Oral Abuse Potential Study of Nalbuphine

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Nalbuphine, Opioid Abuse

Intervention / Treatment
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* Drug: Nalbuphine HCl solution
* Drug: Placebo solution


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo 150 mL flavored beverage | Drug: Placebo solution<br>* Placebo<br>|
| Experimental: 90 mg nalbuphine HCl solution<br>90 mg nalbuphine HCl solution 9 mL × 10 mg/mL hydromorphone HCl + 141 mL flavored beverage | Drug: Nalbuphine HCl solution<br>* nalbuphine solution administered at various strengths<br>* Other names: NAL ER;|
| Experimental: 120 mg nalbuphine HCl solution<br>120 mg nalbuphine HCl solution 12 mL × 10 mg/mL hydromorphone HCl + 138 mL flavored beverage | Drug: Nalbuphine HCl solution<br>* nalbuphine solution administered at various strengths<br>* Other names: NAL ER;|
| Experimental: 150 mg nalbuphine HCl solution<br>150 mg nalbuphine HCl solution 15 mL × 10 mg/mL hydromorphone HCl + 135 mL flavored beverage | Drug: Nalbuphine HCl solution<br>* nalbuphine solution administered at various strengths<br>* Other names: NAL ER;|
| Experimental: 180 mg nalbuphine HCl solution<br>180 mg nalbuphine HCl solution 18 mL × 10 mg/mL hydromorphone HCl + 132 mL flavored beverage | Drug: Nalbuphine HCl solution<br>* nalbuphine solution administered at various strengths<br>* Other names: NAL ER;|
| Experimental: 270 mg nalbuphine HCl solution<br>270 mg nalbuphine HCl solution 27 mL × 10 mg/mL hydromorphone HCl + 123 mL flavored beverage | Drug: Nalbuphine HCl solution<br>* nalbuphine solution administered at various strengths<br>* Other names: NAL ER;|
| Experimental: Up to 405 mg nalbuphine HCl solution<br>Up to 405 mg nalbuphine HCl solution Up to 40.5 mL × 10 mg/mL hydromorphone HCl + at least 109.5 mL flavored beverage | Drug: Nalbuphine HCl solution<br>* nalbuphine solution administered at various strengths<br>* Other names: NAL ER;|
| Experimental: Up to 540 mg nalbuphine HCl solution<br>Up to 540 mg nalbuphine HCl solution Up to 54 mL × 10 mg/mL hydromorphone HCl + at least 96 mL flavored beverage | Drug: Nalbuphine HCl solution<br>* nalbuphine solution administered at various strengths<br>* Other names: NAL ER;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nalbuphine, abuse potential