Study to Test the Efficacy and Safety of Padsevonil as Ad... | NCT03373383

NCT03373383

ID	Type	Description	Link
2017-003200-48	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Padsevonil dosing regimen 1	Experimental	Subjects will be randomized to receive a combination of tablets of Padsevonil and Placebo (as appropriate) to maintain the blinding.	Drug: Padsevonil Other: Placebo
Padsevonil dosing regimen 2	Experimental	Subjects will be randomized to receive a combination of tablets of Padsevonil and Placebo (as appropriate) to maintain the blinding.	Drug: Padsevonil Other: Placebo
Padsevonil dosing regimen 3	Experimental	Subjects will be randomized to receive a combination of tablets of Padsevonil and Placebo (as appropriate) to maintain the blinding.	Drug: Padsevonil Other: Placebo
Padsevonil dosing regimen 4	Experimental	Subjects will be randomized to receive a combination of tablets of Padsevonil and Placebo (as appropriate) to maintain the blinding.	Drug: Padsevonil Other: Placebo
Placebo	Placebo Comparator	Subjects randomized to the placebo group will receive a combination of several Placebo tablets to maintain the blinding.

Name	Type	Description	Arm Group Labels	Other Names
Padsevonil	Drug	Padsevonil in different dosages.	Padsevonil dosing regimen 1 Padsevonil dosing regimen 2 Padsevonil dosing regimen 3

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in Log-transformed Observable Focal Onset Seizure Frequency From Baseline Over the 12 Week Maintenance Period	During the study, participants kept diaries to record daily seizure activity. Seizure frequency refers to 28-day adjusted frequency. Seizure frequency was based on investigator assessment of participants' reports of daily seizure type and frequency. Observable focal-onset seizures refer to Type IA1, IB, and IC (ILAE Classification of Epileptic Seizures, 1981). Based on ANCOVA on change in log-transformed, 28-day adjusted seizure frequency from Baseline with treatment group as the main factor, Baseline log-transformed seizure frequency as a continuous covariate, Baseline SV2A use (yes or no) and Region (Europe, Non-Europe) as categorical factors.	From Baseline over the 12 Week Maintenance Period
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Reported by the Subject and/or Caregiver or Observed by the Investigator During the Entire Study	An Adverse Event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment.	From Baseline until Safety Follow-Up (up to Week 23)
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Study Withdrawal	An Adverse Event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment.	From Baseline until Safety Follow-Up (up to Week 23)
Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) During the Entire Study	A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: Results in death Is life-threatening Requires in patient hospitalization or prolongation of existing hospitalization Is a congenital anomaly or birth defect Is an infection that requires treatment parenteral antibiotics Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above.

Secondary Outcomes

Measure	Description	Time Frame
75 % Responder Rate Over the 12 Week Maintenance Period	The 75% responder rate, where a responder is a participant experiencing a ≥75% reduction in observable focal-onset seizure frequency from Baseline, over the 12-Week Maintenance Period.	End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Diagnosis of focal epilepsy per 1989 International League Against Epilepsy (ILAE) criteria at least 3 years before study entry
Subject has failed to achieve seizure control with 4 tolerated and appropriately chosen prior antiepileptic drugs (AED), including past and ongoing treatment, that were individually optimized for adequate dose and duration. Prior discontinued AED treatment would need to be assessed by the Investigator considering the patient medical records and patient and/or caregiver interview. 'Prior AED' is defined as all past and ongoing AED treatments with a start date before the Screening Visit (Visit 1)
Average of >= 4 spontaneous and observable focal seizures (type IA1 (i.e. focal aware), IB (i.e. focal impaired awareness), IC (i.e. focal to bilateral tonic-clonic)) per month
Current treatment with an individually optimized and stable dose of at least 1 and up to 3 AEDs for the 8 weeks prior to the Screening Visit with or without additional Vagus Nerve Stimulation (VNS) or other neurostimulation treatments

Exclusion Criteria:

Subject has a history of or signs of generalized or combined generalized and focal epilepsy
Cluster seizures which are uncountable in the previous 8 weeks before study entry and during 4 weeks prospective baseline
Current treatment with carbamazepine, phenytoin, primidone, phenobarbital
Current treatment/ use of (non-AED) prescription, nonprescription, dietary (eg, grapefruit or passion fruit), or herbal products that are potent inducers or inhibitors of the CYP3A4 or 2C19 pathway for 2 weeks (or 5 half-lives, whichever is longer) prior to the Baseline Visit
Subjects taking sensitive substrates of CYP2C19 for 2 weeks (or 5 half-lives, whichever is longer) prior to the Baseline Visit
Subject has been taking vigabatrin less than 2 years at study entry
Subject has been taking felbamate for less than 12 months
Subject taking retigabine for less than 4 years
Current treatment with benzodiazepines (i.e. GABA-A-ergic drugs like zolpidem, zaleplon, or zopiclone, excluding GABA-A-ergic AEDs) <3 times per week for emergencies
Subject has a current medical condition that occurred within the last 12 months which, in the opinion of the investigator, could compromise his/her safety or ability to participate in this study

Name	Affiliation	Role
UCB Cares	001 844 599 2273 (UCB)	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Ep0091 839		Chandler	Arizona	85226	United States
Ep0091 810

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
36176044	Result	Rademacher M, Toledo M, Van Paesschen W, Liow KK, Milanov IG, Esch ML, Wang N, MacPherson M, Byrnes WJ, Minh TDC, Webster E, Werhahn KJ. Efficacy and safety of adjunctive padsevonil in adults with drug-resistant focal epilepsy: Results from two double-blind, randomized, placebo-controlled trials. Epilepsia Open. 2022 Dec;7(4):758-770. doi: 10.1002/epi4.12656. Epub 2022 Oct 22.
37973662

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding up to week 19.
FG001	Padsevonil 50mg BID	Participants were randomized to receive a combination of tablets of padsevonil 50 milligrams (mg) and placebo (as appropriate) to maintain the blinding, twice daily (bid) up to week 19

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Oct 12, 2018	Jan 28, 2021

Arm/Group Information

ID	Title	Description
BG000	Placebo	Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding up to week 19.
BG001	Padsevonil 50mg BID	Participants were randomized to receive a combination of tablets of padsevonil 50 milligrams (mg) and placebo (as appropriate) to maintain the blinding, twice daily (bid) up to week 19
BG002	Padsevonil 100mg BID	Participants were randomized to receive a combination of tablets of padsevonil 100 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19.
BG003	Padsevonil 200mg BID	Participants were randomized to receive a combination of tablets of padsevonil 200 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19.
BG004	Padsevonil 400mg BID	Participants were randomized to receive a combination of tablets of padsevonil 400 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19.
BG005	Total Title

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0022 BG003

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00040.0± 12.9 BG00142.5± 11.6 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00048 BG00146 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0001 BG0011 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

Change in Log-transformed Observable Focal Onset Seizure Frequency From Baseline Over the 12 Week Maintenance Period

During the study, participants kept diaries to record daily seizure activity. Seizure frequency refers to 28-day adjusted frequency. Seizure frequency was based on investigator assessment of participants' reports of daily seizure type and frequency. Observable focal-onset seizures refer to Type IA1, IB, and IC (ILAE Classification of Epileptic Seizures, 1981). Based on ANCOVA on change in log-transformed, 28-day adjusted seizure frequency from Baseline with treatment group as the main factor, Baseline log-transformed seizure frequency as a continuous covariate, Baseline SV2A use (yes or no) and Region (Europe, Non-Europe) as categorical factors.

The Full Analysis Set (FAS) consisted of all study participants in the RS who were administered at least 1 dose or a partial dose of IMP and had Baseline and at least 1 post-Baseline seizure frequency data during the 16-week Treatment Period.

Posted

Least Squares Mean

95% Confidence Interval

loge seizures per 28 days

From Baseline over the 12 Week Maintenance Period

ID	Title	Description
OG000	Placebo (FAS)	Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding up to week 19. Participants formed the Full Analysis Set (FAS).
OG001	Padsevonil 50mg BID (FAS)	Participants were randomized to receive a combination of tablets of padsevonil 50 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the FAS.
OG002	Padsevonil 100mg BID (FAS)	Participants were randomized to receive a combination of tablets of padsevonil 100 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the FAS.
OG003	Padsevonil 200mg BID (FAS)	Participants were randomized to receive a combination of tablets of padsevonil 200 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the FAS.
OG004	Padsevonil 400mg BID (FAS)	Participants were randomized to receive a combination of tablets of padsevonil 400 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the FAS.

Units	Counts
Participants	OG00081 OG00180 OG00282 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-0.27585(-0.44311 to -0.10858) OG001-0.46424(-0.63276 to -0.29573) OG002-0.48804(-0.65436 to -0.32172)

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	Percent reduction over placebo was calculated as 100*(1-exp(diff)), where diff was the model estimate of the log ratio between each PSL group and placebo group.	ANCOVA		=0.102	Adjusted p-values were from the Hochberg step-up procedure within SAS® Proc Multtest to control Type I error.	Percent reduction	17.2			2-Sided	95	-3.8	33.9					Superiority

Secondary

75 % Responder Rate Over the 12 Week Maintenance Period

The 75% responder rate, where a responder is a participant experiencing a ≥75% reduction in observable focal-onset seizure frequency from Baseline, over the 12-Week Maintenance Period.

Posted

Number

percentage of participants

End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization

ID	Title	Description
OG000	Placebo (FAS)	Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding up to week 19. Participants formed the Full Analysis Set (FAS).
OG001	Padsevonil 50mg BID (FAS)	Participants were randomized to receive a combination of tablets of padsevonil 50 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the FAS.
OG002	Padsevonil 100mg BID (FAS)	Participants were randomized to receive a combination of tablets of padsevonil 100 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the FAS.

Primary

Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Reported by the Subject and/or Caregiver or Observed by the Investigator During the Entire Study

An Adverse Event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment.

The Safety Set consisted of all study participants who were administered at least 1 dose or a partial dose of IMP.

Posted

Number

percentage of participants

From Baseline until Safety Follow-Up (up to Week 23)

ID	Title	Description
OG000	Placebo (SS)	Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding up to week 19. Participants formed the Safety Set (SS).
OG001	Padsevonil 50mg BID (SS)	Participants were randomized to receive a combination of tablets of padsevonil 50 mg and Placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the SS.
OG002	Padsevonil 100mg BID (SS)	Participants were randomized to receive a combination of tablets of padsevonil 100 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the SS.

Primary

Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Study Withdrawal

The Safety Set consisted of all study participants who were administered at least 1 dose or a partial dose of IMP.

Posted

Number

percentage of participants

From Baseline until Safety Follow-Up (up to Week 23)

ID	Title	Description
OG000	Placebo (SS)	Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding up to week 19. Participants formed the Safety Set (SS).
OG001	Padsevonil 50mg BID (SS)	Participants were randomized to receive a combination of tablets of padsevonil 50 mg and Placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the SS.
OG002	Padsevonil 100mg BID (SS)	Participants were randomized to receive a combination of tablets of padsevonil 100 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the SS.

Primary

Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) During the Entire Study

A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose:

Results in death
Is life-threatening
Requires in patient hospitalization or prolongation of existing hospitalization
Is a congenital anomaly or birth defect
Is an infection that requires treatment parenteral antibiotics
Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above.

The Safety Set consisted of all study participants who were administered at least 1 dose or a partial dose of IMP.

Posted

Number

percentage of participants

From Baseline until Safety Follow-Up (up to Week 23)

ID	Title	Description
OG000	Placebo (SS)	Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding up to week 19. Participants formed the Safety Set (SS).
OG001	Padsevonil 50mg BID (SS)	Participants were randomized to receive a combination of tablets of padsevonil 50 mg and Placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the SS.
OG002	Padsevonil 100mg BID (SS)

Secondary

50 % Responder Rate Over the 12 Week Maintenance Period

The 50% responder rate, where a responder was a participant experiencing a ≥50% reduction in observable focal-onset seizure frequency from Baseline, over the 12-Week Maintenance Period.

