Trial Outcomes & Findings for An Open-label, Multinational, Multicenter, Follow-up Study to Evaluate the Long-term Safety and Efficacy of Brivaracetam (NCT NCT00761774)
NCT ID: NCT00761774
Last Updated: 2018-07-11
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
108 participants
Primary outcome timeframe
During the Evaluation Period (up to 9 years)
Results posted on
2018-07-11
Participant Flow
The study started to enroll patients in November 2008 and concluded in March 2017.
Participant Flow refers to the Safety Set, which consisted of all subjects who took at least 1 dose of study drug.
Participant milestones
| Measure |
Brivaracetam
This arm consisted of subjects who received Brivaracetam (BRV) at flexible dosing up to 200 mg/day.
|
|---|---|
|
Overall Study
STARTED
|
108
|
|
Overall Study
COMPLETED
|
29
|
|
Overall Study
NOT COMPLETED
|
79
|
Reasons for withdrawal
| Measure |
Brivaracetam
This arm consisted of subjects who received Brivaracetam (BRV) at flexible dosing up to 200 mg/day.
|
|---|---|
|
Overall Study
Adverse Event
|
17
|
|
Overall Study
Lack of Efficacy
|
37
|
|
Overall Study
Lost to Follow-up
|
2
|
|
Overall Study
Withdrawal by Subject
|
9
|
|
Overall Study
Non-compliance
|
4
|
|
Overall Study
End of study
|
2
|
|
Overall Study
Reclassification of seizures
|
1
|
|
Overall Study
Medical decision to read SUSAR reports
|
1
|
|
Overall Study
Sponsor decision
|
1
|
|
Overall Study
Investigator clinical judgement
|
1
|
|
Overall Study
Patient moved out of study area
|
1
|
|
Overall Study
Coordinator leaving site
|
1
|
|
Overall Study
Subject IP non-compliance
|
1
|
|
Overall Study
IP stopped by hospital physician
|
1
|
Baseline Characteristics
An Open-label, Multinational, Multicenter, Follow-up Study to Evaluate the Long-term Safety and Efficacy of Brivaracetam
Baseline characteristics by cohort
| Measure |
Brivaracetam
n=108 Participants
This arm consisted of subjects who received Brivaracetam (BRV) at flexible dosing up to 200 mg/day.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
103 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
5 Participants
n=5 Participants
|
|
Age, Continuous
|
40.8 years
STANDARD_DEVIATION 13 • n=5 Participants
|
|
Sex: Female, Male
Female
|
56 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
52 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
7 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
97 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other/Mixed
|
4 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: During the Evaluation Period (up to 9 years)Population: The Safety Analysis Set consisted of all subjects who took at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Brivaracetam (SS)
n=108 Participants
This arm consisted of subjects who received Brivaracetam (BRV) at flexible dosing up to 200 mg/day.
|
|---|---|
|
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)
|
90.7 percentage of participants
|
PRIMARY outcome
Timeframe: During the Evaluation Period (up to 9 years)Population: The Safety Analysis Set consisted of all subjects who took at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Brivaracetam (SS)
n=108 Participants
This arm consisted of subjects who received Brivaracetam (BRV) at flexible dosing up to 200 mg/day.
|
|---|---|
|
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)
|
15.7 percentage of participants
|
PRIMARY outcome
Timeframe: During the Evaluation Period (up to 9 years)Population: The Safety Analysis Set consisted of all subjects who took at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Brivaracetam (SS)
n=108 Participants
This arm consisted of subjects who received Brivaracetam (BRV) at flexible dosing up to 200 mg/day.
|
|---|---|
|
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)
|
24.1 percentage of participants
|
SECONDARY outcome
Timeframe: During the Evaluation Period (up to 9 years)Population: The Efficacy Analysis Set consisted of all subjects who took at least 1 dose of study drug and had at least 1 seizure Daily Record Card (DRC) day during the Evaluation Period.
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.
Outcome measures
| Measure |
Brivaracetam (SS)
n=108 Participants
This arm consisted of subjects who received Brivaracetam (BRV) at flexible dosing up to 200 mg/day.
|
|---|---|
|
Percentage of Subjects on Continuous Brivaracetam Monotherapy for at Least 3 Months of the Evaluation Period (up to 9 Years)
|
38.89 percentage of participants
|
SECONDARY outcome
Timeframe: During the Evaluation Period (up to 9 years)Population: The Efficacy Analysis Set consisted of all subjects who took at least 1 dose of study drug and had at least 1 seizure Daily Record Card (DRC) day during the Evaluation Period.
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.
Outcome measures
| Measure |
Brivaracetam (SS)
n=108 Participants
This arm consisted of subjects who received Brivaracetam (BRV) at flexible dosing up to 200 mg/day.
|
|---|---|
|
Percentage of Subjects on Continuous Brivaracetam Monotherapy for at Least 6 Months, of the Evaluation Period (up to 9 Years)
|
32.41 percentage of participants
|
SECONDARY outcome
Timeframe: During the Evaluation Period (up to 9 years)Population: The Efficacy Analysis Set consisted of all subjects who took at least 1 dose of study drug and had at least 1 seizure Daily Record Card (DRC) day during the Evaluation Period.
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.
Outcome measures
| Measure |
Brivaracetam (SS)
n=108 Participants
This arm consisted of subjects who received Brivaracetam (BRV) at flexible dosing up to 200 mg/day.
|
|---|---|
|
Percentage of Subjects on Continuous Brivaracetam Monotherapy for at Least 12 Months of the Evaluation Period (up to 9 Years)
|
25 percentage of participants
|
Adverse Events
Brivaracetam (SS)
Serious events: 26 serious events
Other events: 81 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Brivaracetam (SS)
n=108 participants at risk
This arm consisted of subjects who received Brivaracetam (BRV) at flexible dosing up to 200 mg/day.
|
|---|---|
|
Cardiac disorders
Angina pectoris
|
2.8%
3/108 • Number of events 3 • Adverse events were collected throughout the study (up to 9 years).
|
|
Cardiac disorders
Atrial fibrillation
|
1.9%
2/108 • Number of events 2 • Adverse events were collected throughout the study (up to 9 years).
|
|
Cardiac disorders
Cardiac failure congestive
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Gastrointestinal disorders
Abdominal pain
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Gastrointestinal disorders
Vomiting
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
General disorders
Sudden unexplained death in epilepsy
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Hepatobiliary disorders
Cholecystitis
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Hepatobiliary disorders
Cholelithiasis
|
1.9%
2/108 • Number of events 2 • Adverse events were collected throughout the study (up to 9 years).
|
|
Infections and infestations
Pneumonia
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Infections and infestations
Urinary tract infection
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Injury, poisoning and procedural complications
Contusion
|
1.9%
2/108 • Number of events 3 • Adverse events were collected throughout the study (up to 9 years).
|
|
Injury, poisoning and procedural complications
Craniocerebral injury
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Injury, poisoning and procedural complications
Facial bones fracture
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Injury, poisoning and procedural complications
Intentional overdose
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Injury, poisoning and procedural complications
Joint injury
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Injury, poisoning and procedural complications
Laceration
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Injury, poisoning and procedural complications
Snake bite
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Nervous system disorders
Convulsion
|
4.6%
5/108 • Number of events 7 • Adverse events were collected throughout the study (up to 9 years).
|
|
Nervous system disorders
Dysarthria
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Nervous system disorders
Epilepsy
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Nervous system disorders
Grand mal convulsion
|
1.9%
2/108 • Number of events 4 • Adverse events were collected throughout the study (up to 9 years).
|
|
Nervous system disorders
Hemiparesis
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Nervous system disorders
Migraine
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Nervous system disorders
Monoplegia
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Nervous system disorders
Postictal state
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Psychiatric disorders
Anxiety
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Psychiatric disorders
Factitious disorder
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Psychiatric disorders
Psychotic disorder
|
0.93%
1/108 • Number of events 2 • Adverse events were collected throughout the study (up to 9 years).
|
|
Psychiatric disorders
Somnambulism
|
0.93%
1/108 • Number of events 2 • Adverse events were collected throughout the study (up to 9 years).
|
|
Psychiatric disorders
Suicide attempt
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
|
Social circumstances
Pregnancy of partner
|
0.93%
1/108 • Number of events 1 • Adverse events were collected throughout the study (up to 9 years).
|
Other adverse events
| Measure |
Brivaracetam (SS)
n=108 participants at risk
This arm consisted of subjects who received Brivaracetam (BRV) at flexible dosing up to 200 mg/day.
|
|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
11.1%
12/108 • Number of events 16 • Adverse events were collected throughout the study (up to 9 years).
|
|
Gastrointestinal disorders
Abdominal pain
|
8.3%
9/108 • Number of events 12 • Adverse events were collected throughout the study (up to 9 years).
|
|
Gastrointestinal disorders
Nausea
|
8.3%
9/108 • Number of events 11 • Adverse events were collected throughout the study (up to 9 years).
|
|
Gastrointestinal disorders
Toothache
|
6.5%
7/108 • Number of events 10 • Adverse events were collected throughout the study (up to 9 years).
|
|
Gastrointestinal disorders
Vomiting
|
5.6%
6/108 • Number of events 9 • Adverse events were collected throughout the study (up to 9 years).
|
|
General disorders
Fatigue
|
15.7%
17/108 • Number of events 19 • Adverse events were collected throughout the study (up to 9 years).
|
|
General disorders
Chest pain
|
8.3%
9/108 • Number of events 10 • Adverse events were collected throughout the study (up to 9 years).
|
|
General disorders
Oedema peripheral
|
5.6%
6/108 • Number of events 7 • Adverse events were collected throughout the study (up to 9 years).
|
|
Infections and infestations
Nasopharyngitis
|
17.6%
19/108 • Number of events 42 • Adverse events were collected throughout the study (up to 9 years).
|
|
Infections and infestations
Bronchitis
|
7.4%
8/108 • Number of events 13 • Adverse events were collected throughout the study (up to 9 years).
|
|
Infections and infestations
Upper respiratory tract infection
|
7.4%
8/108 • Number of events 11 • Adverse events were collected throughout the study (up to 9 years).
|
|
Infections and infestations
Viral infection
|
5.6%
6/108 • Number of events 8 • Adverse events were collected throughout the study (up to 9 years).
|
|
Injury, poisoning and procedural complications
Fall
|
13.9%
15/108 • Number of events 19 • Adverse events were collected throughout the study (up to 9 years).
|
|
Injury, poisoning and procedural complications
Contusion
|
8.3%
9/108 • Number of events 11 • Adverse events were collected throughout the study (up to 9 years).
|
|
Investigations
Weight increased
|
5.6%
6/108 • Number of events 6 • Adverse events were collected throughout the study (up to 9 years).
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
11.1%
12/108 • Number of events 12 • Adverse events were collected throughout the study (up to 9 years).
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
9.3%
10/108 • Number of events 16 • Adverse events were collected throughout the study (up to 9 years).
|
|
Nervous system disorders
Convulsion
|
15.7%
17/108 • Number of events 28 • Adverse events were collected throughout the study (up to 9 years).
|
|
Nervous system disorders
Headache
|
13.9%
15/108 • Number of events 20 • Adverse events were collected throughout the study (up to 9 years).
|
|
Nervous system disorders
Dizziness
|
13.0%
14/108 • Number of events 18 • Adverse events were collected throughout the study (up to 9 years).
|
|
Nervous system disorders
Migraine
|
6.5%
7/108 • Number of events 11 • Adverse events were collected throughout the study (up to 9 years).
|
|
Nervous system disorders
Paraesthesia
|
5.6%
6/108 • Number of events 6 • Adverse events were collected throughout the study (up to 9 years).
|
|
Nervous system disorders
Tremor
|
5.6%
6/108 • Number of events 7 • Adverse events were collected throughout the study (up to 9 years).
|
|
Psychiatric disorders
Depression
|
16.7%
18/108 • Number of events 21 • Adverse events were collected throughout the study (up to 9 years).
|
|
Psychiatric disorders
Anxiety
|
13.9%
15/108 • Number of events 24 • Adverse events were collected throughout the study (up to 9 years).
|
|
Psychiatric disorders
Insomnia
|
13.9%
15/108 • Number of events 16 • Adverse events were collected throughout the study (up to 9 years).
|
|
Psychiatric disorders
Suicidal ideation
|
5.6%
6/108 • Number of events 7 • Adverse events were collected throughout the study (up to 9 years).
|
|
Skin and subcutaneous tissue disorders
Rash
|
12.0%
13/108 • Number of events 16 • Adverse events were collected throughout the study (up to 9 years).
|
|
Vascular disorders
Hypertension
|
5.6%
6/108 • Number of events 8 • Adverse events were collected throughout the study (up to 9 years).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60