Clinical trial NCT03509285: A Study of the Abuse Liability Potential of Cenobamate in Recreational Drug Users
Official title: Randomized, Double-Blind, Double-Dummy, 5-Way Crossover Study to Evaluate the Abuse Potential of Cenobamate Relative to Alprazolam and Placebo When Administered Orally in Non-Dependent, Recreational Drug Users with Sedative Experience
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: SK Life Science, Inc.
Sponsor class: INDUSTRY
First posted: 2018-04-26
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: This randomized, single-dose, placebo- and active-controlled, crossover study will evaluate the abuse liability potential of cenobamate in recreational drug users with sedative drug use experience.

In the Qualification phase, subjects will receive a single dose of either alprazolam or placebo in a crossover design, with a wash-out period of at least 24 hours between treatments. Subjects who are clearly able to distinguish the positive control from placebo will be enrolled in the Treatment phase and will be randomized to single oral doses of cenobamate (2 dose levels), alprazolam (2 dose levels), and placebo in a double-blind, double-dummy, 5-way crossover design. Washout-periods between the 5 treatment periods in the Treatment phase will be at least 16 days.


Eligibility criteria: Inclusion Criteria:

1. Healthy male or female subjects 18 to 55 years of age, inclusive.
2. Body mass index (BMI) within the range of 19.0 to 32.0 kg/m2, inclusive, and a minimum weight of 50.0 kg.
3. Current recreational drug users who have used benzodiazepines for recreational (non-therapeutic) purposes (i.e., for psychoactive effects) at least 5 times in the past year and used benzodiazepines at least once in the 12 weeks before Screening.
4. Female subjects of childbearing potential with male sexual partners must be using and willing to continue using medically acceptable contraception (as specified in Section 4.5.2) for at least 1 month prior to Screening (at least 3 months for oral and transdermal contraceptives) and for at least 30 days after the last study drug administration.
5. Female subjects of non-childbearing potential must meet the criteria specified in Section 4.5.2.
6. Male subjects with female sexual partners of childbearing potential must be using and willing to continue using medically acceptable contraception (as specified in Section 4.5.2) from Screening and for at least 30 days after the last study drug administration.
7. Able to speak, read, and understand English sufficiently to allow completion of all study assessments.
8. Must understand and provide written informed consent, prior to the initiation of any protocol-specific procedures.
9. Must be willing to comply with the requirements and restrictions of the study.

Exclusion Criteria:

1. Substance or alcohol dependence within the past 2 years, as defined by the Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition - Text Revision (DSM IV-TR), and/or has ever participated or plans to participate in a substance or alcohol rehabilitation program to treat their substance or alcohol dependence (excluding nicotine and caffeine).
2. Heavy smoker (\>20 cigarettes per day) and/or is unable to abstain from smoking or unable to abstain from the use of prohibited nicotine-containing products for at least 10 hours during the in-clinic periods (including e-cigarettes, pipes, cigars, chewing tobacco, nicotine-topical patches, nicotine gum, or nicotine lozenges).
3. History or presence of clinically significant abnormality as assessed by physical examination, medical history (including cholecystectomy), ECGs, vital signs, or laboratory values, which in the opinion of the investigator would jeopardize the safety of the subject or the validity of the study results.
4. History or presence of myasthenia gravis, severe hepatic insufficiency, severe respiratory insufficiency, sleep apnea syndrome, or acute narrow angle glaucoma.
5. Positive for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
6. Evidence of clinically significant hepatic or renal impairment including alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>1.5× the upper limit of normal (ULN), or bilirubin \>1× ULN. Repeat safety laboratory tests are allowed once for Screening, unless the principal investigator and sponsor agree to an additional repeat.
7. Donation or loss of more than 500 mL whole blood within 30 days preceding entry into the Treatment Phase.
8. Difficulty with venous access or unsuitable or unwilling to undergo catheter insertion.
9. Female subjects who are currently pregnant (have a positive pregnancy test) or lactating or who are planning to become pregnant within 30 days of last study drug administration.
10. History of severe allergic reaction (including anaphylaxis) to any substance, or previous status asthmaticus.
11. Subject history of allergy, hypersensitivity, or DRESS syndrome to any drug product including anti-convulsants (e.g., alprazolam, carbamazepine) or related drugs (e.g., other benzodiazepines) or known excipients of any of the drug products in this study. History of a first degree relative with a serious cutaneous drug-induced adverse reaction.
12. Subjects with any history of suicidal ideation or suicidal behavior, as assessed by the Columbia-Suicide Severity Rating Scale (C SSRS; baseline version).
13. Use of a prohibited medication or investigational drug, including exposure to any drugs associated with DRESS syndrome (e.g., allopurinol, minocycline, abacavir, lamotrigine) in the 6 months prior to Screening.
14. Use of a prohibited medication, as specified in Section 4.5.1.
15. Treatment with an investigational drug within 5 times the elimination half-life, if known (e.g., a marketed product), or within 30 days (if the elimination half-life is unknown) prior to the first study drug administration or is concurrently enrolled in any research judged not be scientifically or medically compatible with this study.
16. An employee of the sponsor or research site personnel directly affiliated with this study or their immediate family member defined as a spouse, parent, child or sibling, whether biological or legally adopted.
17. A subject who has pending legal charges or is on probation.
18. A subject who, in the opinion of the investigator or designee, is considered unsuitable or unlikely to comply with the study protocol for any reason.
19. Anyone who has previously been exposed to cenobamate (prior to participation in this study).

Primary outcomes:
measure: Pharmacodynamics using Visual Analogue Scales (VAS)
timeFrame: Measured for 24 hrs in each Treatment Period
Secondary outcomes:
measure: Pharmacokinetics
timeFrame: Measured for 24 hrs in each Treatment Period
measure: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
timeFrame: 21 weeks
measure: Pharmacodynamics using Visual Analogue Scales (VAS)
timeFrame: Measured at 12 hr and 24 hr timepoints in each Treatment Period
measure: Pharmacodynamics using Visual Analogue Scales (VAS)
timeFrame: Measured at 12 hr and 24 hr timepoints in each Treatment Period
measure: Pharmacodynamics using Visual Analogue Scales (VAS)
timeFrame: Measured for 24 hrs in each Treatment Period
measure: Pharmacodynamics using Visual Analogue Scales (VAS)
timeFrame: Measured for 24 hrs in each Treatment Period
Other outcomes:
Locations:
city: Overland Park
country: United States
facility: Vince & Associates Clinical Research, Inc
state: Kansas
city: Toronto
country: Canada
facility: INC Research, Inc.
state: Ontario
Study officials:
References: