Epilepsy
Conditions
Keywords
Brivaracetam, Epilepsy, Partial Onset Seizures, open label
Brief summary
This trial, evaluating the long-term safety and tolerability of brivaracetam will provide subjects suffering from epilepsy, who may have benefited from brivaracetam as adjunctive treatment, the opportunity to receive open label brivaracetam treatment.
Detailed description
Study access was limited to subjects having completed one of the previous brivaracetam (BRV) studies: N01193 \[NCT00175825\], N01252 \[NCT00490035\], N01253 \[NCT00464269\], N01254 \[NCT00504881\].
Interventions
DRUGBrivaracetam
* Active Substance: Brivaracetam * Pharmaceutical Form: Tablet * Concentration: 10 mg and 25 mg * Route of Administration: Oral
Sponsors
UCB PHARMA Inc. (US)
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 and on. Subjects under 18 years may only be included where legally permitted and ethically accepted * Subjects with epilepsy who have participated in previous brivaracetam trials 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 * Female subjects without childbearing potential. Female subjects with child bearing potential are eligible if they use a medically accepted contraceptive method for the duration of the study * Subject/ legally acceptable representative considered as reliable and capable of adhering to the protocol, visit schedule or medication intake according to the judgment of the Investigator
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 the visit schedule or medication intake in the previous brivaracetam study * Pregnant or lactating women * Participation in any clinical study of another investigational drug or device during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) During the Study Period | Visit 1 through last Evaluation Period, Down-Titration, or Post-Treatment Periods (up to 11 years) | Treatment-Emergent Adverse Events (TEAEs) are any untoward medical incidence in a subject during administered study treatment, whether or not these events are related to study treatment. |
| Percentage of Participants Who Withdrew Due to an Adverse Event (AE) During the Study Period | Visit 1 through last Evaluation Period, Down-Titration, or Post-Treatment Periods (up to 11 years) | Adverse Events (AE) are any untoward medical incidence in a subject during administered study treatment, whether or not these events are related to study treatment. |
| Percentage of Participants With a Serious Adverse Event (SAE) During the Study Period | Visit 1 through last Evaluation Period, Down-Titration, or Post-Treatment Periods (up to 11 years) | A Serious Adverse Event (SAE) is any untoward medical incidence that occurs at any dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Partial Onset Seizure (POS) (Type I) Frequency Per 28 Days During the Evaluation Period | From Baseline of the previous study to the Evaluation Period (up to 11 years) | Baseline is the Baseline from subject's previous study of enrollment period. N01193 \[NCT00175825\], N01252 \[NCT00490035\], N01253 \[NCT00464269\], N01254 \[NCT00504881\]. A 28 day Type 1 seizure frequency is the total number of Type 1 seizures divided by the total number of days evaluated multiplied by 28. |
| Percent Change in Partial Onset Seizure (POS) (Type I) Frequency Per 28 Days From Baseline of the Previous Study to the Evaluation Period | From Baseline of the previous study to the Evaluation Period (up to 11 years) | 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. |
| Percentage of Participants With Response for Partial Onset Seizure (POS) (Type I) Frequency Over the Evaluation Period | From Baseline of the previous study to the Evaluation Period (up to 11 years) | A responder is defined as a subject with a higher than or equal to (\>=) 50 % change in seizure frequency from Baseline period of the previous study. |
Countries
Australia, Brazil, Canada, India, Mexico, United States
Participant flow
Recruitment details
The study started to enroll patients in January 2006 and concluded in September 2017. 668 subjects were included in the Enrolled Set but 1 subject from India lost to follow up and was excluded from the Safety Analysis Set due to lack of medical data.
Pre-assignment details
The Participant Flow refers to the Safety Analysis Set which included all subjects who took at least 1 dose of study drug.
Participants by arm
| Arm | Count |
|---|---|
| Brivaracetam Brivaracetam (BRV) used as adjunctive treatment, flexible dosing up to 200 mg /day in b.i.d (twice daily) administration. Dose increase or decrease can be made in increments of maximum 50 mg /day on a weekly basis. | 667 |
| Total | 667 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 89 |
| Overall Study | BRV monotherapy | 1 |
| Overall Study | Death | 18 |
| Overall Study | Distance too long for patient | 1 |
| Overall Study | Generalized Epilepsy | 1 |
| Overall Study | IP misshandling | 1 |
| Overall Study | Lack of Efficacy | 166 |
| Overall Study | Lost to Follow-up | 58 |
| Overall Study | Moved from area/country | 8 |
| Overall Study | Neurosurgery | 2 |
| Overall Study | Nobody to accompany patient | 1 |
| Overall Study | No compliance | 18 |
| Overall Study | Patient insurance | 1 |
| Overall Study | PI discontinuation request | 1 |
| Overall Study | PI leaving site | 2 |
| Overall Study | PI retiring | 2 |
| Overall Study | Pregnancy planned | 1 |
| Overall Study | Protocol non-adherence | 2 |
| Overall Study | Site closure | 24 |
| Overall Study | Sponsor's request | 2 |
| Overall Study | Subject's choice | 90 |
| Overall Study | Surgical intervention | 4 |
| Overall Study | Visit refusal | 3 |
Baseline characteristics
| Characteristic | Brivaracetam |
|---|---|
| Age, Categorical <=18 years | 30 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 632 Participants |
| Age, Continuous | 34.3 years STANDARD_DEVIATION 12.2 |
| Race/Ethnicity, Customized American Indian/Alaskan Native | 21 Participants |
| Race/Ethnicity, Customized Asian | 206 Participants |
| Race/Ethnicity, Customized Black | 18 Participants |
| Race/Ethnicity, Customized Native Hawaiian Or Other Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Other/Mixed | 60 Participants |
| Race/Ethnicity, Customized White | 361 Participants |
| Sex: Female, Male Female | 303 Participants |
| Sex: Female, Male Male | 364 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 18 / 667 |
| other Total, other adverse events | 521 / 667 |
| serious Total, serious adverse events | 152 / 667 |
Outcome results
Primary
Percentage of Participants Who Withdrew Due to an Adverse Event (AE) During the Study Period
Adverse Events (AE) are any untoward medical incidence in a subject during administered study treatment, whether or not these events are related to study treatment.
Time frame: Visit 1 through last Evaluation Period, Down-Titration, or Post-Treatment Periods (up to 11 years)
Population: The Safety Analysis Set consisted of all subjects who took at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brivaracetam (SS) | Percentage of Participants Who Withdrew Due to an Adverse Event (AE) During the Study Period | 14.8 percentage of participants |
Primary
Percentage of Participants With a Serious Adverse Event (SAE) During the Study Period
A Serious Adverse Event (SAE) is any untoward medical incidence that occurs at any dose.
Time frame: Visit 1 through last Evaluation Period, Down-Titration, or Post-Treatment Periods (up to 11 years)
Population: The Safety Analysis Set consisted of all subjects who took at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brivaracetam (SS) | Percentage of Participants With a Serious Adverse Event (SAE) During the Study Period | 22.8 percentage of participants |
Primary
Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) During the Study Period
Treatment-Emergent Adverse Events (TEAEs) are any untoward medical incidence in a subject during administered study treatment, whether or not these events are related to study treatment.
Time frame: Visit 1 through last Evaluation Period, Down-Titration, or Post-Treatment Periods (up to 11 years)
Population: The Safety Analysis Set consisted of all subjects who took at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brivaracetam (SS) | Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) During the Study Period | 91.2 percentage of participants |
Secondary
Partial Onset Seizure (POS) (Type I) Frequency Per 28 Days During the Evaluation Period
Baseline is the Baseline from subject's previous study of enrollment period. N01193 \[NCT00175825\], N01252 \[NCT00490035\], N01253 \[NCT00464269\], N01254 \[NCT00504881\]. A 28 day Type 1 seizure frequency is the total number of Type 1 seizures divided by the total number of days evaluated multiplied by 28.
Time frame: From Baseline of the previous study to the Evaluation Period (up to 11 years)
Population: The Partial Onset Seizure (POS) Efficacy Analysis Set consisted of all subjects with POS who took at least 1 dose of study drug and had at least 1 seizure diary day during the Evaluation Period.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Brivaracetam (SS) | Partial Onset Seizure (POS) (Type I) Frequency Per 28 Days During the Evaluation Period | baseline | 9.2 Seizures per 28 days |
| Brivaracetam (SS) | Partial Onset Seizure (POS) (Type I) Frequency Per 28 Days During the Evaluation Period | on treatment | 4.2 Seizures per 28 days |
Secondary
Percentage of Participants With Response for Partial Onset Seizure (POS) (Type I) Frequency Over the Evaluation Period
A responder is defined as a subject with a higher than or equal to (\>=) 50 % change in seizure frequency from Baseline period of the previous study.
Time frame: From Baseline of the previous study to the Evaluation Period (up to 11 years)
Population: The Partial Onset Seizures (POS) Efficacy Analysis Set consisted of all subjects with POS who took at least 1 dose of study drug and had at least 1 seizure diary day during the Evaluation Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brivaracetam (SS) | Percentage of Participants With Response for Partial Onset Seizure (POS) (Type I) Frequency Over the Evaluation Period | 55.6 percentage of participants |
Secondary
Percent Change in Partial Onset Seizure (POS) (Type I) Frequency Per 28 Days From Baseline of the Previous Study to the Evaluation Period
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.
Time frame: From Baseline of the previous study to the Evaluation Period (up to 11 years)
Population: The Partial Onset Seizures (POS) Efficacy Analysis Set consisted of all subjects with POS who took at least 1 dose of study drug and had at least 1 seizure diary day during the Evaluation Period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brivaracetam (SS) | Percent Change in Partial Onset Seizure (POS) (Type I) Frequency Per 28 Days From Baseline of the Previous Study to the Evaluation Period | 57.3 percent change |