Posted

Number

percentage of participants

End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization

ID	Title	Description
OG000	Placebo (FAS)	Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding up to week 19. Participants formed the Full Analysis Set (FAS).
OG001	Padsevonil 50mg BID (FAS)	Participants were randomized to receive a combination of tablets of padsevonil 50 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the FAS.
OG002	Padsevonil 100mg BID (FAS)	Participants were randomized to receive a combination of tablets of padsevonil 100 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the FAS.

Secondary

Percent Change in Observable Focal-onset Seizure Frequency From Baseline Over the 12 Week Maintenance Period

During the study, participants kept diaries to record daily seizure activity. The percentage of participants who experienced a 50 % or greater reduction in seizure frequency per 28 days relative to Baseline (responders) was assessed.

Posted

Mean

Standard Deviation

percent change

End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization

ID	Title	Description
OG000	Placebo (FAS)	Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding up to week 19. Participants formed the Full Analysis Set (FAS).
OG001	Padsevonil 50mg BID (FAS)	Participants were randomized to receive a combination of tablets of padsevonil 50 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the FAS.
OG002	Padsevonil 100mg BID (FAS)	Participants were randomized to receive a combination of tablets of padsevonil 100 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the FAS.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo Treatment Period (SS)	Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding up to week 19. Participants formed the Safety Set (SS).	83	3	83	45	83
EG001	Padsevonil 50mg BID Treatment Period (SS)	Participants were randomized to receive a combination of tablets of padsevonil 50 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the SS.	81	5	81	54	81
EG002	Padsevonil 100mg BID Treatment Period (SS)	Participants were randomized to receive a combination of tablets of padsevonil 100 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the SS.	83	4	83	60	83
EG003	Padsevonil 200mg BID Treatment Period (SS)	Participants were randomized to receive a combination of tablets of padsevonil 200 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the SS.	82	3	82	53	82
EG004	Padsevonil 400mg BID Treatment Period (SS)	Participants were randomized to receive a combination of tablets of padsevonil 400 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the SS.	81	5	81	65	81
EG005	Placebo Conversion Period (SS)	A 3-week Conversion Period was required for study participants who chose to enroll in the open-label extension (OLE) study at the end of the 12-week Maintenance Period. Participants initially randomized to placebo progressively received padsevonil in a blinded way to reach the entry dose of 400mg/day for the OLE. Participants formed the Safety Set (SS).	69	0	69	11	69
EG006	Padsevonil 50mg BID Conversion Period (SS)	A 3-week Conversion Period was required for study participants who chose to enroll in the OLE study at the end of the 12-week Maintenance Period. The dose for participants initially randomized to padsevonil 50mg bid was gradually adapted (increased or decreased) in a blinded way to reach the entry dose of 400mg/day for the OLE. Participants formed the SS.	64	0	64	18	64
