DUET: A Study to Test the Efficacy and Safety of Padsevonil as Treatment of Focal-onset Seizures in Adult Subjects With Drug-resistant Epilepsy

• Sponsor: UCB Biopharma SRL (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03739840
• Collaborator: (none)
• Enrollment: 232
• Locations: 141
• Arms: 4
• Actual Duration (Months): 18.8
• Patients Per Site: 1.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the efficacy, safety and tolerability of the 3 selected dose regimens of padsevonil (PSL) administered concomitantly with up to 3 anti-epileptic drugs (AEDs) compared with placebo 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; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 232 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group 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: Mar 6, 2019
• Actual Primary Completion Date: Sep 28, 2020
• Actual Study Completion Date: Sep 28, 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.; Drug: 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.; Drug: 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.; Drug: 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.	Drug: Placebo; Placebo will be provided matching padsevonil.

Outcome Measures

Primary Outcome Measures

1. 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 (up to Week 16)]

   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 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.

2. Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) [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. A TEAE was defined as any event not present before the initiation of the first dose of study treatment or any unresolved event already present before initiation of the first dose that worsened in intensity following exposure to the treatment.

3. 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. A TEAE was defined as any event not present before the initiation of the first dose of study treatment or any unresolved event already present before initiation of the first dose that worsened in intensity following exposure to the treatment.

4. Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) [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 as 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. A TEAE was defined as any event not present before the initiation of the first dose of study treatment or any unresolved event already present before initiation of the first dose that worsened in intensity following exposure to the treatment.

Secondary Outcome Measures

1. 75% Responder Rate From Baseline Over the 12-week Maintenance Period [From Baseline over the 12 Week Maintenance Period (up to Week 16)]

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

2. 50% Responder Rate From Baseline Over the 12-week Maintenance Period [From Baseline over the 12 Week Maintenance Period (up to Week 16)]

   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.

3. Percent Change in Observable Focal-onset Seizure Frequency From Baseline Over the 12-week Maintenance Period [From Baseline over the 12 Week Maintenance Period (up to Week 16)]

