Cannabidiol Oral Solution in Pediatric Participants With... | NCT03336242

Label	Type	Description	Intervention Names
Cohort 1: Cannabidiol Oral Solution 20 mg/kg/day	Experimental	Treatment Period: Cannabidiol Oral Solution 20 milligrams per kilogram per day (mg/kg/day) divided twice daily (BID) for 4 weeks.	Drug: Cannabidiol Oral Solution
Cohort 2: Cannabidiol Oral Solution 30 mg/kg/day	Experimental	Titration Period: Cannabidiol Oral Solution 20 mg/kg/day divided BID for 5 days. Treatment Period: Cannabidiol Oral Solution 30 mg/kg/day divided BID for 4 weeks.	Drug: Cannabidiol Oral Solution
Cohort 3: Cannabidiol Oral Solution 10 mg/kg/day	Experimental	Treatment Period: Cannabidiol Oral Solution 10 mg/kg/day divided BID for 4 weeks.	Drug: Cannabidiol Oral Solution

Name	Type	Description	Arm Group Labels	Other Names
Cannabidiol Oral Solution	Drug	An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).	Cohort 1: Cannabidiol Oral Solution 20 mg/kg/day Cohort 2: Cannabidiol Oral Solution 30 mg/kg/day

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percent Change From Baseline in Absence Seizure Counts Assessed by Video-electroencephalogram (EEG) at Visit 5	A 4-hour video-EEG was performed for all participants at Baseline, during the Treatment Period, and at the End of the Study/Early Withdrawal Visit. Hyperventilation was conducted during the video-EEG to count the number of absence seizures. A negative change value indicates an improvement in seizure activity. A positive change value indicates a worsening in seizure activity. Percent change from baseline was calculated as (100*(week 4-baseline)/baseline).	Baseline (Visit 2, Day 1 of Titration Period) and Visit 5 (Week 4, Day 6 of Treatment Period)
Percent Change From Baseline in Time to Absence Seizure During Hyperventilation Testing on Video-EEG at Visit 5	A 4-hour video-EEG was performed for all participants at Baseline, during the Treatment Period, and at the End of the Study/Early Withdrawal Visit. Hyperventilation was conducted during the video-EEG to count the number of absence seizures. Percent change from baseline calculated as (100*(week 4-baseline)/baseline).	Baseline (Visit 2, Day 1 of Titration Period) and Visit 5 (Week 4, Day 6 of Treatment Period)
Number of Participants Seizure-Free at Visit 5	Daily seizure activity was recorded in a diary. Each day, the participant or parent/caregiver responded to the question: "How many absence seizures did the patient have today?".	Visit 5 (Week 4, Day 6 of Treatment Period)
Clinical Global Impression of Improvement (CGI-I) Score at Visit 5	The CGI-I questionnaire was completed by the parents/caregivers and the investigator and was used to assess participants' global status of their condition at Week 4 of the Treatment Period using a 7-point scale, where 1=very much improved and 7=very much worse since the initiation of treatment.	Visit 5 (Week 4, Day 6 of Treatment Period)

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is defined as any untoward medical occurrence in a patient administered a pharmaceutical product during the course of a clinical investigation. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product, whether or not thought to be related to the investigational product. A treatment-emergent AE is an AE with onset that occurs after receiving study drug. A SAE is any untoward medical occurrence that results in death, is life-threatening, requires the participant be at a risk of death at the time of the event, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality/birth defect, or other serious event that requires medical or surgical intervention. A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported AEs module.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patient and/or parent(s)/caregiver(s) fully comprehend the informed consent form and assent form, understand all study procedures, and can communicate satisfactorily with the investigator and study coordinator, in accordance with applicable laws, regulations, and local requirements.
Male or female between 3 and 12 years (inclusive) at the time of onset and between 3 and 17 years of age (inclusive) at the time of consent.
Body weight ≥ 10 kg.
Diagnosed with childhood absence epilepsy, confirmed by electroencephalogram (EEG) with at least 3 bursts of general spike wave of 2.7 to 5 hertz lasting ≥3 seconds during the 4-hour EEG, and has had an adequate trial of at least 2 antiepileptic drugs (AEDs) and are treatment-resistant to at least one AED.
Willingness to not start a ketogenic diet during the Baseline or Treatment Period.
A female patient is eligible to participate in the study if she is premenarchal, or of childbearing potential with a negative urine pregnancy test at the Screening Visit. If sexually active, she must agree to either complete abstinence from intercourse or use acceptable methods of contraception throughout the study and for 4 weeks after completion of study participation or discontinuation from investigational product.
A sexually active male patient must be willing to use acceptable methods of contraception throughout the study and for 4 weeks after completion of study participation or discontinuation from investigational product.
In the opinion of the investigator, the parent(s)/caregiver(s) is willing and able to comply with the study procedures and visit schedules and the Follow-up Visits.
General good health based on physical and neurological examinations, medical history, and clinical laboratory values completed during the Screening Visit that would prohibit the patient from safely participating in the trial as judged by the investigator.