EG007	Padsevonil 100mg BID Conversion Period (SS)	A 3-week Conversion Period was required for study participants who chose to enroll in the OLE study at the end of the 12-week Maintenance Period. The dose for participants initially randomized to padsevonil 100mg bid was gradually adapted (increased or decreased) in a blinded way to reach the entry dose of 400mg/day for the OLE. Participants formed the SS.	66	0	66	10	66
EG008	Padsevonil 200mg BID Conversion Period (SS)	A 3-week Conversion Period was required for study participants who chose to enroll in the OLE study at the end of the 12-week Maintenance Period. The dose for participants initially randomized to padsevonil 200mg bid was gradually adapted (increased or decreased) in a blinded way to reach the entry dose of 400mg/day for the OLE. Participants formed the SS.	55	2	55	5	55
EG009	Padsevonil 400mg BID Conversion Period (SS)	A 3-week Conversion Period was required for study participants who chose to enroll in the OLE study at the end of the 12-week Maintenance Period. The dose for participants initially randomized to padsevonil 400mg bid was gradually adapted (increased or decreased) in a blinded way to reach the entry dose of 400mg/day for the OLE. Participants formed the SS.	57	0	57	5	57
EG010	Placebo Taper and SFU Period (SS)	A 4-week Taper Period was required for participants who chose not to enroll in the OLE study or who discontinued prior to the end of the 12-week Maintenance Period. Participants initially randomized to placebo group received 5-6 placebo tablets to maintain the blinding and have been gradually tapered off the IMP over a 3-week period followed by 1-week drug-free period. Afterwards, participants had a Safety Follow-Up visit 30 days after the last IMP intake. Participants formed the Safety Set (SS).	9	1	9	3	9
EG011	Padsevonil 50mg BID Taper and SFU Period (SS)	A 4-week Taper Period was required for participants who chose not to enroll in the OLE study or who discontinued prior to the end of the 12-week Maintenance Period. Participants initially randomized to padsevonil 50 mg bid have been gradually tapered off the IMP over a 3-week period followed by 1-week drug-free period. Afterwards, participants had a Safety Follow-Up visit 30 days after the last IMP intake. Participants formed the SS.	14	1	14	3	14
EG012	Padsevonil 100mg BID Taper and SFU Period (SS)	A 4-week Taper Period was required for participants who chose not to enroll in the OLE study or who discontinued prior to the end of the 12-week Maintenance Period. Participants initially randomized to padsevonil 100 mg bid have been gradually tapered off the IMP over a 3-week period followed by 1-week drug-free period. Afterwards, participants had a Safety Follow-Up visit 30 days after the last IMP intake. Participants formed the SS.	11	0	11	0	11
EG013	Padsevonil 200mg BID Taper and SFU Period (SS)	A 4-week Taper Period was required for participants who chose not to enroll in the OLE study or who discontinued prior to the end of the 12-week Maintenance Period. Participants initially randomized to padsevonil 200 mg bid have been gradually tapered off the IMP over a 3-week period followed by 1-week drug-free period. Afterwards, participants had a Safety Follow-Up visit 30 days after the last IMP intake. Participants formed the SS.	24	0	24	3	24
EG014	Padsevonil 400mg BID Taper and SFU Period (SS)	A 4-week Taper Period was required for participants who chose not to enroll in the OLE study or who discontinued prior to the end of the 12-week Maintenance Period. Participants initially randomized to padsevonil 400 mg bid have been gradually tapered off the IMP over a 3-week period followed by 1-week drug-free period. Afterwards, participants had a Safety Follow-Up visit 30 days after the last IMP intake. Participants formed the SS.	22	0	22	4	22

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrial flutter	Cardiac disorders	MedDRA22.1	Non-systematic Assessment	EG0000 events0 affected83 at risk EG0011 events1 affected81 at risk EG0020 events0 affected83 at risk EG0030 events0 affected82 at risk EG0040 events0 affected81 at risk EG0050 events0 affected69 at risk EG0060 events0 affected64 at risk EG0070 events0 affected66 at risk EG0080 events0 affected55 at risk EG0090 events0 affected57 at risk EG0100 events0 affected9 at risk EG0110 events0 affected14 at risk EG0120 events0 affected11 at risk EG0130 events0 affected24 at risk EG0140 events0 affected22 at risk
Diverticulitis	Infections and infestations	MedDRA22.1	Non-systematic Assessment	EG0000 events0 affected83 at risk EG0011 events1 affected81 at risk EG0020 events0 affected83 at risk EG003
Concussion	Injury, poisoning and procedural complications	MedDRA22.1	Non-systematic Assessment	EG0000 events0 affected83 at risk EG0010 events0 affected81 at risk EG0021 events1 affected83 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA22.1	Non-systematic Assessment	EG0000 events0 affected83 at risk EG0010 events0 affected81 at risk EG0020 events0 affected83 at risk EG003
Head injury	Injury, poisoning and procedural complications	MedDRA22.1	Non-systematic Assessment	EG0000 events0 affected83 at risk EG0010 events0 affected81 at risk EG0021 events1 affected83 at risk EG003
Toxicity to various agents	Injury, poisoning and procedural complications	MedDRA22.1	Non-systematic Assessment	EG0000 events0 affected83 at risk EG0010 events0 affected81 at risk EG0020 events0 affected83 at risk EG003
Traumatic haemothorax	Injury, poisoning and procedural complications	MedDRA22.1	Non-systematic Assessment	EG0001 events1 affected83 at risk EG0010 events0 affected81 at risk EG0020 events0 affected83 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA22.1	Non-systematic Assessment	EG0000 events0 affected83 at risk EG0010 events0 affected81 at risk EG0021 events1 affected83 at risk EG003
Altered state of consciousness	Nervous system disorders	MedDRA22.1	Non-systematic Assessment	EG0000 events0 affected83 at risk EG0010 events0 affected81 at risk EG0020 events0 affected83 at risk EG003
Encephalopathy	Nervous system disorders	MedDRA22.1	Non-systematic Assessment	EG0000 events0 affected83 at risk EG0010 events0 affected81 at risk EG0020 events0 affected83 at risk EG003
Focal dyscognitive seizures	Nervous system disorders	MedDRA22.1	Non-systematic Assessment	EG0000 events0 affected83 at risk EG0011 events1 affected81 at risk EG0020 events0 affected83 at risk EG003
Partial seizures	Nervous system disorders	MedDRA22.1	Non-systematic Assessment	EG0000 events0 affected83 at risk EG0011 events1 affected81 at risk EG0020 events0 affected83 at risk EG003
Seizure cluster	Nervous system disorders	MedDRA22.1	Non-systematic Assessment	EG0001 events1 affected83 at risk EG0010 events0 affected81 at risk EG0020 events0 affected83 at risk EG003
Status epilepticus	Nervous system disorders	MedDRA22.1	Non-systematic Assessment	EG0001 events1 affected83 at risk EG0011 events1 affected81 at risk EG0021 events1 affected83 at risk EG003
Syncope	Nervous system disorders	MedDRA22.1	Non-systematic Assessment	EG0000 events0 affected83 at risk EG0010 events0 affected81 at risk EG0020 events0 affected83 at risk EG003
Renal disorder	Renal and urinary disorders	MedDRA22.1	Non-systematic Assessment	EG0000 events0 affected83 at risk EG0010 events0 affected81 at risk EG0021 events1 affected83 at risk EG003
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA22.1	Non-systematic Assessment	EG0000 events0 affected83 at risk EG0010 events0 affected81 at risk EG0021 events1 affected83 at risk EG003
Medical device battery replacement	Surgical and medical procedures	MedDRA22.1	Non-systematic Assessment	EG0000 events0 affected83 at risk EG0010 events0 affected81 at risk EG0021 events1 affected83 at risk EG003
Depression	Psychiatric disorders	MedDRA22.1	Non-systematic Assessment	EG0000 events0 affected83 at risk EG0010 events0 affected81 at risk EG0020 events0 affected83 at risk EG003
Acute psychosis	Psychiatric disorders	MedDRA22.1	Non-systematic Assessment	EG0000 events0 affected83 at risk EG0010 events0 affected81 at risk EG0020 events0 affected83 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Vertigo	Ear and labyrinth disorders	MedDRA22.1	Non-systematic Assessment	EG0007 events7 affected83 at risk EG0013 events3 affected81 at risk EG0022 events2 affected83 at risk EG0033 events3 affected82 at risk EG0045 events4 affected81 at risk EG0051 events1 affected69 at risk EG0060 events0 affected64 at risk EG0070 events0 affected66 at risk EG0080 events0 affected55 at risk EG0090 events0 affected57 at risk EG0100 events0 affected9 at risk EG0110 events0 affected14 at risk EG0120 events0 affected11 at risk EG0130 events0 affected24 at risk EG0140 events0 affected22 at risk