   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) were assessed.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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	Ep0092 839	Chandler	Arizona	United States	85226
2	Ep0092 881	Tucson	Arizona	United States	85724
3	Ep0092 633	Carlsbad	California	United States	92011
4	Ep0092 629	Orange	California	United States	92868
5	Ep0092 845	Washington	District of Columbia	United States	20037
6	Ep0092 892	Bradenton	Florida	United States	34209
7	Ep0092 640	Hialeah	Florida	United States	33016
8	Ep0092 641	Jacksonville	Florida	United States	32209
9	Ep0092 823	Orlando	Florida	United States	32806
10	Ep0092 803	Honolulu	Hawaii	United States	96817
11	Ep0092 637	Urbana	Illinois	United States	61801
12	Ep0092 880	Anderson	Indiana	United States	46011
13	Ep0092 638	Fort Wayne	Indiana	United States	46804
14	Ep0092 630	Ames	Iowa	United States	50010
15	Ep0092 707	Lexington	Kentucky	United States	40536
16	Ep0092 822	Baltimore	Maryland	United States	21287
17	Ep0092 818	Bethesda	Maryland	United States	20817
18	Ep0092 889	Boston	Massachusetts	United States	02215
19	Ep0092 645	Golden Valley	Minnesota	United States	55422
20	Ep0092 644	Minneapolis	Minnesota	United States	55416
21	Ep0092 895	Bronx	New York	United States	10467
22	Ep0092 878	Brooklyn	New York	United States	11203
23	Ep0092 876	New York	New York	United States	10075
24	Ep0092 893	Syracuse	New York	United States	13210
25	Ep0092 890	Chapel Hill	North Carolina	United States	27599
26	Ep0092 884	Charlotte	North Carolina	United States	28204
27	Ep0092 642	Columbus	Ohio	United States	43210
28	Ep0092 647	Oklahoma City	Oklahoma	United States	73106
29	Ep0092 882	Portland	Oregon	United States	97225
30	Ep0092 802	Philadelphia	Pennsylvania	United States	19107
31	Ep0092 829	Charlottesville	Virginia	United States	22903
32	Ep0092 639	Renton	Washington	United States	98055
33	Ep0092 855	Box Hill		Australia
34	Ep0092 861	Camperdown		Australia
35	Ep0092 850	Fitzroy		Australia
36	Ep0092 853	Heidelberg		Australia
37	Ep0092 852	Melbourne		Australia
38	Ep0092 109	Brussels		Belgium
39	Ep0092 107	Ottignies		Belgium
40	Ep0092 080	Bihać		Bosnia and Herzegovina
41	Ep0092 077	Mostar		Bosnia and Herzegovina
42	Ep0092 075	Sarajevo		Bosnia and Herzegovina
43	Ep0092 082	Tuzla		Bosnia and Herzegovina
44	Ep0092 150	Blagoevgrad		Bulgaria
45	Ep0092 151	Pleven		Bulgaria
46	Ep0092 156	Pleven		Bulgaria
47	Ep0092 154	Sofia		Bulgaria
48	Ep0092 125	Zagreb		Croatia
49	Ep0092 126	Zagreb		Croatia
50	Ep0092 127	Zagreb		Croatia
51	Ep0092 128	Zagreb		Croatia
52	Ep0092 254	Brno		Czechia
53	Ep0092 258	Ostrava		Czechia
54	Ep0092 250	Praha 5		Czechia
55	Ep0092 251	Praha 6		Czechia
56	Ep0092 016	Aarhus		Denmark
57	Ep0092 015	Odense		Denmark
58	Ep0092 276	Tallinn		Estonia
59	Ep0092 277	Tallinn		Estonia
60	Ep0092 275	Tartu		Estonia
61	Ep0092 027	Tampere		Finland
62	Ep0092 312	Lyon		France
63	Ep0092 310	Paris		France
64	Ep0092 301	Strasbourg		France
65	Ep0092 365	Berlin		Germany
66	Ep0092 362	Bernau		Germany
67	Ep0092 363	Bielefeld		Germany
68	Ep0092 350	Frankfurt		Germany
69	Ep0092 368	Jena		Germany
70	Ep0092 357	Leipzig		Germany
71	Ep0092 376	Regensburg		Germany
72	Ep0092 425	Ioánnina		Greece
73	Ep0092 426	Thessaloníki		Greece
74	Ep0092 427	Thessaloníki		Greece
75	Ep0092 428	Thessaloníki		Greece
76	Ep0092 403	Budapest		Hungary
77	Ep0092 405	Debrecen		Hungary
78	Ep0092 404	Pécs		Hungary
79	Ep0092 035	Cork		Ireland
80	Ep0092 036	Dublin		Ireland
81	Ep0092 452	Milano		Italy
82	Ep0092 526	Asahikawa		Japan
83	Ep0092 501	Asaka		Japan
84	Ep0092 521	Bunkyō-Ku		Japan
85	Ep0092 525	Bunkyō-Ku		Japan
86	Ep0092 504	Hamamatsu		Japan
87	Ep0092 505	Hiroshima		Japan
88	Ep0092 513	Hōfu		Japan
89	Ep0092 507	Itami		Japan
90	Ep0092 531	Izumi		Japan
91	Ep0092 539	Kumamoto		Japan
92	Ep0092 533	Kure		Japan
93	Ep0092 514	Kyoto		Japan
94	Ep0092 512	Nagakute		Japan
95	Ep0092 515	Saitama		Japan
96	Ep0092 508	Sapporo		Japan
97	Ep0092 527	Shinagawa-Ku		Japan
98	Ep0092 509	Shizuoka		Japan
99	Ep0092 529	Yonago		Japan
100	Ep0092 522	Ōmura		Japan
101	Ep0092 530	Ōsaka-sayama		Japan
102	Ep0092 775	Sandvika		Norway
103	Ep0092 605	Katowice		Poland
104	Ep0092 616	Katowice		Poland
105	Ep0092 603	Kraków		Poland
106	Ep0092 614	Kraków		Poland
107	Ep0092 610	Lublin		Poland
108	Ep0092 620	Lublin		Poland
109	Ep0092 606	Nowa Sól		Poland
110	Ep0092 611	Warszawa		Poland
111	Ep0092 615	Wrocław		Poland
112	Ep0092 619	Zamość		Poland
113	Ep0092 618	Zgierz		Poland
114	Ep0092 612	Łódź		Poland
115	Ep0092 952	Aveiro		Portugal
116	Ep0092 950	Matosinhos		Portugal
117	Ep0092 925	Bucuresti		Romania
118	Ep0092 926	Bucuresti		Romania
119	Ep0092 927	Târgu-Mureş		Romania
120	Ep0092 327	Belgrade		Serbia
121	Ep0092 325	Novi Sad		Serbia
122	Ep0092 004	Bardejov		Slovakia
123	Ep0092 662	Alicante		Spain
124	Ep0092 651	Barcelona		Spain
125	Ep0092 652	Barcelona		Spain
126	Ep0092 658	Barcelona		Spain
127	Ep0092 674	Madrid		Spain
128	Ep0092 657	Valencia		Spain
129	Ep0092 676	Zaragoza		Spain
130	Ep0092 576	Göteborg		Sweden
131	Ep0092 575	Linköping		Sweden
132	Ep0092 053	Zürich		Switzerland
133	Ep0092 913	Ankara		Turkey
134	Ep0092 915	Antalya		Turkey
135	Ep0092 900	Istanbul		Turkey
136	Ep0092 906	Istanbul		Turkey
137	Ep0092 909	Istanbul		Turkey
138	Ep0092 908	Trabzon		Turkey
139	Ep0092 766	Brighton		United Kingdom
140	Ep0092 750	Manchester		United Kingdom
141	Ep0092 764	Swansea		United Kingdom