Exclusion Criteria:

Patient or parent(s)/caregiver(s) have daily commitments during the study duration that would interfere with attending all study visits.
Has a history of nonfebrile seizures other than absence seizures.
Has a history of febrile seizures after 3 years of age.
Has a history consistent with juvenile absence epilepsy or juvenile myoclonic epilepsy.
Currently taking felbamate.
Currently taking phenytoin, fluvoxamine, carbamazepine, or St. John's Wort.
Currently taking concomitant medications that are strong inhibitors/inducers/sensitive substrates with a narrow therapeutic index for cytochrome P450 3A4 (CYP3A4), CYP2C9, or CYP2C19. (Stable doses of Valproic Acid during the screening, titration, treatment, and follow-up periods are permitted).
Currently on a ketogenic diet.
In the opinion of the investigator, any clinically significant, unstable medical abnormality, chronic disease, or a history of a clinically significant abnormality of the cardiovascular, gastrointestinal, respiratory, hepatic, or renal systems.
Clinically significant abnormal liver function test (LFT) values, including albumin, direct bilirubin, total bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) ≥3 times the upper limit of normal (ULN).
History or presence of abnormal electrocardiograms (ECGs) that are clinically significant in the opinion of the investigator.
Has a current or history of clinically significant intellectual disability or major psychiatric disease, including autism spectrum disorder, which would interfere with compliance.
For patients aged 7 to 17 years of age and for whom the Columbia Suicide Severity Rating Scale (C-SSRS) is developmentally appropriate, an affirmative answer to queries regarding active suicidal ideation with some intent to act but without a specific plan or active suicidal ideation with a specific plan and intent on the C-SSRS assessment at the Screening Visit.
Any history of attempted suicide.
Previously received any investigational drug or device or investigational therapy within 30 days before Screening.
Taken any cannabinoids in the 30 days prior to the Screening Visit.
History of an allergic reaction or a known or suspected sensitivity to any substance that is contained in the investigational product formulation.
Known infection with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
In the opinion of the investigator, the patient is unsuitable in any other way to participate in this study.
Body weight <10 kg or >90 kg.

Name	Affiliation	Role
Ahmed Elkashef, MD	INSYS Therapeutics Inc	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Nicklaus Children's Hospital		Miami	Florida	33155	United States
Pediatric Epilepsy and Neurology Specialists

ID	Title	Description
FG000	Cohort 1	Treatment Period: Cannabidiol Oral Solution 20 milligrams per kilogram per day (mg/kg/day) divided twice daily (BID) for 4 weeks. Cannabidiol Oral Solution: An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).
FG001	Cohort 2

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 6, 2019	Nov 23, 2022

ID	Title	Description
BG000	Cohort 1	Treatment Period: Cannabidiol Oral Solution 20 mg/kg/day divided BID for 4 weeks. Cannabidiol Oral Solution: An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).
BG001	Cohort 2	Titration Period: Cannabidiol Oral Solution 20 mg/kg/day divided BID for 5 days. Treatment Period: Cannabidiol Oral Solution 30 mg/kg/day divided BID for 4 weeks. Cannabidiol Oral Solution: An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00010 BG00110 BG00220

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

Percent Change From Baseline in Absence Seizure Counts Assessed by Video-electroencephalogram (EEG) at Visit 5

A 4-hour video-EEG was performed for all participants at Baseline, during the Treatment Period, and at the End of the Study/Early Withdrawal Visit. Hyperventilation was conducted during the video-EEG to count the number of absence seizures. A negative change value indicates an improvement in seizure activity. A positive change value indicates a worsening in seizure activity. Percent change from baseline was calculated as (100*(week 4-baseline)/baseline).

The Sponsor terminated this study and no participants were enrolled on Cohort 3.

Posted

Mean

Standard Deviation

percent change

Baseline (Visit 2, Day 1 of Titration Period) and Visit 5 (Week 4, Day 6 of Treatment Period)

ID	Title	Description
OG000	Cohort 1	Treatment Period: Cannabidiol Oral Solution 20 mg/kg/day divided BID for 4 weeks. Cannabidiol Oral Solution: An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).
OG001	Cohort 2	Titration Period: Cannabidiol Oral Solution 20 mg/kg/day divided BID for 5 days. Treatment Period: Cannabidiol Oral Solution 30 mg/kg/day divided BID for 4 weeks. Cannabidiol Oral Solution: An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).

Units	Counts
Participants	OG00010 OG0019

Title

Denominators

Categories

Title	Measurements
	OG00040.67± 180.919 OG00135.12± 121.518

Primary

Percent Change From Baseline in Time to Absence Seizure During Hyperventilation Testing on Video-EEG at Visit 5

The Sponsor terminated this study and no participants were enrolled on Cohort 3.

Posted

Mean

Standard Deviation

percent change

Baseline (Visit 2, Day 1 of Titration Period) and Visit 5 (Week 4, Day 6 of Treatment Period)

ID	Title	Description
OG000	Cohort 1	Treatment Period: Cannabidiol Oral Solution 20 mg/kg/day divided BID for 4 weeks. Cannabidiol Oral Solution: An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).
OG001	Cohort 2	Titration Period: Cannabidiol Oral Solution 20 mg/kg/day divided BID for 5 days. Treatment Period: Cannabidiol Oral Solution 30 mg/kg/day divided BID for 4 weeks. Cannabidiol Oral Solution: An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).

Units	Counts

Primary

Number of Participants Seizure-Free at Visit 5

Daily seizure activity was recorded in a diary. Each day, the participant or parent/caregiver responded to the question: "How many absence seizures did the patient have today?".

The Sponsor terminated this study and no participants were enrolled on Cohort 3.

Posted

Count of Participants

Participants

Visit 5 (Week 4, Day 6 of Treatment Period)

ID	Title	Description
OG000	Cohort 1	Treatment Period: Cannabidiol Oral Solution 20 mg/kg/day divided BID for 4 weeks. Cannabidiol Oral Solution: An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).
OG001	Cohort 2	Titration Period: Cannabidiol Oral Solution 20 mg/kg/day divided BID for 5 days. Treatment Period: Cannabidiol Oral Solution 30 mg/kg/day divided BID for 4 weeks. Cannabidiol Oral Solution: An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).

Units	Counts
Participants

Primary

Clinical Global Impression of Improvement (CGI-I) Score at Visit 5

The CGI-I questionnaire was completed by the parents/caregivers and the investigator and was used to assess participants' global status of their condition at Week 4 of the Treatment Period using a 7-point scale, where 1=very much improved and 7=very much worse since the initiation of treatment.

The Sponsor terminated this study and no participants were enrolled on Cohort 3.

Posted

Mean

Standard Deviation

units on a scale

Visit 5 (Week 4, Day 6 of Treatment Period)

ID	Title	Description
OG000	Cohort 1	Treatment Period: Cannabidiol Oral Solution 20 mg/kg/day divided BID for 4 weeks. Cannabidiol Oral Solution: An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).
OG001	Cohort 2	Titration Period: Cannabidiol Oral Solution 20 mg/kg/day divided BID for 5 days. Treatment Period: Cannabidiol Oral Solution 30 mg/kg/day divided BID for 4 weeks. Cannabidiol Oral Solution: An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).

Units	Counts
Participants

Secondary

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE is defined as any untoward medical occurrence in a patient administered a pharmaceutical product during the course of a clinical investigation. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product, whether or not thought to be related to the investigational product. A treatment-emergent AE is an AE with onset that occurs after receiving study drug. A SAE is any untoward medical occurrence that results in death, is life-threatening, requires the participant be at a risk of death at the time of the event, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality/birth defect, or other serious event that requires medical or surgical intervention. A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported AEs module.

All participants who were enrolled and received at least 1 dose of study drug. The Sponsor terminated this study and no participants were enrolled on Cohort 3.

Posted

Number

participants

Day 1 (after dosing) up to Visit 7 (Week 4 of the Follow-Up Period)

ID	Title	Description
OG000	Cohort 1	Treatment Period: Cannabidiol Oral Solution 20 mg/kg/day divided BID for 4 weeks. Cannabidiol Oral Solution: An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).
OG001	Cohort 2

Secondary

Maximum Plasma Concentration (Cmax) and Dose-normalized Cmax (Cmax/D) for Cannabidiol Under Fed and Fasted Conditions

The Cmax and Cmax/D for cannabidiol were evaluated under fed and fasted conditions.

Fed: Participant arrived at the site on Day 1 of Week 4 of the Treatment Period without food and the morning dose. The site provided a high fat/high-calorie food and then dosed the participant. Blood samples were collected pre-dose (before meal/morning dose) and 2, 4, and 6 hours after the morning dose (but before the next dose).

Fasted (2 hours before dose until 2 hours after dose): Participants arrived at the site on Day 2 of Week 4 of the Treatment Period without food and the morning dose. The site provided a standard meal 2 hours after the dose. Blood samples were collected pre-dose and 2 (before meal), 4, 6 hours after the morning dose (but before the next dose).

The Sponsor terminated this study and no participants were enrolled in Cohort 3. No data was collected for any pharmacokinetic analysis, therefore no clinical data will be reported on this outcome measure.

Posted

Visit 3 (Week 1, Day 1 of Treatment Period; Pre-dose, 2, 4, 6 Hours Post-dose), Visit 5 (Week 4, Day 6 of Treatment Period; Pre-dose, 2, 4, 6 Hours Post-dose), and Visit 6 (Week 4, Day 7 of Treatment Period; Pre-dose, 2, 4, 6 Hours Post-dose)

ID	Title	Description
OG000	Cohort 1	Treatment Period: Cannabidiol Oral Solution 20 mg/kg/day divided BID for 4 weeks. Cannabidiol Oral Solution: An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).
OG001	Cohort 2

Secondary

Area Under the Plasma Concentration Curve From Time 0 to the Last Measured Concentration (AUC(0-t)) and Dose Normalized AUC(0-t) [AUC(0-t)/Dose] for Cannabidiol Under Fed and Fasted Conditions

The AUC(0-t) and AUC(0-t)/dose for cannabidiol were evaluated under fed and fasted conditions.

Posted

ID	Title	Description
OG000	Cohort 1	Treatment Period: Cannabidiol Oral Solution 20 mg/kg/day divided BID for 4 weeks. Cannabidiol Oral Solution: An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).

Secondary

Trough Plasma Concentration (Ctrough) and Dose Normalized Ctrough (Ctrough/Dose) for Cannabidiol Under Fed, Fasted, and Normal Conditions

The Ctrough and Ctrough/dose for cannabidiol were evaluated under fed, fasted, and normal conditions.

Posted

ID	Title	Description
OG000	Cohort 1	Treatment Period: Cannabidiol Oral Solution 20 mg/kg/day divided BID for 4 weeks. Cannabidiol Oral Solution: An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).
OG001

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Tympanic membrane perforation	Ear and labyrinth disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected10 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0013 events2 affected10 at risk
Vomiting	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected10 at risk EG0011 events1 affected10 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected10 at risk
Retching	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected10 at risk
Fatigue	General disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected10 at risk EG0011 events1 affected10 at risk
Pyrexia	General disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected10 at risk EG0011 events1 affected10 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0017 events4 affected10 at risk
Ear infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected10 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected10 at risk
Influenza	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected10 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected10 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0004 events4 affected10 at risk EG0010 events0 affected10 at risk
Arthropod sting	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected10 at risk
Wound	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected10 at risk
Alanine aminotransferase increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected10 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected10 at risk
Hepatic enzyme increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected10 at risk
Liver function test increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected10 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected10 at risk
Headache	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0013 events3 affected10 at risk
Seizure	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0012 events2 affected10 at risk
Coordination abnormal	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected10 at risk
Dizziness	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected10 at risk
Dysarthria	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected10 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected10 at risk EG0011 events1 affected10 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected10 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected10 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected10 at risk EG0011 events1 affected10 at risk
Rash generalised	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected10 at risk

ID	Term
D004829	Epilepsy, Generalized
D004827	Epilepsy
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D000073376	Epileptic Syndromes

ID	Term
D002186	Cannabinoids
D013729	Terpenes
D006838	Hydrocarbons
D009930	Organic Chemicals

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cohort 1	Treatment Period: Cannabidiol Oral Solution 20 mg/kg/day divided BID for 4 weeks. Cannabidiol Oral Solution: An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).	0	10	0	10	6	10
EG001	Cohort 2	Titration Period: Cannabidiol Oral Solution 20 mg/kg/day divided BID for 5 days. Treatment Period: Cannabidiol Oral Solution 30 mg/kg/day divided BID for 4 weeks. Cannabidiol Oral Solution: An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).	0	10	0	10	7	10