A Study to Evaluate the Efficacy and Safety of Brivaracetam in Study Participants (>=16 to 80 Years of Age) With Epilepsy

A Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel-group Study to Evaluate the Efficacy and Safety of Adjunctive Brivaracetam in Subjects (>=16 to 80 Years of Age) With Partial Seizures With or Without Secondary Generalization

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.

Study Overview

• Status: Completed
• Conditions: Epilepsy; Partial Seizures With or Without Secondary Generalization
• Intervention / Treatment: Drug: Placebo; Drug: Brivaracetam

• Study Type: Interventional
• Enrollment (Actual): 449
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Ep0083 905
  • Beijing, China
    • Ep0083 906
  • Changchun, China
    • Ep0083 907
  • Chengdu, China
    • Ep0083 901
  • Guangzhou, China
    • Ep0083 902
  • Guangzhou, China
    • Ep0083 909
  • Guangzhou, China
    • Ep0083 917
  • Guangzhou, China
    • Ep0083 920
  • Guangzhou, China
    • Ep0083 922
  • Guangzhou, China
    • Ep0083 924
  • Hangzhou, China
    • Ep0083 912
  • Lanzhou, China
    • Ep0083 908
  • Nanchang, China
    • Ep0083 921
  • Pingxiang, China
    • Ep0083 926
  • Shijiazhuang, China
    • Ep0083 910
  • Suzhou, China
    • Ep0083 925
  • Wenzhou, China
    • Ep0083 913
  • Xi'an, China
    • Ep0083 927
  • Xinxiang, China
    • Ep0083 930
  • Yinchuan, China
    • Ep0083 916
  • Zhanjiang, China
    • Ep0083 918
  • Zhengzhou, China
    • Ep0083 904
  • Zunyi, China
    • Ep0083 923
• Japan
  • Adachi-ku, Japan
    • Ep0083 148
  • Asaka, Japan
    • Ep0083 116
  • Bunkyo-ku, Japan
    • Ep0083 126
  • Bunkyo-ku, Japan
    • Ep0083 127
  • Chiba-shi, Japan
    • Ep0083 146
  • Hachinohe, Japan
    • Ep0083 122
  • Hamamatsu, Japan
    • Ep0083 111
  • Higashisonogi-gun Kawatana-cho, Japan
    • Ep0083 141
  • Hiroshima, Japan
    • Ep0083 110
  • Itami, Japan
    • Ep0083 121
  • Kagoshima, Japan
    • Ep0083 102
  • Kamakura, Japan
    • Ep0083 142
  • Kawasaki, Japan
    • Ep0083 140
  • Kodaira, Japan
    • Ep0083 123
  • Kokubunji, Japan
    • Ep0083 115
  • Koriyama, Japan
    • Ep0083 132
  • Koshi, Japan
    • Ep0083 112
  • Kurume, Japan
    • Ep0083 128
  • Kyoto, Japan
    • Ep0083 124
  • Kyoto, Japan
    • Ep0083 147
  • Nagakute, Japan
    • Ep0083 105
  • Nagoya, Japan
    • Ep0083 118
  • Nagoya, Japan
    • Ep0083 136
  • Nara, Japan
    • Ep0083 117
  • Neyagawa, Japan
    • Ep0083 129
  • Niigata, Japan
    • Ep0083 106
  • Saitama, Japan
    • Ep0083 114
  • Sapporo, Japan
    • Ep0083 101
  • Sendai, Japan
    • Ep0083 103
  • Shinjuku-ku, Japan
    • Ep0083 144
  • Shizuoka, Japan
    • Ep0083 104
  • Suita, Japan
    • Ep0083 108
  • Suita, Japan
    • Ep0083 137
  • Tsukuba, Japan
    • Ep0083 138
  • Ushiku, Japan
    • Ep0083 133
  • Yamagata, Japan
    • Ep0083 109
  • Yokohama, Japan
    • Ep0083 120
  • Yokohama, Japan
    • Ep0083 150
  • Ôsaka, Japan
    • Ep0083 130
  • Ōtsu, Japan
    • Ep0083 131
• Malaysia
  • Kota Bharu, Malaysia
    • Ep0083 207
  • Kuala Lumpur, Malaysia
    • Ep0083 201
  • Kuala Terengganu, Malaysia
    • Ep0083 206
  • Kuching, Malaysia
    • Ep0083 204
  • Miri, Malaysia
    • Ep0083 209
  • Perai, Malaysia
    • Ep0083 202
  • Pulau Pinang, Malaysia
    • Ep0083 208
  • Sungai Buloh, Malaysia
    • Ep0083 203
• Philippines
  • Cebu City, Philippines
    • Ep0083 303
  • Cebu City, Philippines
    • Ep0083 304
  • Davao City, Philippines
    • Ep0083 306
  • Iloilo City, Philippines
    • Ep0083 307
  • Manila, Philippines
    • Ep0083 301
  • Manila, Philippines
    • Ep0083 302
  • Manila, Philippines
    • Ep0083 310
  • Quezon City, Philippines
    • Ep0083 309
• Singapore
  • Singapore, Singapore
    • Ep0083 401
  • Singapore, Singapore
    • Ep0083 402
• Taiwan
  • Chiayi City, Taiwan
    • Ep0083 502
  • Kaohsiung, Taiwan
    • Ep0083 505
  • Taichung, Taiwan
    • Ep0083 503
  • Taichung City, Taiwan
    • Ep0083 504
  • Tainan, Taiwan
    • Ep0083 501
• Thailand
  • Bangkok, Thailand
    • Ep0083 602
  • Bangkok, Thailand
    • Ep0083 605
  • Bangkok, Thailand
    • Ep0083 606
  • Bangkok, Thailand
    • Ep0083 607
  • Bangkok, Thailand
    • Ep0083 609
  • Khon Kaen, Thailand
    • Ep0083 601
  • Muang, Thailand
    • Ep0083 603
  • Muang, Thailand
    • Ep0083 608