Sponsors and Collaborators

• UCB Biopharma SRL

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Jan 21, 2020
• Statistical Analysis Plan - Aug 18, 2020

More Information

Publications

None provided.

• Responsible Party: UCB Biopharma SRL
• ClinicalTrials.gov Identifier: NCT03739840
• Other Study ID Numbers: EP0092; 2018-002303-33
• First Posted: Nov 14, 2018
• Last Update Posted: Nov 30, 2021
• Last Verified: Nov 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: No
• Keywords provided by UCB Biopharma SRL: Epilepsy; Padsevonil
• Additional relevant MeSH terms: Epilepsy; Seizures; Drug Resistant Epilepsy

Study Results

Participant Flow

Recruitment Details	The study started to enroll participants in March 2019 and concluded in September 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. The Participant Flow refers to the Randomized Set.

Arm/Group Title	Placebo	Padsevonil 100 mg BID	Padsevonil 200 mg BID	Padsevonil 400 mg BID
Arm/Group Description	Participants randomized to the placebo group received 5-6 placebo tablets 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	56	60	57	59
Completed Titration and Stabilization	54	58	51	54
Completed Maintenance Period	46	44	44	36
COMPLETED	46	44	44	36
NOT COMPLETED	10	16	13	23
Period Title: Treatment Period: Wk0-16
STARTED	46	44	44	36
Started Conversion Period	33	31	29	28
Completed Conversion Period	33	31	29	28
Started Taper and Safety Follow-up	19	18	21	13
Completed Taper and Safety Follow-up	15	16	18	12
Enrolled in EP0093	27	26	23	23
COMPLETED	42	42	41	35
NOT COMPLETED	4	2	3	1