Nausea	Gastrointestinal disorders	MedDRA22.1	Non-systematic Assessment	EG0007 events7 affected83 at risk EG0014 events4 affected81 at risk EG0027 events7 affected83 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA22.1	Non-systematic Assessment	EG0003 events3 affected83 at risk EG0018 events6 affected81 at risk EG0024 events3 affected83 at risk EG003
Fatigue	General disorders	MedDRA22.1	Non-systematic Assessment	EG00010 events10 affected83 at risk EG00127 events20 affected81 at risk EG00217 events12 affected83 at risk EG003
Gait disturbance	General disorders	MedDRA22.1	Non-systematic Assessment	EG0001 events1 affected83 at risk EG0012 events2 affected81 at risk EG0020 events0 affected83 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA22.1	Non-systematic Assessment	EG0005 events5 affected83 at risk EG0015 events5 affected81 at risk EG00213 events9 affected83 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA22.1	Non-systematic Assessment	EG0003 events1 affected83 at risk EG0015 events5 affected81 at risk EG0020 events0 affected83 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA22.1	Non-systematic Assessment	EG0002 events2 affected83 at risk EG0011 events1 affected81 at risk EG0021 events1 affected83 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA22.1	Non-systematic Assessment	EG0004 events4 affected83 at risk EG0012 events2 affected81 at risk EG0021 events1 affected83 at risk EG003
Ligament sprain	Injury, poisoning and procedural complications	MedDRA22.1	Non-systematic Assessment	EG0000 events0 affected83 at risk EG0012 events2 affected81 at risk EG0020 events0 affected83 at risk EG003
Burns second degree	Injury, poisoning and procedural complications	MedDRA22.1	Non-systematic Assessment	EG0000 events0 affected83 at risk EG0010 events0 affected81 at risk EG0020 events0 affected83 at risk EG003
Platelet count decreased	Investigations	MedDRA22.1	Non-systematic Assessment	EG0000 events0 affected83 at risk EG0010 events0 affected81 at risk EG0021 events1 affected83 at risk EG003
Anticonvulsant drug level increased	Investigations	MedDRA22.1	Non-systematic Assessment	EG0000 events0 affected83 at risk EG0010 events0 affected81 at risk EG0020 events0 affected83 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA22.1	Non-systematic Assessment	EG0000 events0 affected83 at risk EG0011 events1 affected81 at risk EG0022 events2 affected83 at risk EG003
Dizziness	Nervous system disorders	MedDRA22.1	Non-systematic Assessment	EG0009 events9 affected83 at risk EG00119 events18 affected81 at risk EG00231 events23 affected83 at risk EG003
Somnolence	Nervous system disorders	MedDRA22.1	Non-systematic Assessment	EG00011 events10 affected83 at risk EG00124 events19 affected81 at risk EG00229 events24 affected83 at risk EG003
Headache	Nervous system disorders	MedDRA22.1	Non-systematic Assessment	EG00014 events10 affected83 at risk EG00129 events17 affected81 at risk EG00216 events9 affected83 at risk EG003
Memory impairment	Nervous system disorders	MedDRA22.1	Non-systematic Assessment	EG0001 events1 affected83 at risk EG0013 events3 affected81 at risk EG0021 events1 affected83 at risk EG003
Tremor	Nervous system disorders	MedDRA22.1	Non-systematic Assessment	EG0000 events0 affected83 at risk EG0015 events5 affected81 at risk EG0022 events2 affected83 at risk EG003
Balance disorder	Nervous system disorders	MedDRA22.1	Non-systematic Assessment	EG0002 events1 affected83 at risk EG0013 events3 affected81 at risk EG0023 events3 affected83 at risk EG003
Nystagmus	Nervous system disorders	MedDRA22.1	Non-systematic Assessment	EG0000 events0 affected83 at risk EG0010 events0 affected81 at risk EG0020 events0 affected83 at risk EG003
Irritability	Psychiatric disorders	MedDRA22.1	Non-systematic Assessment	EG0008 events8 affected83 at risk EG0014 events4 affected81 at risk EG0027 events7 affected83 at risk EG003
Anxiety	Psychiatric disorders	MedDRA22.1	Non-systematic Assessment	EG0003 events3 affected83 at risk EG0011 events1 affected81 at risk EG0022 events1 affected83 at risk EG003
Paranoia	Psychiatric disorders	MedDRA22.1	Non-systematic Assessment	EG0000 events0 affected83 at risk EG0010 events0 affected81 at risk EG0020 events0 affected83 at risk EG003

ID	Term
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D000069279	Drug Resistant Epilepsy
D012640	Seizures
D004827	Epilepsy