A Study to Evaluate the Efficacy and Safety of Brivaracetam in Study Participants (>=16 to 80 Years of Age) With Epilepsy
- Conditions
- Partial Seizures With or Without Secondary GeneralizationEpilepsy
- Interventions
- Drug: PlaceboDrug: Brivaracetam
- Registration Number
- NCT03083665
- Lead Sponsor
- UCB Biopharma SRL
- Brief Summary
The purpose of the study is to evaluate the efficacy of brivaracetam (BRV) compared to placebo (PBO) as adjunctive treatment in subjects (\>=16 to 80 years of age) with partial seizures with or without secondary generalization despite current treatment with 1 or 2 concomitant antiepileptic drugs (AEDs) and to assess the safety and tolerability of BRV in subjects \>= 16 years to 80 years of age.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 449
- Subjects (male or female) from 16 to 80 years of age at Visit 1, both inclusive
- Female subjects with childbearing potential are eligible if they use a medically accepted contraceptive method
- Subjects having at least 8 partial seizures (according to the 1981 ILAE classification) during the 8-Week Baseline Period with at least 2 partial seizures during each 4-week interval of the Baseline Period
- Subjects having at least 2 partial seizures whether or not secondary generalization per month during the 3 months preceding Visit 1
- Subjects uncontrolled while treated by 1 or 2 permitted concomitant antiepileptic drug [AED](s). Vagal Nerve Stimulation (VNS) is allowed and will be counted as a concomitant AED
- Subject has history or presence of status epilepticus during the year preceding Visit 1 or during Baseline
- Subject is currently treated with levetiracetam
- Subject has taken levetiracetam within 90 days prior to Visit 1
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BRV 50 mg/day Brivaracetam 12 weeks Treatment Period: Subjects will receive BRV 50 mg/day - Subjects entering into the Long term follow up (LTFU) study or managed access program (MAP): 2 weeks Transition Period: Subjects will receive BRV 50 mg/day followed by LTFU or MAP: Subjects will receive BRV 100 mg/day - Subjects not entering into the LTFU study or MAP: 4 weeks Down-Titration Period: Subjects will receive BRV 25 mg/day for 1 week followed by Placebo for 3 weeks, followed by a Study Drug-Free Period Placebo Placebo * 12 weeks Treatment Period: Subjects will receive Placebo * 4 weeks Down-Titration Period: Subjects will receive Placebo BRV 200 mg/day Placebo 12 weeks Treatment Period: Subjects will receive BRV 200 mg/day - Subjects entering into the Long term follow up (LTFU) study or managed access program (MAP): 2 weeks Transition Period: Subjects will receive BRV 150 mg/day followed by LTFU or MAP: Subjects will receive BRV 100 mg/day - Subjects not entering into the LTFU study or MAP: 4 weeks Down-Titration Period: Subjects will receive BRV 150 mg/day for 1 week followed by BRV 100 mg/day for 1 week, followed by BRV 50 mg/day for 1 week, followed by BRV 25 mg/day for 1 week followed by a Study Drug-Free Period BRV 50 mg/day Placebo 12 weeks Treatment Period: Subjects will receive BRV 50 mg/day - Subjects entering into the Long term follow up (LTFU) study or managed access program (MAP): 2 weeks Transition Period: Subjects will receive BRV 50 mg/day followed by LTFU or MAP: Subjects will receive BRV 100 mg/day - Subjects not entering into the LTFU study or MAP: 4 weeks Down-Titration Period: Subjects will receive BRV 25 mg/day for 1 week followed by Placebo for 3 weeks, followed by a Study Drug-Free Period BRV 200 mg/day Brivaracetam 12 weeks Treatment Period: Subjects will receive BRV 200 mg/day - Subjects entering into the Long term follow up (LTFU) study or managed access program (MAP): 2 weeks Transition Period: Subjects will receive BRV 150 mg/day followed by LTFU or MAP: Subjects will receive BRV 100 mg/day - Subjects not entering into the LTFU study or MAP: 4 weeks Down-Titration Period: Subjects will receive BRV 150 mg/day for 1 week followed by BRV 100 mg/day for 1 week, followed by BRV 50 mg/day for 1 week, followed by BRV 25 mg/day for 1 week followed by a Study Drug-Free Period
- Primary Outcome Measures
Name Time Method Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) From start of the Treatment Period (Week 0) until Safety Visit (up to Week 18); only for OLTP- From last visit of Transition Period to beginning of MAP (up to 4 Years 10 Months) An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. Treatment-Emergent AEs were defined as AEs which had onset on or after the first dose of IMP. As per planned analysis, safety data for all study periods was combined excluding Open-Label Temporary period.
Percentage of Participants With Treatment-Emergent AEs (TEAEs) Leading to Study Withdrawal From start of the Treatment Period (Week 0) until Safety Visit (up to Week 18); only for OLTP- From last visit of Transition Period to beginning of MAP (up to 4 Years 10 Months) An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. Treatment-Emergent AEs were defined as AEs which had onset on or after the first dose of IMP. As per planned analysis, safety data for all study periods was combined excluding Open-Label Temporary period.
Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) From start of the Treatment Period (Week 0) until Safety Visit (up to Week 18); only for OLTP- From last visit of Transition Period to beginning of MAP (up to 4 Years 10 Months) Serious Adverse event (SAE) was defined as any events which: • results in death, • is life-threatening threatening (note that this did not include a reaction that might have caused death had it occurred in a more severe form.), •results in significant or persistent disability/incapacity, • results in a congenital anomaly/birth defect (including that occurring in a fetus), • results in Important medical event that, based upon appropriate medical judgment, may jeopardize the participant and might require medical or surgical intervention to prevent 1 of the other outcomes listed here, and • results in initial inpatient hospitalization or prolongation of hospitalization. As per planned analysis, safety data for all study periods was combined excluding Open-Label Temporary period.
Partial Seizure Frequency Per 28 Days During the 12-week Treatment Period From Baseline to 12-week Treatment Period According to International League Against Epilepsy (ILAE) classification (1981), seizures were classified as type IA (IA1, IA2, IA3, and IA4), IB, IC, II (IIA, IIB, IIC, IID, IIE, and IIF) or III. 28 day adjusted seizure frequency for partial seizures (seizure types IA+IB+IC) was calculated for treatment period by dividing the number of partial seizures by the number of days for which the DRC was completed for treatment period and multiplying the resulting value by 28.
- Secondary Outcome Measures
Name Time Method Time to 10th Partial Seizure During the 12-week Treatment Period During the 12-week Treatment Period The evaluation of time to 10th partial seizure was based on the relative day of occurrence of the 10th partial seizure during the Treatment Period.
Brivaracetam Plasma Concentration Plasma samples were collected at >0-4hours, >4-8hours, >8hours in weeks 2, 4, 8, 12, and 14 Blood samples were collected at indicated time points for the 50mg/day and 200mg/day groups to determine the brivaracetam plasma concentration. Participants of arm 'BRV 200 mg/day' received BRV 200 mg/day until Week 12 only and 150 mg/day during the Transition Period at Week 14. Therefore, the data is reported according to the dosage information at specified time point. As per planned analysis, one blood sample was collected for BRV plasma levels during each dosing interval between 0 to 4 hours, 4 to 8 hours, and 8 to 12 hours postdose.
Percentage of Participants With Categorized Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period From Baseline to 12-week Treatment Period The percentage of participants within each of the following categories of percent change in partial seizure frequency from Baseline to the Treatment Period were summarized for each treatment group: 100%, 75% to less than 100%, 50% to less than 75%, 25% to less than 50%, -25% to less than 25%, and less than -25%. Percent change from Baseline to the Treatment Period in partial seizure frequency was calculated by subtracting 28-day adjusted Treatment Period partial seizure frequency from 28-day adjusted Baseline Period partial seizure frequency and multiplying the resulting quantity by 100 and dividing by the Baseline Period 28-day adjusted partial seizure frequency.
All Seizure Frequency (Partial, Generalized, and Unclassified Epileptic Seizures) Per 28 Days During the 12-week Treatment Period During the 12-week Treatment Period There were three types of epileptic seizures: Partial epileptic seizures (Type I), Generalized epileptic seizures (Type II) and unclassified epileptic seizures (Type III). 28 day adjusted seizure frequency for all seizure types was calculated for treatment period by dividing the number of targeted seizures by the number of days for which the DRC was completed for treatment period and multiplying the resulting value by 28.
50% Responder Rate Based on Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period From Baseline to 12-week Treatment Period Responders were those participants with at least 50% reduction from Baseline to the 12-week Treatment Period in partial seizure frequency per 28 days. 50% Responder rate was calculated for treatment period by dividing the number of 50% responders by the number of participants in the analysis set and multiplying the resulting value by 100.
Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period From Baseline to 12-week Treatment Period Percent change from Baseline to the Treatment Period in partial seizure frequency was calculated by subtracting 28-day adjusted Treatment Period partial seizure frequency from 28-day adjusted Baseline Period partial seizure frequency, and multiplying the resulting quantity by 100 and dividing by the Baseline Period 28-day adjusted partial seizure frequency. A negative value in percent change from Baseline indicates a decrease in partial seizure frequency from Baseline to the Treatment Period.
Time to 1st Partial Seizure During the 12-week Treatment Period During the 12-week Treatment Period The evaluation of time to 1st partial seizure was based on the relative day of occurrence of the 1st partial seizure during the Treatment Period.
Percentage of Participants Who Are Seizure Free (Partial, All Epileptic Seizures) During the 12-week Treatment Period During the 12-week Treatment Period Participants were defined as seizure free, if they did not have missing diary days and no reported seizures during the Treatment Period.
Time to 5th Partial Seizure During the 12-week Treatment Period During the 12-week Treatment Period The evaluation of time to 5th partial seizure was based on the relative day of occurrence of the 5th partial seizure during the Treatment Period.
Trial Locations
- Locations (94)
Ep0083 902
🇨🇳Guangzhou, China
Ep0083 912
🇨🇳Hangzhou, China
Ep0083 910
🇨🇳Shijiazhuang, China
Ep0083 927
🇨🇳Xi'an, China
Ep0083 904
🇨🇳Zhengzhou, China
Ep0083 121
🇯🇵Itami, Japan
Ep0083 129