Baseline Characteristics

Arm/Group Title	Placebo	Padsevonil 100 mg BID	Padsevonil 200 mg BID	Padsevonil 400 mg BID	Total Title
Arm/Group Description	Participants randomized to the placebo group received 5-6 placebo tablets 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	56	60	57	59	232
Age (Count of Participants)
<=18 years	1 1.8%	0 0%	4 7%	0 0%	5 2.2%
Between 18 and 65 years	52 92.9%	57 95%	48 84.2%	56 94.9%	213 91.8%
>=65 years	3 5.4%	3 5%	5 8.8%	3 5.1%	14 6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.9 (13.6)	40.7 (13.0)	39.5 (14.3)	39.7 (13.6)	40.4 (13.6)
Sex: Female, Male (Count of Participants)
Female	34 60.7%	34 56.7%	29 50.9%	34 57.6%	131 56.5%
Male	22 39.3%	26 43.3%	28 49.1%	25 42.4%	101 43.5%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	1 1.8%	0 0%	0 0%	0 0%	1 0.4%
Asian	5 8.9%	5 8.3%	7 12.3%	7 11.9%	24 10.3%
Black	0 0%	1 1.7%	1 1.8%	1 1.7%	3 1.3%
Native Hawaiian or Other Pacific Islander	0 0%	2 3.3%	0 0%	0 0%	2 0.9%
White	49 87.5%	50 83.3%	49 86%	51 86.4%	199 85.8%
Other/mixed	1 1.8%	2 3.3%	0 0%	0 0%	3 1.3%

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 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 (up to Week 16)

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. Here, number of participants were included who were evaluable for the assessment.

Arm/Group Title	Placebo (FAS)	Padsevonil 100 mg BID (FAS)	Padsevonil 200 mg BID (FAS)	Padsevonil 400 mg BID (FAS)
Arm/Group Description	Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding, bid up to Week 19. Participants formed the Full Analysis Set (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	54	59	56	56
Least Squares Mean (95% Confidence Interval) [log e seizures per 28 days]	-0.41	-0.35	-0.47	-0.47

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Padsevonil 100 mg 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	=0.687
	Comments	Adjusted p-values are 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	-5.6
	Confidence Interval	(2-Sided) 95%; -38.1 to 19.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Padsevonil 200 mg 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	=0.687
	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	6.5
	Confidence Interval	(2-Sided) 95%; -22.7 to 28.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Padsevonil 400 mg 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	=0.687
	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	6.3
	Confidence Interval	(2-Sided) 95%; -22.9 to 28.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
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. A TEAE was defined as any event not present before the initiation of the first dose of study treatment or any unresolved event already present before initiation of the first dose that worsened in intensity following exposure to the 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 100 mg BID (SS)	Padsevonil 200 mg BID (SS)	Padsevonil 400 mg BID (SS)
Arm/Group Description	Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding, bid up to Week 19. Participants formed the Safety Set (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.
Measure Participants	55	60	57	59
Number [percentage of participants]	69.1 123.4%	83.3 138.8%	78.9 138.4%	84.7 143.6%

3. 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. A TEAE was defined as any event not present before the initiation of the first dose of study treatment or any unresolved event already present before initiation of the first dose that worsened in intensity following exposure to the 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 100 mg BID (SS)	Padsevonil 200 mg BID (SS)	Padsevonil 400 mg BID (SS)
Arm/Group Description	Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding, bid up to Week 19. Participants formed the Safety Set (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.
Measure Participants	55	60	57	59
Number [percentage of participants]	7.3 13%	10.0 16.7%	10.5 18.4%	20.3 34.4%

4. Primary Outcome

Title	Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)
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 as 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. A TEAE was defined as any event not present before the initiation of the first dose of study treatment or any unresolved event already present before initiation of the first dose that worsened in intensity following exposure to the 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 100 mg BID (SS)	Padsevonil 200 mg BID (SS)	Padsevonil 400 mg BID (SS)
Arm/Group Description	Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding, bid up to Week 19. Participants formed the Safety Set (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.
Measure Participants	55	60	57	59
Number [percentage of participants]	9.1 16.3%	3.3 5.5%	1.8 3.2%	10.2 17.3%

5. Secondary Outcome

Title	75% Responder Rate From Baseline Over the 12-week Maintenance Period
Description	The 75 % responder rate, where a responder was a participant experiencing a ≥75 % reduction in observable focal-onset seizure frequency from Baseline, over the 12-Week Maintenance Period.
Time Frame	From Baseline over the 12 Week Maintenance Period (up to Week 16)

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. Here, number of participants were included who were evaluable for the assessment.

