Abuse Potential of Gabapentin Taken Orally Concomitantly With Oxycodone Hydrochloride in Healthy, Non-Drug-Dependent, Recreational Opioid Users

A Phase 4, Randomized, Double-Blind, Placebo and Active-Controlled, Single-Dose, Six-Way Crossover Study Evaluating the Abuse Potential of Gabapentin Taken Orally Concomitantly With Oxycodone Hydrochloride in Healthy, Non-Drug- Dependent, Recreational Opioid Users

The purpose of the present study is to assess prospectively the abuse potential of gabapentin when taken with and without oxycodone compared to placebo in healthy non-drug-dependent recreational opioid drug users under fasted condition.

This study consists of a Screening Visit (Visit 1), followed within 28 days by a Qualification Phase (Visit 2) which will require inpatient stay at the clinical research unit (CRU) for 3 nights. After a washout of at least 4 days, eligible participants will enter the Treatment Phase which will include 6 treatment periods with each dosing day separated by a washout period of at least 4 days. Participants will remain residential at the CRU from admission to the Qualification Phase through to completion of the assessments of the last treatment period in the Treatment Phase (approximately 28 days). A follow-up visit (Visit 3) will be scheduled from 7 to 14 days after the administration of the final dose of investigational product.

Inclusion Criteria:

1. Male and female participants must be 18 to 55 years of age, inclusive, at the time of screening. Participants must meet reproductive criteria as outlined in the protocol.
2. 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 ECG, and/or clinical laboratory tests.
3. Participants must have drug abuse experience with opioids; ie, must have used opioids for non-therapeutic purposes (ie, for psychoactive effects) on at least 10 occasions within the last year and at least once in the 12 weeks before the Screening Visit (Visit 1).
4. Participants must satisfactorily complete both the Naloxone Challenge and the Drug Discrimination.
5. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
6. Body mass index (BMI) of 17.5 to 34 kg/m2, inclusive; and a total body weight ≥50 kg (110 lb).
7. 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 5-Text Revision (DSM 5-TR) criteria performed at Screening. Current drug use will be allowed if the candidate can produce a negative urine sample excluding tetrahydrocannabinol (THC) prior to first dose and are free of any signs/symptoms of withdrawal. The candidate will be informed if they have a positive breathalyzer test or urine ethanol test.
2. Participants who are heavy smokers (>20 cigarettes equivalents per day).
3. Participants who 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. Patients with any history of sleep apnea, myasthenia gravis and glaucoma.
6. Any condition or surgery possibly affecting drug absorption (e.g., gastrectomy) excluding cholecystectomy.
7. Abnormal baseline end-tidal carbon dioxide (EtCO2) <35mm Hg or >45 mm Hg.
8. Participants with a positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibody (HCVab).
9. Participants with active suicidal ideation or suicidal behavior within 5 years 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.
10. 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.
11. 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 6.8 for additional details).
12. Herbal supplements and herbal medications must be discontinued at least 14 days prior to the first dose of study medication.
13. Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half lives (whichever is longer) prior to screening.
14. Positive urine drug screen (UDS) for substances of abuse at admission to the Qualification Phase, excluding tetrahydrocannabinol (THC).
15. Participants who are unable to abstain from using THC during the inpatient stays in the Qualification and Treatment Phases of the study.
16. Has participated in, is currently participating in, or is seeking treatment for substance and/or alcohol related disorders (excluding nicotine and caffeine). If participation in a rehabilitation program was court-mandated as part of a plea agreement, entry may be permissible at the Investigator's discretion.
17. Has a positive urine ethanol test at Screening or upon admission to the study center.
18. Screening sitting blood pressure (BP) ≥145 mm Hg (systolic) or ≥95 mm Hg (diastolic), following at least 5 minutes rest.
19. Baseline (screening) 12 lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.
20. Participants with abnormalities in clinical laboratory tests for liver function tests at screening if deemed to be clinically significant in the opinion of the investigator.
21. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 56 days prior to dosing.
22. History of sensitivity to heparin or heparin induced thrombocytopenia.
23. History of hypersensitivity to gabapentin or oxycodone or any of the components in the formulation of the study products.