ARISE: Study to Test the Efficacy and Safety of Padsevonil as Adjunctive Treatment of Focal-onset Seizures in Adults With Drug-resistant Epilepsy

Sponsor

UCB Biopharma S.P.R.L. (Industry)

Overall Status

Completed

CT.gov ID

NCT03373383

Collaborator

(none)

411

Enrollment

148

Locations

Arms

23.6

Actual Duration (Months)

2.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the study is to characterize the dose-response relationship with respect to efficacy of Padsevonil administered concomitantly with up to 3 anti-epileptic drugs (AEDs) for treatment of observable focal-onset seizures in subjects with drug-resistant epilepsy.

Condition or Disease	Intervention/Treatment	Phase
Drug-resistant Epilepsy Focal-Onset Seizures	Drug: Padsevonil Other: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

411 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-Blind, Placebo-Controlled, Dose Finding Study to Evaluate the Efficacy and Safety of Padsevonil as Adjunctive Treatment of Focal-Onset Seizures in Adult Subjects With Drug-Resistant Epilepsy

Actual Study Start Date :

Feb 12, 2018

Actual Primary Completion Date :

Jan 30, 2020

Actual Study Completion Date :

Jan 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Padsevonil dosing regimen 1 Subjects will be randomized to receive a combination of tablets of Padsevonil and Placebo (as appropriate) to maintain the blinding.	Drug: Padsevonil Padsevonil in different dosages. Other: Placebo Placebo will be provided matching Padsevonil.
Experimental: Padsevonil dosing regimen 2 Subjects will be randomized to receive a combination of tablets of Padsevonil and Placebo (as appropriate) to maintain the blinding.	Drug: Padsevonil Padsevonil in different dosages. Other: Placebo Placebo will be provided matching Padsevonil.
Experimental: Padsevonil dosing regimen 3 Subjects will be randomized to receive a combination of tablets of Padsevonil and Placebo (as appropriate) to maintain the blinding.	Drug: Padsevonil Padsevonil in different dosages. Other: Placebo Placebo will be provided matching Padsevonil.
Experimental: Padsevonil dosing regimen 4 Subjects will be randomized to receive a combination of tablets of Padsevonil and Placebo (as appropriate) to maintain the blinding.	Drug: Padsevonil Padsevonil in different dosages. Other: Placebo Placebo will be provided matching Padsevonil.
Placebo Comparator: Placebo Subjects randomized to the placebo group will receive a combination of several Placebo tablets to maintain the blinding.	Other: Placebo Placebo will be provided matching Padsevonil.

Outcome Measures

Primary Outcome Measures

Change in Log-transformed Observable Focal Onset Seizure Frequency From Baseline Over the 12 Week Maintenance Period [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.
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 [From Baseline until Safety Follow-Up (up to Week 23)]
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.
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Study Withdrawal [From Baseline until Safety Follow-Up (up to Week 23)]
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.
Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) During the Entire Study [From Baseline until Safety Follow-Up (up to Week 23)]
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 Outcome Measures

