Trial Outcomes & Findings for Trial Evaluating the Efficacy and Safety of Perampanel Added to Monotherapy in Participants With Partial Onset Seizures With or Without Secondary Generalization (NCT NCT02726074)
NCT ID: NCT02726074
Last Updated: 2020-02-05
Results Overview
The 50% responder rate was defined as the percentage of participants who achieved at least 50% reduction from baseline in the frequency of partial onset seizure with or without secondary generalization during the Maintenance Period.
COMPLETED
PHASE4
106 participants
Baseline up to Week 36
2020-02-05
Participant Flow
Participants took part in the study at 11 investigative sites in Korea from 03 May 2016 to 26 April 2018.
A total of 106 participants were enrolled in this study, 102 participants were included in the safety set excluding 3 participants who did not received the investigational product and 1 participant who was not assessed for safety at least once after study treatment.
Participant milestones
| Measure |
Perampanel 12 mg
During the Titration Period, participants received perampanel 2 milligrams per day (mg/day) and were up-titrated in no less than 2-week intervals in increments of 2 mg up to 12 mg according to the investigator's judgment. Upon entering the Maintenance Period, participants received the last dose they achieved at the end of the Titration Period and continued receiving this dose once daily for up to Week 36. At the discretion of investigators, dose adjustments were allowed based on the participant's clinical response and tolerability.
|
|---|---|
|
Overall Study
STARTED
|
106
|
|
Overall Study
Treated
|
102
|
|
Overall Study
COMPLETED
|
80
|
|
Overall Study
NOT COMPLETED
|
26
|
Reasons for withdrawal
| Measure |
Perampanel 12 mg
During the Titration Period, participants received perampanel 2 milligrams per day (mg/day) and were up-titrated in no less than 2-week intervals in increments of 2 mg up to 12 mg according to the investigator's judgment. Upon entering the Maintenance Period, participants received the last dose they achieved at the end of the Titration Period and continued receiving this dose once daily for up to Week 36. At the discretion of investigators, dose adjustments were allowed based on the participant's clinical response and tolerability.
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
4
|
|
Overall Study
Adverse Event
|
14
|
|
Overall Study
Protocol Violation
|
3
|
|
Overall Study
Lost to Follow-up
|
2
|
|
Overall Study
Others
|
3
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Perampanel 12 mg
n=102 Participants
During the Titration Period, participants received perampanel 2 mg/day and were up-titrated in no less than 2-week intervals in increments of 2 mg up to 12 mg according to the investigator's judgment. Upon entering the Maintenance Period, participants received the last dose they achieved at the end of the Titration Period and continued receiving this dose once daily for up to Week 36. At the discretion of investigators, dose adjustments were allowed based on the participant's clinical response and tolerability.
|
|---|---|
|
Age, Continuous
|
42.25 years
STANDARD_DEVIATION 14.26 • n=102 Participants
|
|
Sex: Female, Male
Female
|
61 Participants
n=102 Participants
|
|
Sex: Female, Male
Male
|
41 Participants
n=102 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Week 36Population: The full analysis set included participants who received at least one dose of investigational product and were assessed for primary efficacy at least once after study treatment.
The 50% responder rate was defined as the percentage of participants who achieved at least 50% reduction from baseline in the frequency of partial onset seizure with or without secondary generalization during the Maintenance Period.
Outcome measures
| Measure |
Perampanel 12 mg
n=85 Participants
During the Titration Period, participants received perampanel 2 mg/day and were up-titrated in no less than 2-week intervals in increments of 2 mg up to 12 mg according to the investigator's judgment. Upon entering the Maintenance Period, participants received the last dose they achieved at the end of the Titration Period and continued receiving this dose once daily for up to Week 36. At the discretion of investigators, dose adjustments were allowed based on the participant's clinical response and tolerability.
|
|---|---|
|
50 Percent (%) Responder Rate for Partial Onset Seizure With or Without Secondary Generalization
|
80.0 percentage of participants
Interval 69.92 to 87.9
|
SECONDARY outcome
Timeframe: Baseline up to Week 36Population: The full analysis set included participants who received at least one dose of investigational product and were assessed for primary efficacy at least once after study treatment.
The 75% responder rate was defined as the percentage of participants who achieved at least 75% reduction from baseline in the frequency of partial onset seizure with or without secondary generalization during the Maintenance Period.
Outcome measures
| Measure |
Perampanel 12 mg
n=85 Participants
During the Titration Period, participants received perampanel 2 mg/day and were up-titrated in no less than 2-week intervals in increments of 2 mg up to 12 mg according to the investigator's judgment. Upon entering the Maintenance Period, participants received the last dose they achieved at the end of the Titration Period and continued receiving this dose once daily for up to Week 36. At the discretion of investigators, dose adjustments were allowed based on the participant's clinical response and tolerability.
|
|---|---|
|
75% Responder Rate for Partial Onset Seizure With or Without Secondary Generalization
|
71.76 percentage of participants
Interval 60.96 to 81.0
|
SECONDARY outcome
Timeframe: Baseline up to Week 36Population: The full analysis set included participants who received at least one dose of investigational product and were assessed for primary efficacy at least once after study treatment.
The 100% responder rate was defined as the percentage of participants who achieved at least 100% reduction from baseline in the frequency of partial onset seizure with or without secondary generalization during the Maintenance Period.
Outcome measures
| Measure |
Perampanel 12 mg
n=85 Participants
During the Titration Period, participants received perampanel 2 mg/day and were up-titrated in no less than 2-week intervals in increments of 2 mg up to 12 mg according to the investigator's judgment. Upon entering the Maintenance Period, participants received the last dose they achieved at the end of the Titration Period and continued receiving this dose once daily for up to Week 36. At the discretion of investigators, dose adjustments were allowed based on the participant's clinical response and tolerability.
|
|---|---|
|
100% Responder Rate (Seizure Free Rate) for Partial Onset Seizure With or Without Secondary Generalization
|
47.06 percentage of participants
Interval 36.13 to 58.19
|
SECONDARY outcome
Timeframe: Weeks 12 and 36Population: The full analysis set included participants who received at least one dose of investigational product and were assessed for primary efficacy at least once after study treatment. Participants who were evaluable for this given measure at a given time point were included for this assessment.
Percent change in the frequency of partial onset seizure with or without secondary generalization was defined as the percent reduction in seizure frequency from baseline to titration period and maintenance period. Percent change from Baseline was calculated as: (\[post-Baseline value minus the Baseline value\] / Baseline value)\*100. A negative percent change from baseline indicates a decrease in partial seizure frequency.
Outcome measures
| Measure |
Perampanel 12 mg
n=85 Participants
During the Titration Period, participants received perampanel 2 mg/day and were up-titrated in no less than 2-week intervals in increments of 2 mg up to 12 mg according to the investigator's judgment. Upon entering the Maintenance Period, participants received the last dose they achieved at the end of the Titration Period and continued receiving this dose once daily for up to Week 36. At the discretion of investigators, dose adjustments were allowed based on the participant's clinical response and tolerability.
|
|---|---|
|
Percent Change From Baseline in Partial Onset Seizure Frequency With or Without Secondary Generalization to the Titration and Maintenance Period
Percent Change at Week 12
|
-90.48 percent change
Interval -100.0 to 317.25
|
|
Percent Change From Baseline in Partial Onset Seizure Frequency With or Without Secondary Generalization to the Titration and Maintenance Period
Percent Change at Week 36
|
-95.02 percent change
Interval -100.0 to 1457.33
|
SECONDARY outcome
Timeframe: Baseline up to Week 36Population: The full analysis set included participants who received at least one dose of investigational product and were assessed for primary efficacy at least once after study treatment. Participants who were evaluable for this given measure at a given time point were included for this assessment.
The 50% responder rate was defined as the percentage of participants who have achieved at least a 50% reduction from baseline in the frequency of secondary GTC seizure during the Maintenance Period. GTC seizures are defined as seizures involved with generalized stiffening and rhythmic jerking of the limbs, caused by bilateral malfunction of the brain.
Outcome measures
| Measure |
Perampanel 12 mg
n=16 Participants
During the Titration Period, participants received perampanel 2 mg/day and were up-titrated in no less than 2-week intervals in increments of 2 mg up to 12 mg according to the investigator's judgment. Upon entering the Maintenance Period, participants received the last dose they achieved at the end of the Titration Period and continued receiving this dose once daily for up to Week 36. At the discretion of investigators, dose adjustments were allowed based on the participant's clinical response and tolerability.
|
|---|---|
|
50% Responder Rate in Secondary Generalized Tonic Clonic (GTC) Seizures
|
87.50 percentage of participants
Interval 61.65 to 98.45
|
SECONDARY outcome
Timeframe: Baseline up to Week 36Population: The full analysis set included participants who received at least one dose of investigational product and were assessed for primary efficacy at least once after study treatment. Participants who were evaluable for this given measure at a given time point were included for this assessment.
The 75% responder rate was defined as the percentage of participants who achieved at least a 75% reduction from baseline in seizure frequency of secondary GTC seizure during the Maintenance Period. GTC seizures are defined as seizures involved with generalized stiffening and rhythmic jerking of the limbs, caused by bilateral malfunction of the brain.
Outcome measures
| Measure |
Perampanel 12 mg
n=16 Participants
During the Titration Period, participants received perampanel 2 mg/day and were up-titrated in no less than 2-week intervals in increments of 2 mg up to 12 mg according to the investigator's judgment. Upon entering the Maintenance Period, participants received the last dose they achieved at the end of the Titration Period and continued receiving this dose once daily for up to Week 36. At the discretion of investigators, dose adjustments were allowed based on the participant's clinical response and tolerability.
|
|---|---|
|
75% Responder Rate in Secondary GTC Seizures
|
87.50 percentage of participants
Interval 61.65 to 98.45
|
SECONDARY outcome
Timeframe: Baseline up to Week 36Population: The full analysis set included participants who received at least one dose of investigational product and were assessed for primary efficacy at least once after study treatment. Participants who were evaluable for this given measure at a given time point were included for this assessment.
The 100% responder rate was defined as the percentage of participants who have at least a 100% reduction from baseline in the frequency of secondary GTC seizures during the Maintenance Period. GTC seizures are defined as seizures involved with generalized stiffening and rhythmic jerking of the limbs, caused by bilateral malfunction of the brain.
Outcome measures
| Measure |
Perampanel 12 mg
n=16 Participants
During the Titration Period, participants received perampanel 2 mg/day and were up-titrated in no less than 2-week intervals in increments of 2 mg up to 12 mg according to the investigator's judgment. Upon entering the Maintenance Period, participants received the last dose they achieved at the end of the Titration Period and continued receiving this dose once daily for up to Week 36. At the discretion of investigators, dose adjustments were allowed based on the participant's clinical response and tolerability.
|
|---|---|
|
100% Responder Rate (Seizure Free Rate) in Secondary GTC Seizures
|
75.00 percentage of participants
Interval 47.62 to 92.73
|
SECONDARY outcome
Timeframe: Weeks 12 and 36Population: The full analysis set included participants who received at least one dose of investigational product and were assessed for primary efficacy at least once after study treatment. Participants who were evaluable for this given measure at a given time point were included for this assessment.
Percent change in the frequency of secondary GTC seizure was defined as the percent reduction in seizure frequency from baseline to Titration Period and Maintenance Period. GTC seizures are defined as seizures involved with generalized stiffening and rhythmic jerking of the limbs, caused by bilateral malfunction of the brain. Percent change from Baseline was calculated as: (\[post-Baseline value minus the Baseline value\] / Baseline value)\*100. A negative percent change from baseline indicates a decrease in partial seizure frequency.
Outcome measures
| Measure |
Perampanel 12 mg
n=85 Participants
During the Titration Period, participants received perampanel 2 mg/day and were up-titrated in no less than 2-week intervals in increments of 2 mg up to 12 mg according to the investigator's judgment. Upon entering the Maintenance Period, participants received the last dose they achieved at the end of the Titration Period and continued receiving this dose once daily for up to Week 36. At the discretion of investigators, dose adjustments were allowed based on the participant's clinical response and tolerability.
|
|---|---|
|
Percent Change From Baseline in Secondary GTC Seizure Frequency to the Titration and Maintenance Period
Percent Change at Week 12
|
-100.00 percent change
Interval -100.0 to 6.33
|
|
Percent Change From Baseline in Secondary GTC Seizure Frequency to the Titration and Maintenance Period
Percent Change at Week 36
|
-100.00 percent change
Interval -100.0 to -19.54
|
SECONDARY outcome
Timeframe: From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)Population: The safety set included participants who received at least one dose of investigational product and were assessed for safety at least once after study treatment.
Outcome measures
| Measure |
Perampanel 12 mg
n=102 Participants
During the Titration Period, participants received perampanel 2 mg/day and were up-titrated in no less than 2-week intervals in increments of 2 mg up to 12 mg according to the investigator's judgment. Upon entering the Maintenance Period, participants received the last dose they achieved at the end of the Titration Period and continued receiving this dose once daily for up to Week 36. At the discretion of investigators, dose adjustments were allowed based on the participant's clinical response and tolerability.
|
|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
TEAEs
|
77 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
SAEs
|
8 Participants
|
Adverse Events
Perampanel 12 mg
Serious adverse events
| Measure |
Perampanel 12 mg
n=102 participants at risk
During the Titration Period, participants received perampanel 2 mg/day and were up-titrated in no less than 2-week intervals in increments of 2 mg up to 12 mg according to the investigator's judgment. Upon entering the Maintenance Period, participants received the last dose they achieved at the end of the Titration Period and continued receiving this dose once daily for up to Week 36. At the discretion of investigators, dose adjustments were allowed based on the participant's clinical response and tolerability.
|
|---|---|
|
Nervous system disorders
Seizure
|
2.9%
3/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Psychiatric disorders
Suicidal ideation
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Psychiatric disorders
Suicide attempt
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
General disorders
Perforation
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Infections and infestations
Furuncle
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Injury, poisoning and procedural complications
Clavicle fracture
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
Other adverse events
| Measure |
Perampanel 12 mg
n=102 participants at risk
During the Titration Period, participants received perampanel 2 mg/day and were up-titrated in no less than 2-week intervals in increments of 2 mg up to 12 mg according to the investigator's judgment. Upon entering the Maintenance Period, participants received the last dose they achieved at the end of the Titration Period and continued receiving this dose once daily for up to Week 36. At the discretion of investigators, dose adjustments were allowed based on the participant's clinical response and tolerability.
|
|---|---|
|
Nervous system disorders
Dizziness
|
50.0%
51/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Nervous system disorders
Somnolence
|
9.8%
10/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Nervous system disorders
Headache
|
8.8%
9/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Nervous system disorders
Dysarthria
|
4.9%
5/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Nervous system disorders
Memory impairment
|
2.0%
2/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Nervous system disorders
Hypoaesthesia
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Nervous system disorders
Lethargy
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Nervous system disorders
Paraesthesia
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Nervous system disorders
Parkinsonism
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Nervous system disorders
Seizure
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Nervous system disorders
Speech disorder
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Nervous system disorders
Syncope
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Psychiatric disorders
Anger
|
2.0%
2/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Psychiatric disorders
Irritability
|
2.0%
2/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Psychiatric disorders
Confusional state
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Psychiatric disorders
Depression
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Psychiatric disorders
Tearfulness
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
General disorders
Fatigue
|
2.0%
2/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
General disorders
Oedema
|
2.0%
2/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
General disorders
Face oedema
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
General disorders
Gait disturbance
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Injury, poisoning and procedural complications
Contusion
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Injury, poisoning and procedural complications
Head injury
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Injury, poisoning and procedural complications
Lip injury
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Respiratory, thoracic and mediastinal disorders
Nasal discomfort
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Eye disorders
Diplopia
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Eye disorders
Vision blurred
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Eye disorders
Visual impairment
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Gastrointestinal disorders
Dry mouth
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Gastrointestinal disorders
Nausea
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc disorder
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
2.0%
2/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Blood and lymphatic system disorders
Bicytopenia
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Infections and infestations
Nasopharyngitis
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Investigations
Weight increased
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
|
Vascular disorders
Labile hypertension
|
0.98%
1/102 • From the first dose of investigational product to the last visit or 28 days after the last dose (up to 1 year 11 months)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place