🇯🇵Neyagawa, Japan
Ep0083 207
🇲🇾Kota Bharu, Malaysia
Ep0083 209
🇲🇾Miri, Malaysia
Ep0083 106
🇯🇵Niigata, Japan
Ep0083 120
🇯🇵Yokohama, Japan
Ep0083 204
🇲🇾Kuching, Malaysia
Ep0083 202
🇲🇾Perai, Malaysia
Ep0083 301
🇵🇭Manila, Philippines
Ep0083 605
🇹🇭Bangkok, Thailand
Ep0083 203
🇲🇾Sungai Buloh, Malaysia
Ep0083 303
🇵🇭Cebu City, Philippines
Ep0083 304
🇵🇭Cebu City, Philippines
Ep0083 310
🇵🇭Manila, Philippines
Ep0083 602
🇹🇭Bangkok, Thailand
Ep0083 306
🇵🇭Davao City, Philippines
Ep0083 307
🇵🇭Iloilo City, Philippines
Ep0083 302
🇵🇭Manila, Philippines
Ep0083 309
🇵🇭Quezon City, Philippines
Ep0083 504
🇨🇳Taichung City, Taiwan
Ep0083 606
🇹🇭Bangkok, Thailand
Ep0083 607
🇹🇭Bangkok, Thailand
Ep0083 608
🇹🇭Muang, Thailand
Ep0083 146
🇯🇵Chiba-shi, Japan
Ep0083 111
🇯🇵Hamamatsu, Japan
Ep0083 123
🇯🇵Kodaira, Japan
Ep0083 128
🇯🇵Kurume, Japan
Ep0083 905
🇨🇳Beijing, China
Ep0083 907
🇨🇳Changchun, China
Ep0083 901
🇨🇳Chengdu, China
Ep0083 920
🇨🇳Guangzhou, China
Ep0083 922
🇨🇳Guangzhou, China
Ep0083 921
🇨🇳Nanchang, China
Ep0083 918
🇨🇳Zhanjiang, China
Ep0083 909
🇨🇳Guangzhou, China
Ep0083 908
🇨🇳Lanzhou, China
Ep0083 926
🇨🇳Pingxiang, China
Ep0083 930
🇨🇳Xinxiang, China
Ep0083 925
🇨🇳Suzhou, China
Ep0083 913
🇨🇳Wenzhou, China
Ep0083 916
🇨🇳Yinchuan, China
Ep0083 147
🇯🇵Kyoto, Japan
Ep0083 118
🇯🇵Nagoya, Japan
Ep0083 117
🇯🇵Nara, Japan
Ep0083 402
🇸🇬Singapore, Singapore
Ep0083 603
🇹🇭Muang, Thailand
Ep0083 401
🇸🇬Singapore, Singapore
Ep0083 505
🇨🇳Kaohsiung, Taiwan
Ep0083 917
🇨🇳Guangzhou, China
Ep0083 906
🇨🇳Beijing, China
Ep0083 924
🇨🇳Guangzhou, China
Ep0083 923
🇨🇳Zunyi, China
Ep0083 116
🇯🇵Asaka, Japan
Ep0083 122
🇯🇵Hachinohe, Japan
Ep0083 140
🇯🇵Kawasaki, Japan
Ep0083 102
🇯🇵Kagoshima, Japan
Ep0083 142
🇯🇵Kamakura, Japan
Ep0083 115
🇯🇵Kokubunji, Japan
Ep0083 132
🇯🇵Koriyama, Japan
Ep0083 124
🇯🇵Kyoto, Japan
Ep0083 112
🇯🇵Koshi, Japan
Ep0083 105
🇯🇵Nagakute, Japan
Ep0083 136
🇯🇵Nagoya, Japan
Ep0083 114
🇯🇵Saitama, Japan
Ep0083 101
🇯🇵Sapporo, Japan
Ep0083 103
🇯🇵Sendai, Japan
Ep0083 144
🇯🇵Shinjuku-ku, Japan
Ep0083 108
🇯🇵Suita, Japan
Ep0083 137
🇯🇵Suita, Japan
Ep0083 138
🇯🇵Tsukuba, Japan
Ep0083 150
🇯🇵Yokohama, Japan
Ep0083 130
🇯🇵Ôsaka, Japan
Ep0083 201
🇲🇾Kuala Lumpur, Malaysia
Ep0083 601
🇹🇭Khon Kaen, Thailand
Ep0083 502
🇨🇳Chiayi City, Taiwan
Ep0083 609
🇹🇭Bangkok, Thailand
Ep0083 126
🇯🇵Bunkyo-ku, Japan
Ep0083 127
🇯🇵Bunkyo-ku, Japan
Ep0083 110
🇯🇵Hiroshima, Japan
Ep0083 104
🇯🇵Shizuoka, Japan
Ep0083 133
🇯🇵Ushiku, Japan
Ep0083 131
🇯🇵Ōtsu, Japan
Ep0083 206
🇲🇾Kuala Terengganu, Malaysia
Ep0083 208
🇲🇾Pulau Pinang, Malaysia
Ep0083 148
🇯🇵Adachi-ku, Japan
Ep0083 141
🇯🇵Higashisonogi-gun Kawatana-cho, Japan
Ep0083 109
🇯🇵Yamagata, Japan
Ep0083 503
🇨🇳Taichung, Taiwan
Ep0083 501
🇨🇳Tainan, Taiwan