Evaluating the Abuse Potential of NEURONTIN® When Taken Orally in Healthy Non-drug Dependent Participants With Sedative Drug Abuse Experience

Sponsor
Viatris Specialty LLC (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04570436
Collaborator
(none)
40
1
5
21.1
1.9

Study Details

Study Description

Brief Summary

This will be a randomized, double-blind, double-dummy, placebo- and active controlled, 5 treatment, 10 sequence, 5 period crossover single dose, Williams square design study in healthy adult, non drug dependent male and female participants with drug abuse experience with sedative drugs.

Condition or Disease Intervention/Treatment Phase
  • Drug: gabapentin 600 mg
  • Drug: gabapentin 1200 mg
  • Drug: gabapentin 1800 mg
  • Drug: diazepam 20 mg
  • Other: placebo
Phase 4

Detailed Description

The study includes Screening, a Qualification Phase consisting of a Naloxone Challenge and Drug Discrimination crossover study, a Treatment Phase and Follow-up. Following successful completion of the Qualification Phase the participants will be enrolled in the Treatment phase. The Treatment Phase is a randomized, double-blind, double dummy, placebo- and active controlled, 5 treatment, 10-sequence, 5 period crossover, single-dose, Williams square design study in healthy male and/or female adult, non drug-dependent recreational users. On Day 1 of each of the Treatment Phase 5 periods, which will be separated by a washout of at least 14 days, participants will receive an oral dose of either NEURONTIN® 1800 mg, 1200 mg or 600 mg or 20 mg diazepam, or placebo. Study treatments will be administered under fasted conditions (overnight fast and no food until 4 hours after dosing). Water will be allowed without restriction until 1 hour prior to dosing and 1 hour after dosing.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
40 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Other
Official Title:
A Phase 4, Randomized, Double-blind, Double-dummy, Placebo and Active-controlled, Single-dose, Five-way Crossover Study Evaluating the Abuse Potential of Three Doses of NEURONTIN® Taken Orally in Healthy, Non-drug Dependent Participants With Sedative Drug Abuse Experience
Actual Study Start Date :
Mar 29, 2021
Anticipated Primary Completion Date :
Jan 1, 2023
Anticipated Study Completion Date :
Jan 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: gabapentin 600 mg

single dose

Drug: gabapentin 600 mg
participants will receive an oral dose of gabapentin 600 mg

Active Comparator: diazepam 20 mg

single dose

Drug: diazepam 20 mg
participants will receive an oral dose of 20 mg dose of diazepam

Placebo Comparator: placebo

single dose

Other: placebo
participants will receive an oral dose of placebo

Experimental: gabapentin 1200 mg

single dose

Drug: gabapentin 1200 mg
participants will receive an oral dose of gabapentin 1200 mg

Experimental: gabapentin 1800 mg

single dose

Drug: gabapentin 1800 mg
participants will receive an oral dose of gabapentin 1800 mg

Outcome Measures

Primary Outcome Measures

  1. Bipolar visual analog scale (VAS) for "Drug Liking" maximum effect (Emax). [up to 72 hours after treatments]

    Drug liking assesses how much a participant likes or dislikes a drug effect at the time the question is being asked. It is scored using a 100 mm visual analogue scale (VAS), where 0 mm = "Strong Disliking", 50 mm = "Neither Like nor Dislike", and 100 mm = "Strong Liking"

Secondary Outcome Measures

  1. Bipolar VAS for "Drug Liking" (Time for maximum effect, Emax [TEmax]) [up to 72 hours after treatments]

  2. Bipolar VAS for "Drug Liking" (area under the effect-time profile from time 0 to the time of the last quantifiable concentration [AUEClast]) [up to 72 hours after treatments]

  3. Bipolar VAS for "Drug Liking" (Area under the effect curve to 1 hour (AUEC1)) [up to 72 hours after treatments]

  4. Bipolar VAS for "Drug Liking" (Area under the effect curve to 2 hours (AUEC2)) [up to 72 hours after treatments]

  5. Bipolar VAS for "Drug Liking" (Area under the effect curve to 3 hours (AUEC3)) [up to 72 hours after treatments]

  6. Bipolar VAS for "Drug Liking" (Area under the effect curve to 4 hours (AUEC4)) [up to 72 hours after treatments]

  7. Bipolar VAS for "Drug Liking" (Area under the effect curve to 8 hours (AUEC8)) [up to 72 hours after treatments]

  8. Unipolar VAS for "High" (maximum effect, Emax) [up to 72 hours after treatments]

  9. Unipolar VAS for "High" (Time for maximum effect, Emax [TEmax]) [up to 72 hours after treatments]

  10. Unipolar VAS for "High" (area under the effect-time profile from time 0 to the time of the last quantifiable concentration [AUEClast]) [up to 72 hours after treatments]

