Epilepsy
Conditions
Keywords
N01258, Brivaracetam, Epilepsy, IV, intravenous
Brief summary
This is a multicenter, open-label, 4-arm, randomized, parallel-group study to evaluate safety and tolerability of Brivaracetam Intravenous (BRV iv) as adjunctive treatment for adults with epilepsy according to an initiation or a conversion scheme, during repeated dosing (100 mg/administration twice daily for 4.5 days).
Detailed description
Eligible subjects will be randomized in a 1:1:1:1 ratio to the 4 treatment arms
Interventions
DRUGBrivaracetam tablets
100 mg, intake twice daily (BID) for 7 days during Run-In Period
DRUGBrivaracetam bolus
10 mL (= 100 mg) of Brivaracetam administered intravenously over 2 minutes twice daily (BID) during Evaluation Period
DRUGBrivaracetam infusion
10 mL (= 100 mg) of Brivaracetam diluted in 90 mL 0.9 % isotonic saline sterile solution for intravenous administration infused over 15 minutes twice daily (BID) during Evaluation Period
OTHERPlacebo
100 mg twice daily (BID) for 7 days during Run-In Period
Sponsors
UCB Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* An Institutional Review Board/Independent Ethics Committee (IRB/IEC) approved written Informed Consent form signed and dated by the subject or by parent(s) or legal representative * Subjects from 16 to 70 years * Subjects with a body weight of \>/= 40 kg * Female subjects without childbearing potential or female subjects with childbearing potential if they use a medically accepted contraceptive method * Subject/legal representative considered as reliable and capable of adhering to the protocol * Subjects with well-characterized focal or generalized epilepsy or epileptic syndrome * Subjects with a history of partial-onset seizures whether or not secondarily generalized or primary generalized seizures * Subjects being uncontrolled while treated with 1 to 2 permitted concomitant antiepileptic drugs (AEDs) * Permitted concomitant antiepileptic drugs (AEDs) and vagus nerve stimulation (VNS) being stable and at optimal dosage for the subject from at least 1 month before Visit 1 and expected to be kept stable during the Run-In and Evaluation Periods
Exclusion criteria
* Mentally impaired subjects unable to understand the study purpose * History or presence of status epilepticus during 1 year preceding Visit 1 or Baseline * Subjects on felbamate with less than 18 months continuous exposure before Visit 1 * Subjects currently on vigabatrin * Subject taking any drug with possible relevant central nervous system effects except is stable from at least 1 month before Visit 1 and expected to be kept stable during the trial * Subjects taking any drug that may significantly influence the metabolism of Brivaracetam (BRV) except if the dose has been kept stable at least 1 month before Visit 1, and is expected to be kept stable during the trial * History of cerebrovascular accident in the last 6 months * Subjects suffering from severe cardiovascular disease or peripheral vascular disease * Presence of any sign suggesting rapidly progressing brain disorder or brain tumor * Any clinical conditions which impair reliable participation in the study or necessitate the use of medication not allowed by protocol * Presence of a terminal illness * Presence of a serious infection * Subjects with a history of sever adverse hematologic reaction to any drug * Subjects suffering from severe disturbance of hemostasis * Impaired hepatic function: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT) values of more than 3 times the upper limit of the reference range * Subjects having clinically significant deviations from reference range values for laboratory parameters: creatinine clearance calculated \< 50 ml / min, platelets \< 100,000 / µL, or neutrophil cells \< 1,800 / µL * Clinically significant electrocardiogram (ECG) abnormalities according to the Investigator * History of suicide attempt * In the Investigator's medical judgment, any current suicidal ideation or other serious psychiatric disorders requiring of having required hospitalization or medication * Known allergic reaction or intolerance to pyrrolidone derivatives and / or investigational product excipients * Known multiple drug allergies or severe drug allergy * Pregnant or lactating women * Known alcohol or drug addiction or abuse within the last 2 years * Subject institutionalized under judicial decision * Problems of venous accessibility * Subject taking part in another clinical / pharmacological study in the month preceding enrollment (Visit 1) * Investigators, coinvestigators, their spouses or children, or any study collaborators * Subjects previously treated with Brivaracetam (BRV) * Subject previously screened within this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With at Least One Treatment-emergent Adverse Event During the Study (Maximum 40 Days) | 40 days | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Who Withdrew Due to a Treatment-emergent Adverse Event During the Study (Maximum 40 Days) | 40 days | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. |
| Number of Subjects With at Least One Injection-related Treatment-emergent Adverse Event (TEAE) During the Evaluation Period. | 4.5-day Evaluation Period | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. |
Countries
Czechia, Germany, Poland, United States
Participant flow
Recruitment details
This study started to recruit patients in August 2011 and concluded in July 2012. 105 subjects were randomized to 4 different treatment groups.
Pre-assignment details
Participant Flow refers to the Randomized Set (RS).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Tablets / Brivaracetam Bolus Subjects will receive Placebo (PBO) tablets for one week followed by Brivaracetam (BRV) bolus for 4.5 days.
Down-Titration:
* If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In
* If subject discontinues during the Evaluation Period or after Day 12, the subject will receive Placebo tablets during Down-Titration:
Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week | 26 |
| Placebo Tablets / Brivaracetam Infusion Subjects will receive Placebo (PBO) tablets for one week followed by Brivaracetam (BRV) intravenous infusion for 4.5 days.
Down-Titration:
* If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In
* If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration:
Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week | 26 |
| Brivaracetam (BRV) Tablets / BRV Bolus Subjects will receive Brivaracetam (BRV) tablets for one week followed by BRV bolus for 4.5 days.
Down-Titration:
* If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In
* If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration:
Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake bid for the fourth week | 27 |
| Brivaracetam (BRV) Tablets / BRV Infusion Subjects will receive Brivaracetam (BRV) tablets for one week followed by Brivaracetam intravenous infusion for 4.5 days.
Down-Titration:
* If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In
* If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration:
Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week | 26 |
| Total Title | 105 |
| Total | 210 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | AE, non-serious non-fatal | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo Tablets / Brivaracetam Bolus | Placebo Tablets / Brivaracetam Infusion | Brivaracetam (BRV) Tablets / BRV Bolus | Brivaracetam (BRV) Tablets / BRV Infusion | Total Title |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants | 25 Participants | 27 Participants | 25 Participants | 103 Participants |
| Age, Continuous | 40.6 years STANDARD_DEVIATION 12.2 | 39.5 years STANDARD_DEVIATION 14.4 | 42.0 years STANDARD_DEVIATION 9.2 | 44.4 years STANDARD_DEVIATION 12.6 | 41.6 years STANDARD_DEVIATION 12.2 |
| Sex: Female, Male Female | 12 Participants | 10 Participants | 17 Participants | 17 Participants | 56 Participants |
| Sex: Female, Male Male | 14 Participants | 16 Participants | 10 Participants | 9 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 17 / 26 | 15 / 26 | 15 / 27 | 14 / 26 |
| serious Total, serious adverse events | 0 / 26 | 0 / 26 | 0 / 27 | 0 / 26 |
Outcome results
Primary
Number of Subjects With at Least One Treatment-emergent Adverse Event During the Study (Maximum 40 Days)
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time frame: 40 days
Population: Safety Population consisting of all subjects who took at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Tablets / Brivaracetam Bolus | Number of Subjects With at Least One Treatment-emergent Adverse Event During the Study (Maximum 40 Days) | 20 Participants |
| Placebo Tablets / Brivaracetam Infusion | Number of Subjects With at Least One Treatment-emergent Adverse Event During the Study (Maximum 40 Days) | 19 Participants |
| Brivaracetam (BRV) Tablets / BRV Bolus | Number of Subjects With at Least One Treatment-emergent Adverse Event During the Study (Maximum 40 Days) | 21 Participants |
| Brivaracetam (BRV) Tablets / BRV Infusion | Number of Subjects With at Least One Treatment-emergent Adverse Event During the Study (Maximum 40 Days) | 20 Participants |
Secondary
Number of Subjects Who Withdrew Due to a Treatment-emergent Adverse Event During the Study (Maximum 40 Days)
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time frame: 40 days
Population: Safety Population consisting of all subjects who took at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Tablets / Brivaracetam Bolus | Number of Subjects Who Withdrew Due to a Treatment-emergent Adverse Event During the Study (Maximum 40 Days) | 1 Participants |
| Placebo Tablets / Brivaracetam Infusion | Number of Subjects Who Withdrew Due to a Treatment-emergent Adverse Event During the Study (Maximum 40 Days) | 1 Participants |
| Brivaracetam (BRV) Tablets / BRV Bolus | Number of Subjects Who Withdrew Due to a Treatment-emergent Adverse Event During the Study (Maximum 40 Days) | 0 Participants |
| Brivaracetam (BRV) Tablets / BRV Infusion | Number of Subjects Who Withdrew Due to a Treatment-emergent Adverse Event During the Study (Maximum 40 Days) | 0 Participants |
Secondary
Number of Subjects With at Least One Injection-related Treatment-emergent Adverse Event (TEAE) During the Evaluation Period.
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time frame: 4.5-day Evaluation Period
Population: Safety Population consisting of all subjects who took at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Tablets / Brivaracetam Bolus | Number of Subjects With at Least One Injection-related Treatment-emergent Adverse Event (TEAE) During the Evaluation Period. | 1 Participants |
| Placebo Tablets / Brivaracetam Infusion | Number of Subjects With at Least One Injection-related Treatment-emergent Adverse Event (TEAE) During the Evaluation Period. | 3 Participants |
| Brivaracetam (BRV) Tablets / BRV Bolus | Number of Subjects With at Least One Injection-related Treatment-emergent Adverse Event (TEAE) During the Evaluation Period. | 4 Participants |
| Brivaracetam (BRV) Tablets / BRV Infusion | Number of Subjects With at Least One Injection-related Treatment-emergent Adverse Event (TEAE) During the Evaluation Period. | 3 Participants |