ID
Title
Description
OG000
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
Secondary
Part 1: Change From Baseline in Number of Seizure-free Days During T+M and M Period
A day with no seizures leading to a drop was defined as a day for which electronic (e) diary data were available and no drop seizures were reported. The total number of drop seizure-free days was calculated per 28 days for Baseline and for T+M.
The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number analyzed included those participants who were evaluable for specified category.
Posted
Median
Full Range
seizure free days per 28 days
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline
ID
Title
Description
OG000
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG001
Cohort A: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
Secondary
Part 1: Duration of Longest Interval (Days) Between Seizures That Result in Drops Comparing the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo
The longest interval between seizures leading to drops were obtained from the eDiary entries in Titration and Maintenance Period. The interval was derived as the maximum value of the number of days between consecutive drop seizures.
The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.
Posted
Median
Full Range
days
From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]
ID
Title
Description
OG000
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG001
Cohort A: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
Secondary
Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
CGI-I scale measures improvement in the participant's condition from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved, 2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse.
The mITT population included all randomized participants who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available. Here, number of participants analyzed included those participants who were evaluable for the assessment. Number analyzed included those participants who were evaluable at specified time point.
Posted
Number
percentage of participants
At Days 15, 43, 71 and 99
ID
Title
Description
OG000
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG001
Cohort A: ZX008 0.2 mg/kg/Day
Secondary
Part 1: Percentage of Participants With TEAEs
Adverse events were defined as any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. A TEAE in Part 1 was defined as any AE that, based on start date information, occurred after the first dose of study drug in Part 1, but not on or after the first dose of study drug in Part 2.
The Safety Population included all randomized participants who received at least 1 dose of study drug.
Posted
Number
percentage of participants
Baseline up to 14 weeks + Taper/Transition (2 weeks)
ID
Title
Description
OG000
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG001
Cohort A: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
Secondary
Part 1: Percentage of Participants With Serious TEAEs
A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose: Results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is medically significant.
The Safety Population included all randomized participants who received at least 1 dose of study drug.
Posted
Number
percentage of participants
Baseline up to 14 weeks + Taper/Transition (2 weeks)
ID
Title
Description
OG000
Cohort A: Placebo
Part 1: Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG001
Cohort A: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
Secondary
Part 1: Maximum Observed Plasma Concentration of Fenfluramine and Norfenfluramine Determined Directly From the Concentration Time Profile [Cmax] at Steady State
Cmax is the maximum plasma concentration determined directly from the concentration time profile.
The Pharmacokinetic (PK) analysis set included those participants who received at least one dose of ZX008 and at least one plasma concentration measurement in Study ZX008-1601.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanograms per milliliter (ng/mL)
At Visit 8 (Day 43) of the Maintenance Period: pre-dose, 1, 2, and 4-6 hours post-dose
ID
Title
Description
OG000
Cohort A: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG001
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
Secondary
Part 1: Minimum Observed Plasma Concentration of Fenfluramine and Norfenfluramine at Steady State Determined Directly From the Concentration-time Profile [Cmin] at Steady State
Cmin is the minimum plasma concentration determined directly from the concentration-time profile.
The PK analysis set included those participants who received at least one dose of ZX008 and at least one plasma concentration measurement in Study ZX008-1601.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
At Visit 8 (Day 43) of the Maintenance Period: pre-dose, 1, 2, and 4-6 hours post-dose
ID
Title
Description
OG000
Cohort A: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG001
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
Secondary
Part 1: Area Under the Concentration-time Curve of Fenfluramine and Norfenfluramine From Time Zero to Time 24 Hours [AUC0-24hours] at Steady State
AUC0-24 is the area under the concentration-time curve from time 0 to 24 hours.
The PK analysis set included those participants who received at least one dose of ZX008 and at least one plasma concentration measurement in Study ZX008-1601.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanograms*hour per milliliter (ng*h/mL)
At Visit 8 (Day 43) of the Maintenance Period: pre-dose, 1, 2, and 4-6 hours post-dose
ID
Title
Description
OG000
Cohort A: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG001
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
Secondary
Part 2: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC Confirmed) in OLE Period
The frequency of drop seizures during a given interval was derived from the number and type of events recorded in participant electronic diaries. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops.
The Open-Label Extension Modified Intent-To-Treat (mITT) Population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
Posted
Median
Full Range
percent change
From OLE Month 1 to Month12, compared to Baseline (Part 1)
ID
Title
Description
OG000
Part 2: Cohort A- Overall
All Cohort A participants who continued in Part 2 received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period.
Secondary
Part 2: Percent Change From Baseline in the Frequency of All Seizures That Typically Result in Drops Between Baseline and the OLE Period Whether ESC Confirmed as Drop or Not
Seizures that typically result in drops included all: generalized tonic-clonic seizures [GTC], secondarily generalized tonic-clonic [SGTC], tonic seizures [TS], atonic seizures [AS], and tonic/atonic seizures [TA], whether confirmed by the ESC or not. Seizures that result in a drop were defined as seizures involving the entire body, trunk, or head that led to a fall, injury, slumping in a chair, or the participant's head hitting a surface or that could have led to a fall or injury, depending on the patient's position at the time of the seizure.
The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
Posted
Median
Full Range
percent change
From OLE Month 1 to Month12, compared to Baseline (Part 1)
ID
Title
Description
OG000
Part 2: Cohort A- Overall
All Cohort A participants who continued in Part 2 received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period.
Secondary
Part 2: Percent Change From Baseline in the Frequency of All Countable Motor Seizures in OLE Period
Countable motor seizures included: GTC, SGTC, TS, AS, TA, clonic seizures [CS], hemiclonic seizures [HS], and focal seizures [FS] with clearly observable signs.
The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
Posted
Median
Full Range
percent change
From OLE Month 1 to Month12, compared to Baseline (Part 1)
ID
Title
Description
OG000
Part 2: Cohort A- Overall
All Cohort A participants who continued in Part 2 received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period.
OG001
Part 2: Cohort B- Overall
Secondary
Part 2: Change From Baseline in the Frequency of All Countable Non-motor Seizures in OLE Period
Countable non-motor seizures included: focal seizures [FS] without clear observable signs, myoclonic seizures [MS], absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28.
The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
Posted
Median
Full Range
seizure frequency per 28 days
From OLE Month 1 to Month12, compared to Baseline (Part 1)
ID
Title
Description
OG000
Part 2: Cohort A- Overall
All Cohort A participants who continued in Part 2 received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period.
Secondary
Part 2: Percent Change From Baseline in the Frequency of All Countable Seizures (ESC Confirmed or Not) in OLE Period
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures.
The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
Posted
Median
Full Range
percent change
From OLE Month 1 to Month12, compared to Baseline (Part 1)
ID
Title
Description
OG000
Part 2: Cohort A- Overall
All Cohort A participants who continued in Part 2 received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period.
OG001
Secondary
Part 2: Change From Baseline in the Frequency of All Countable Seizures That Did Not Result in Drops (ESC Confirmed) in OLE Period
Nondrop seizures were defined as any countable seizure types that did not meet the criteria of drop seizures, ie, are classified as CS, HC, FS with or without observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, or other; or are seizures of the following classifications that were approved for each subject as non-drop seizure types by the ESC: GTC, SGTC, TS, AS, or TA. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28.
The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
Posted
Median
Full Range
seizure frequency per 28 days
From OLE Month 1 to Month12, compared to Baseline (Part 1)
ID
Title
Description
OG000
Part 2: Cohort A- Overall
All Cohort A participants who continued in Part 2 received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period.
Secondary
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of Seizures That Result in Drops (ESC Confirmed)
The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
Posted
Number
percentage of participants
From OLE Month 1 to Month12, compared to Baseline (Part 1)
ID
Title
Description
OG000
Part 2: Cohort A- Overall
All Cohort A participants who continued in Part 2 received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period.
Secondary
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of Seizures That Typically Result in Drops
Seizures that typically result in drops included all: GTC, SGTC, TS, AS, and TA, whether confirmed by the ESC or not. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
Posted
Number
percentage of participants
From OLE Month 1 to Month12, compared to Baseline (Part 1)
ID
Title
Description
OG000
Part 2: Cohort A- Overall
All Cohort A participants who continued in Part 2 received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period.
Secondary
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Motor Seizures
Countable motor seizures included: GTC, SGTC, TS, AS, TA, CS, HS, and FS with clearly observable signs. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
Posted
Number
percentage of participants
From OLE Month 1 to Month12, compared to Baseline (Part 1)
ID
Title
Description
OG000
Part 2: Cohort A- Overall
All Cohort A participants who continued in Part 2 received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period.
Secondary
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Non-motor Seizures
Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
Posted
Number
percentage of participants
From OLE Month 1 to Month12, compared to Baseline (Part 1)
ID
Title
Description
OG000
Part 2: Cohort A- Overall
All Cohort A participants who continued in Part 2 received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period.
Secondary
Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Seizures
Countable motor seizures included: GTC, SGTC; TS, AS, TA, CS, HS, and FS with clearly observable signs. Countable non-motor seizures included: FS without clear observable signs, MS, absence/atypical absence, infantile spasms, epileptic spasms, and other seizures. The participants who experienced a worsening or no change from Baseline (ie <= 0% reduction); >0%, >=25%, >=50%, >=75%, and 100% reduction (a 100% reduction was equivalent to achieving seizure freedom during OLE Period); and "near seizure freedom," (defined as 0 or 1 seizure leading to a drop) during OLE Period were reported.
The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
Posted
Number
percentage of participants
From OLE Month 1 to Month12, compared to Baseline (Part 1)
ID
Title
Description
OG000
Part 2: Cohort A- Overall
All Cohort A participants who continued in Part 2 received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period.
Secondary
Part 2: Change From Baseline in Number of Seizure-free Days Per 28 Days (ESC Confirmed) in OLE Period
A day with no seizures leading to a drop was defined as a day for which ediary data were available and no drop seizures were reported.
The OLE mITT population included all participants who received at least 1 dose of ZX008 and had a valid estimate of the frequency of seizures that resulted in drops from Part 1 and at least 1 month (30 days) of valid seizure data during the OLE. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
Posted
Median
Full Range
seizure free days per 28 days
From Part 2 Baseline until end of OLE Period (up to 72 months)
ID
Title
Description
OG000
Part 2: Cohort A- Overall
All Cohort A participants who continued in Part 2 received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period.
OG001
Part 2: Cohort B- Overall
Secondary
Part 2: Change From Baseline in Duration of Longest Interval Between Seizures That Result in Drops (ESC Confirmed) in OLE Period
The longest interval between seizures leading to drops were obtained from the eDiary entries in OLE Period. The interval was derived as the maximum value of the number of days between consecutive drop seizures.
OLE mITT:all participants who received at least 1 dose of ZX008 and had valid estimate of frequency of seizures that resulted in drops from Part 1 and at least 1 month(30 days) of valid seizure data during OLE. Number of participants analyzed=participants who were evaluable for assessment. As pre-specified in study design, participants in Part 2 received individualized optimized treatment(0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
Posted
Median
Full Range
days
From Part 2 Baseline until end of the OLE Period (up to 72 months)
ID
Title
Description
OG000
Part 2: Cohort A- Overall
All Cohort A participants who continued in Part 2 received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period.
OG001
Secondary
Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator
CGI-I scale measures improvement in the participant's condition from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved,2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse.
OLE mITT:participants who received >=1 dose of ZX008, had valid estimate of frequency of seizures that resulted in drops from Part 1 and at least 1 month(30 days) of valid seizure data during OLE. N: participants evaluable for assessment. n: participants evaluable at specified time point. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
Posted
Number
percentage of participants
At OLE Day 1, OLE Months (M) 1, 2, 3, 6, 9, 12, and Last Assessment (up to 72 months)
ID
Title
Description
OG000
Part 2: Cohort A- Overall
All Cohort A participants who continued in Part 2 received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period.
Secondary
Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver
CGI-I scale measures improvement in the participant's condition from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved,2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse.
OLE mITT:all participants who received >= 1 dose of ZX008, had valid estimate of frequency of seizures that resulted in drops from Part 1 and >= 1 month(30 days) of valid seizure data during OLE. N: participants evaluable for assessment. n: participants evaluable at specified time point. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
Posted
Number
percentage of participants
At OLE Day 1, OLE Months (M) 1, 2, 3, 6, 9, 12, and Last Assessment (up to 72 months)
ID
Title
Description
OG000
Part 2: Cohort A- Overall
All Cohort A participants who continued in Part 2 received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period.
Time Frame
From Day 1 up to 72 months
Description
AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2. Safety Population and OLE Safety Population were assessed. As pre-specified in study design, participants in Part 2 received individualized optimized treatment (0.2 mg/kg/day to 0.8 mg/kg/day) based on Investigator discretion. Hence overall data for Part 2 is reported.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Part 1: Cohort A- Placebo
Participants received matching placebo as an oral solution, twice a day (bid) over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days.
0
87
4
87
60
87
EG001
Part 1: Cohort A- ZX008 0.2 mg/kg/Day
Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days.
0
89
4
89
64
89
EG002
Part 1: Cohort A- ZX008 0.8 mg/kg/Day
Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days.
1
87
10
87
68
87
EG003
Part 2: Cohort A- Overall
All Cohort A participants who continued in Part 2 received ZX008 0.2 milligram per kilogram per day (mg/kg/day) as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period.
1
247
41
247
166
247
EG004
Part 1: Cohort B- Placebo
Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days.
0
11
1
11
8
11
EG005
Part 1: Cohort B- ZX008 0.2 mg/kg/Day
Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days.
0
11
1
11
10
11
EG006
Part 1: Cohort B- ZX008 0.8 mg/kg/Day
Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days.
0
11
0
11
7
11
EG007
Part 2: Cohort B- Overall
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Browse Leaves
Not provided
Browse Branches
Not provided
0 subjects
FG0050 subjects
0 subjects
FG0050 subjects
0 subjects
FG0050 subjects
1 subjects
FG0055 subjects
9 subjects
FG0056 subjects
0 subjects
FG0041 subjects
FG0051 subjects
Death
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Lack of Efficacy
FG00013 subjects
FG00121 subjects
FG00223 subjects
FG0030 subjects
FG0040 subjects
FG0051 subjects
Switching to commercial ZX008
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0035 subjects
FG0046 subjects
FG0053 subjects
Withdrawal by Subject
FG0006 subjects
FG0015 subjects
FG0024 subjects
FG0030 subjects
FG0042 subjects
FG0050 subjects
Physician Decision
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG0040 subjects
FG0051 subjects
Rollover into ZX008-1900
FG0001 subjects
FG0010 subjects
FG0022 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
18.5
± 7.78
BG00420.1± 7.79
BG00518.5± 7.94
BG00614.3± 7.76
37
BG0032
BG0043
BG0052
BG006117
12 - < 18 years
BG00029
BG00123
BG00225
BG0035
BG0042
BG0053
BG00687
18 - 35 years
BG00026
BG00125
BG00225
BG0034
BG0046
BG0056
BG00692
33
BG0035
BG0042
BG0052
BG006126
Male
BG00046
BG00146
BG00254
BG0036
BG0049
BG0059
BG006170
70
BG0030
BG0040
BG0050
BG006208
Black or African American
BG0004
BG0015
BG0023
BG0030
BG0040
BG0050
BG00612
Asian
BG0002
BG0013
BG0024
BG00311
BG00411
BG00511
BG00642
Native Hawaiian or Other Pacific Islander
BG0000
BG0011
BG0020
BG0030
BG0040
BG0050
BG0061
Not Reported
BG0006
BG00111
BG0027
BG0030
BG0040
BG0050
BG00624
Unknown
BG0002
BG0012
BG0022
BG0030
BG0040
BG0050
BG0066
Multiple
BG0002
BG0010
BG0021
BG0030
BG0040
BG0050
BG0063
14
BG0030
BG0040
BG0050
BG00651
Not Hispanic or Latino
BG00065
BG00158
BG00266
BG00311
BG00411
BG00511
BG006222
Not Reported
BG0006
BG00110
BG0027
BG0030
BG0040
BG0050
BG00623
11
-34.52
(-69.4 to 45.5)
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG000247
OG00132
Title
Denominators
Categories
Title
Measurements
OG00083.0
OG00196.9
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG000247
OG00132
Title
Denominators
Categories
Title
Measurements
OG00016.6
OG00118.8
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG002
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG003
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG00087
OG00189
OG00211
OG00311
Title
Denominators
Categories
Title
Measurements
OG000-7.59(-100.0 to 557.1)
OG001-14.16(-100.0 to 3307.3)
OG002-17.89(-97.3 to 61.8)
OG003-14.12(-95.6 to 66.4)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Wilcoxon (Mann-Whitney)
0.1460
Median Difference (A-P)
-10.50
2-Sided
95
-24.99
3.99
Hodges-Lehmann (HL) method
Superiority
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG002
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG003
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG004
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG005
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG00087
OG00189
OG00287
OG00311
OG00411
OG00511
Title
Denominators
Categories
Title
Measurements
OG00010.3
OG00128.1
OG00225.3
OG0039.1
OG00436.4
OG00536.4
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Regression, Logistic
0.0051
Odds Ratio (OR)
3.30
2-Sided
95
1.43
7.59
Superiority
OG000
OG002
Regression, Logistic
0.0150
Odds Ratio (OR)
2.87
2-Sided
95
1.23
6.70
Superiority
Cohort A: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG002
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG003
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG004
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG005
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG00080
OG00185
OG00280
OG00311
OG00411
OG00511
Title
Denominators
Categories
Title
Measurements
OG00033.8
OG00144.7
OG00248.8
OG0039.1
OG00445.5
OG00572.7
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Visit 12
Cochran-Mantel-Haenszel
0.1565
Odds Ratio (OR)
1.58
2-Sided
95
0.84
2.97
Superiority
OG000
OG002
Visit 12
Cochran-Mantel-Haenszel
0.0567
Odds Ratio (OR)
1.86
2-Sided
95
0.98
3.52
Superiority
OG001
Cohort A: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG002
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG003
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG004
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG005
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG00087
OG00189
OG00287
OG00311
OG00411
OG00511
Title
Denominators
Categories
Title
Measurements
OG000-8.43(-100.0 to 557.1)
OG001-11.75(-100.0 to 3307.3)
OG002-26.28(-95.2 to 402.1)
OG003-17.89(-97.3 to 61.8)
OG004-14.12(-95.6 to 66.4)
OG005-34.04(-69.4 to 45.5)
OG002
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG003
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG004
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG005
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG00087
OG00189
OG00287
OG00311
OG00411
OG00511
Title
Denominators
Categories
Title
Measurements
OG000-8.43(-80.8 to 497.8)
OG001-11.75(-100.0 to 3307.3)
OG002-26.28(-91.9 to 402.1)
OG003-17.89(-97.3 to 61.8)
OG004-14.12(-95.6 to 174.1)
OG005-34.04(-69.4 to 45.5)
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG002
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG003
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG004
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG005
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG00087
OG00189
OG00287
OG00311
OG00411
OG00511
Title
Denominators
Categories
Title
Measurements
OG0000.00(-338.3 to 364.3)
OG0010.00(-418.7 to 675.8)
OG0020.00(-364.0 to 2952.7)
OG003-7.16(-30.3 to 13.1)
OG0040.00(-32.3 to 104.8)
OG0050.00(-61.6 to 209.5)
OG002
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG003
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG004
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG005
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG00087
OG00189
OG00287
OG00311
OG00411
OG00511
Title
Denominators
Categories
Title
Measurements
OG000-9.40(-85.4 to 497.8)
OG001-23.55(-100.0 to 882.1)
OG002-21.70(-91.9 to 224.9)
OG003-17.69(-97.2 to 61.8)
OG004-20.41(-87.1 to 826.2)
OG005-13.85(-64.9 to 63.8)
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG002
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG003
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG004
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG005
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG00087
OG00188
OG00286
OG00311
OG00411
OG00511
Title
Denominators
Categories
Title
Measurements
OG000-7.28(-100.0 to 516.7)
OG001-18.63(-100.0 to 964.0)
OG002-27.16(-100.0 to 643.3)
OG003-18.18(-99.4 to 66.7)
OG004-12.88(-100.0 to 239.4)
OG005-45.07(-77.8 to 52.2)
OG002
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG003
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG004
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG005
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG00087
OG00188
OG00286
OG00311
OG00411
OG00511
Title
Denominators
Categories
Title
Measurements
OG000-9.37(-100.0 to 516.7)
OG001-17.30(-100.0 to 964.0)
OG002-26.30(-100.0 to 643.3)
OG003-18.18(-99.4 to 66.7)
OG004-12.88(-100.0 to 239.4)
OG005-46.88(-77.8 to 52.2)
OG002
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG003
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG004
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG005
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG00087
OG00188
OG00286
OG00311
OG00411
OG00511
Title
Denominators
Categories
Title
Measurements
OG000-10.21(-81.1 to 439.8)
OG001-17.30(-100.0 to 964.0)
OG002-28.33(-100.0 to 643.3)
OG003-18.18(-99.4 to 66.7)
OG004-12.88(-100.0 to 472.7)
OG005-46.88(-77.8 to 52.2)
Cohort A: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG002
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG003
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG004
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG005
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG00087
OG00188
OG00286
OG00311
OG00411
OG00511
Title
Denominators
Categories
Title
Measurements
OG000-0.04(-340.6 to 362.3)
OG001-0.13(-442.3 to 588.1)
OG0020.00(-368.3 to 3219.3)
OG003-4.00(-30.7 to 15.3)
OG0040.00(-37.2 to 192.0)
OG0050.00(-86.8 to 250.7)
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG002
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG003
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG004
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG005
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG00087
OG00188
OG00286
OG00311
OG00411
OG00511
Title
Denominators
Categories
Title
Measurements
OG000-9.49(-85.7 to 439.8)
OG001-27.63(-100.0 to 211.1)
OG002-23.34(-100.0 to 254.5)
OG003-18.18(-99.5 to 66.7)
OG004-20.33(-95.7 to 1626.7)
OG005-17.68(-72.3 to 80.5)
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG002
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG003
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG004
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG005
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG00070
OG00173
OG00264
OG0038
OG0047
OG0059
Title
Denominators
Categories
Title
Measurements
OG000-26.92(-100.0 to 5070.3)
OG001-31.32(-100.0 to 571.8)
OG002-22.68(-100.0 to 481.3)
OG003-23.38(-96.9 to 657.1)
OG0040.27(-32.3 to 2915.4)
OG005-22.99(-85.7 to 138.8)
OG001
Cohort A: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG002
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG003
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG004
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG005
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG00087
OG00189
OG00287
OG00311
OG00411
OG00511
Title
Denominators
Categories
Worsening or No Change (T+M)
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
ParticipantsOG00411
ParticipantsOG00511
Title
Measurements
OG00037.9
OG00134.8
OG00221.8
OG003
> 0% reduction (T+M)
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
>= 25% reduction (T+M)
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
>= 50% reduction (T+M)
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
>= 75% reduction (T+M)
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
100% reduction (T+M)
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
Near Seizure free (T+M)
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
Worsening or No Change (M)
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
> 0% reduction (M)
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
>= 25% reduction (M)
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
>= 50% reduction (M)
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
>= 75% reduction (M)
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
100% reduction (M)
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
Near Seizure free (M)
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
OG001
Cohort A: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG002
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG003
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG004
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG005
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG00087
OG00189
OG00287
OG00311
OG00411
OG00511
Title
Denominators
Categories
Worsening or No Change (T+M)
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
ParticipantsOG00411
ParticipantsOG00511
Title
Measurements
OG00035.6
OG00136.0
OG00220.7
OG003
> 0% reduction (T+M)
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
>= 25% reduction (T+M)
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
>= 50% reduction (T+M)
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
>= 75% reduction (T+M)
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
100% reduction (T+M)
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
Near Seizure free (T+M)
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
Worsening or No Change (M)
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
> 0% reduction (M)
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
>= 25% reduction (M)
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
>= 50% reduction (M)
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
>= 75% reduction (M)
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
100% reduction (M)
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
Near Seizure free (M)
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
OG001
Cohort A: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG002
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG003
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG004
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG005
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG00087
OG00189
OG00287
OG00311
OG00411
OG00511
Title
Denominators
Categories
Worsening or No Change (T+M)
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
ParticipantsOG00411
ParticipantsOG00511
Title
Measurements
OG00034.5
OG00138.2
OG00220.7
OG003
> 0% reduction (T+M)
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
>= 25% reduction (T+M)
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
>= 50% reduction (T+M)
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
>= 75% reduction (T+M)
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
100% reduction (T+M)
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
Near Seizure free (T+M)
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
Worsening or No Change (M)
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
> 0% reduction (M)
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
>= 25% reduction (M)
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
>= 50% reduction (M)
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
>= 75% reduction (M)
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
100% reduction (M)
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
Near Seizure free (M)
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
OG001
Cohort A: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG002
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG003
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG004
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG005
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG00070
OG00173
OG00264
OG0038
OG0047
OG0059
Title
Denominators
Categories
Worsening or No Change (T+M)
ParticipantsOG00070
ParticipantsOG00173
ParticipantsOG00264
ParticipantsOG0038
ParticipantsOG0047
ParticipantsOG0059
Title
Measurements
OG00035.7
OG00134.2
OG00234.4
OG003
> 0% reduction (T+M)
ParticipantsOG00070
ParticipantsOG00173
ParticipantsOG00264
ParticipantsOG0038
>= 25% reduction (T+M)
ParticipantsOG00070
ParticipantsOG00173
ParticipantsOG00264
ParticipantsOG0038
>= 50% reduction (T+M)
ParticipantsOG00070
ParticipantsOG00173
ParticipantsOG00264
ParticipantsOG0038
>= 75% reduction (T+M)
ParticipantsOG00070
ParticipantsOG00173
ParticipantsOG00264
ParticipantsOG0038
100% reduction (T+M)
ParticipantsOG00070
ParticipantsOG00173
ParticipantsOG00264
ParticipantsOG0038
Near Seizure free (T+M)
ParticipantsOG00070
ParticipantsOG00173
ParticipantsOG00264
ParticipantsOG0038
Worsening or No Change (M)
ParticipantsOG00070
ParticipantsOG00172
ParticipantsOG00263
ParticipantsOG0038
> 0% reduction (M)
ParticipantsOG00070
ParticipantsOG00172
ParticipantsOG00263
ParticipantsOG0038
>= 25% reduction (M)
ParticipantsOG00070
ParticipantsOG00172
ParticipantsOG00263
ParticipantsOG0038
>= 50% reduction (M)
ParticipantsOG00070
ParticipantsOG00172
ParticipantsOG00263
ParticipantsOG0038
>= 75% reduction (M)
ParticipantsOG00070
ParticipantsOG00172
ParticipantsOG00263
ParticipantsOG0038
100% reduction (M)
ParticipantsOG00070
ParticipantsOG00172
ParticipantsOG00263
ParticipantsOG0038
Near Seizure free (M)
ParticipantsOG00070
ParticipantsOG00172
ParticipantsOG00263
ParticipantsOG0038
OG001
Cohort A: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG002
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG003
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG004
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG005
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG00087
OG00189
OG00287
OG00311
OG00411
OG00511
Title
Denominators
Categories
Worsening or No Change (T+M)
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
ParticipantsOG00411
ParticipantsOG00511
Title
Measurements
OG00036.8
OG00132.6
OG00228.7
OG003
> 0% reduction (T+M)
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
>= 25% reduction (T+M)
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
>= 50% reduction (T+M)
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
>= 75% reduction (T+M)
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
100% reduction (T+M)
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
Near Seizure free (T+M)
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
Worsening or No Change (M)
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
> 0% reduction (M)
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
>= 25% reduction (M)
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
>= 50% reduction (M)
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
>= 75% reduction (M)
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
100% reduction (M)
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
Near Seizure free (M)
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
OG001
Cohort A: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG002
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG003
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG004
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG005
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG00063
OG00164
OG00257
OG0038
OG0047
OG0058
Title
Denominators
Categories
Worsening or No Change (T+M)
ParticipantsOG00063
ParticipantsOG00164
ParticipantsOG00257
ParticipantsOG0038
ParticipantsOG0047
ParticipantsOG0058
Title
Measurements
OG00033.3
OG00134.4
OG00236.8
OG003
> 0% reduction (T+M)
ParticipantsOG00063
ParticipantsOG00164
ParticipantsOG00257
ParticipantsOG0038
>= 25% reduction (T+M)
ParticipantsOG00063
ParticipantsOG00164
ParticipantsOG00257
ParticipantsOG0038
>= 50% reduction (T+M)
ParticipantsOG00063
ParticipantsOG00164
ParticipantsOG00257
ParticipantsOG0038
>= 75% reduction (T+M)
ParticipantsOG00063
ParticipantsOG00164
ParticipantsOG00257
ParticipantsOG0038
100% reduction (T+M)
ParticipantsOG00063
ParticipantsOG00164
ParticipantsOG00257
ParticipantsOG0038
Near Seizure free (T+M)
ParticipantsOG00063
ParticipantsOG00164
ParticipantsOG00257
ParticipantsOG0038
Worsening or No Change (M)
ParticipantsOG00063
ParticipantsOG00163
ParticipantsOG00256
ParticipantsOG0038
> 0% reduction (M)
ParticipantsOG00063
ParticipantsOG00163
ParticipantsOG00256
ParticipantsOG0038
>= 25% reduction (M)
ParticipantsOG00063
ParticipantsOG00163
ParticipantsOG00256
ParticipantsOG0038
>= 50% reduction (M)
ParticipantsOG00063
ParticipantsOG00163
ParticipantsOG00256
ParticipantsOG0038
>= 75% reduction (M)
ParticipantsOG00063
ParticipantsOG00163
ParticipantsOG00256
ParticipantsOG0038
100% reduction (M)
ParticipantsOG00063
ParticipantsOG00163
ParticipantsOG00256
ParticipantsOG0038
Near Seizure free (M)
ParticipantsOG00063
ParticipantsOG00163
ParticipantsOG00256
ParticipantsOG0038
OG002
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG003
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG004
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG005
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG00087
OG00189
OG00287
OG00311
OG00411
OG00511
Title
Denominators
Categories
T+M Period
ParticipantsOG00087
ParticipantsOG00189
ParticipantsOG00287
ParticipantsOG00311
ParticipantsOG00411
ParticipantsOG00511
Title
Measurements
OG0000.27(-5.0 to 16.0)
OG0010.00(-9.0 to 16.8)
OG0020.29(-6.1 to 20.0)
OG003
M Period
ParticipantsOG00087
ParticipantsOG00188
ParticipantsOG00286
ParticipantsOG00311
OG002
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG003
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG004
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG005
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG00087
OG00189
OG00287
OG00311
OG00411
OG00511
Title
Denominators
Categories
Title
Measurements
OG0005.00(1.0 to 39.0)
OG0014.00(1.0 to 97.0)
OG0025.00(1.0 to 89.0)
OG0034.00(1.0 to 91.0)
OG0044.00(1.0 to 32.0)
OG0056.00(2.0 to 16.0)
Part 1: Participants received ZX008 0.2 milligram per kilogram per day (mg/kg/day) during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG002
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG003
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG004
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG005
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG00085
OG00185
OG00281
OG00311
OG00411
OG00511
Title
Denominators
Categories
1=Very much improved (D15)
ParticipantsOG00085
ParticipantsOG00185
ParticipantsOG00281
ParticipantsOG00311
ParticipantsOG00410
ParticipantsOG00511
Title
Measurements
OG0002.4
OG0015.9
OG0029.9
OG003
2=Much improved (D15)
ParticipantsOG00085
ParticipantsOG00185
ParticipantsOG00281
ParticipantsOG00311
3=Minimally improved (D15)
ParticipantsOG00085
ParticipantsOG00185
ParticipantsOG00281
ParticipantsOG00311
4=No Change (D15)
ParticipantsOG00085
ParticipantsOG00185
ParticipantsOG00281
ParticipantsOG00311
5=Minimally worse (D15)
ParticipantsOG00085
ParticipantsOG00185
ParticipantsOG00281
ParticipantsOG00311
6=Much worse (D15)
ParticipantsOG00085
ParticipantsOG00185
ParticipantsOG00281
ParticipantsOG00311
7=Very much worse (D15)
ParticipantsOG00085
ParticipantsOG00185
ParticipantsOG00281
ParticipantsOG00311
1=Very much improved (D43)
ParticipantsOG00085
ParticipantsOG00182
ParticipantsOG00280
ParticipantsOG00311
2=Much improved (D43)
ParticipantsOG00085
ParticipantsOG00182
ParticipantsOG00280
ParticipantsOG00311
3=Minimally improved (D43)
ParticipantsOG00085
ParticipantsOG00182
ParticipantsOG00280
ParticipantsOG00311
4=No Change (D43)
ParticipantsOG00085
ParticipantsOG00182
ParticipantsOG00280
ParticipantsOG00311
5=Minimally worse (D43)
ParticipantsOG00085
ParticipantsOG00182
ParticipantsOG00280
ParticipantsOG00311
6=Much worse (D43)
ParticipantsOG00085
ParticipantsOG00182
ParticipantsOG00280
ParticipantsOG00311
7=Very much worse (D43)
ParticipantsOG00085
ParticipantsOG00182
ParticipantsOG00280
ParticipantsOG00311
1=Very much improved (D71)
ParticipantsOG00082
ParticipantsOG00175
ParticipantsOG00275
ParticipantsOG00311
2=Much improved (D71)
ParticipantsOG00082
ParticipantsOG00175
ParticipantsOG00275
ParticipantsOG00311
3=Minimally improved (D71)
ParticipantsOG00082
ParticipantsOG00175
ParticipantsOG00275
ParticipantsOG00311
4=No Change (D71)
ParticipantsOG00082
ParticipantsOG00175
ParticipantsOG00275
ParticipantsOG00311
5=Minimally worse (D71)
ParticipantsOG00082
ParticipantsOG00175
ParticipantsOG00275
ParticipantsOG00311
6=Much worse (D71)
ParticipantsOG00082
ParticipantsOG00175
ParticipantsOG00275
ParticipantsOG00311
7=Very much worse (D71)
ParticipantsOG00082
ParticipantsOG00175
ParticipantsOG00275
ParticipantsOG00311
1=Very much improved (D99)
ParticipantsOG00081
ParticipantsOG00185
ParticipantsOG00280
ParticipantsOG00311
2=Much improved (D99)
ParticipantsOG00081
ParticipantsOG00185
ParticipantsOG00280
ParticipantsOG00311
3=Minimally improved (D99)
ParticipantsOG00081
ParticipantsOG00185
ParticipantsOG00280
ParticipantsOG00311
4=No Change (D99)
ParticipantsOG00081
ParticipantsOG00185
ParticipantsOG00280
ParticipantsOG00311
5=Minimally worse (D99)
ParticipantsOG00081
ParticipantsOG00185
ParticipantsOG00280
ParticipantsOG00311
6=Much worse (D99)
ParticipantsOG00081
ParticipantsOG00185
ParticipantsOG00280
ParticipantsOG00311
7=Very much worse (D99)
ParticipantsOG00081
ParticipantsOG00185
ParticipantsOG00280
ParticipantsOG00311
OG002
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG003
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG004
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG005
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG00087
OG00189
OG00287
OG00311
OG00411
OG00511
Title
Denominators
Categories
Title
Measurements
OG00080.5
OG00178.7
OG00289.7
OG00372.7
OG00490.9
OG00563.6
OG002