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 12 weeks Treatment Period: Subjects will receive Placebo; 4 weeks Down-Titration Period: Subjects will receive Placebo	Drug: Placebo; Pharmaceutical form: Film-coated tablets; Route of administration: Oral use
Experimental: BRV 50 mg/day; 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	Drug: Placebo; Pharmaceutical form: Film-coated tablets; Route of administration: Oral use; Drug: Brivaracetam; Pharmaceutical form: Film-coated tablets; Concentration: 25 mg tablets and 50 mg tablets; Route of administration: Oral use; Other Names: Briviact
Experimental: BRV 200 mg/day; 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	Drug: Placebo; Pharmaceutical form: Film-coated tablets; Route of administration: Oral use; Drug: Brivaracetam; Pharmaceutical form: Film-coated tablets; Concentration: 25 mg tablets and 50 mg tablets; Route of administration: Oral use; Other Names: Briviact

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)	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.	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)
Percentage of Participants With Treatment-Emergent AEs (TEAEs) Leading to Study Withdrawal	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.	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)
Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)	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.	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)
Partial Seizure Frequency Per 28 Days During the 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.	From Baseline to 12-week Treatment Period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
50% Responder Rate Based on Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 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.	From Baseline to 12-week Treatment Period
Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 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.	From Baseline to 12-week Treatment Period
Percentage of Participants With Categorized Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 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.	From Baseline to 12-week Treatment Period
All Seizure Frequency (Partial, Generalized, and Unclassified Epileptic Seizures) Per 28 Days 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.	During the 12-week Treatment Period
Percentage of Participants Who Are Seizure Free (Partial, All Epileptic Seizures) 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.	During the 12-week Treatment Period
Time to 1st Partial Seizure 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.	During the 12-week Treatment Period
Time to 5th Partial Seizure 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.	During the 12-week Treatment Period
Time to 10th Partial Seizure 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.	During the 12-week Treatment Period
Brivaracetam Plasma Concentration	Blood samples were collected at indicated time points 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.	Plasma samples were collected at >0-4hours, >4-8hours, >8hours in weeks 2, 4, 8, 12, and 14

Collaborators and Investigators

• Sponsor: UCB Biopharma SRL
• Investigators: Study Director: UCB Cares, 001 844 599 2273 (UCB)

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2017
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: February 28, 2017
• First Submitted That Met QC Criteria: March 14, 2017
• First Posted (Actual): March 20, 2017

Study Record Updates

• Last Update Posted (Estimated): November 9, 2023
• Last Update Submitted That Met QC Criteria: November 8, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Epilepsy; Brivaracetam; Briviact; Partial seizures with or without secondary generalization
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neurologic Manifestations; Neoplastic Processes; Epilepsy; Neoplasm Metastasis; Seizures; Anticonvulsants; Brivaracetam
• Other Study ID Numbers: EP0083

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.
• IPD Sharing Time Frame: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
• IPD Sharing Access Criteria: Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No