Arm/Group Title	Placebo (FAS)	Padsevonil 100 mg BID (FAS)	Padsevonil 200 mg BID (FAS)	Padsevonil 400 mg BID (FAS)
Arm/Group Description	Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding, bid up to Week 19. Participants formed the Full Analysis Set (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	54	59	56	56
Number [percentage of participants]	13.0 23.2%	15.3 25.5%	12.5 21.9%	14.3 24.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Padsevonil 100 mg 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 (Yes, No) and log-transformed Baseline seizure frequency as a continuous covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.803
	Comments	Nominal p-values were not adjusted for multiplicity.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.15
	Confidence Interval	(2-Sided) 95%; 0.39 to 3.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Padsevonil 200 mg 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 (Yes, No) and log-transformed Baseline seizure frequency as a continuous covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.772
	Comments	Nominal p-values were not adjusted for multiplicity.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.27 to 2.65
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Padsevonil 400 mg 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 (Yes, No) and log-transformed Baseline seizure frequency as a continuous covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.989
	Comments	Nominal p-values were not adjusted for multiplicity.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.33 to 3.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	50% Responder Rate From Baseline 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	From Baseline over the 12 Week Maintenance Period (up to Week 16)

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. Here, number of participants were included who were evaluable for the assessment.

Arm/Group Title	Placebo (FAS)	Padsevonil 100 mg BID (FAS)	Padsevonil 200 mg BID (FAS)	Padsevonil 400 mg BID (FAS)
Arm/Group Description	Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding, bid up to Week 19. Participants formed the Full Analysis Set (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	54	59	56	56
Number [percentage of participants]	27.8 49.6%	35.6 59.3%	33.9 59.5%	42.9 72.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Padsevonil 100 mg 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 (Yes, No) and log-transformed Baseline seizure frequency as a continuous covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.425
	Comments	Nominal p-values were not adjusted for multiplicity.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.40
	Confidence Interval	(2-Sided) 95%; 0.61 to 3.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Padsevonil 200 mg 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 (Yes, No) and log-transformed Baseline seizure frequency as a continuous covariate
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.625
	Comments	Nominal p-values were not adjusted for multiplicity.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.23
	Confidence Interval	(2-Sided) 95%; 0.53 to 2.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Padsevonil 400 mg 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 (Yes, No) and log-transformed Baseline seizure frequency as a continuous covariate
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.125
	Comments	Nominal p-values were not adjusted for multiplicity.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.90
	Confidence Interval	(2-Sided) 95%; 0.84 to 4.34
	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) were assessed.
Time Frame	From Baseline over the 12 Week Maintenance Period (up to Week 16)

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. Here, number of participants were included who were evaluable for the assessment.

