A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, THREE-WAY CROSSOVER STUDY TO INVESTIGATE THE DRUG-DRUG INTERACTIONS OF BRIVARACETAM AND ETHANOL IN HEALTHY MALE SUBJECTS
- Conditions
- epilepsy / seizures10039911
- Registration Number
- NL-OMON37186
- Lead Sponsor
- CB Pharma
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 18
1. Subject understands and has signed and dated an Independent Ethics Committee (IEC) approved written Informed Consent form.
2. Subject is able to communicate well with the Investigator in the local language, and to understand and comply with the requirements of the study.
3. Subject is considered reliable and capable of adhering to the protocol according to the judgment of the Investigator.
4. Subject is male and between 18 to 55 years of age, inclusive, at Screening.
5. Subject has a body mass index (BMI) of 18 to 30kg/m2, inclusive, at Screening.
6. Subject has blood pressure and PR within normal range in a supine position after 5 minutes rest, measured on the dominant arm at Screening:
a. SBP: 100 mmHg to 145mmHg, inclusive
b. DBP: 50mmHg to 90mmHg, inclusive
c. PR: 45bpm to 90bpm, inclusive.
7. Subject*s 12-lead electrocardiogram (ECG) is free of any clinically relevant abnormal ECG findings according to the Investigator at Screening.
8. Subject is in good physical and mental health, in the opinion of the Investigator, determined on the basis of medical history and a general clinical examination at Screening.
9. Subject has normal renal and hepatic function as assessed by clinical laboratory test results (clinical chemistry, hematology, and urinalysis) within the reference ranges of the laboratory at Screening. Subjects with test results that are outside the specified ranges and that are
deemed as not clinically significant will be allowed at the discretion of the Investigator.
10. Subject has adequate venous access.
11. Subject agrees that, during the study period and for a period of 3 months after dosing with BRV, when having sexual intercourse (for males - with a woman of childbearing potential), a highly effective contraceptive barrier (condom+spermicide) will be used, AND that the respective partner will use an additional highly effective contraceptive method:
a. Diaphragm or cervical cap with spermicide, or
b. Intrauterine device, or
c. Stable oral, transdermal, injectable, or sustained-release vaginal hormonal contraceptive
1. Subject has previously participated in this study or has previously been assigned to treatment in a study of the investigational medicinal product (IMP) under investigation in this study.
2. Subject has participated in another study of an IMP (or a medical device) within the previous 3 months prior to Screening or has participated in more than 4 IMP (or medical device) studies within 1 year prior to Screening.
3. Subject has received treatment with any prescribed or over-the-counter medications (including herbal medicines such as St John*s Wort) within 7 days or 5 half-lives (whichever is longer) prior to Screening. Note: Use of paracetamol within this period prior to Screening may be acceptable, subject to approval by the Investigator.
4. Subject has a known hypersensitivity to any components of the IMP as stated in this protocol.
5. Subject has a history or presence of drug or alcohol abuse.
6. Subject has history of an average alcohol consumption of more than 21 units of alcohol per week or an average daily intake of greater than 3 units, within 6 months of the study. One unit is equivalent to a half-pint (220mL) of beer or 1 measure (25mL) of spirits or 1 glass (125mL) of wine.
7. Subject tests positive for alcohol (breath test) and/or drugs (urine test) at Screening.
8. Subject has ethanol intolerance.
9. Subject has an average caffeine consumption of more than 800mg of caffeine per day (1 cup of coffee contains approximately 100mg of caffeine, 1 cup of tea approximately 30mg, and 1 glass of cola approximately 20mg).
10. Subject has history of smoking within 3 months prior to Screening or is not able to refrain from smoking during the course of the study.
11. Subject has consumed any grapefruit, grapefruit juice, grapefruit-containing products, or star fruit within 14 days prior to dosing or is not able to refrain from these products during the course of the study.
12. Subject has not been vaccinated for hepatitis and tests positive for hepatitis at Screening.
13. Subject tests positive for Human Immunodeficiency Virus (HIV) at Screening.
14. Subject has had significant blood loss (500mL) within 3 months prior to Screening.
15. Subject has history or clinical evidence of any disease and/or existence of any surgical or medical condition that, in the opinion of the Investigator, might interfere with the absorption, distribution, metabolism, or excretion of BRV or ethanol.
16. Subject has a lifetime history of suicide attempt (including an actual attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response (*Yes*) to either Question 4 or 5 of the Columbia Suicide Severity Rating Scale (C-SSRS) at Screening.
17. Subject is an employee of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, or subject is a first line family member of an employee working in the respective study center or of the Investigator.
18. Any circumstances or conditions of the subject, which, in the opinion of the Investigator, may affect full participation in the study or compliance with the study.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>PD variables<br /><br>• Saccadic eye movements to assess sedation<br /><br>• Smooth pursuit eye movements to assess attention and eye movement coordination<br /><br>• Adaptive tracking to assess visuo-motor control and attention</p><br>
- Secondary Outcome Measures
Name Time Method <p>PK variables<br /><br><br /><br>BRV<br /><br>The area under the plasma concentration-time curve, maximum concentration, and<br /><br>the terminal half-life, amongst others<br /><br><br /><br>Ethanol<br /><br>Serum ethanol concentrations, Breath ethanol concentrations (BrEC), Total<br /><br>ethanol dose used, etc..<br /><br><br /><br>Safety variables<br /><br>Incidence and severity of adverse events, Vital signs, and Clinical laboratory<br /><br>test results</p><br>