An Open-label, Multinational, Multicenter, Follow-up Study to Evaluate the Long-term Safety and Efficacy of Brivaracetam

An Open-label, Multinational, Multicenter, Follow-up Study to Evaluate the Long-term Safety and Efficacy of Brivaracetam Used at a Flexible Dose up to a Maximum of 200 mg/Day in Subjects Aged 16 Years or Older Suffering From Epilepsy.

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00761774

Enrollment

108

Registered

2008-09-30

Start date

2008-11-30

Completion date

2017-03-31

Last updated

2018-07-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Epilepsy

Keywords

Epilepsy, Monotherapy, Partial Onset Seizures

Brief summary

The Sponsor wishes to develop brivaracetam as an anti-epileptic treatment in subjects 16 years and older with epilepsy. This study permits continued access to treatment for subjects who participated in a previous epilepsy study. The study will explore the long-term safety and efficacy of brivaracetam.

Interventions

DRUGBrivaracetam

Subjects will begin at a recommended dose of Brivaracetam 100 mg/day. Subjects will continue treatment at a dose up to a maximum of 200 mg/day with a twice per day administration. Up- and down-titration steps may be performed in steps of a maximum of 50 mg/day on a weekly basis. Full down-titration should include a one week step on 20 mg/day. The study medication will come in 10 mg and 25 mg tablet strengths.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

16 Years to No maximum

Healthy volunteers

Inclusion criteria

* Subjects with epilepsy who participated in previous brivaracetam trials which allow access to the present trial. * Subjects from whom the Investigator believes a reasonable potential benefit from the long-term administration of brivaracetam may be expected.

Exclusion criteria

• Severe medical, neurological and psychiatric disorders, including current suicidal ideation or behaviour, or laboratory values which may have an impact on the safety of the subject, as determined by the investigator.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Subjects With at Least One Treatment-emergent Adverse Event (TEAE) During the Evaluation Period From Entry Visit 1 Through End of Treatment (up to 9 Years)	During the Evaluation Period (up to 9 years)	Treatment-emergent Adverse events (TEAE) are any untoward medical occurrences in a subject during administered study treatment, whether or not these events are related to study treatment.
Percentage of Subjects Who Withdrew Due to Adverse Event (AE) During the Evaluation Period From Entry Visit 1 Through End of Treatment (up to 9 Years)	During the Evaluation Period (up to 9 years)	Adverse Events (AE) are any untoward medical occurrences in a subject during administered study treatment, whether or not these events are related to study treatment.
Percentage of Subjects With a Serious Adverse Event (SAE) During the Evaluation Period From Entry Visit 1 Through End of Treatment (up to 9 Years)	During the Evaluation Period (up to 9 years)	An SAE was any untoward medical occurrence that, at any dose resulted in death, was life threatening, required in-subject hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect.

Secondary

Measure	Time frame	Description
Percentage of Subjects on Continuous Brivaracetam Monotherapy for at Least 3 Months of the Evaluation Period (up to 9 Years)	During the Evaluation Period (up to 9 years)	BRV monotherapy is defined as continuous treatment with BRV only (ie, no treatment with another anti-epileptic drug (AED)). Use of rescue AED for a duration of no more than 2 consecutive days will not disqualify a subject from being defined as on continuous monotherapy provided the use of rescue AED does not exceed more than 1 time per week.
Percentage of Subjects on Continuous Brivaracetam Monotherapy for at Least 6 Months, of the Evaluation Period (up to 9 Years)	During the Evaluation Period (up to 9 years)	BRV monotherapy is defined as continuous treatment with BRV only (ie, no treatment with another anti-epileptic drug (AED)). Use of rescue AED for a duration of no more than 2 consecutive days will not disqualify a subject from being defined as on continuous monotherapy provided the use of rescue AED does not exceed more than 1 time per week.
Percentage of Subjects on Continuous Brivaracetam Monotherapy for at Least 12 Months of the Evaluation Period (up to 9 Years)	During the Evaluation Period (up to 9 years)	BRV monotherapy is defined as continuous treatment with BRV only (ie, no treatment with another anti-epileptic drug (AED)). Use of rescue AED for a duration of no more than 2 consecutive days will not disqualify a subject from being defined as on continuous monotherapy provided the use of rescue AED does not exceed more than 1 time per week.

Countries

Australia, Belgium, Canada, Czechia, France, Germany, Hungary, Italy, Spain, Sweden, United States

Participant flow

Recruitment details

The study started to enroll patients in November 2008 and concluded in March 2017.

Pre-assignment details

Participant Flow refers to the Safety Set, which consisted of all subjects who took at least 1 dose of study drug.

Participants by arm

Arm	Count
Brivaracetam This arm consisted of subjects who received Brivaracetam (BRV) at flexible dosing up to 200 mg/day.	108
Total	108

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	17
Overall Study	Coordinator leaving site	1
Overall Study	End of study	2
Overall Study	Investigator clinical judgement	1
Overall Study	IP stopped by hospital physician	1
Overall Study	Lack of Efficacy	37
Overall Study	Lost to Follow-up	2
Overall Study	Medical decision to read SUSAR reports	1
Overall Study	Non-compliance	4
Overall Study	Patient moved out of study area	1
Overall Study	Reclassification of seizures	1
Overall Study	Sponsor decision	1
Overall Study	Subject IP non-compliance	1
Overall Study	Withdrawal by Subject	9

Baseline characteristics

Characteristic	Brivaracetam
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	5 Participants
Age, Categorical Between 18 and 65 years	103 Participants
Age, Continuous	40.8 years STANDARD_DEVIATION 13
Race/Ethnicity, Customized Black or African American	7 Participants
Race/Ethnicity, Customized Other/Mixed	4 Participants
Race/Ethnicity, Customized White	97 Participants
Sex: Female, Male Female	56 Participants
Sex: Female, Male Male	52 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	1 / 108
other Total, other adverse events	81 / 108
serious Total, serious adverse events	26 / 108

Outcome results

Primary

Percentage of Subjects Who Withdrew Due to Adverse Event (AE) During the Evaluation Period From Entry Visit 1 Through End of Treatment (up to 9 Years)

Adverse Events (AE) are any untoward medical occurrences in a subject during administered study treatment, whether or not these events are related to study treatment.