Evaluating the Abuse Potential of NEURONTIN® When Taken Orally in Healthy Non-drug Dependent Participants With Sedative Drug Abuse Experience
Condition: Abuse Potential
MeSH terms: Substance-Related Disorders
Intervention: gabapentin 600 mg; gabapentin 1200 mg; gabapentin 1800 mg; diazepam 20 mg; placebo
Intervention description: participants will receive an oral dose of gabapentin 600 mg; participants will receive an oral dose of gabapentin 1200 mg; participants will receive an oral dose of gabapentin 1800 mg; participants will receive an oral dose of 20 mg dose of diazepam; participants will receive an oral dose of placebo
Intervention MeSH terms: Diazepam; Gabapentin
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 52.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Neurontin; Diazepam; Abuse Liability; Gabapentin

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.
    

Eligibility criteria:

        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.

         20. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more
             within 60 days prior to dosing.

         21. History of sensitivity to heparin or heparin-induced thrombocytopenia.

         22. Unwilling or unable to comply with the criteria in the Lifestyle Considerations
             section of this protocol.

         23. History of hypersensitivity to gabapentin or diazepam or any of the components in the
             formulation of the study products.

         24. 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.