Oral Abuse Potential Study of Nalbuphine

A Study to Evaluate the Oral Abuse Potential of Nalbuphine Solution and Extended-Release Intact Tablets in Non-Dependent, Recreational Opioid Users

The purpose of this study is to measure the effects of a drug called nalbuphine (an opioid drug) compared with the effects of hydromorphone (an opioid drug) and placebo (contains no active drug ingredients). The amount of nalbuphine levels in the blood will also be measured and the safety of the study drugs will be evaluated. This study has 2 parts: Part A and Part B.

This study will be a single-dose, randomized, double-blind, active- and placebo-controlled, double dummy, 2-part, 7-way crossover study to determine the abuse potential of orally administered nalbuphine solution and nalbuphine ER intact tablets relative to hydromorphone solution and placebo, in non-dependent, recreational opioid users. The study will be conducted in a single clinical research unit (CRU). The purpose of Part A is to find the appropriate doses (a low, intermediate, and high dose) of nalbuphine solution to use in Part B. Part A of the study has two visits to the research clinic: a screening visit and dose selection visit. The visits will involve a 2-night stay (3 days total) in the research clinic. In the Main Study Treatment Phase in Part B, the total estimated duration between each dose of study drug is approximately up to 7 days, of which the subject will spend 3 days/2 nights in the research clinic and approximately up to 4 days at home. The primary objective of the Main Study is to evaluate the abuse potential of orally administered nalbuphine solution and nalbuphine ER intact tablets relative to hydromorphone solution (the active comparator) and placebo in non-dependent, recreational opioid users.

Single-dose, randomized, double-blind, active- and placebo-controlled, double-dummy, 2-part, 7-way crossover study. Part A: Dose selection phase Part B: Treatment Periods 1-7

For each dosing cohort, an unblinded statistician, not otherwise involved in the study, will prepare a list of subject randomization numbers. These randomization numbers will be used to prepare individual subject doses. Sealed qualification code break envelopes will be available for each subject in case of emergency. Upon completion of each cohort of subjects, the randomization codes for the completed subjects will be unblinded by the CRU pharmacy. After unblinding, the safety data will be reviewed to determine if dosing can proceed for the next planned dosing cohort,

Up to 405 mg nalbuphine HCl solution Up to 40.5 mL × 10 mg/mL hydromorphone HCl + at least 109.5 mL flavored beverage

Up to 540 mg nalbuphine HCl solution Up to 54 mL × 10 mg/mL hydromorphone HCl + at least 96 mL flavored beverage

To Identify the Appropriate Low, Intermediarte, and High Doses of Nalbuphine Solution (Part A) to be Administered as Single Doses in the Treatment Phase of the Main Study (Part B).

Only Part A of thie study was conducted because of closure the clinical research unit (CRU) before Part B could be initiated. Summary statistics are provided for C-max

Inclusion Criteria: Healthy male or female subjects 18 to 55 years of age Current opioid users who have used opioids for recreational (non-therapeutic) purposes Exclusion Criteria: Self-reported substance or alcohol dependence (excluding nicotine and caffeine) Heavy smoker (≥ 20 cigarettes per day) and/or who is unable to abstain from smoking for at least 8 hours during the in clinic periods. History or presence of clinically significant abnormality as assessed by physical examination, medical history, ECGs, vital signs, or laboratory values. History or presence of any clinically significant illness History of major mental illness that may affect the ability of the subject to participate in the study.