Follow-up Trial to Evaluate Long-term Safety and Efficacy of Brivaracetam in Subjects Suffering From Epilepsy

Conditions

Epilepsy

Keywords

Brivaracetam, Epilepsy, long term

Brief summary

This trial, evaluating the long-term safety and tolerability of brivaracetam, will give subjects suffering from epilepsy, who may have benefited from brivaracetam, the opportunity to continue the treatment. The study will also evaluate the maintenance of efficacy over time of brivaracetam for subjects with partial onset seizures (POS)/primary generalized seizures (PGS).

Klein P, Bourikas D.

2024-05-2910 citations

10.1007/s12325-024-02876-z

Long-term efficacy and tolerability of adjunctive brivaracetam in adults with focal to bilateral tonic-clonic (secondary generalized) seizures: Post hoc pooled analysis

Brian D. Moseley, Svetlana Dimova, Sami Elmoufti, Cédric Laloyaux, Ali A. Asadi‐Pooya

Epilepsy Research2021-06-248 citations

10.1016/j.eplepsyres.2021.106694

Safety, tolerability, and efficacy of brivaracetam as adjunctive therapy in patients with focal seizures, generalized onset seizures, or Unverricht-Lundborg disease: An open-label, long-term follow-up trial.

Ben-Menachem E, Baulac M, Hong SB, Cleveland JM, Reichel C, Schulz AL, Wagener G, Brandt C.

2020-12-0412 citations

10.1016/j.eplepsyres.2020.106526

P.006 Efficacy of adjunctive brivaracetam in adult patients with secondarily generalized tonic-clonic seizures at baseline: pooled results from long-term follow-up trials

BD Moseley, A Diaz, S Elmoufti, J Whitesides

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques2019-06-01

10.1017/cjn.2019.107

Efficacy and safety of brivaracetam for partial-onset seizures in 3 pooled clinical studies.

Ben-Menachem E, Mameniškienė R, Quarato PP, Klein P, Gamage J, Schiemann J, Johnson ME, Whitesides J, McDonough B, Eckhardt K.

2016-06-2291 citations

10.1212/wnl.0000000000002864

Safety, tolerability, and seizure control during long-term treatment with adjunctive brivaracetam for partial-onset seizures.

Toledo M, Whitesides J, Schiemann J, Johnson ME, Eckhardt K, McDonough B, Borghs S, Kwan P.

2016-06-0655 citations

10.1111/epi.13416

Seizure and Quality of Life Outcomes in Patients with Long-Term Adjunctive Brivaracetam Treatment for Partial-Onset Seizures (P2.032)

Manuel Toledo, Patrick Kwan, Martin Johnson, Simon Borghs, Klaus Eckhardt et al. (7 authors)

Neurology2016-04-05

10.1212/wnl.86.16_supplement.p2.032

Interventions

DRUGBrivaracetam (ucb 34714)

10 mg and 25 mg tablets. Flexible dosing up to 200 mg/day, twice daily. For each subject, the study will last from study entry until either regulatory approval of brivaracetam has been granted by any Health Authority in an indication of adjunctive treatment of partial onset seizures; or until the Sponsor decides to close the study; until a managed access program, named patient program, compassionate use program, or similar type of access program is established as allowed per country-specific requirements in addition to legal and regulatory guidelines, or until the investigational product development is stopped by the Sponsor.

Study design

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

16 Years to No maximum

Healthy volunteers

No

Inclusion criteria

* Male/female subjects from 16 years (where legally permitted and ethically accepted) or 18 years onwards suffering from epilepsy and having completed a previous study with brivaracetam as adjunctive treatment, which allowed access to this study * Subjects with POS/PGS: inpatients or outpatients with epilepsy who participated in previous brivaracetam studies / programs which allow access to the present study * Subjects with ULD: inpatients or outpatients with epilepsy who were treated with brivaracetam in previous studies / programs which allow access to the present study * Subjects for whom the Investigator believes a reasonable benefit from the long-term administration of brivaracetam may be expected

Exclusion criteria

* Severe medical, neurological and psychiatric disorders, or laboratory values which may have an impact on the safety of the subject * Poor compliance with visit schedule or medication intake in previous brivaracetam study * Participation in any clinical study of another investigational drug or device during the study * Pregnant or lactating woman

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With at Least One Treatment-emergent Adverse Event (TEAE)	From Entry Visit until Last Visit (up to 162 months)	Treatment-emergent adverse events (TEAEs) were defined as those events which started on or after the date of first dose of investigational medicinal product (IMP), or events in which severity worsened on or after the date of first dose of study medication. The event does not necessarily have a causal relationship with that treatment or usage.
Percentage of Participants Who Withdrew Due to an Adverse Event (AE)	From Entry Visit until Last Visit (up to 162 months)	An AE is any untoward medical occurrence in a participant or trial participant that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage.
Percentage of Participants With at Least One Serious Adverse Event (SAE)	From Entry Visit until Last Visit (up to 162 months)	A serious adverse event (SAE) is any untoward medical occurrence that at any dose: * Results in death * Is life-threatening * Requires in patient hospitalization or prolongation of existing hospitalization * Is a congenital anomaly or birth defect * Is an infection that requires treatment parenteral antibiotics * Other important medical events which based on medical or scientific judgement may jeopardize the patients or may require medical or surgical intervention to prevent any of the above.

Secondary

Measure	Time frame	Description
Partial Onset Seizure (POS) (Type I) Frequency Per 28 Days During the Evaluation Period	From Entry Visit until Last Visit (up to 162 months)	The 28 day adjusted seizure frequency was calculated by dividing the number of partial seizures by the number of days for which the diary was completed, and multiplying the resulting value by 28. Baseline values for seizure frequency were calculated based on the seizure diary data collected during the baseline period of the previous double-blind studies: N01114 \[NCT00175929\], N01252 \[NCT00490035\] and N01254 \[NCT00504881\].
Percent Change in Partial Onset Seizure (POS) (Type I) Frequency Per 28 Days From Baseline of the Previous Study to the Evaluation Period	From Entry Visit until Last Visit (up to 162 months)	The percent change from the previous study baselines, in Partial Onset Seizure (POS) (Type I) frequency per 28 days is defined as: (the value at the previous study baselines) minus (the value at each time-points during the evaluation period) divided by the value at the previous study baselines. Baseline values for seizure frequency were calculated based on the seizure diary data collected during the baseline period of the previous double-blind studies: N01114 \[NCT00175929\], N01252 \[NCT00490035\] and N01254 \[NCT00504881\].
Responder Rate in POS (Type I) Frequency Over the Evaluation Period	From Entry Visit until Last Visit (up to 162 months)	A responder is defined as a participant with a ≥ 50% reduction in seizure frequency from the Baseline Period of the previous study. Baseline values for seizure frequency were calculated based on the seizure diary data collected during the baseline period of the previous double-blind studies: N01114 \[NCT00175929\], N01252 \[NCT00490035\] and N01254 \[NCT00504881\].

Countries

Austria, Belgium, Canada, Czechia, Finland, France, Germany, Hong Kong, Hungary, Israel, Italy, Netherlands, Norway, Poland, Russia, Serbia, Singapore, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Tunisia, Ukraine, United States

Participant flow

Recruitment details

The study started to enroll patients in September 2005 and concluded in May 2019.

Pre-assignment details

Participants Flow refers to the Safety Set (SS).

Participants by arm

Arm	Count
Brivaracetam Brivaracetam (BRV) was administered with a maximum of 200 mg/day, twice, daily, incremented by 50 mg/day on a weekly basis, during the Up-Titration. During the Down- Titration Period, the BRV dose was decreased in steps of a maximum of 50 mg/day on a weekly basis. A last down-titration step at 20 mg/day for 1 week was included prior to the Post-Treatment Period.	853
Total	853

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Administrative reason	1
Overall Study	Adverse Event	81
Overall Study	Death	19
Overall Study	Lack of compliance	8
Overall Study	Lack of Efficacy	354
Overall Study	Loss of job and economic burden	1
Overall Study	Lost to Follow-up	17
Overall Study	Moved overseas	1
Overall Study	Patient cannot record seizures	1
Overall Study	Patient's request	2
Overall Study	Patient went to prison	1
Overall Study	Pregnancy	1
Overall Study	Seizure - free	4
Overall Study	Site was closed	9
Overall Study	Sponsor decision	17
Overall Study	Subject Choice	98
Overall Study	Suicidal behaviour	1
Overall Study	Treating physiciant's choice	1
Overall Study	Vigabatrin intake	1
Overall Study	Withdrawal by Subject	1

Baseline characteristics

Characteristic	Brivaracetam
Age, Categorical <=18 years	14 Participants
Age, Categorical >=65 years	12 Participants
Age, Categorical Between 18 and 65 years	827 Participants
Age, Continuous	37.5 years STANDARD_DEVIATION 11.8
Race/Ethnicity, Customized Asian	123 Participants
Race/Ethnicity, Customized Black	2 Participants
Race/Ethnicity, Customized Other	7 Participants
Race/Ethnicity, Customized White	721 Participants
Sex: Female, Male Female	418 Participants
Sex: Female, Male Male	435 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	19 / 853
other Total, other adverse events	569 / 853
serious Total, serious adverse events	248 / 853

Outcome results

Primary

Percentage of Participants Who Withdrew Due to an Adverse Event (AE)

An AE is any untoward medical occurrence in a participant or trial participant that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage.