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

Epilepsy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03083665
• Other study ID #: EP0083
• Status: Completed
• Phase: Phase 3
• Start date: August 22, 2017
• Est. completion date: June 30, 2022

Study information

• Verified date: May 2024
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 449
• Est. completion date: June 30, 2022
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Epilepsy
• Neoplasm Metastasis
• Partial Seizures With or Without Secondary Generalization
• Seizures

Intervention

Drug:
• Placebo
Pharmaceutical form: Film-coated tablets Route of administration: Oral use
• Brivaracetam
Pharmaceutical form: Film-coated tablets Concentration: 25 mg tablets and 50 mg tablets Route of administration: Oral use

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
UCB Biopharma SRL

Countries where clinical trial is conducted

China,  Japan,  Malaysia,  Philippines,  Singapore,  Taiwan,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Brivaracetam Plasma Concentration	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.	Plasma samples were collected at >0-4hours, >4-8hours, >8hours in weeks 2, 4, 8, 12, and 14