Cohort A: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant stiripentol [STP]). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period.
OG003
Cohort B: Placebo
Part 1: Participants received matching placebo as an oral solution, bid over 2 weeks of Titration Period and an additional 12 weeks of Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG004
Cohort B: ZX008 0.2 mg/kg/Day
Part 1: Participants received ZX008 0.2 mg/kg/day during the 2-week Titration. Following titration, participants received ZX008 0.2 mg/kg/day as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
OG005
Cohort B: ZX008 0.8 mg/kg/Day
Part 1: Participants were titrated to their blinded randomized dose of ZX008 over the 2-week Titration from 0.2 mg/kg/day to ZX008 0.8 mg/kg/day (or a maximum dose of 30 mg/day or 20 mg/day for participants taking concomitant STP). Following titration, participants continued to receive the randomized dose of ZX008 as an oral solution, bid for an additional 12 weeks during Maintenance Period. Participants who completed the Maintenance Period and did not continue in Part 2, and participants who discontinued from Part 1 early, were tapered off study medication over 8 days. In Part 2 (OLE Period): Participants initially received ZX008 0.2 mg/kg/day for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG00087
OG00189
OG00287
OG00311
OG00411
OG00511
Title
Denominators
Categories
Title
Measurements
OG0004.6
OG0014.5
OG00211.5
OG0039.1
OG0049.1
OG0050
Units
Counts
Participants
OG00084
OG00180
Title
Denominators
Categories
Fenfluramine
Title
Measurements
OG00011.9± 56.1
OG00144.8± 47.0
Norfenfluramine
Title
Measurements
OG0009.04± 53.4
OG00128.9± 52.9
Units
Counts
Participants
OG00084
OG00180
Title
Denominators
Categories
Fenfluramine
Title
Measurements
OG0008.19± 75.6
OG00131.8± 60.8
Norfenfluramine
Title
Measurements
OG0008.23± 61.3
OG00126.2± 58.9
Units
Counts
Participants
OG00084
OG00180
Title
Denominators
Categories
Fenfluramine
Title
Measurements
OG000246± 63.0
OG001933± 52.1
Norfenfluramine
Title
Measurements
OG000209± 56.3
OG001667± 55.1
OG001
Part 2: Cohort B- Overall
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG000241
OG00132
Title
Denominators
Categories
Title
Measurements
OG000-29.53(-100.0 to 2625.3)
OG001-43.42(-99.0 to 64.2)
OG001
Part 2: Cohort B- Overall
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG000241
OG00132
Title
Denominators
Categories
Title
Measurements
OG000-27.94(-100.0 to 2625.3)
OG001-43.78(-99.0 to 64.2)
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG000241
OG00132
Title
Denominators
Categories
Title
Measurements
OG000-28.18(-100.0 to 2625.3)
OG001-41.94(-99.0 to 64.2)
OG001
Part 2: Cohort B- Overall
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG000241
OG00132
Title
Denominators
Categories
Title
Measurements
OG0000.00(-4257.2 to 1774.3)
OG0010.00(-89.4 to 258.9)
Part 2: Cohort B- Overall
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG000241
OG00132
Title
Denominators
Categories
Title
Measurements
OG000-28.83(-100.0 to 606.1)
OG001-28.00(-99.1 to 83.3)
OG001
Part 2: Cohort B- Overall
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG000241
OG00132
Title
Denominators
Categories
Title
Measurements
OG000-0.99(-4482.2 to 1774.3)
OG0010.00(-89.4 to 258.9)
OG001
Part 2: Cohort B- Overall
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG000241
OG00132
Title
Denominators
Categories
Worsening or No Change
Title
Measurements
OG00031.5
OG00118.8
> 0%
Title
Measurements
OG00068.5
OG00181.3
>= 25%
Title
Measurements
OG00055.6
OG00162.5
>= 50%
Title
Measurements
OG00032.8
OG00143.8
>= 75%
Title
Measurements
OG00012.4
OG00121.9
100%
Title
Measurements
OG0001.2
OG0010
Near Seizure free
Title
Measurements
OG0001.7
OG0010
OG001
Part 2: Cohort B- Overall
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG000241
OG00132
Title
Denominators
Categories
Worsening or No Change
Title
Measurements
OG00032.0
OG00121.9
> 0%
Title
Measurements
OG00068.0
OG00178.1
>= 25%
Title
Measurements
OG00053.1
OG00165.6
>= 50%
Title
Measurements
OG00029.9
OG00143.8
>= 75%
Title
Measurements
OG00011.2
OG00121.9
100%
Title
Measurements
OG0000.8
OG0010
Near Seizure free
Title
Measurements
OG0001.2
OG0010
OG001
Part 2: Cohort B- Overall
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG000241
OG00132
Title
Denominators
Categories
Worsening or No Change
Title
Measurements
OG00029.5
OG00121.9
> 0%
Title
Measurements
OG00070.5
OG00178.1
>= 25%
Title
Measurements
OG00054.8
OG00162.5
>= 50%
Title
Measurements
OG00029.9
OG00140.6
>= 75%
Title
Measurements
OG0009.1
OG00121.9
100%
Title
Measurements
OG0000.4
OG0010
Near Seizure free
Title
Measurements
OG0000.8
OG0010
OG001
Part 2: Cohort B- Overall
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG000241
OG00132
Title
Denominators
Categories
Worsening or No Change
Title
Measurements
OG00024.1
OG00137.5
> 0%
Title
Measurements
OG00046.1
OG00131.3
>= 25%
Title
Measurements
OG00041.9
OG00125.0
>= 50%
Title
Measurements
OG00034.0
OG00118.8
>= 75%
Title
Measurements
OG00022.8
OG0016.3
100%
Title
Measurements
OG0004.6
OG0013.1
Near Seizure free
Title
Measurements
OG0007.5
OG0016.3
OG001
Part 2: Cohort B- Overall
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG000241
OG00132
Title
Denominators
Categories
Worsening or No Change
Title
Measurements
OG00030.3
OG00137.5
> 0%
Title
Measurements
OG00069.7
OG00162.5
>= 25%
Title
Measurements
OG00053.1
OG00156.3
>= 50%
Title
Measurements
OG00030.7
OG00128.1
>= 75%
Title
Measurements
OG0009.1
OG00112.5
100%
Title
Measurements
OG0000.4
OG0010
Near Seizure free
Title
Measurements
OG0000.4
OG0010
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG000241
OG00132
Title
Denominators
Categories
Title
Measurements
OG0002.16(-23.0 to 27.8)
OG0014.24(-3.6 to 24.5)
Part 2: Cohort B- Overall
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG000241
OG00127
Title
Denominators
Categories
Title
Measurements
OG0004.0(-10 to 360)
OG0016.0(0 to 200)
OG001
Part 2: Cohort B- Overall
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.
Units
Counts
Participants
OG000237
OG00132
Title
Denominators
Categories
1=Very much improved (OLE D1)
ParticipantsOG000236
ParticipantsOG00132
Title
Measurements
OG0002.5
OG0013.1
2=Much improved (OLE D1)
ParticipantsOG000236
ParticipantsOG00132
Title
Measurements
OG00015.3
OG001
3=Minimally improved (OLE D1)
ParticipantsOG000236
ParticipantsOG00132
Title
Measurements
OG00025.8
OG001
4=No Change (OLE D1)
ParticipantsOG000236
ParticipantsOG00132
Title
Measurements
OG00048.3
OG001
5=Minimally worse (OLE D1)
ParticipantsOG000236
ParticipantsOG00132
Title
Measurements
OG0007.2
OG001
6=Much worse (OLE D1)
ParticipantsOG000236
ParticipantsOG00132
Title
Measurements
OG0000.8
OG001
7=Very much worse (OLE D1)
ParticipantsOG000236
ParticipantsOG00132
Title
Measurements
OG0000
OG001
1=Very much improved (OLE M1)
ParticipantsOG000225
ParticipantsOG00132
Title
Measurements
OG0004.4
OG001
2=Much improved (OLE M1)
ParticipantsOG000225
ParticipantsOG00132
Title
Measurements
OG00020.0
OG001
3=Minimally improved (OLE M1)
ParticipantsOG000225
ParticipantsOG00132
Title
Measurements
OG00032.4
OG001
4=No Change (OLE M1)
ParticipantsOG000225
ParticipantsOG00132
Title
Measurements
OG00034.2
OG001
5=Minimally worse (OLE M1)
ParticipantsOG000225
ParticipantsOG00132
Title
Measurements
OG0007.6
OG001
6=Much worse (OLE M1)
ParticipantsOG000225
ParticipantsOG00132
Title
Measurements
OG0001.3
OG001
7=Very much worse (OLE M1)
ParticipantsOG000225
ParticipantsOG00132
Title
Measurements
OG0000
OG001
1=Very much improved (OLE M2)
ParticipantsOG000220
ParticipantsOG00131
Title
Measurements
OG0005.5
OG001
2=Much improved (OLE M2)
ParticipantsOG000220
ParticipantsOG00131
Title
Measurements
OG00024.5
OG001
3=Minimally improved (OLE M2)
ParticipantsOG000220
ParticipantsOG00131
Title
Measurements
OG00034.1
OG001
4=No Change (OLE M2)
ParticipantsOG000220
ParticipantsOG00131
Title
Measurements
OG00027.7
OG001
5=Minimally worse (OLE M2)
ParticipantsOG000220
ParticipantsOG00131
Title
Measurements
OG0005.0
OG001
6=Much worse (OLE M2)
ParticipantsOG000220
ParticipantsOG00131
Title
Measurements
OG0003.2
OG001
7=Very much worse (OLE M2)
ParticipantsOG000220
ParticipantsOG00131
Title
Measurements
OG0000
OG001
1=Very much improved (OLE M3)
ParticipantsOG000207
ParticipantsOG00129
Title
Measurements
OG0007.2
OG001
2=Much improved (OLE M3)
ParticipantsOG000207
ParticipantsOG00129
Title
Measurements
OG00025.1
OG001
3=Minimally improved (OLE M3)
ParticipantsOG000207
ParticipantsOG00129
Title
Measurements
OG00036.2
OG001
4=No Change (OLE M3)
ParticipantsOG000207
ParticipantsOG00129
Title
Measurements
OG00021.7
OG001
5=Minimally worse (OLE M3)
ParticipantsOG000207
ParticipantsOG00129
Title
Measurements
OG0007.2
OG001
6=Much worse (OLE M3)
ParticipantsOG000207
ParticipantsOG00129
Title
Measurements
OG0002.4
OG001
7=Very much worse (OLE M3)
ParticipantsOG000207
ParticipantsOG00129
Title
Measurements
OG0000
OG001
1=Very much improved (OLE M6)
ParticipantsOG000184
ParticipantsOG00129
Title
Measurements
OG0008.2
OG001
2=Much improved (OLE M6)
ParticipantsOG000184
ParticipantsOG00129
Title
Measurements
OG00033.7
OG001
3=Minimally improved (OLE M6)
ParticipantsOG000184
ParticipantsOG00129
Title
Measurements
OG00031.0
OG001
4=No Change (OLE M6)
ParticipantsOG000184
ParticipantsOG00129
Title
Measurements
OG00020.1
OG001
5=Minimally worse (OLE M6)
ParticipantsOG000184
ParticipantsOG00129
Title
Measurements
OG0003.8
OG001
6=Much worse (OLE M6)
ParticipantsOG000184
ParticipantsOG00129
Title
Measurements
OG0003.3
OG001
7=Very much worse (OLE M6)
ParticipantsOG000184
ParticipantsOG00129
Title
Measurements
OG0000
OG001
1=Very much improved (OLE M9)
ParticipantsOG000133
ParticipantsOG00128
Title
Measurements
OG0009.0
OG001
2=Much improved (OLE M9)
ParticipantsOG000133
ParticipantsOG00128
Title
Measurements
OG00037.6
OG001
3=Minimally improved (OLE M9)
ParticipantsOG000133
ParticipantsOG00128
Title
Measurements
OG00027.1
OG001
4=No Change (OLE M9)
ParticipantsOG000133
ParticipantsOG00128
Title
Measurements
OG00018.8
OG001
5=Minimally worse (OLE M9)
ParticipantsOG000133
ParticipantsOG00128
Title
Measurements
OG0006.0
OG001
6=Much worse (OLE M9)
ParticipantsOG000133
ParticipantsOG00128
Title
Measurements
OG0001.5
OG001
7=Very much worse (OLE M9)
ParticipantsOG000133
ParticipantsOG00128
Title
Measurements
OG0000
OG001
1=Very much improved (OLE M12)
ParticipantsOG000145
ParticipantsOG00126
Title
Measurements
OG0009.7
OG001
2=Much improved (OLE M12)
ParticipantsOG000145
ParticipantsOG00126
Title
Measurements
OG00039.3
OG001
3=Minimally improved (OLE M12)
ParticipantsOG000145
ParticipantsOG00126
Title
Measurements
OG00026.2
OG001
4=No Change (OLE M12)
ParticipantsOG000145
ParticipantsOG00126
Title
Measurements
OG00018.6
OG001
5=Minimally worse (OLE M12)
ParticipantsOG000145
ParticipantsOG00126
Title
Measurements
OG0003.4
OG001
6=Much worse (OLE M12)
ParticipantsOG000145
ParticipantsOG00126
Title
Measurements
OG0002.8
OG001
7=Very much worse (OLE M12)
ParticipantsOG000145
ParticipantsOG00126
Title
Measurements
OG0000
OG001
1=Very much improved (Last Assessment)
ParticipantsOG000237
ParticipantsOG00132
Title
Measurements
OG0007.6
OG001
2=Much improved (Last Assessment)
ParticipantsOG000237
ParticipantsOG00132
Title
Measurements
OG00027.4
OG001
3=Minimally improved (Last Assessment)
ParticipantsOG000237
ParticipantsOG00132
Title
Measurements
OG00021.9
OG001
4=No Change (Last Assessment)
ParticipantsOG000237
ParticipantsOG00132
Title
Measurements
OG00028.3
OG001
5=Minimally worse (Last Assessment)
ParticipantsOG000237
ParticipantsOG00132
Title
Measurements
OG0007.2
OG001
6=Much worse (Last Assessment)
ParticipantsOG000237
ParticipantsOG00132
Title
Measurements
OG0007.6
OG001
7=Very much worse (Last Assessment)
ParticipantsOG000237
ParticipantsOG00132
Title
Measurements
OG0000
OG001
OG001
Part 2: Cohort B- Overall
All Cohort B participants who continued in Part 2 received ZX008 0.2 mg/kg/day as an oral solution, twice a day (bid), for 1 month. After 1 month at a dose of ZX008 0.2 mg/kg/day, the Investigator could adjust the dose if needed. Dose changes were made in maximum increments of 0.2 mg/kg/day, to a maximum of 0.8 mg/kg/day (or 0.5 mg/kg/day for participants taking concomitant STP) but not to exceed a total dose of 30 mg/day (or 20 mg/kg/day for participants taking concomitant STP). Participants received ZX008 for up to 12 months in OLE Period. Participants who completed 12 months OLE Period had option to receive ZX008 for up to 72 months, or until ZX008 is approved in the participant's country.