Study of Nalbuphine ER in Participants With Hepatic Impairment

NCT04020016 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: Protocol 182018 (TR10)
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 3

Brief Summary

This research study will evaluate the effect of hepatic impairment on the pharmacokinetics (the breakdown of the drug in the body) of parallel-group, multiple oral doses nalbuphine extended release (NAL ER), tablets in people with hepatic impairment (mild, moderate and severe), compared to people with normal liver function. The study will also test the safety and tolerability of the NAL ER, when it is given to participants with mild, moderate and severe hepatic impairment, compared to participants with normal liver function. This protocol will also study the effects of this drug on itching in hepatic impairment participants if they report some itching prior to taking part in this study.

Conditions

Hepatic Impairment

Keywords

nalbuphine; Pharmacokinetic; hepatic impairment

Outcome Measures

Primary Outcomes (11)

• Part 1: Maximum Observed Plasma Concentration (Cmax) of NAL ER

  Pre-dose and 1.5, 3, 5, 7, 9, 12, 24, 36, 48, and 72 hours post-dose at Day 1 in each dose level

• Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of NAL ER

  Pre-dose and 1.5, 3, 5, 7, 9, 12, 24, 36, 48, and 72 hours post-dose at Day 1 in each dose level

• Part 1: Terminal Elimination Half-Life (T1/2 el) of NAL ER

  Pre-dose and 1.5, 3, 5, 7, 9, 12, 24, 36, 48, and 72 hours post-dose at Day 1 in each dose level

• Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of NAL ER

  Pre-dose and 1.5, 3, 5, 7, 9, 12, 24, 36, 48, and 72 hours post-dose at Day 1 in each dose level

• Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of NAL ER

  Pre-dose and 1.5, 3, 5, 7, 9, 12, 24, 36, 48, and 72 hours post-dose at Day 1 in each dose level

• Part 1: Number of Participants Who Experienced at Least One Treatment Emergent Adverse Event (TEAE)

  An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A TEAE was defined as any AE that occurs after the first dose of study drug. TEAEs included both serious and non-serious TEAEs.

  From signing the informed consent form up to Day 4

• Part 1: Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters

  The clinical laboratory parameters included the clinical chemistry, hematology, coagulation, and urinalysis. Clinical significance was determined by the investigator.

  From signing the informed consent form up to Day 4

• Part 1: Number of Participants With Clinically Significant Findings in Vital Sign Parameters

  Vital signs measurements included diastolic and systolic blood pressure, heart rate, respiratory rate, and body temperature. Clinical significance was determined by the investigator.

  From signing the informed consent form up to Day 4

• Part 1: Number of Participants With Clinically Significant Findings in Physical Examination Parameters

  Physical examination included examination of at least the following components: head, eyes, ears, nose, throat (HEENT), neck, lungs, abdomen, skin, cardiovascular and musculoskeletal evaluation, and general neurological examination. Clinical significance was determined by the investigator.

  From signing the informed consent form up to Day 4

• Part 1: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECG)

  ECG data included the measurement of heart rate and aggregate PR interval, QRS duration, QT interval, QTcB interval, and QTcF interval.

  From signing the informed consent form up to Day 4

• Part 1: Number of Participants With Clinically Significant Findings in Pulse Oximetry

  Oxygen saturation was measured via pulse oximetry. Pulse oximetry measurements were to be collected within 10 min before or after the specified time point. Clinical significance was determined by the investigator.

  Pre-dose and 1.5, 4, 5, and 8 hours post-dose in each dose level

Secondary Outcomes (1)

• Part 2: Change From Baseline in Worst Itch Numerical Rating Scale (WI-NRS)

  Baseline, Day 16

Study Arms (1)

Part 1 Single Ascending Dose

EXPERIMENTAL

Participants with mild (group 1), moderate (group 2) and severe (group 3) hepatic impairment received single dose ranging from 27 mg up to 162 mg of NAL ER tablet under fasting conditions. There was a washout period of at least 7 days between the drug administration between each dose level. Participants with no hepatic impairment (group 4) received a single dose of NAL ER of up to 162 mg under fasting conditions.

Drug: Nalbuphine ER

Interventions

Nalbuphine ER DRUG

Oral tablet

Also known as: NAL ER

Part 1 Single Ascending Dose

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For participants with Hepatic Impairment (Cohort 1 to 4 and Cohort 6):
• Male or female with stable hepatic impairment, non-smoker and/or light smoker.
• Clinical diagnosis of liver cirrhosis
• Stable for study participation based upon medical history, physical examination, vital signs, ECGs, and screening clinical laboratory evaluations
• For Healthy participants (Cohort 5):
• Male or female, non-smoker and/or light smoker (up to 5 cigarettes or equivalent/day)
• Healthy as defined by:
• Normal hepatic function
• The absence of clinically significant illness and surgery within 4 weeks prior to dosing.

You may not qualify if:

• For participants with Hepatic Impairment (Cohort 1 to 4 and Cohort 6):
• Clinically significant unstable medical conditions
• Clinically significant abnormalities of laboratory, ECG, pulse oximetry, or clinical data that would preclude participation in the study.
• History of any illness that might confound the results of the study or pose an additional risk to the participant by participation in the study.
• For Healthy participants (Cohort 5):
• Diagnosis of liver disease
• History of heart problems.
• History of significant alcohol abuse or drug abuse

Sponsors & Collaborators

• Trevi Therapeutics: lead
• Syneos Health: collaborator

Study Sites (3)

01

Miami, Florida, 33136, United States

Location

02

Miami, Florida, 33146, United States

Location

03

Orlando, Florida, 32809, United States

Location

Limitations and Caveats

As per the judgement of the safety committee, the Part 2 (MAD) was not conducted based on protocol defined criteria.

Results Point of Contact

• Title: Chief Development Officer
• Organization: Trevi Therapeutics, Inc.

info@trevitherapeutics.com

203-304-2499

Study Officials

• Chief Development Officer

  Trevi Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2019
• First Posted: July 15, 2019
• Study Start: June 12, 2019
• Primary Completion: February 5, 2020
• Study Completion: February 5, 2020
• Last Updated: March 19, 2026
• Results First Posted: March 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)