Comparison of Brivaracetam Oral Tablet (10 mg, 50 mg, 75 mg and 100 mg) and Brivaracetam Injection (100 mg) in Healthy Volunteers

Study Overview
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Brief Summary
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To investigate the bioavailability/bioequivalence of Brivaracetam oral tablets (10 mg, 50 mg, 75 mg and 100 mg) and Brivaracetam intravenous injection (100 mg) in healthy volunteers.

Official Title
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A Randomized, Single-center, Open-label, 5-way Crossover, Single-dose Bioavailability/Bioequivalence Comparison of Brivaracetam Oral Tablets (10 mg, 50 mg,75 mg, and 100 mg) and Brivaracetam Intravenous Bolus Injection (100 mg) in Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Other: Brivaracetam 10 mg oral tablet
* Other: Brivaracetam 50 mg oral tablet
* Other: Brivaracetam 75 mg oral tablet
* Other: Brivaracetam 100 mg oral tablet
* Other: 10 mL of Brivaracetam intravenous bolus injection (10 mg/mL)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is a healthy male or female volunteer aged 18-55 years inclusive Subject has a Body Mass Index (BMI) of 18.0 - 30.0 kg/m^2 and a weight of at least 50 kg (males) or 45 kg (females) Subject has normal vital signs values, Electrocardiograms (ECGs) and clinical laboratory values Female subjects should have a negative pregnancy test or be of non-childbearing potential Exclusion Criteria: Volunteer has participated or is participating in any other clinical studies of investigational drug or another Investigational Medicinal Product (IMP) within the last 3 months Volunteer is not healthy (eg, taking any drug treatments, excessive amount of alcohol, cigarettes or caffeine, having any medical or emotional/psychological problems, a drug/alcohol abuse, having abnormal safety parameters) Subject has an intolerance or allergy against the compound or related drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Brivaracetam 10 mg oral tablet<br>Subjects check into the clinic the afternoon prior to the day of Brivaracetam (BRV) administration. The next day, a single dose of BRV 10 mg oral tablet will be administered in the morning. Following BRV administration, subjects will be observed for up to 48 hours. A Wash-Out Period of at least 7 days will separate the subsequent drug administrations. Strength: 10 mg Form: Oral tablet Frequency: Once daily Duration: 1 day | Other: Brivaracetam 10 mg oral tablet<br> <br> |
| Other: Brivaracetam 50 mg oral tablet<br>Subjects check into the clinic the afternoon prior to the day of Brivaracetam (BRV) administration. The next day, a single dose of BRV 50 mg oral tablet will be administered in the morning. Following BRV administration, subjects will be observed for up to 48 hours. A Wash-Out Period of at least 7 days will separate the subsequent drug administrations. Strength: 50 mg Form: Oral tablet Frequency: Once daily Duration: 1 day | Other: Brivaracetam 50 mg oral tablet<br> <br> |
| Other: Brivaracetam 75 mg oral tablet<br>Subjects check into the clinic the afternoon prior to the day of Brivaracetam (BRV) administration. The next day, a single dose of BRV 75 mg oral tablet will be administered in the morning. Following BRV administration, subjects will be observed for up to 48 hours. A Wash-Out Period of at least 7 days will separate the subsequent drug administrations. Strength: 75 mg Form: Oral tablet Frequency: Once daily Duration: 1 day | Other: Brivaracetam 75 mg oral tablet<br> <br> |
| Other: Brivaracetam 100 mg oral tablet<br>Subjects check into the clinic the afternoon prior to the day of Brivaracetam (BRV) administration. The next day, a single dose of BRV 100 mg oral tablet will be administered in the morning. Following BRV administration, subjects will be observed for up to 48 hours. A Wash-Out Period of at least 7 days will separate the subsequent drug administrations. Strength: 100 mg Form: Oral tablet Frequency: Once daily Duration: 1 day | Other: Brivaracetam 100 mg oral tablet<br> <br> |
| Other: 10 mL of Brivaracetam intravenous bolus injection (10 mg/mL)<br>Subjects check into the clinic the afternoon prior to the day of Brivaracetam (BRV) administration. The next day, a single dose of 10 mL of BRV intravenous bolus injection (10 mg/mL) will be administered in the morning. Following BRV administration, subjects will be observed for up to 48 hours. A Wash-Out Period of at least 7 days will separate the subsequent drug administrations. Strength: 100 mg (10 mg/mL) Form: Intravenous bolus injection Frequency: Once daily Duration: 1 day | Other: 10 mL of Brivaracetam intravenous bolus injection (10 mg/mL)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration of Brivaracetam dose-normalized to the 50 mg reference treatment (Cmax) |  | Pharmacokinetic samples will be taken predose and 5 min, 15 min, 30 min, 1 h, 1.5 h, 2 h, 3 h, 6 h, 9 h, 12 h, 24 h, 36 h, and 48 h post dose | 
| Area under the plasma concentration-time curve from zero to the time of the last measured concentration above the limit of quantification dose-normalized to the 50 mg reference treatment (AUC[0-t]) |  | Pharmacokinetic samples will be taken predose and 5 min, 15 min, 30 min, 1 h, 1.5 h, 2 h, 3 h, 6 h, 9 h, 12 h, 24 h, 36 h, and 48 h post dose | 
| Area under the plasma concentration-time curve from zero to infinity dose-normalized to the 50 mg reference treatment (AUC) |  | Pharmacokinetic samples will be taken predose and 5 min, 15 min, 30 min, 1 h, 1.5 h, 2 h, 3 h, 6 h, 9 h, 12 h, 24 h, 36 h, and 48 h post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma half-life of Brivaracetam |  | Pharmacokinetic samples will be taken predose and 5 min, 15 min, 30 min, 1 h, 1.5 h, 2 h, 3 h, 6 h, 9 h, 12 h, 24 h, 36 h, and 48 h post dose | 
| Time to reach the maximum plasma concentration of Brivaracetam (tmax) |  | Pharmacokinetic samples will be taken predose and 5 min, 15 min, 30 min, 1 h, 1.5 h, 2 h, 3 h, 6 h, 9 h, 12 h, 24 h, 36 h, and 48 h post dose | 
| Apparent oral clearance of Brivaracetam (CL/F) |  | Pharmacokinetic samples will be taken predose and 5 min, 15 min, 30 min, 1 h, 1.5 h, 2 h, 3 h, 6 h, 9 h, 12 h, 24 h, 36 h, and 48 h post dose | 
| Apparent volume of Brivaracetam distribution at the terminal elimination phase |  | Pharmacokinetic samples will be taken predose and 5 min, 15 min, 30 min, 1 h, 1.5 h, 2 h, 3 h, 6 h, 9 h, 12 h, 24 h, 36 h, and 48 h post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Volunteers, Brivaracetam