Arm/Group Title	Placebo (FAS)	Padsevonil 100 mg BID (FAS)	Padsevonil 200 mg BID (FAS)	Padsevonil 400 mg BID (FAS)
Arm/Group Description	Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding, bid up to Week 19. Participants formed the Full Analysis Set (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	54	59	56	56
Mean (Standard Deviation) [percent change]	22.34 (44.56)	11.72 (81.52)	30.29 (39.58)	22.41 (62.80)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Padsevonil 100 mg BID (FAS)
	Comments	Dose group comparisons to Placebo p-value are based on the Wilcoxon-Mann-Whitney test. Hodges Lehmann nonparametric effect estimates and corresponding two-sided 95% asymptotic confidence intervals are provided for the effect difference between each PSL dose and placebo.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.737
	Comments	Nominal p-values were not adjusted for multiplicity.
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	3.25
	Confidence Interval	(2-Sided) 95%; -17.08 to 20.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Padsevonil 200 mg BID (FAS)
	Comments	Dose group comparisons to Placebo p-value are based on the Wilcoxon-Mann-Whitney test. Hodges Lehmann nonparametric effect estimates and corresponding two-sided 95% asymptotic confidence intervals are provided for the effect difference between each PSL dose and placebo.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.458
	Comments	Nominal p-values were not adjusted for multiplicity.
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	6.17
	Confidence Interval	(2-Sided) 95%; -10.00 to 21.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Padsevonil 400 mg BID (FAS)
	Comments	Dose group comparisons to Placebo p-value are based on the Wilcoxon-Mann-Whitney test. Hodges Lehmann nonparametric effect estimates and corresponding two-sided 95% asymptotic confidence intervals are provided for the effect difference between each PSL dose and placebo.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.341
	Comments	Nominal p-values were not adjusted for multiplicity.
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	9.31
	Confidence Interval	(2-Sided) 95%; -10.92 to 28.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	TEAEs were collected from Baseline until Safety Follow-Up (up to Week 23)
Adverse Event Reporting Description	TEAEs counts are for the number of study participants who entered the respective study period regardless of whether or not they completed the previous period. This is the reason for the difference in number of participants in Taper and SFU period in adverse events section and participant flow.
Arm/Group Title	Placebo Treatment Period (SS)		Padsevonil 100 mg BID Treatment Period (SS)		Padsevonil 200 mg BID Treatment Period (SS)		Padsevonil 400 mg BID Treatment Period (SS)		Placebo Conversion Period (SS)		Padsevonil 100 mg BID Conversion Period (SS)		Padsevonil 200 mg BID Conversion Period (SS)		Padsevonil 400 mg BID Conversion Period (SS)		Placebo Taper and SFU Period (SS)		Padsevonil 100 mg BID Taper and SFU Period (SS)		Padsevonil 200 mg BID Taper and SFU Period (SS)		Padsevonil 400 mg BID Taper and SFU Period (SS)
Arm/Group Description	Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding, bid up to Week 19. Participants formed the Safety Set (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 400 mg/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 100 mg bid was gradually adapted (increased or decreased) in a blinded way to reach the entry dose of 400 mg/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 200 mg bid was gradually adapted (increased or decreased) in a blinded way to reach the entry dose of 400 mg/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 400 mg bid was gradually adapted (increased or decreased) in a blinded way to reach the entry dose of 400 mg/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 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
	Placebo Treatment Period (SS)		Padsevonil 100 mg BID Treatment Period (SS)		Padsevonil 200 mg BID Treatment Period (SS)		Padsevonil 400 mg BID Treatment Period (SS)		Placebo Conversion Period (SS)		Padsevonil 100 mg BID Conversion Period (SS)		Padsevonil 200 mg BID Conversion Period (SS)		Padsevonil 400 mg BID Conversion Period (SS)		Placebo Taper and SFU Period (SS)		Padsevonil 100 mg BID Taper and SFU Period (SS)		Padsevonil 200 mg BID Taper and SFU Period (SS)		Padsevonil 400 mg 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
Total	0/55 (0%)		0/60 (0%)		0/57 (0%)		0/59 (0%)		0/33 (0%)		0/31 (0%)		0/29 (0%)		0/28 (0%)		0/27 (0%)		0/30 (0%)		0/31 (0%)		0/32 (0%)
Serious Adverse Events
	Placebo Treatment Period (SS)		Padsevonil 100 mg BID Treatment Period (SS)		Padsevonil 200 mg BID Treatment Period (SS)		Padsevonil 400 mg BID Treatment Period (SS)		Placebo Conversion Period (SS)		Padsevonil 100 mg BID Conversion Period (SS)		Padsevonil 200 mg BID Conversion Period (SS)		Padsevonil 400 mg BID Conversion Period (SS)		Placebo Taper and SFU Period (SS)		Padsevonil 100 mg BID Taper and SFU Period (SS)		Padsevonil 200 mg BID Taper and SFU Period (SS)		Padsevonil 400 mg 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
Total	3/55 (5.5%)		0/60 (0%)		1/57 (1.8%)		5/59 (8.5%)		1/33 (3%)		0/31 (0%)		0/29 (0%)		0/28 (0%)		1/27 (3.7%)		2/30 (6.7%)		0/31 (0%)		1/32 (3.1%)
Injury, poisoning and procedural complications
Radius fracture	0/55 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	1/59 (1.7%)	2	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Skin laceration	1/55 (1.8%)	1	0/60 (0%)	0	0/57 (0%)	0	0/59 (0%)	0	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Subdural haematoma	1/55 (1.8%)	1	0/60 (0%)	0	0/57 (0%)	0	0/59 (0%)	0	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Wrist fracture	0/55 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	1/59 (1.7%)	1	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Contusion	0/55 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	0/59 (0%)	0	1/33 (3%)	1	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Humerus fracture	0/55 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	0/59 (0%)	0	1/33 (3%)	1	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Rib fracture	0/55 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	0/59 (0%)	0	1/33 (3%)	1	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Metabolism and nutrition disorders
Hyponatraemia	0/55 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	1/59 (1.7%)	1	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Musculoskeletal and connective tissue disorders
Muscular weakness	0/55 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	1/59 (1.7%)	1	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Nervous system disorders
Epilepsy	0/55 (0%)	0	0/60 (0%)	0	1/57 (1.8%)	1	1/59 (1.7%)	1	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Focal dyscognitive seizures	1/55 (1.8%)	1	0/60 (0%)	0	0/57 (0%)	0	0/59 (0%)	0	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Seizure	0/55 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	0/59 (0%)	0	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	1/30 (3.3%)	1	0/31 (0%)	0	0/32 (0%)	0
Status epilepticus	0/55 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	0/59 (0%)	0	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	1/32 (3.1%)	1
Psychiatric disorders
Aggression	0/55 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	1/59 (1.7%)	1	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Emotional disorder	0/55 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	0/59 (0%)	0	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	1/27 (3.7%)	1	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Suicidal ideation	0/55 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	0/59 (0%)	0	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	1/27 (3.7%)	1	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pneumothorax	0/55 (0%)	0	0/60 (0%)	0	0/57 (0%)	0	0/59 (0%)	0	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	1/30 (3.3%)	1	0/31 (0%)	0	0/32 (0%)	0
Surgical and medical procedures
Abortion induced	1/55 (1.8%)	1	0/60 (0%)	0	0/57 (0%)	0	0/59 (0%)	0	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo Treatment Period (SS)		Padsevonil 100 mg BID Treatment Period (SS)		Padsevonil 200 mg BID Treatment Period (SS)		Padsevonil 400 mg BID Treatment Period (SS)		Placebo Conversion Period (SS)		Padsevonil 100 mg BID Conversion Period (SS)		Padsevonil 200 mg BID Conversion Period (SS)		Padsevonil 400 mg BID Conversion Period (SS)		Placebo Taper and SFU Period (SS)		Padsevonil 100 mg BID Taper and SFU Period (SS)		Padsevonil 200 mg BID Taper and SFU Period (SS)		Padsevonil 400 mg 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
Total	25/55 (45.5%)		37/60 (61.7%)		40/57 (70.2%)		41/59 (69.5%)		7/33 (21.2%)		0/31 (0%)		1/29 (3.4%)		1/28 (3.6%)		2/27 (7.4%)		6/30 (20%)		4/31 (12.9%)		2/32 (6.3%)
Gastrointestinal disorders
Nausea	3/55 (5.5%)	5	1/60 (1.7%)	1	3/57 (5.3%)	4	1/59 (1.7%)	1	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Diarrhoea	3/55 (5.5%)	4	1/60 (1.7%)	1	0/57 (0%)	0	2/59 (3.4%)	2	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
General disorders
Fatigue	4/55 (7.3%)	4	5/60 (8.3%)	5	7/57 (12.3%)	7	14/59 (23.7%)	15	1/33 (3%)	1	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Asthenia	2/55 (3.6%)	2	6/60 (10%)	6	3/57 (5.3%)	4	2/59 (3.4%)	2	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	1/31 (3.2%)	1	0/32 (0%)	0
Gait disturbance	0/55 (0%)	0	2/60 (3.3%)	2	2/57 (3.5%)	3	4/59 (6.8%)	4	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Infections and infestations
Nasopharyngitis	4/55 (7.3%)	4	1/60 (1.7%)	1	4/57 (7%)	4	1/59 (1.7%)	1	1/33 (3%)	1	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Injury, poisoning and procedural complications
Fall	0/55 (0%)	0	0/60 (0%)	0	3/57 (5.3%)	4	2/59 (3.4%)	2	0/33 (0%)	0	0/31 (0%)	0	1/29 (3.4%)	1	0/28 (0%)	0	1/27 (3.7%)	1	0/30 (0%)	0	1/31 (3.2%)	1	1/32 (3.1%)	1
Contusion	3/55 (5.5%)	4	1/60 (1.7%)	1	2/57 (3.5%)	2	1/59 (1.7%)	1	1/33 (3%)	1	0/31 (0%)	0	1/29 (3.4%)	1	0/28 (0%)	0	0/27 (0%)	0	1/30 (3.3%)	1	0/31 (0%)	0	0/32 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	1/55 (1.8%)	1	0/60 (0%)	0	3/57 (5.3%)	3	1/59 (1.7%)	1	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Nervous system disorders
Somnolence	2/55 (3.6%)	2	10/60 (16.7%)	11	19/57 (33.3%)	22	20/59 (33.9%)	23	1/33 (3%)	1	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	1/30 (3.3%)	1	0/31 (0%)	0	0/32 (0%)	0
Dizziness	4/55 (7.3%)	5	14/60 (23.3%)	14	10/57 (17.5%)	13	18/59 (30.5%)	19	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	1/27 (3.7%)	1	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Headache	8/55 (14.5%)	13	10/60 (16.7%)	22	9/57 (15.8%)	16	5/59 (8.5%)	8	0/33 (0%)	0	0/31 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	4/30 (13.3%)	12	2/31 (6.5%)	2	1/32 (3.1%)	1
Memory impairment	1/55 (1.8%)	1	0/60 (0%)	0	3/57 (5.3%)	3	6/59 (10.2%)	6	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Tremor	1/55 (1.8%)	1	3/60 (5%)	5	0/57 (0%)	0	4/59 (6.8%)	4	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	1/28 (3.6%)	1	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Disturbance in attention	1/55 (1.8%)	1	1/60 (1.7%)	1	5/57 (8.8%)	5	2/59 (3.4%)	2	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Balance disorder	0/55 (0%)	0	1/60 (1.7%)	1	3/57 (5.3%)	3	2/59 (3.4%)	2	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	1/31 (3.2%)	1	0/32 (0%)	0
Dysarthria	1/55 (1.8%)	1	0/60 (0%)	0	0/57 (0%)	0	5/59 (8.5%)	5	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Seizure	1/55 (1.8%)	1	0/60 (0%)	0	4/57 (7%)	5	0/59 (0%)	0	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Psychiatric disorders
Insomnia	0/55 (0%)	0	1/60 (1.7%)	1	5/57 (8.8%)	6	4/59 (6.8%)	4	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Irritability	3/55 (5.5%)	3	4/60 (6.7%)	4	3/57 (5.3%)	3	3/59 (5.1%)	3	1/33 (3%)	1	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Anxiety	1/55 (1.8%)	1	0/60 (0%)	0	1/57 (1.8%)	2	3/59 (5.1%)	3	0/33 (0%)	0	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0
Vascular disorders
Hypotension	0/55 (0%)	0	1/60 (1.7%)	1	0/57 (0%)	0	0/59 (0%)	0	2/33 (6.1%)	2	0/31 (0%)	0	0/29 (0%)	0	0/28 (0%)	0	0/27 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

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.