75 % Responder Rate Over the 12 Week Maintenance Period [End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization]
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.
50 % Responder Rate Over the 12 Week Maintenance Period [End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization]
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.
Percent Change 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]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ep0091 839	Chandler	Arizona	United States	85226
2	Ep0091 810	Little Rock	Arkansas	United States	72205
3	Ep0091 815	La Jolla	California	United States	92037
4	Ep0091 801	San Francisco	California	United States	94115
5	Ep0091 845	Washington	District of Columbia	United States	20037
6	Ep0091 809	Ocala	Florida	United States	34471
7	Ep0091 823	Orlando	Florida	United States	32806
8	Ep0091 825	Port Charlotte	Florida	United States	33952
9	Ep0091 820	Tallahassee	Florida	United States	32308
10	Ep0091 873	Atlanta	Georgia	United States	30303
11	Ep0091 803	Honolulu	Hawaii	United States	96817
12	Ep0091 832	Peoria	Illinois	United States	61637
13	Ep0091 822	Baltimore	Maryland	United States	21287
14	Ep0091 818	Bethesda	Maryland	United States	20817
15	Ep0091 817	Saint Paul	Minnesota	United States	55102
16	Ep0091 806	Hackensack	New Jersey	United States	07601
17	Ep0091 827	New York	New York	United States	10016-48
18	Ep0091 800	Philadelphia	Pennsylvania	United States	19104
19	Ep0091 802	Philadelphia	Pennsylvania	United States	19107
20	Ep0091 838	Cordova	Tennessee	United States	38018
21	Ep0091 835	Nashville	Tennessee	United States	37232
22	Ep0091 805	Austin	Texas	United States	78701
23	Ep0091 844	Austin	Texas	United States	78758
24	Ep0091 836	Dallas	Texas	United States	75231
25	Ep0091 830	Dallas	Texas	United States	75390-91
26	Ep0091 824	Round Rock	Texas	United States	78681
27	Ep0091 870	San Antonio	Texas	United States	78229
28	Ep0091 855	Box Hill		Australia
29	Ep0091 857	Clayton		Australia
30	Ep0091 850	Fitzroy		Australia
31	Ep0091 859	Herston		Australia
32	Ep0091 852	Melbourne		Australia
33	Ep0091 853	Melbourne		Australia
34	Ep0091 856	Randwick		Australia
35	Ep0091 854	Westmead		Australia
36	Ep0091 102	Brugge		Belgium
37	Ep0091 101	Brussels		Belgium
38	Ep0091 105	Gent		Belgium
39	Ep0091 100	Leuven		Belgium
40	Ep0091 150	Blagoevgrad		Bulgaria
41	Ep0091 151	Pleven		Bulgaria
42	Ep0091 153	Pleven		Bulgaria
43	Ep0091 152	Sofia		Bulgaria
44	Ep0091 154	Sofia		Bulgaria
45	Ep0091 155	Sofia		Bulgaria
46	Ep0091 200	Greenfield Park		Canada
47	Ep0091 205	London		Canada
48	Ep0091 201	Montréal		Canada
49	Ep0091 254	Brno		Czechia
50	Ep0091 255	Ostrava-Poruba		Czechia
51	Ep0091 252	Praha 4		Czechia
52	Ep0091 250	Praha 5		Czechia
53	Ep0091 253	Praha 8		Czechia
54	Ep0091 251	Praha		Czechia
55	Ep0091 307	Clermont-Ferrand Cedex 1		France
56	Ep0091 309	Dijon		France
57	Ep0091 300	Lille		France
58	Ep0091 302	Montpellier		France
59	Ep0091 305	Paris		France
60	Ep0091 303	Rennes		France
61	Ep0091 306	Toulouse Cedex 9		France
62	Ep0091 361	Bad Neustadt An Der Saale		Germany
63	Ep0091 365	Berlin		Germany
64	Ep0091 362	Bernau		Germany
65	Ep0091 363	Bielefeld		Germany
66	Ep0091 358	Bonn		Germany
67	Ep0091 350	Frankfurt am main		Germany
68	Ep0091 360	Freiburg		Germany
69	Ep0091 364	Hamburg		Germany
70	Ep0091 368	Jena		Germany
71	Ep0091 366	Kork		Germany
72	Ep0091 357	Leipzig		Germany
73	Ep0091 353	Marburg		Germany
74	Ep0091 354	München		Germany
75	Ep0091 351	Münster		Germany
76	Ep0091 356	Osnabrück		Germany
77	Ep0091 367	Ravensburg		Germany
78	Ep0091 301	Strausberg		Germany
79	Ep0091 352	Tübingen		Germany
80	Ep0091 400	Budapest		Hungary
81	Ep0091 403	Budapest		Hungary
82	Ep0091 402	Debrecen		Hungary
83	Ep0091 462	Bologna		Italy
84	Ep0091 450	Cagliari		Italy
85	Ep0091 461	Foggia		Italy
86	Ep0091 452	Milano		Italy
87	Ep0091 459	Pavia		Italy
88	Ep0091 453	Perugia		Italy
89	Ep0091 458	Pozzilli		Italy
90	Ep0091 454	Reggio Calabria		Italy
91	Ep0091 455	Roma		Italy
92	Ep0091 457	Roma		Italy
93	Ep0091 460	Roma		Italy
94	Ep0091 501	Asaka		Japan
95	Ep0091 511	Fukuoka		Japan
96	Ep0091 505	Hiroshima		Japan
97	Ep0091 513	Hōfu		Japan
98	Ep0091 507	Itami		Japan
99	Ep0091 503	Kodaira		Japan
100	Ep0091 514	Kyoto		Japan
101	Ep0091 512	Nagakute		Japan
102	Ep0091 510	Niigata		Japan
103	Ep0091 515	Saitama		Japan
104	Ep0091 509	Shizuoka		Japan
105	Ep0091 703	Kaunas		Lithuania
106	Ep0091 701	Vilnius		Lithuania
107	Ep0091 702	Vilnius		Lithuania
108	Ep0091 553	Culiacán		Mexico
109	Ep0091 552	Mexico Distrito Federal		Mexico
110	Ep0091 601	Gdańsk		Poland
111	Ep0091 607	Grodzisk Mazowiecki		Poland
112	Ep0091 605	Katowice		Poland
113	Ep0091 608	Katowice		Poland
114	Ep0091 603	Kraków		Poland
115	Ep0091 604	Lublin		Poland
116	Ep0091 606	Nowa Sól		Poland
117	Ep0091 600	Poznań		Poland
118	Ep0091 609	Poznań		Poland
119	Ep0091 602	Świdnik		Poland
120	Ep0091 952	Santa Maria Da Feira		Portugal
121	Ep0091 004	Bardejov		Slovakia
122	Ep0091 001	Hlohovec		Slovakia
123	Ep0091 662	Alicante		Spain
124	Ep0091 651	Barcelona		Spain
125	Ep0091 652	Barcelona		Spain
126	Ep0091 658	Barcelona		Spain
127	Ep0091 664	Barcelona		Spain
128	Ep0091 668	Bilbao		Spain
129	Ep0091 666	Córdoba		Spain
130	Ep0091 650	Madrid		Spain
131	Ep0091 656	Madrid		Spain
132	Ep0091 660	Madrid		Spain
133	Ep0091 661	Madrid		Spain
134	Ep0091 659	Málaga		Spain
135	Ep0091 663	Sevilla		Spain
136	Ep0091 665	Terrassa		Spain
137	Ep0091 657	Valencia		Spain
138	Ep0091 667	Valencia		Spain
139	Ep0091 653	Valladolid		Spain
140	Ep0091 904	Eskişehir		Turkey
141	Ep0091 900	Istanbul		Turkey
142	Ep0091 901	Istanbul		Turkey
143	Ep0091 752	Birmingham		United Kingdom
144	Ep0091 751	Cardiff		United Kingdom
145	Ep0091 756	Inverness		United Kingdom
146	Ep0091 757	London		United Kingdom
147	Ep0091 750	Manchester		United Kingdom
148	Ep0091 753	Swansea		United Kingdom

Sponsors and Collaborators

UCB Biopharma S.P.R.L.

Investigators

Study Director: UCB Cares, 001 844 599 2273 (UCB)

Study Documents (Full-Text)

More Information

Publications

None provided.

Responsible Party:

UCB Biopharma S.P.R.L.

ClinicalTrials.gov Identifier:

NCT03373383

Other Study ID Numbers:

EP0091
2017-003200-48

First Posted:

Dec 14, 2017

Last Update Posted:

Apr 9, 2021

Last Verified:

Mar 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by UCB Biopharma S.P.R.L.

Epilepsy

Padsevonil

Additional relevant MeSH terms:

Epilepsy

Seizures

Drug Resistant Epilepsy

Study Results

Participant Flow

Recruitment Details	The study started to enroll patients in February 2018 and concluded in January 2020.
Pre-assignment Detail	The study included: a 4-week Baseline Period, a 16-week Treatment Period, a 4-week Taper Period (for participants who discontinued or choose not to enroll in the open-label extension study) and a Safety Follow-up Period. Participants continuing to the OLE study had a 3-week Conversion Period. Participant Flow refers to the Randomized Set.

Arm/Group Title	Placebo	Padsevonil 50mg BID	Padsevonil 100mg BID	Padsevonil 200mg BID	Padsevonil 400mg BID
Arm/Group Description	Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding up to week 19.	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	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 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 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.
Period Title: Treatment Period: Wk0-16
STARTED	83	81	83	82	82
Completed Titration and Stabilization	78	72	71	68	65
Completed Maintenance Period	70	66	68	61	58
Had Taper and Safety Follow-up	6	11	8	18	21
COMPLETED	70	66	68	61	58
NOT COMPLETED	13	15	15	21	24
Period Title: Treatment Period: Wk0-16
STARTED	70	66	68	61	58
Started Conversion Period	69	64	66	55	57
Completed Conversion Period	68	64	66	55	57
Had Taper and Safety Follow-up	3	3	3	6	1
Enrolled in EP0093	67	63	65	55	57
COMPLETED	69	66	68	61	58
NOT COMPLETED	1	0	0	0	0

Baseline Characteristics

Arm/Group Title	Placebo	Padsevonil 50mg BID	Padsevonil 100mg BID	Padsevonil 200mg BID	Padsevonil 400mg BID	Total Title
Arm/Group Description	Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding up to week 19.	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	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 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 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.
Overall Participants	83	81	83	82	82	411
Age (Count of Participants)
<=18 years	0 0%	0 0%	2 2.4%	1 1.2%	1 1.2%	4 1%
Between 18 and 65 years	82 98.8%	76 93.8%	80 96.4%	79 96.3%	80 97.6%	397 96.6%
>=65 years	1 1.2%	5 6.2%	1 1.2%	2 2.4%	1 1.2%	10 2.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.0 (12.9)	42.5 (11.6)	36.9 (13.1)	40.9 (12.0)	38.8 (12.1)	39.8 (12.4)
Sex: Female, Male (Count of Participants)
Female	48 57.8%	46 56.8%	47 56.6%	51 62.2%	43 52.4%	235 57.2%
Male	35 42.2%	35 43.2%	36 43.4%	31 37.8%	39 47.6%	176 42.8%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	1 1.2%	1 1.2%	1 1.2%	2 2.4%	0 0%	5 1.2%
Asian	7 8.4%	7 8.6%	5 6%	7 8.5%	7 8.5%	33 8%
Black or African American	2 2.4%	1 1.2%	1 1.2%	2 2.4%	2 2.4%	8 1.9%
Native Hawaiian or Other Pacific Islander	1 1.2%	1 1.2%	1 1.2%	1 1.2%	1 1.2%	5 1.2%
White	69 83.1%	69 85.2%	73 88%	69 84.1%	71 86.6%	351 85.4%
Other/mixed	3 3.6%	2 2.5%	2 2.4%	1 1.2%	1 1.2%	9 2.2%

Outcome Measures

1. Primary Outcome

Title	Change in Log-transformed Observable Focal Onset Seizure Frequency From Baseline Over the 12 Week Maintenance Period
Description	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.
Time Frame	From Baseline over the 12 Week Maintenance Period

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Placebo (FAS)	Padsevonil 50mg BID (FAS)	Padsevonil 100mg BID (FAS)	Padsevonil 200mg BID (FAS)	Padsevonil 400mg BID (FAS)
Arm/Group Description	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).	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.	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.	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.	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.
Measure Participants	81	80	82	81	81
Least Squares Mean (95% Confidence Interval) [loge seizures per 28 days]	-0.27585	-0.46424	-0.48804	-0.48960	-0.40831

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Padsevonil 50mg BID (FAS)
	Comments	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.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	=0.102
	Comments	Adjusted p-values were from the Hochberg step-up procedure within SAS® Proc Multtest to control Type I error.
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Percent reduction
	Estimated Value	17.2
	Confidence Interval	(2-Sided) 95% -3.8 to 33.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Padsevonil 100mg BID (FAS)
	Comments	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.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	=0.064
	Comments	Adjusted p-values were from the Hochberg step-up procedure within SAS® Proc Multtest to control Type I error.
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Percent reduction
	Estimated Value	19.1
	Confidence Interval	(2-Sided) 95% -1.2 to 35.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Padsevonil 200mg BID (FAS)
	Comments	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.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	=0.063
	Comments	Adjusted p-values were from the Hochberg step-up procedure within SAS® Proc Multtest to control Type I error.
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Percent reduction
	Estimated Value	19.2
	Confidence Interval	(2-Sided) 95% -1.2 to 35.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Padsevonil 400mg BID (FAS)
	Comments	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.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	=0.248
	Comments	Adjusted p-values were from the Hochberg step-up procedure within SAS® Proc Multtest to control Type I error.
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Percent reduction
	Estimated Value	12.4
	Confidence Interval	(2-Sided) 95% -9.7 to 30.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	75 % Responder Rate Over the 12 Week Maintenance Period
Description	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.
Time Frame	End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Placebo (FAS)	Padsevonil 50mg BID (FAS)	Padsevonil 100mg BID (FAS)	Padsevonil 200mg BID (FAS)	Padsevonil 400mg BID (FAS)
Arm/Group Description	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).	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.	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.	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.	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.
Measure Participants	81	80	82	81	81
Number [percentage of participants]	6.2 7.5%	13.8 17%	12.2 14.7%	11.1 13.5%	16.0 19.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Padsevonil 50mg BID (FAS)
	Comments	PSL dose/Placebo was calculated using logistic regression with categorical factors for treatment group, Region (Europe, Non-Europe), Baseline SV2A use (0, 1) and log-transformed Baseline seizure frequency as a continuous covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	=0.081
	Comments	Nominal p-values were not adjusted for multiplicity.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.72
	Confidence Interval	(2-Sided) 95% 0.88 to 8.39
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Padsevonil 100mg BID (FAS)
	Comments	PSL dose/Placebo was calculated using logistic regression with categorical factors for treatment group, Region (Europe, Non-Europe), Baseline SV2A use (0, 1) and log-transformed Baseline seizure frequency as a continuous covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	=0.137
	Comments	Nominal p-values were not adjusted for multiplicity.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.37
	Confidence Interval	(2-Sided) 95% 0.76 to 7.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Padsevonil 200mg BID (FAS)
	Comments	PSL dose/Placebo was calculated using logistic regression with categorical factors for treatment group, Region (Europe, Non-Europe), Baseline SV2A use (0, 1) and log-transformed Baseline seizure frequency as a continuous covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	=0.192
	Comments	Nominal p-values were not adjusted for multiplicity.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.16
	Confidence Interval	(2-Sided) 95% 0.68 to 6.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Padsevonil 400mg BID (FAS)
	Comments	PSL dose/Placebo was calculated using logistic regression with categorical factors for treatment group, Region (Europe, Non-Europe), Baseline SV2A use (0, 1) and log-transformed Baseline seizure frequency as a continuous covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	=0.041
	Comments	Nominal p-values were not adjusted for multiplicity.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.14
	Confidence Interval	(2-Sided) 95% 1.05 to 9.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	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
Description	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.
Time Frame	From Baseline until Safety Follow-Up (up to Week 23)

Outcome Measure Data

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

Arm/Group Title	Placebo (SS)	Padsevonil 50mg BID (SS)	Padsevonil 100mg BID (SS)	Padsevonil 200mg BID (SS)	Padsevonil 400mg BID (SS)
Arm/Group Description	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).	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.	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.	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.	Participants were randomized to receive tablets of padsevonil 400 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the SS.
Measure Participants	83	81	83	82	81
Number [percentage of participants]	78.3 94.3%	84.0 103.7%	80.7 97.2%	75.6 92.2%	92.6 112.9%

4. Primary Outcome

Title	Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Study Withdrawal
Description	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.
Time Frame	From Baseline until Safety Follow-Up (up to Week 23)

Outcome Measure Data

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

Arm/Group Title	Placebo (SS)	Padsevonil 50mg BID (SS)	Padsevonil 100mg BID (SS)	Padsevonil 200mg BID (SS)	Padsevonil 400mg BID (SS)
Arm/Group Description	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).	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.	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.	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.	Participants were randomized to receive tablets of padsevonil 400 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the SS.
Measure Participants	83	81	83	82	81
Number [percentage of participants]	8.4 10.1%	7.4 9.1%	12.0 14.5%	18.3 22.3%	25.9 31.6%

5. Primary Outcome

Title	Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) During the Entire Study
Description	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.
Time Frame	From Baseline until Safety Follow-Up (up to Week 23)

Outcome Measure Data

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

Arm/Group Title	Placebo (SS)	Padsevonil 50mg BID (SS)	Padsevonil 100mg BID (SS)	Padsevonil 200mg BID (SS)	Padsevonil 400mg BID (SS)
Arm/Group Description	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).	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.	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.	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.	Participants were randomized to receive tablets of padsevonil 400 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the SS.
Measure Participants	83	81	83	82	81
Number [percentage of participants]	4.8 5.8%	7.4 9.1%	4.8 5.8%	6.1 7.4%	6.2 7.6%

6. Secondary Outcome

Title	50 % Responder Rate Over the 12 Week Maintenance Period
Description	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.
Time Frame	End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Placebo (FAS)	Padsevonil 50mg BID (FAS)	Padsevonil 100mg BID (FAS)	Padsevonil 200mg BID (FAS)	Padsevonil 400mg BID (FAS)
Arm/Group Description	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).	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.	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.	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.	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.
Measure Participants	81	80	82	81	81
Number [percentage of participants]	21.0 25.3%	33.8 41.7%	31.7 38.2%	25.9 31.6%	32.1 39.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Padsevonil 50mg BID (FAS)
	Comments	PSL dose/placebo calculated using logistic regression with categorical factors for treatment group (each PSL dose group referenced to the placebo group), region (Europe, Non-Europe), Baseline SV2A use (0, 1) and log-transformed Baseline seizure frequency as a continuous covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	=0.045
	Comments	Nominal p-values were not adjusted for multiplicity.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.09
	Confidence Interval	(2-Sided) 95% 1.02 to 4.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Padsevonil 100mg BID (FAS)
	Comments	PSL dose/placebo calculated using logistic regression with categorical factors for treatment group (each PSL dose group referenced to the placebo group), region (Europe, Non-Europe), Baseline SV2A use (0, 1) and log-transformed Baseline seizure frequency as a continuous covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	=0.079
	Comments	Nominal p-values were not adjusted for multiplicity.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.91
	Confidence Interval	(2-Sided) 95% 0.93 to 3.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Padsevonil 200mg BID (FAS)
	Comments	PSL dose/placebo calculated using logistic regression with categorical factors for treatment group (each PSL dose group referenced to the placebo group), region (Europe, Non-Europe), Baseline SV2A use (0, 1) and log-transformed Baseline seizure frequency as a continuous covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	=0.338
	Comments	Nominal p-values were not adjusted for multiplicity.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.44
	Confidence Interval	(2-Sided) 95% 0.68 to 3.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Padsevonil 400mg BID (FAS)
	Comments	PSL dose/Placebo calculated using logistic regression with categorical factors for treatment group, Region (Europe, Non-Europe), Baseline SV2A use (0, 1) and log-transformed Baseline seizure frequency as a continuous covariate.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	=0.087
	Comments	Nominal p-values were not adjusted for multiplicity.
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.88
	Confidence Interval	(2-Sided) 95% 0.91 to 3.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Percent Change in Observable Focal-onset Seizure Frequency From Baseline Over the 12 Week Maintenance Period
Description	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.
Time Frame	End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Placebo (FAS)	Padsevonil 50mg BID (FAS)	Padsevonil 100mg BID (FAS)	Padsevonil 200mg BID (FAS)	Padsevonil 400mg BID (FAS)
Arm/Group Description	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).	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.	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.	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.	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.
Measure Participants	81	80	82	81	81
Mean (Standard Deviation) [percent change]	12.49 (58.26)	24.70 (46.62)	25.25 (51.73)	20.79 (66.54)	15.79 (67.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Padsevonil 50mg BID (FAS)
	Comments	Dose group comparisons to Placebo p-value were based on the Wilcoxon-Mann-Whitney test. The Hodges-Lehmann nonparametric estimator was used to estimate the median difference between each PSL dose group versus placebo, along with the corresponding 95% CI of the estimate.
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	=0.316
	Comments	Nominal p-values were not adjusted for multiplicity.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	7.40
	Confidence Interval	(2-Sided) 95% -6.59 to 21.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Padsevonil 100mg BID (FAS)
	Comments	Dose group comparisons to Placebo p-value were based on the Wilcoxon-Mann-Whitney test. The Hodges-Lehmann nonparametric estimator was used to estimate the median difference between each PSL dose group versus placebo, along with the corresponding 95% CI of the estimate.
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	=0.133
	Comments	Nominal p-values were not adjusted for multiplicity.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	9.99
	Confidence Interval	(2-Sided) 95% -3.15 to 23.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Padsevonil 200mg BID (FAS)
	Comments	Dose group comparisons to Placebo p-value were based on the Wilcoxon-Mann-Whitney test. The Hodges-Lehmann nonparametric estimator was used to estimate the median difference between each PSL dose group versus placebo, along with the corresponding 95% CI of the estimate.
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	=0.203
	Comments	Nominal p-values were not adjusted for multiplicity.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	8.19
	Confidence Interval	(2-Sided) 95% -3.95 to 21.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Padsevonil 400mg BID (FAS)
	Comments	Dose group comparisons to Placebo p-value were based on the Wilcoxon-Mann-Whitney test. The Hodges-Lehmann nonparametric estimator was used to estimate the median difference between each PSL dose group versus placebo, along with the corresponding 95% CI of the estimate.
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	=0.784
	Comments	Nominal p-values were not adjusted for multiplicity.
	Method	Wilcoxon (Mann-Whitney)
	Comments

Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	2.39
	Confidence Interval	(2-Sided) 95% -13.65 to 17.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

	Placebo Treatment Period (SS)		Padsevonil 50mg BID Treatment Period (SS)		Padsevonil 100mg BID Treatment Period (SS)		Padsevonil 200mg BID Treatment Period (SS)		Padsevonil 400mg BID Treatment Period (SS)		Placebo Conversion Period (SS)		Padsevonil 50mg BID Conversion Period (SS)		Padsevonil 100mg BID Conversion Period (SS)		Padsevonil 200mg BID Conversion Period (SS)		Padsevonil 400mg BID Conversion Period (SS)		Placebo Taper and SFU Period (SS)		Padsevonil 50mg BID Taper and SFU Period (SS)		Padsevonil 100mg BID Taper and SFU Period (SS)		Padsevonil 200mg BID Taper and SFU Period (SS)		Padsevonil 400mg BID Taper and SFU Period (SS)
Time Frame	Treatment-emergent AEs were collected from Baseline to Safety Follow-Up (up to Week 23)
Adverse Event Reporting Description	Adverse events refer to the SS which consisted of all participants who were administered at least 1 dose or a partial dose of IMP. TEAEs counts are for each study period: Treatment Period, Conversion Period for participants who entered the OLE study and Taper Period followed by SFU for participants not entering OLE study.

Arm/Group Title	Placebo Treatment Period (SS)		Padsevonil 50mg BID Treatment Period (SS)		Padsevonil 100mg BID Treatment Period (SS)		Padsevonil 200mg BID Treatment Period (SS)		Padsevonil 400mg BID Treatment Period (SS)		Placebo Conversion Period (SS)		Padsevonil 50mg BID Conversion Period (SS)		Padsevonil 100mg BID Conversion Period (SS)		Padsevonil 200mg BID Conversion Period (SS)		Padsevonil 400mg BID Conversion Period (SS)		Placebo Taper and SFU Period (SS)		Padsevonil 50mg BID Taper and SFU Period (SS)		Padsevonil 100mg BID Taper and SFU Period (SS)		Padsevonil 200mg BID Taper and SFU Period (SS)		Padsevonil 400mg BID Taper and SFU Period (SS)
Arm/Group Description	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).		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.		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.		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.		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.		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).		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.		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.		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.		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.		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).		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.		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.		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.		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.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/83 (0%)		0/81 (0%)		0/83 (0%)		0/82 (0%)		0/81 (0%)		0/69 (0%)		0/64 (0%)		0/66 (0%)		0/55 (0%)		0/57 (0%)		0/9 (0%)		0/14 (0%)		0/11 (0%)		0/24 (0%)		0/22 (0%)
Serious Adverse Events
	Placebo Treatment Period (SS)		Padsevonil 50mg BID Treatment Period (SS)		Padsevonil 100mg BID Treatment Period (SS)		Padsevonil 200mg BID Treatment Period (SS)		Padsevonil 400mg BID Treatment Period (SS)		Placebo Conversion Period (SS)		Padsevonil 50mg BID Conversion Period (SS)		Padsevonil 100mg BID Conversion Period (SS)		Padsevonil 200mg BID Conversion Period (SS)		Padsevonil 400mg BID Conversion Period (SS)		Placebo Taper and SFU Period (SS)		Padsevonil 50mg BID Taper and SFU Period (SS)		Padsevonil 100mg BID Taper and SFU Period (SS)		Padsevonil 200mg BID Taper and SFU Period (SS)		Padsevonil 400mg BID Taper and SFU Period (SS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/83 (3.6%)		5/81 (6.2%)		4/83 (4.8%)		3/82 (3.7%)		5/81 (6.2%)		0/69 (0%)		0/64 (0%)		0/66 (0%)		2/55 (3.6%)		0/57 (0%)		1/9 (11.1%)		1/14 (7.1%)		0/11 (0%)		0/24 (0%)		0/22 (0%)
Cardiac disorders
Atrial flutter	0/83 (0%)	0	1/81 (1.2%)	1	0/83 (0%)	0	0/82 (0%)	0	0/81 (0%)	0	0/69 (0%)	0	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Infections and infestations
Diverticulitis	0/83 (0%)	0	1/81 (1.2%)	1	0/83 (0%)	0	0/82 (0%)	0	0/81 (0%)	0	0/69 (0%)	0	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Injury, poisoning and procedural complications
Concussion	0/83 (0%)	0	0/81 (0%)	0	1/83 (1.2%)	1	0/82 (0%)	0	0/81 (0%)	0	0/69 (0%)	0	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Fall	0/83 (0%)	0	0/81 (0%)	0	0/83 (0%)	0	1/82 (1.2%)	1	0/81 (0%)	0	0/69 (0%)	0	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Head injury	0/83 (0%)	0	0/81 (0%)	0	1/83 (1.2%)	1	0/82 (0%)	0	1/81 (1.2%)	1	0/69 (0%)	0	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	1/14 (7.1%)	1	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Toxicity to various agents	0/83 (0%)	0	0/81 (0%)	0	0/83 (0%)	0	1/82 (1.2%)	1	0/81 (0%)	0	0/69 (0%)	0	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Traumatic haemothorax	1/83 (1.2%)	1	0/81 (0%)	0	0/83 (0%)	0	0/82 (0%)	0	0/81 (0%)	0	0/69 (0%)	0	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Metabolism and nutrition disorders
Hyperkalaemia	0/83 (0%)	0	0/81 (0%)	0	1/83 (1.2%)	1	0/82 (0%)	0	0/81 (0%)	0	0/69 (0%)	0	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Nervous system disorders
Altered state of consciousness	0/83 (0%)	0	0/81 (0%)	0	0/83 (0%)	0	0/82 (0%)	0	1/81 (1.2%)	1	0/69 (0%)	0	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Encephalopathy	0/83 (0%)	0	0/81 (0%)	0	0/83 (0%)	0	0/82 (0%)	0	1/81 (1.2%)	1	0/69 (0%)	0	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Focal dyscognitive seizures	0/83 (0%)	0	1/81 (1.2%)	1	0/83 (0%)	0	0/82 (0%)	0	0/81 (0%)	0	0/69 (0%)	0	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Partial seizures	0/83 (0%)	0	1/81 (1.2%)	1	0/83 (0%)	0	0/82 (0%)	0	0/81 (0%)	0	0/69 (0%)	0	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Seizure cluster	1/83 (1.2%)	1	0/81 (0%)	0	0/83 (0%)	0	0/82 (0%)	0	0/81 (0%)	0	0/69 (0%)	0	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Status epilepticus	1/83 (1.2%)	1	1/81 (1.2%)	1	1/83 (1.2%)	1	1/82 (1.2%)	1	1/81 (1.2%)	1	0/69 (0%)	0	0/64 (0%)	0	0/66 (0%)	0	1/55 (1.8%)	1	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Syncope	0/83 (0%)	0	0/81 (0%)	0	0/83 (0%)	0	0/82 (0%)	0	1/81 (1.2%)	1	0/69 (0%)	0	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Psychiatric disorders
Depression	0/83 (0%)	0	0/81 (0%)	0	0/83 (0%)	0	0/82 (0%)	0	0/81 (0%)	0	0/69 (0%)	0	0/64 (0%)	0	0/66 (0%)	0	1/55 (1.8%)	1	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Acute psychosis	0/83 (0%)	0	0/81 (0%)	0	0/83 (0%)	0	0/82 (0%)	0	0/81 (0%)	0	0/69 (0%)	0	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	1/9 (11.1%)	1	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Renal and urinary disorders
Renal disorder	0/83 (0%)	0	0/81 (0%)	0	1/83 (1.2%)	1	0/82 (0%)	0	0/81 (0%)	0	0/69 (0%)	0	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration	0/83 (0%)	0	0/81 (0%)	0	1/83 (1.2%)	1	0/82 (0%)	0	0/81 (0%)	0	0/69 (0%)	0	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Surgical and medical procedures
Medical device battery replacement	0/83 (0%)	0	0/81 (0%)	0	1/83 (1.2%)	1	0/82 (0%)	0	1/81 (1.2%)	1	0/69 (0%)	0	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo Treatment Period (SS)		Padsevonil 50mg BID Treatment Period (SS)		Padsevonil 100mg BID Treatment Period (SS)		Padsevonil 200mg BID Treatment Period (SS)		Padsevonil 400mg BID Treatment Period (SS)		Placebo Conversion Period (SS)		Padsevonil 50mg BID Conversion Period (SS)		Padsevonil 100mg BID Conversion Period (SS)		Padsevonil 200mg BID Conversion Period (SS)		Padsevonil 400mg BID Conversion Period (SS)		Placebo Taper and SFU Period (SS)		Padsevonil 50mg BID Taper and SFU Period (SS)		Padsevonil 100mg BID Taper and SFU Period (SS)		Padsevonil 200mg BID Taper and SFU Period (SS)		Padsevonil 400mg BID Taper and SFU Period (SS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	45/83 (54.2%)		54/81 (66.7%)		60/83 (72.3%)		53/82 (64.6%)		65/81 (80.2%)		11/69 (15.9%)		18/64 (28.1%)		10/66 (15.2%)		5/55 (9.1%)		5/57 (8.8%)		3/9 (33.3%)		3/14 (21.4%)		0/11 (0%)		3/24 (12.5%)		4/22 (18.2%)
Ear and labyrinth disorders
Vertigo	7/83 (8.4%)	7	3/81 (3.7%)	3	2/83 (2.4%)	2	3/82 (3.7%)	3	4/81 (4.9%)	5	1/69 (1.4%)	1	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Gastrointestinal disorders
Nausea	7/83 (8.4%)	7	4/81 (4.9%)	4	7/83 (8.4%)	7	2/82 (2.4%)	3	7/81 (8.6%)	13	1/69 (1.4%)	1	0/64 (0%)	0	1/66 (1.5%)	1	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Diarrhoea	3/83 (3.6%)	3	6/81 (7.4%)	8	3/83 (3.6%)	4	5/82 (6.1%)	7	4/81 (4.9%)	5	1/69 (1.4%)	1	1/64 (1.6%)	1	1/66 (1.5%)	1	0/55 (0%)	0	1/57 (1.8%)	1	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	1/24 (4.2%)	1	0/22 (0%)	0
General disorders
Fatigue	10/83 (12%)	10	20/81 (24.7%)	27	12/83 (14.5%)	17	14/82 (17.1%)	22	20/81 (24.7%)	21	3/69 (4.3%)	3	5/64 (7.8%)	5	2/66 (3%)	2	1/55 (1.8%)	1	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	1/24 (4.2%)	2	0/22 (0%)	0
Gait disturbance	1/83 (1.2%)	1	2/81 (2.5%)	2	0/83 (0%)	0	1/82 (1.2%)	1	5/81 (6.2%)	5	0/69 (0%)	0	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Infections and infestations
Nasopharyngitis	5/83 (6%)	5	5/81 (6.2%)	5	9/83 (10.8%)	13	7/82 (8.5%)	11	5/81 (6.2%)	5	1/69 (1.4%)	1	1/64 (1.6%)	1	0/66 (0%)	0	1/55 (1.8%)	1	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Upper respiratory tract infection	1/83 (1.2%)	3	5/81 (6.2%)	5	0/83 (0%)	0	0/82 (0%)	0	2/81 (2.5%)	3	0/69 (0%)	0	1/64 (1.6%)	1	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	1/14 (7.1%)	1	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Urinary tract infection	2/83 (2.4%)	2	1/81 (1.2%)	1	1/83 (1.2%)	1	0/82 (0%)	0	2/81 (2.5%)	2	1/69 (1.4%)	1	0/64 (0%)	0	1/66 (1.5%)	1	0/55 (0%)	0	0/57 (0%)	0	1/9 (11.1%)	1	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	1/22 (4.5%)	1
Injury, poisoning and procedural complications
Fall	4/83 (4.8%)	4	2/81 (2.5%)	2	1/83 (1.2%)	1	1/82 (1.2%)	2	7/81 (8.6%)	7	0/69 (0%)	0	0/64 (0%)	0	1/66 (1.5%)	2	1/55 (1.8%)	1	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Ligament sprain	0/83 (0%)	0	2/81 (2.5%)	2	0/83 (0%)	0	0/82 (0%)	0	0/81 (0%)	0	0/69 (0%)	0	2/64 (3.1%)	2	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	1/9 (11.1%)	1	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Burns second degree	0/83 (0%)	0	0/81 (0%)	0	0/83 (0%)	0	0/82 (0%)	0	0/81 (0%)	0	0/69 (0%)	0	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	1/14 (7.1%)	1	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Investigations
Platelet count decreased	0/83 (0%)	0	0/81 (0%)	0	1/83 (1.2%)	1	0/82 (0%)	0	0/81 (0%)	0	0/69 (0%)	0	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	1/9 (11.1%)	1	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Anticonvulsant drug level increased	0/83 (0%)	0	0/81 (0%)	0	0/83 (0%)	0	0/82 (0%)	0	0/81 (0%)	0	0/69 (0%)	0	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	1/9 (11.1%)	1	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/83 (0%)	0	1/81 (1.2%)	1	2/83 (2.4%)	2	2/82 (2.4%)	2	5/81 (6.2%)	5	0/69 (0%)	0	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	1/9 (11.1%)	1	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Nervous system disorders
Dizziness	9/83 (10.8%)	9	18/81 (22.2%)	19	23/83 (27.7%)	31	19/82 (23.2%)	25	28/81 (34.6%)	55	3/69 (4.3%)	3	2/64 (3.1%)	2	1/66 (1.5%)	1	2/55 (3.6%)	2	2/57 (3.5%)	6	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	1/24 (4.2%)	1	1/22 (4.5%)	1
Somnolence	10/83 (12%)	11	19/81 (23.5%)	24	24/83 (28.9%)	29	25/82 (30.5%)	26	30/81 (37%)	35	1/69 (1.4%)	1	4/64 (6.3%)	5	1/66 (1.5%)	1	1/55 (1.8%)	1	2/57 (3.5%)	2	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Headache	10/83 (12%)	14	17/81 (21%)	29	9/83 (10.8%)	16	15/82 (18.3%)	21	9/81 (11.1%)	31	0/69 (0%)	0	3/64 (4.7%)	3	2/66 (3%)	3	0/55 (0%)	0	1/57 (1.8%)	5	1/9 (11.1%)	1	0/14 (0%)	0	0/11 (0%)	0	2/24 (8.3%)	2	1/22 (4.5%)	1
Memory impairment	1/83 (1.2%)	1	3/81 (3.7%)	3	1/83 (1.2%)	1	8/82 (9.8%)	9	14/81 (17.3%)	14	1/69 (1.4%)	1	0/64 (0%)	0	1/66 (1.5%)	1	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	1/22 (4.5%)	1
Tremor	0/83 (0%)	0	5/81 (6.2%)	5	2/83 (2.4%)	2	6/82 (7.3%)	6	5/81 (6.2%)	5	1/69 (1.4%)	1	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Balance disorder	1/83 (1.2%)	2	3/81 (3.7%)	3	3/83 (3.6%)	3	5/82 (6.1%)	5	3/81 (3.7%)	3	0/69 (0%)	0	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Nystagmus	0/83 (0%)	0	0/81 (0%)	0	0/83 (0%)	0	0/82 (0%)	0	0/81 (0%)	0	1/69 (1.4%)	1	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	1/14 (7.1%)	1	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Psychiatric disorders
Irritability	8/83 (9.6%)	8	4/81 (4.9%)	4	7/83 (8.4%)	7	1/82 (1.2%)	1	5/81 (6.2%)	6	0/69 (0%)	0	1/64 (1.6%)	1	1/66 (1.5%)	1	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	1/22 (4.5%)	1
Anxiety	3/83 (3.6%)	3	1/81 (1.2%)	1	1/83 (1.2%)	2	7/82 (8.5%)	9	0/81 (0%)	0	1/69 (1.4%)	1	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0
Paranoia	0/83 (0%)	0	0/81 (0%)	0	0/83 (0%)	0	0/82 (0%)	0	0/81 (0%)	0	0/69 (0%)	0	0/64 (0%)	0	0/66 (0%)	0	0/55 (0%)	0	0/57 (0%)	0	0/9 (0%)	0	1/14 (7.1%)	1	0/11 (0%)	0	0/24 (0%)	0	0/22 (0%)	0

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

Results Point of Contact

Name/Title	UCB
Organization	Cares
Phone	+1844 599 ext 2273
Email	UCBCares@ucb.com

Responsible Party:

UCB Biopharma S.P.R.L.

ClinicalTrials.gov Identifier:

NCT03373383

Other Study ID Numbers:

EP0091
2017-003200-48

First Posted:

Dec 14, 2017

Last Update Posted:

Apr 9, 2021

Last Verified:

Mar 1, 2021

ARISE: Study to Test the Efficacy and Safety of Padsevonil as Adjunctive Treatment of Focal-onset Seizures in Adults With Drug-resistant Epilepsy

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Statistical Analysis 3

Statistical Analysis 4

Outcome Measure Data

Statistical Analysis 1

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Statistical Analysis 3

Statistical Analysis 4

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

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Statistical Analysis 2

Statistical Analysis 3

Statistical Analysis 4

Outcome Measure Data

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Statistical Analysis 4

Adverse Events

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