  11. Unipolar VAS for "High" (Area under the effect curve to 1 hour (AUEC1)) [up to 72 hours after treatments]

  12. Unipolar VAS for "High" (Area under the effect curve to 2 hours (AUEC2)) [up to 72 hours after treatments]

  13. Unipolar VAS for "High" (Area under the effect curve to 3 hours (AUEC3)) [up to 72 hours after treatments]

  14. Unipolar VAS for "High" (Area under the effect curve to 4 hours (AUEC4)) [up to 72 hours after treatments]

  15. Unipolar VAS for "High" (Area under the effect curve to 8 hours (AUEC8)) [up to 72 hours after treatments]

  16. Bipolar VAS for "Take Drug Again" at 24 hour post dose [up to 72 hours after treatment]

  17. Bipolar VAS for "Take Drug Again" at 36 hour post dose [up to 72 hours after treatment]

  18. Bipolar VAS for "Take Drug Again" at 48 hour post dose [up to 72 hours after treatment]

  19. Bipolar VAS for "Take Drug Again" at 72 hour post dose [up to 72 hours after treatment]

  20. Bipolar VAS for "Overall Drug Liking" at 24 hour post dose [up to 72 hours after treatment]

  21. Bipolar VAS for "Overall Drug Liking" at 36 hour post dose [up to 72 hours after treatment]

  22. Bipolar VAS for "Overall Drug Liking" at 48 hour post dose [up to 72 hours after treatment]

  23. Bipolar VAS for "Overall Drug Liking" at 72 hour post dose [up to 72 hours after treatment]

  24. Unipolar VAS for "Good Drug Effect" [up to 72 hours after treatment]

  25. Unipolar VAS for "Bad Drug Effect" [up to 72 hours after treatment]

  26. Unipolar VAS for "Any Drug Effect" [up to 72 hours after treatment]

  27. Observer-rated assessment of alertness/sedation [up to 72 hours after treatment]

  28. Maximum plasma concentration, Cmax of gabapentin [up to 72 hours after treatment]

  29. Time for Cmax (Tmax) of gabapentin [up to 72 hours after treatment]

  30. Area under the effect time profile from time 0 to the time of the last quantifiable concentration (AUClast) of gabapentin [up to 72 hours after treatment]

  31. Area under the plasma concentration-time profile from time 0 extrapolated to infinity time (AUCinf), if data permits, of gabapentin [up to 72 hours after treatment]

  32. Terminal half-life (t½), if data permits, of gabapentin [up to 72 hours after treatment]

  33. Partial Area under the plasma concentration-time profile from time 0 to 1 hour postdose (AUC1) of gabapentin [up to 72 hours after treatment]

  34. Partial Area under the plasma concentration-time profile from time 0 to 2 hour postdose (AUC2) of gabapentin [up to 72 hours after treatment]

  35. Partial Area under the plasma concentration-time profile from time 0 to 3 hour postdose (AUC3) of gabapentin [up to 72 hours after treatment]

  36. Partial Area under the plasma concentration-time profile from time 0 to 4 hour postdose (AUC4) of gabapentin [up to 72 hours after treatment]

  37. Partial Area under the plasma concentration-time profile from time 0 to 8 hour postdose (AUC8) of gabapentin [up to 72 hours after treatment]

  38. Number of participants experiencing abnormal vital signs [up to 72 hours after treatment]

  39. Oxygen saturation of hemoglobin (SpO2) [up to 72 hours after treatment]

  40. Number of participants experiencing abnormal physical examination [up to 72 hours after treatment]

  41. Number of participants experiencing abnormal 12-lead electrocardiogram (ECG) [up to 72 hours after treatment]

  42. Number of participants with abnormal clinical laboratory findings [up to 72 hours after treatment]

  43. Number of participants experiencing of adverse events [Throughout the study and 28-35 days after the last treatment]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
  1. Male and female participants must be 18 to 65 years of age, inclusive, at the time of screening.

  2. Participants must meet reproductive criteria as outlined in the protocol.

  3. Male and female participants who are overtly healthy. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, complete physical examination, vital signs, 12-lead electrocardiogram (ECG), and/or clinical laboratory tests.

  4. Participants must be recreational sedative users, defined as those reporting using a sedative agent (eg, barbiturates, benzodiazepines) for its intoxicating effects on at least 10 lifetime occasions and at least once in the 12 weeks before the Screening Visit (Visit 1), but who have no signs of dependence and are not seeking treatment for their sedative use.

