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Oral Abuse Potential Study of Nalbuphine

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT04018664
Recruitment Status : Suspended (Part A has been completed. Part B is pending protocol revisions.)
First Posted : July 12, 2019
Last Update Posted : August 12, 2019
Sponsor:
Collaborator:
Syneos Health
Information provided by (Responsible Party):
Trevi Therapeutics

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Nalbuphine Opioid Abuse Drug: Nalbuphine 162 Mg ER Drug: Nalbuphine HCl solution Drug: Hydromorphone HCl 8 mg Drug: Hydromorphone HCl 16 Mg Drug: Placebo Tablet Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 112 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention 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 (Participant, Care Provider, Investigator)
Masking Description:

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,

Primary Purpose: Other
Official Title: A Study to Evaluate the Oral Abuse Potential of Nalbuphine Solution and Extended-Release Intact Tablets in Non-Dependent, Recreational Opioid Users
Actual Study Start Date : May 29, 2018
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Treatment Arm A: Placebo

Treatment A: Placebo

150 mL flavored beverage +

1 × nalbuphine matching placebo tablet

Drug: Placebo Tablet
Treatment Arm A
Other Name: Sugar Pill

Active Comparator: Treatment Arm B: Hydromorphone HCL 8 mg

Treatment B: Hydromorphone HCl 8 mg solution

4 mL × 2 mg/mL hydromorphone HCl + 146 mL flavored beverage +

1 × nalbuphine matching placebo tablet

Drug: Hydromorphone HCl 8 mg
Treatment Arm B: 8 mg Solution
Other Names:
  • Hymorphan
  • Tubex
  • Palladon

Drug: Placebo Tablet
Treatment Arm A
Other Name: Sugar Pill

Active Comparator: Treatment C: Hydromorphone HCL 16mg

Treatment C: Hydromorphone HCl 16 mg solution

8 mL × 2 mg/mL hydromorphone HCl + 142 mL flavored beverage +

1 × nalbuphine matching placebo tablet

Drug: Hydromorphone HCl 16 Mg
Treatment Arm C: 16 Mg solution
Other Names:
  • Tubex
  • Palladon

Drug: Placebo Tablet
Treatment Arm A
Other Name: Sugar Pill

Experimental: Treatment D: Nalbuphine HCL low dose

Treatment D: Nalbuphine HCl low dose solution

Low dose nalbuphine HCl solution + TBD mL flavored beverage +

1 × nalbuphine matching placebo tablet

Drug: Nalbuphine HCl solution
Treatment Arm D: given at a low dose Treatment Arm E; given at an intermediate dose Treatment Arm F: given at a high dosing
Other Name: Nubain

Drug: Placebo Tablet
Treatment Arm A
Other Name: Sugar Pill

Experimental: Treatment E: Nalbuphine HCL intermediate dose

Treatment E: Nalbuphine HCl intermediate dose solution

Intermediate dose nalbuphine HCl solution + TBD mL flavored beverage +

1 × nalbuphine matching placebo tablet

Drug: Nalbuphine HCl solution
Treatment Arm D: given at a low dose Treatment Arm E; given at an intermediate dose Treatment Arm F: given at a high dosing
Other Name: Nubain

Drug: Placebo Tablet
Treatment Arm A
Other Name: Sugar Pill

Experimental: Treatment F: Nalbuphine HCL High dose

Treatment F: Nalbuphine HCl high dose solution

High dose nalbuphine HCl solution + TBD mL flavored beverage +

1 × nalbuphine matching placebo tablet

Drug: Nalbuphine HCl solution
Treatment Arm D: given at a low dose Treatment Arm E; given at an intermediate dose Treatment Arm F: given at a high dosing
Other Name: Nubain

Drug: Placebo Tablet
Treatment Arm A
Other Name: Sugar Pill

Experimental: Treatment G: NAL ER 162 mg tablet

Treatment G: Nalbuphine 162 mg ER intact tablet

150 mL flavored beverage +

1 × 162 mg nalbuphine ER tablet

Drug: Nalbuphine 162 Mg ER
Treatment G
Other Name: NAL ER

Drug: Placebo Tablet
Treatment Arm A
Other Name: Sugar Pill




Primary Outcome Measures :
  1. The primary endpoint for the Main Study is the peak (maximum) effect (Emax) for Drug Liking ("at this moment"), assessed on a bipolar, 0 to 100 point visual analog scale (VAS) [ Time Frame: 19 weeks ]
    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


Secondary Outcome Measures :
  1. Overall Drug Liking on the Visual Analog Scale(VAS) (Emax and peak minimum effect [Emin])solution and nalbuphine ER intact tablets [ Time Frame: 19 weeks ]
    To assess the cognitive and psychomotor effects of orally administered nalbuphine solution and nalbuphine ER intact tablets relative to hydromorphone solution and placebo in non-dependent, recreational opioid users

  2. Take Drug Again Visual Analog Scale (VAS) (Emax) [ Time Frame: 19 weeks ]
    To assess the safety and tolerability of orally-administered nalbuphine solution and nalbuphine ER tablets relative to hydromorphone solution and placebo in non-dependent, recreational opioid users.


Other Outcome Measures:
  1. Identification of an Maximum Safe Dose (MSD) of nalbuphine administered as nalbuphine oral solution [ Time Frame: 4.5 weeks ]
    To assess the safety and tolerability of various doses of orally-administered nalbuphine solution and determine the maximum safe dose (MSD) in non-dependent, recreational opioid users.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04018664


Locations
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Canada, Ontario
001
Toronto, Ontario, Canada, M5V 2T3
Sponsors and Collaborators
Trevi Therapeutics
Syneos Health
Investigators
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Study Director: Thomas Sciascia, MD Trevi Therapeutics, Inc.

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Responsible Party: Trevi Therapeutics
ClinicalTrials.gov Identifier: NCT04018664     History of Changes
Other Study ID Numbers: Protocol 1008910 (TR08)
First Posted: July 12, 2019    Key Record Dates
Last Update Posted: August 12, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Trevi Therapeutics:
nalbuphine
abuse potential

Additional relevant MeSH terms:
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Opioid-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Pharmaceutical Solutions
Hydromorphone
Nalbuphine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents