Epilepsy
Conditions
Keywords
Epilepsy; Monotherapy, Partial Onset Seizures, Adults and Adolescents
Brief summary
Antiepileptic drugs (AEDs) are the main treatment for epilepsy; however, only a limited number of AEDs are approved for use as monotherapy. The objective of this study is to evaluate the efficacy of Brivaracetam (BRV) in the conversion of partial onset seizure patients from combination treatment to monotherapy
Interventions
DRUGBrivaracetam
25 mg tablet - 50 mg daily for 17 weeks (or 21 weeks if down-titrated (50 mg \> 20 mg) for subjects not participating in the follow-up study)
Sponsors
UCB Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
16 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subjects from 16 to 75 years, both inclusive * Well-characterized focal epilepsy or epileptic syndrome * Subjects having at least 2 but not exceeding 40 partial onset seizures, whether or not secondarily generalized per 4 weeks during the 8-week Baseline Period * Subjects on a stable dose of at least 1 but no more than 2 concomitant Antiepileptic Drugs (AEDs) with the second AED ≤ 50 % of the minimum recommended maintenance dose
Exclusion criteria
* Seizure type IA non-motor as only seizure type * History or presence of seizures occurring too frequently or indistinctly separated to be reliably counted during the 6 months preceding Visit 1 or during Baseline * Other serious uncontrolled disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Cumulative Exit Rate at 112 Days After the Beginning of the Baseline Antiepileptic Drug (AED) Tapering Phase | From Week 1 up to Week 17 | The cumulative exit rate was estimated using Kaplan-Meier methods and was based on the duration between start of the Evaluation Period (EP) and the earliest date the first exit criterion was met for each subject. Subjects completing the EP without meeting an exit criterion were censored on Day 112. The primary comparison was BRV 50 mg/day vs a historical control. The upper limit of the 2-sided 95 % Confidence Interval for the estimate was compared to the historical lower bound estimate of 0.722. |
Secondary
| Measure | Time frame |
|---|---|
| The Number of Patients Reporting at Least One Treatment-Emergent Adverse Event (TEAE) During the Course of the Study | Baseline through Re-conversion (approximately 31 weeks) |
| The Number of Patient Withdrawal Due to Adverse Events (AEs) During the Course of the Study | Baseline through Re-conversion (approximately 31 weeks) |
| The Number of Patients Reporting at Least One Serious Adverse Event (SAE) During the Course of the Study | Baseline through Re-conversion (approximately 31 weeks) |
Countries
Australia, Belgium, Canada, Czechia, Germany, Sweden, United States
Participant flow
Recruitment details
This study started to enroll patients in August 2008 and concluded in February 2010.
Pre-assignment details
The Participant Flow refers to the Randomized Set (RS). Subjects withdrawn due to meeting an exit criterion are included in the count of early discontinuations with a reason of Adverse Event or Lack of efficacy as reported by the Investigator.
Participants by arm
| Arm | Count |
|---|---|
| Brivaracetam 50 mg/Day Brivaracetam: 25 mg tablet - 50 mg daily for 17 weeks (or 21 weeks if down-titrated (50 mg \> 20 mg) for subjects not participating in the follow-up study) | 68 |
| Brivaracetam 100 mg/Day Brivaracetam: 25 mg tablet - 100 mg daily for 17 weeks (or 21 weeks if down-titrated (100 mg \> 50 mg \> 20 mg) for subjects not participating in the follow-up study) | 20 |
| Total Title | 88 |
| Total | 176 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | AE, non-serious non-fatal | 4 | 0 |
| Overall Study | AE of unknown type | 1 | 0 |
| Overall Study | Lack of Efficacy | 23 | 11 |
| Overall Study | Other reason | 9 | 1 |
| Overall Study | SAE, non-fatal | 1 | 0 |
| Overall Study | SAE, non-fatal+AE, non-serious non-fatal | 1 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 0 |
Baseline characteristics
| Characteristic | Brivaracetam 50 mg/Day | Brivaracetam 100 mg/Day | Total Title |
|---|---|---|---|
| Age, Continuous | 37.7 years STANDARD_DEVIATION 11.7 | 43.6 years STANDARD_DEVIATION 13.2 | 39.0 years STANDARD_DEVIATION 12.2 |
| Age, Customized < 65 years | 66 participants | 19 participants | 85 participants |
| Age, Customized >= 65 years | 2 participants | 1 participants | 3 participants |
| Sex: Female, Male Female | 33 Participants | 8 Participants | 41 Participants |
| Sex: Female, Male Male | 35 Participants | 12 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 33 / 68 | 10 / 20 |
| serious Total, serious adverse events | 5 / 68 | 0 / 20 |
Outcome results
Primary
The Cumulative Exit Rate at 112 Days After the Beginning of the Baseline Antiepileptic Drug (AED) Tapering Phase
The cumulative exit rate was estimated using Kaplan-Meier methods and was based on the duration between start of the Evaluation Period (EP) and the earliest date the first exit criterion was met for each subject. Subjects completing the EP without meeting an exit criterion were censored on Day 112. The primary comparison was BRV 50 mg/day vs a historical control. The upper limit of the 2-sided 95 % Confidence Interval for the estimate was compared to the historical lower bound estimate of 0.722.
Time frame: From Week 1 up to Week 17
Population: The Efficacy Analysis Set (EFF) consists of all randomized subjects with at least one intake of study medication who also entered into the Baseline antiepileptic drug (AED) Tapering Period and started the withdrawal of Baseline AEDs.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Efficacy Analysis Set (BRV 50 mg/Day Treated Subjects) | The Cumulative Exit Rate at 112 Days After the Beginning of the Baseline Antiepileptic Drug (AED) Tapering Phase | 0.487 proportion of subjects |
Secondary
The Number of Patients Reporting at Least One Serious Adverse Event (SAE) During the Course of the Study
Time frame: Baseline through Re-conversion (approximately 31 weeks)
Population: The Intention-to-Treat (ITT) Set consists of all randomized subjects with at least one intake of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Efficacy Analysis Set (BRV 50 mg/Day Treated Subjects) | The Number of Patients Reporting at Least One Serious Adverse Event (SAE) During the Course of the Study | 5 Participants |
| Brivaracetam 100 mg/Day | The Number of Patients Reporting at Least One Serious Adverse Event (SAE) During the Course of the Study | 0 Participants |
Secondary
The Number of Patients Reporting at Least One Treatment-Emergent Adverse Event (TEAE) During the Course of the Study
Time frame: Baseline through Re-conversion (approximately 31 weeks)
Population: The Intention-to-Treat (ITT) Set consists of all randomized subjects with at least one intake of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Efficacy Analysis Set (BRV 50 mg/Day Treated Subjects) | The Number of Patients Reporting at Least One Treatment-Emergent Adverse Event (TEAE) During the Course of the Study | 53 Participants |
| Brivaracetam 100 mg/Day | The Number of Patients Reporting at Least One Treatment-Emergent Adverse Event (TEAE) During the Course of the Study | 11 Participants |
Secondary
The Number of Patient Withdrawal Due to Adverse Events (AEs) During the Course of the Study
Time frame: Baseline through Re-conversion (approximately 31 weeks)
Population: The Intention-to-Treat (ITT) Set consists of all randomized subjects with at least one intake of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Efficacy Analysis Set (BRV 50 mg/Day Treated Subjects) | The Number of Patient Withdrawal Due to Adverse Events (AEs) During the Course of the Study | 9 Participants |
| Brivaracetam 100 mg/Day | The Number of Patient Withdrawal Due to Adverse Events (AEs) During the Course of the Study | 2 Participants |