Trial Outcomes & Findings for Randomized, Double-Blind Study to Evaluate Efficacy and Safety of Cenobamate Adjunctive Therapy in PGTC Seizures (NCT NCT03678753)

Last Updated: 2026-07-02

Results Overview

The seizure frequency over a specified period was calculated based on available seizure diary data. The percent change from baseline in PGTC seizure frequency during the Double-blind Treatment Period was calculated as the seizure frequency per 28-day interval during the Double-blind Treatment Period minus the seizure frequency per 28-day interval during the baseline period divided by the seizure frequency per 28-day interval during the baseline period and multiplied by 100%.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

169 participants

Primary outcome timeframe

Baseline and 22-week Double-blind Treatment Period.

Results posted on

2026-07-02

Participant Flow

The study randomized 169 participants from 69 investigative sites in 8 countries. Study period was from 03 Oct 2018 (Date of First Participant Screened) to 26 May 2025 (Date of Last Participant Completed).

Of 169 enrolled and randomized participants, 168 were treated; 1 participant discontinued prior to first dose of study drug due to physician decision.

Participant milestones

Participant milestones
Measure	Cenobamate Adult participants received cenobamate tablet orally once daily for 22 weeks. Titration doses were 12.5, 25, 50, 100, and 150 mg increased every 2 weeks across 10 weeks. Adult participants received a maintenance cenobamate 200 mg dose for 12 weeks. Adolescent participants received cenobamate oral suspension once daily for 22 weeks. Titration doses were 0.2 mg/kg (maximum 12.5 mg), 0.4 mg/kg (maximum 25 mg), 0.8 mg/kg (maximum 50 mg), 1.5 mg/kg (maximum 100 mg), 2.0 mg/kg (maximum 150 mg) increased every 2 weeks across 10 weeks. Adolescent participants received a maintenance cenobamate 3.0 mg/kg (maximum 200 mg) dose for 12 weeks.	Placebo Adult participants received matching placebo for cenobamate as a tablet following the same dosing regimen as for active drug. Adolescent participants received matching placebo for cenobamate as an oral suspension (OS) based on weight following the same dosing regimen as for active drug.
Overall Study STARTED	85	84
Overall Study COMPLETED	79	75
Overall Study NOT COMPLETED	6	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Cenobamate Adult participants received cenobamate tablet orally once daily for 22 weeks. Titration doses were 12.5, 25, 50, 100, and 150 mg increased every 2 weeks across 10 weeks. Adult participants received a maintenance cenobamate 200 mg dose for 12 weeks. Adolescent participants received cenobamate oral suspension once daily for 22 weeks. Titration doses were 0.2 mg/kg (maximum 12.5 mg), 0.4 mg/kg (maximum 25 mg), 0.8 mg/kg (maximum 50 mg), 1.5 mg/kg (maximum 100 mg), 2.0 mg/kg (maximum 150 mg) increased every 2 weeks across 10 weeks. Adolescent participants received a maintenance cenobamate 3.0 mg/kg (maximum 200 mg) dose for 12 weeks.	Placebo Adult participants received matching placebo for cenobamate as a tablet following the same dosing regimen as for active drug. Adolescent participants received matching placebo for cenobamate as an oral suspension (OS) based on weight following the same dosing regimen as for active drug.
Overall Study Adverse Event	1	3
Overall Study Withdrawal by Subject	3	4
Overall Study Lack of Efficacy	1	0
Overall Study Physician Decision	0	1
Overall Study Sponsor Decision	1	0
Overall Study Site Withdrawal From Study	0	1

Baseline Characteristics

Randomized, Double-Blind Study to Evaluate Efficacy and Safety of Cenobamate Adjunctive Therapy in PGTC Seizures

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=84 Participants Adult participants received a matched number of placebo tablets and adolescents received a matched volume of placebo oral suspension once daily based on the titration step or maintenance dose for a total of 22 weeks.	Total n=169 Participants Total of all reporting groups	Cenobamate n=85 Participants Adult participants received cenobamate tablet orally once daily for 22 weeks. Titration doses were 12.5, 25, 50, 100, and 150 mg increased every 2 weeks across 10 weeks. Adult participants received a maintenance cenobamate 200 mg dose for 12 weeks. Adolescent participants received cenobamate oral suspension once daily for 22 weeks. Titration doses were 0.2 mg/kg (maximum 12.5 mg), 0.4 mg/kg (maximum 25 mg), 0.8 mg/kg (maximum 50 mg), 1.5 mg/kg (maximum 100 mg), 2.0 mg/kg (maximum 150 mg) increased every 2 weeks across 10 weeks. Adolescent participants received a maintenance cenobamate 3.0 mg/kg (maximum 200 mg) dose for 12 weeks.
Region of Enrollment Bulgaria	10 Participants n=20 Participants	15 Participants n=40 Participants	5 Participants n=20 Participants
Region of Enrollment Czechia	1 Participants n=20 Participants	8 Participants n=40 Participants	7 Participants n=20 Participants
Age, Categorical <=18 years	16 Participants n=20 Participants	34 Participants n=40 Participants	18 Participants n=20 Participants
Age, Categorical Between 18 and 65 years	68 Participants n=20 Participants	135 Participants n=40 Participants	67 Participants n=20 Participants
Age, Categorical >=65 years	0 Participants n=20 Participants	0 Participants n=40 Participants	0 Participants n=20 Participants
Sex: Female, Male Female	49 Participants n=20 Participants	103 Participants n=40 Participants	54 Participants n=20 Participants
Sex: Female, Male Male	35 Participants n=20 Participants	66 Participants n=40 Participants	31 Participants n=20 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=20 Participants	0 Participants n=40 Participants	0 Participants n=20 Participants
Race (NIH/OMB) Asian	0 Participants n=20 Participants	0 Participants n=40 Participants	0 Participants n=20 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=20 Participants	1 Participants n=40 Participants	1 Participants n=20 Participants
Race (NIH/OMB) Black or African American	1 Participants n=20 Participants	2 Participants n=40 Participants	1 Participants n=20 Participants
Race (NIH/OMB) White	79 Participants n=20 Participants	160 Participants n=40 Participants	81 Participants n=20 Participants
Race (NIH/OMB) More than one race	4 Participants n=20 Participants	6 Participants n=40 Participants	2 Participants n=20 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=20 Participants	0 Participants n=40 Participants	0 Participants n=20 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=20 Participants	9 Participants n=40 Participants	6 Participants n=20 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	81 Participants n=20 Participants	160 Participants n=40 Participants	79 Participants n=20 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=20 Participants	0 Participants n=40 Participants	0 Participants n=20 Participants
Region of Enrollment Georgia	1 Participants n=20 Participants	2 Participants n=40 Participants	1 Participants n=20 Participants
Region of Enrollment Hungary	4 Participants n=20 Participants	14 Participants n=40 Participants	10 Participants n=20 Participants
Region of Enrollment Poland	8 Participants n=20 Participants	9 Participants n=40 Participants	1 Participants n=20 Participants
Region of Enrollment Slovakia	12 Participants n=20 Participants	23 Participants n=40 Participants	11 Participants n=20 Participants
Region of Enrollment Ukraine	33 Participants n=20 Participants	69 Participants n=40 Participants	36 Participants n=20 Participants
Region of Enrollment United States	15 Participants n=20 Participants	29 Participants n=40 Participants	14 Participants n=20 Participants
Height	167.42 cm STANDARD_DEVIATION 8.842 • n=20 Participants	167.44 cm STANDARD_DEVIATION 9.217 • n=40 Participants	167.46 cm STANDARD_DEVIATION 9.622 • n=20 Participants
Weight	69.99 kg STANDARD_DEVIATION 15.749 • n=20 Participants	71.62 kg STANDARD_DEVIATION 17.391 • n=40 Participants	73.20 kg STANDARD_DEVIATION 18.816 • n=20 Participants
BMI	24.95 kg/m^2 STANDARD_DEVIATION 5.314 • n=20 Participants	25.45 kg/m^2 STANDARD_DEVIATION 5.538 • n=40 Participants	25.95 kg/m^2 STANDARD_DEVIATION 5.736 • n=20 Participants
Baseline 28 Days Seizure Frequency (PGTC)	2.52 Number of seizures per 28-day interval n=20 Participants	2.64 Number of seizures per 28-day interval n=40 Participants	2.67 Number of seizures per 28-day interval n=20 Participants
Baseline Antiseizure Medications (ASM) per Participants	2.0 Number of ASMs n=20 Participants	2.0 Number of ASMs n=40 Participants	2.0 Number of ASMs n=20 Participants

PRIMARY outcome

Timeframe: Baseline and 22-week Double-blind Treatment Period.

Population: MITT Population: All participants in the Randomized Population who received \>=1 dose of cenobamate or placebo and had \>=1 postbaseline efficacy measurement in the Double-blind Treatment Period.

Outcome measures

Outcome measures
Measure	Cenobamate n=85 Participants Adult participants received cenobamate tablet orally once daily for 22 weeks. Titration doses were 12.5, 25, 50, 100, and 150 mg increased every 2 weeks across 10 weeks. Adult participants received a maintenance cenobamate 200 mg dose for 12 weeks. Adolescent participants received cenobamate oral suspension once daily for 22 weeks. Titration doses were 0.2 mg/kg (maximum 12.5 mg), 0.4 mg/kg (maximum 25 mg), 0.8 mg/kg (maximum 50 mg), 1.5 mg/kg (maximum 100 mg), 2.0 mg/kg (maximum 150 mg) increased every 2 weeks across 10 weeks. Adolescent participants received a maintenance cenobamate 3.0 mg/kg (maximum 200 mg) dose for 12 weeks.	Placebo n=83 Participants Adult participants received a matched number of placebo tablets and adolescents received a matched volume of placebo oral suspension once daily based on the titration step or maintenance dose for a total of 22 weeks.
USA and Rest of World (RoW): Percent Change in PGTC Seizure Frequency Per 28 Days During the Double-blind Treatment Period Relative to Baseline.	-71.90 Percent Change Interval -100.0 to 273.0	-39.61 Percent Change Interval -100.0 to 211.8

PRIMARY outcome

Timeframe: Baseline and 12-week Maintenance Phase.

Population: MITT-M Population: All participants in the Randomized Population who received \>=1 dose of cenobamate or placebo during the Maintenance Phase and had \>=1 efficacy measurement in the Maintenance Phase.

A responder was defined as a participant who achieved at least a 50% reduction in PGTC seizure frequency per 28-day interval during the Maintenance Phase relative to baseline. The percent change from baseline in PGTC seizure frequency during the Maintenance Phase was calculated as the seizure frequency per 28-day interval during the Maintenance Phase minus the seizure frequency per 28-day interval during the baseline period divided by the seizure frequency per 28-day interval during the baseline period and multiplied by 100%.

Outcome measures

Outcome measures
Measure	Cenobamate n=83 Participants Adult participants received cenobamate tablet orally once daily for 22 weeks. Titration doses were 12.5, 25, 50, 100, and 150 mg increased every 2 weeks across 10 weeks. Adult participants received a maintenance cenobamate 200 mg dose for 12 weeks. Adolescent participants received cenobamate oral suspension once daily for 22 weeks. Titration doses were 0.2 mg/kg (maximum 12.5 mg), 0.4 mg/kg (maximum 25 mg), 0.8 mg/kg (maximum 50 mg), 1.5 mg/kg (maximum 100 mg), 2.0 mg/kg (maximum 150 mg) increased every 2 weeks across 10 weeks. Adolescent participants received a maintenance cenobamate 3.0 mg/kg (maximum 200 mg) dose for 12 weeks.	Placebo n=78 Participants Adult participants received a matched number of placebo tablets and adolescents received a matched volume of placebo oral suspension once daily based on the titration step or maintenance dose for a total of 22 weeks.
Europe, South Africa, Australia, and New Zealand: 50% Responder Rate for PGTC Seizures During the Maintenance Phase Relative to Baseline. Responder - No	24 Participants	38 Participants
Europe, South Africa, Australia, and New Zealand: 50% Responder Rate for PGTC Seizures During the Maintenance Phase Relative to Baseline. Responder - Yes	59 Participants	40 Participants

SECONDARY outcome

Timeframe: Baseline and 12-week Maintenance Phase.

A responder was defined as a participant who achieved a 100% reduction in PGTC seizure frequency per 28-day interval during the Maintenance Phase relative to baseline.

Outcome measures

Outcome measures
Measure	Cenobamate n=83 Participants Adult participants received cenobamate tablet orally once daily for 22 weeks. Titration doses were 12.5, 25, 50, 100, and 150 mg increased every 2 weeks across 10 weeks. Adult participants received a maintenance cenobamate 200 mg dose for 12 weeks. Adolescent participants received cenobamate oral suspension once daily for 22 weeks. Titration doses were 0.2 mg/kg (maximum 12.5 mg), 0.4 mg/kg (maximum 25 mg), 0.8 mg/kg (maximum 50 mg), 1.5 mg/kg (maximum 100 mg), 2.0 mg/kg (maximum 150 mg) increased every 2 weeks across 10 weeks. Adolescent participants received a maintenance cenobamate 3.0 mg/kg (maximum 200 mg) dose for 12 weeks.	Placebo n=78 Participants Adult participants received a matched number of placebo tablets and adolescents received a matched volume of placebo oral suspension once daily based on the titration step or maintenance dose for a total of 22 weeks.
100% Responder Rate for PGTC Seizures During the Maintenance Phase Relative to Baseline. Responder Rate (100%) No	47 Participants	62 Participants
100% Responder Rate for PGTC Seizures During the Maintenance Phase Relative to Baseline. Responder Rate (100%) Yes	36 Participants	16 Participants

SECONDARY outcome

Timeframe: Baseline and 12- week Maintenance Phase

A responder was defined as a participant who achieved at least a 75% reduction in PGTC seizure frequency per 28-day interval during the Maintenance Phase relative to baseline.

Outcome measures

Outcome measures
Measure	Cenobamate n=83 Participants Adult participants received cenobamate tablet orally once daily for 22 weeks. Titration doses were 12.5, 25, 50, 100, and 150 mg increased every 2 weeks across 10 weeks. Adult participants received a maintenance cenobamate 200 mg dose for 12 weeks. Adolescent participants received cenobamate oral suspension once daily for 22 weeks. Titration doses were 0.2 mg/kg (maximum 12.5 mg), 0.4 mg/kg (maximum 25 mg), 0.8 mg/kg (maximum 50 mg), 1.5 mg/kg (maximum 100 mg), 2.0 mg/kg (maximum 150 mg) increased every 2 weeks across 10 weeks. Adolescent participants received a maintenance cenobamate 3.0 mg/kg (maximum 200 mg) dose for 12 weeks.	Placebo n=78 Participants Adult participants received a matched number of placebo tablets and adolescents received a matched volume of placebo oral suspension once daily based on the titration step or maintenance dose for a total of 22 weeks.
75% Responder Rate for PGTC Seizures During the Maintenance Phase Relative to Baseline. Responder Rate (>=75%) Yes	46 Participants	28 Participants
75% Responder Rate for PGTC Seizures During the Maintenance Phase Relative to Baseline. Responder Rate (>=75%) No	37 Participants	50 Participants

SECONDARY outcome

Timeframe: Baseline and 12-week Maintenance Phase.

A responder was defined as a participant who achieved at least a 50% reduction in all generalized seizure frequency per 28-day interval during the Maintenance Phase relative to baseline.

Outcome measures

Outcome measures
Measure	Cenobamate n=83 Participants Adult participants received cenobamate tablet orally once daily for 22 weeks. Titration doses were 12.5, 25, 50, 100, and 150 mg increased every 2 weeks across 10 weeks. Adult participants received a maintenance cenobamate 200 mg dose for 12 weeks. Adolescent participants received cenobamate oral suspension once daily for 22 weeks. Titration doses were 0.2 mg/kg (maximum 12.5 mg), 0.4 mg/kg (maximum 25 mg), 0.8 mg/kg (maximum 50 mg), 1.5 mg/kg (maximum 100 mg), 2.0 mg/kg (maximum 150 mg) increased every 2 weeks across 10 weeks. Adolescent participants received a maintenance cenobamate 3.0 mg/kg (maximum 200 mg) dose for 12 weeks.	Placebo n=78 Participants Adult participants received a matched number of placebo tablets and adolescents received a matched volume of placebo oral suspension once daily based on the titration step or maintenance dose for a total of 22 weeks.
50% Responder Rate for All Generalized Seizures During the Maintenance Phase Relative to Baseline. Responder - No	32 Participants	44 Participants
50% Responder Rate for All Generalized Seizures During the Maintenance Phase Relative to Baseline. Responder - Yes	51 Participants	34 Participants

Adverse Events

Cenobamate

Serious events: 5 serious events

Other events: 45 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cenobamate n=85 participants at risk Adult participants received cenobamate tablet orally once daily for 22 weeks. Titration doses were 12.5, 25, 50, 100, and 150 mg increased every 2 weeks across 10 weeks. Adult participants received a maintenance cenobamate 200 mg dose for 12 weeks. Adolescent participants received cenobamate oral suspension once daily for 22 weeks. Titration doses were 0.2 mg/kg (maximum 12.5 mg), 0.4 mg/kg (maximum 25 mg), 0.8 mg/kg (maximum 50 mg), 1.5 mg/kg (maximum 100 mg), 2.0 mg/kg (maximum 150 mg) increased every 2 weeks across 10 weeks. Adolescent participants received a maintenance cenobamate 3.0 mg/kg (maximum 200 mg) dose for 12 weeks.	Placebo n=83 participants at risk Adult participants received a matched number of placebo tablets and adolescents received a matched volume of placebo oral suspension once daily based on the titration step or maintenance dose for a total of 22 weeks.
Nervous system disorders Generalised tonic-clonic seizure	3.5% 3/85 • 9 months All safety analyses were performed by the treatment group on the Safety Population.	0.00% 0/83 • 9 months All safety analyses were performed by the treatment group on the Safety Population.
Nervous system disorders Status epilepticus	0.00% 0/85 • 9 months All safety analyses were performed by the treatment group on the Safety Population.	1.2% 1/83 • 9 months All safety analyses were performed by the treatment group on the Safety Population.
Injury, poisoning and procedural complications Ilium fracture	1.2% 1/85 • 9 months All safety analyses were performed by the treatment group on the Safety Population.	0.00% 0/83 • 9 months All safety analyses were performed by the treatment group on the Safety Population.
Metabolism and nutrition disorders Dehydration	1.2% 1/85 • 9 months All safety analyses were performed by the treatment group on the Safety Population.	0.00% 0/83 • 9 months All safety analyses were performed by the treatment group on the Safety Population.

Other adverse events

Other adverse events
Measure	Cenobamate n=85 participants at risk Adult participants received cenobamate tablet orally once daily for 22 weeks. Titration doses were 12.5, 25, 50, 100, and 150 mg increased every 2 weeks across 10 weeks. Adult participants received a maintenance cenobamate 200 mg dose for 12 weeks. Adolescent participants received cenobamate oral suspension once daily for 22 weeks. Titration doses were 0.2 mg/kg (maximum 12.5 mg), 0.4 mg/kg (maximum 25 mg), 0.8 mg/kg (maximum 50 mg), 1.5 mg/kg (maximum 100 mg), 2.0 mg/kg (maximum 150 mg) increased every 2 weeks across 10 weeks. Adolescent participants received a maintenance cenobamate 3.0 mg/kg (maximum 200 mg) dose for 12 weeks.	Placebo n=83 participants at risk Adult participants received a matched number of placebo tablets and adolescents received a matched volume of placebo oral suspension once daily based on the titration step or maintenance dose for a total of 22 weeks.
Infections and infestations Upper respiratory tract infection	3.5% 3/85 • 9 months All safety analyses were performed by the treatment group on the Safety Population.	7.2% 6/83 • 9 months All safety analyses were performed by the treatment group on the Safety Population.
Injury, poisoning and procedural complications Contusion	5.9% 5/85 • 9 months All safety analyses were performed by the treatment group on the Safety Population.	2.4% 2/83 • 9 months All safety analyses were performed by the treatment group on the Safety Population.
Gastrointestinal disorders Vomiting	1.2% 1/85 • 9 months All safety analyses were performed by the treatment group on the Safety Population.	6.0% 5/83 • 9 months All safety analyses were performed by the treatment group on the Safety Population.
Nervous system disorders Somnolence	16.5% 14/85 • 9 months All safety analyses were performed by the treatment group on the Safety Population.	6.0% 5/83 • 9 months All safety analyses were performed by the treatment group on the Safety Population.
Nervous system disorders Dizziness	8.2% 7/85 • 9 months All safety analyses were performed by the treatment group on the Safety Population.	4.8% 4/83 • 9 months All safety analyses were performed by the treatment group on the Safety Population.
Nervous system disorders Headache	7.1% 6/85 • 9 months All safety analyses were performed by the treatment group on the Safety Population.	6.0% 5/83 • 9 months All safety analyses were performed by the treatment group on the Safety Population.
General disorders Fatigue	10.6% 9/85 • 9 months All safety analyses were performed by the treatment group on the Safety Population.	0.00% 0/83 • 9 months All safety analyses were performed by the treatment group on the Safety Population.

Additional Information

Chief Medical Officer

SK Life Science Inc.

Phone: +14028355977

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place