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A Study of the Abuse Liability Potential of Cenobamate in Recreational Drug Users

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ClinicalTrials.gov Identifier: NCT03509285
Recruitment Status : Completed
First Posted : April 26, 2018
Last Update Posted : May 2, 2018
Sponsor:
Information provided by (Responsible Party):
SK Life Science, Inc.

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.


Condition or disease Intervention/treatment Phase
Healthy Volunteer Drug: Alprazolam Placebo Drug: Cenobamate placebo Drug: Alprazolam Drug: Cenobamate Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 53 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Masking Description: Double-blind
Primary Purpose: Basic Science
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
Actual Study Start Date : March 8, 2017
Actual Primary Completion Date : November 18, 2017
Actual Study Completion Date : December 15, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Drug Abuse
Drug Information available for: Alprazolam

Arm Intervention/treatment
Placebo Comparator: Qualification Y
Placebo; administered orally as a single dose of 2 x 100 mg lactose tablets, over-encapsulated (alprazolam placebo)
Drug: Alprazolam Placebo
100 mg lactose tablets

Active Comparator: Qualification Z
Alprazolam 2.0 mg; administered orally as a single dose of 2 x 1.0 mg alprazolam tablets, over-encapsulated
Drug: Alprazolam
0.5 mg and 1.0 mg alprazolam tablets

Placebo Comparator: Treatment A
Placebo; administered orally as a single dose of 4 x cenobamate-matched placebo tablets and 3 x 100 mg lactose tablets, over-encapsulated (alprazolam placebo)
Drug: Alprazolam Placebo
100 mg lactose tablets

Drug: Cenobamate placebo
Sugar pill manufactured to mimic cenobamate 100 mg tablet

Active Comparator: Treatment B
Alprazolam 1.5 mg; administered orally as a single dose of 3 x 0.5 mg alprazolam tablets, over-encapsulated and 4 x cenobamate-matched placebo tablets
Drug: Cenobamate placebo
Sugar pill manufactured to mimic cenobamate 100 mg tablet

Drug: Alprazolam
0.5 mg and 1.0 mg alprazolam tablets

Active Comparator: Treatment C
Alprazolam 3.0 mg; administered orally as a single dose of 3 x 1.0 mg alprazolam tablets, over-encapsulated and 4 x cenobamate-matched placebo tablets
Drug: Cenobamate placebo
Sugar pill manufactured to mimic cenobamate 100 mg tablet

Drug: Alprazolam
0.5 mg and 1.0 mg alprazolam tablets

Experimental: Treatment D
Cenobamate, 200 mg; administered orally as a single dose of 2 x 100 mg cenobamate tablets, 2 x cenobamate-matched placebo tablets, and 3 x 100 mg lactose tablets, over-encapsulated (alprazolam placebo)
Drug: Alprazolam Placebo
100 mg lactose tablets

Drug: Cenobamate placebo
Sugar pill manufactured to mimic cenobamate 100 mg tablet

Drug: Cenobamate
100 mg tablet

Experimental: Treatment E
Cenobamate, 400 mg; administered orally as a single dose of 4 x 100 mg cenobamate tablets and 3 x 100 mg lactose tablets, over-encapsulated (alprazolam placebo)
Drug: Alprazolam Placebo
100 mg lactose tablets

Drug: Cenobamate
100 mg tablet




Primary Outcome Measures :
  1. Pharmacodynamics using Visual Analogue Scales (VAS) [ Time Frame: Measured for 24 hrs in each Treatment Period ]
    Subjective Effect of Drug Liking "at this moment" [0-100 scale, 0=Strong Disliking, 50=Neither Like nor Dislike, 100=Strong Liking]


Secondary Outcome Measures :
  1. Pharmacokinetics [ Time Frame: Measured for 24 hrs in each Treatment Period ]
    Plasma concentrations of cenobamate and alprazolam

  2. Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [ Time Frame: 21 weeks ]
    Incidence, frequency, and severity of AEs and AEs of Special Interest (which include AEs related to drug reaction with eosinophilia and systemic symptoms [DRESS] and abuse-related adverse events)

  3. Pharmacodynamics using Visual Analogue Scales (VAS) [ Time Frame: Measured at 12 hr and 24 hr timepoints in each Treatment Period ]
    Subjective Effect of Take Drug Again [0-100 scale, 0=Definitely Not, 50=Neutral, 100=Definitely So]

  4. Pharmacodynamics using Visual Analogue Scales (VAS) [ Time Frame: Measured at 12 hr and 24 hr timepoints in each Treatment Period ]
    Subjective Effect of Overall Drug Liking [0-100 scale, 0=Strong Disliking, 50=Neither Like nor Dislike, 100=Strong Liking]

  5. Pharmacodynamics using Visual Analogue Scales (VAS) [ Time Frame: Measured for 24 hrs in each Treatment Period ]
    Subjective Effect of High [0-100 scale, 0=Not at All,100=Extremely]

  6. Pharmacodynamics using Visual Analogue Scales (VAS) [ Time Frame: Measured for 24 hrs in each Treatment Period ]
    Subjective Good Drug Effects [0-100 scale, 0=Not at All,100=Extremely]



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03509285


Locations
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United States, Kansas
Vince & Associates Clinical Research, Inc
Overland Park, Kansas, United States, 66212
Canada, Ontario
INC Research, Inc.
Toronto, Ontario, Canada, M5V 2T3
Sponsors and Collaborators
SK Life Science, Inc.

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Responsible Party: SK Life Science, Inc.
ClinicalTrials.gov Identifier: NCT03509285     History of Changes
Other Study ID Numbers: YKP3089C024
First Posted: April 26, 2018    Key Record Dates
Last Update Posted: May 2, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Alprazolam
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action