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.

Study Overview

• Status: Completed
• Conditions: Opioid Abuse; Nalbuphine
• Intervention / Treatment: Drug: Placebo solution; Drug: Nalbuphine HCl solution

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5V 2T3
      • 001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo 150 mL flavored beverage	Drug: Placebo solution; Placebo
Experimental: 90 mg nalbuphine HCl solution; 90 mg nalbuphine HCl solution 9 mL × 10 mg/mL hydromorphone HCl + 141 mL flavored beverage	Drug: Nalbuphine HCl solution; nalbuphine solution administered at various strengths; Other Names: NAL ER
Experimental: 120 mg nalbuphine HCl solution; 120 mg nalbuphine HCl solution 12 mL × 10 mg/mL hydromorphone HCl + 138 mL flavored beverage	Drug: Nalbuphine HCl solution; nalbuphine solution administered at various strengths; Other Names: NAL ER
Experimental: 150 mg nalbuphine HCl solution; 150 mg nalbuphine HCl solution 15 mL × 10 mg/mL hydromorphone HCl + 135 mL flavored beverage	Drug: Nalbuphine HCl solution; nalbuphine solution administered at various strengths; Other Names: NAL ER
Experimental: 180 mg nalbuphine HCl solution; 180 mg nalbuphine HCl solution 18 mL × 10 mg/mL hydromorphone HCl + 132 mL flavored beverage	Drug: Nalbuphine HCl solution; nalbuphine solution administered at various strengths; Other Names: NAL ER
Experimental: 270 mg nalbuphine HCl solution; 270 mg nalbuphine HCl solution 27 mL × 10 mg/mL hydromorphone HCl + 123 mL flavored beverage	Drug: Nalbuphine HCl solution; nalbuphine solution administered at various strengths; Other Names: NAL ER
Experimental: Up to 405 mg nalbuphine HCl solution; 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; nalbuphine solution administered at various strengths; Other Names: NAL ER
Experimental: Up to 540 mg nalbuphine HCl solution; 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; nalbuphine solution administered at various strengths; Other Names: NAL ER

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Trevi Therapeutics
• Collaborators: Syneos Health
• Investigators: Study Director: Chief Development Officer, Trevi Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2018
• Primary Completion (Actual): December 3, 2018
• Study Completion (Actual): June 2, 2020

Study Registration Dates

• First Submitted: May 30, 2019
• First Submitted That Met QC Criteria: July 11, 2019
• First Posted (Actual): July 12, 2019

Study Record Updates

• Last Update Posted (Actual): May 21, 2025
• Last Update Submitted That Met QC Criteria: May 19, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: abuse potential; nalbuphine
• Additional Relevant MeSH Terms: Narcotic-Related Disorders; Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Opioid-Related Disorders; Physiological Effects of Drugs; Peripheral Nervous System Agents; Central Nervous System Depressants; Sensory System Agents; Analgesics; Analgesics, Opioid; Narcotics; Pharmaceutical Solutions; Nalbuphine
• Other Study ID Numbers: Protocol 1008910 (TR08)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No