  5. Participants must satisfactorily complete both the Naloxone Challenge and the Drug Discrimination phases.

  6. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.

  7. Body mass index (BMI) of 17.5 to 34 kg/m2, inclusive; and a total body weight >50 kg (110 lb).

  8. Capable of giving signed informed consent as described in the protocol, which includes compliance with the requirements and restrictions listed in the informed consent document (ICD) and in this protocol.

Exclusion Criteria

  1. Participants with current or past diagnosis of any type of drug dependence within the past year. Diagnosis of substance and/or alcohol dependence (excluding caffeine and nicotine) will be assessed by the Investigator using the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria performed at Screening. Current drug use will be allowed if the candidate can produce a negative urine sample and are free of any signs/symptoms of withdrawal. The candidate will be informed if they have a positive breathalyzer test.

  2. Participants are heavy smokers or users of other types of nicotine products (>20 cigarettes equivalents per day)

  3. Participants are unable to abstain from smoking for at least 2 hours before and at least 8 hours after study drug administration.

  4. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).

  5. Participants with any history of sleep apnea, myasthenia or glaucoma.

  6. Any condition possibly affecting drug absorption (eg, gastrectomy) excluding cholecystectomy within 1 year prior to study.

  7. Clinical or laboratory evidence of active hepatitis A infection or a history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C, and/or positive testing for HIV, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C antibody (HCVAb).

  8. Participants with active suicidal ideation or suicidal behavior within 5 year prior to Screening as determined through the use of the Columbia-Suicide Severity Rating Scale (C-SSRS) or active ideation identified at Screening or on Day -1.

  9. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.

  10. Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of investigational product. (Refer to Section 6.5 for additional details).

  11. Herbal supplements and herbal medications must be discontinued at least 28 days prior to the first dose of study medication.

  12. Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives (whichever is longer) preceding the first dose of investigational product used in this study.

  13. Positive urine drug screen (UDS) for substances of abuse at each admission in Qualification and Treatment Phase, excluding tetrahydrocannabinol (THC). If a participant presents with a positive UDS excluding THC at any admission or any visit, the investigator, at his/her discretion, may reschedule a repeat UDS until the UDS is negative, excluding THC, before the participant is permitted to participate in any phase of the study.

  14. Participants unable to abstain from using THC during the Qualification and Treatment Phases of the study..

  15. Has participated in, is currently participating in, or is seeking treatment for substance-and/or alcohol-related disorders (excluding nicotine and caffeine).

  16. Has a positive alcohol breathalyzer test at Screening or upon admission to the study center at Visits 2-6. Positive results may be repeated and/or participants re-scheduled at the Investigator's discretions.

  17. Screening sitting BP >=140 mm Hg (systolic) or >=90 mm Hg (diastolic), following at least 5 minutes of rest. If BP is >=140 mm Hg (systolic) or >=90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility. Repeated BP tests should be spaced at least 5 minutes apart.

  18. Baseline (screening) 12-lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, baseline corrected QT (QTc) interval >450 msec, complete left bundle branch block [LBBB], signs of an acute or indeterminate-age myocardial infarction, ST-T interval changes suggestive of myocardial ischemia, second- or third-degree atrioventricular [AV] block, or serious bradyarrhythmias or tachyarrhythmias). If the baseline uncorrected QT interval is >450 msec, this interval should be rate-corrected using the Fridericia method and the resulting QTcF should be used for decision making and reporting. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTc or QRS values should be used to determine the participant's eligibility. Computer-interpreted ECGs should be overread by a physician experienced in reading ECGs before excluding participants.

  19. Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study-specific laboratory and confirmed by a single repeat test, if deemed to be clinically significant in the opinion of the investigator:

  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level >=1.5 × upper limit of normal (ULN);

  • Total bilirubin level >=1.5 × ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is <= ULN.

  1. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.

  2. History of sensitivity to heparin or heparin-induced thrombocytopenia.

  3. Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol.

  4. History of hypersensitivity to gabapentin or diazepam or any of the components in the formulation of the study products.

  5. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or Sponsor employees, including their family members, directly involved in the conduct of the study.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Pharmaceutical Research Associates, Inc. Salt Lake City Utah United States 84124

Sponsors and Collaborators

  • Viatris Specialty LLC

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Viatris Specialty LLC
ClinicalTrials.gov Identifier:
NCT04570436
Other Study ID Numbers:
  • A9451181
First Posted:
Sep 30, 2020
Last Update Posted:
Mar 24, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Keywords provided by Viatris Specialty LLC
Additional relevant MeSH terms:

Study Results

No Results Posted as of Mar 24, 2022