Phase 1 Study of Nalbuphine HCl ER Tablets in Hemodialysis Patients With Uremic Pruritus

NCT02373215 | Completed Phase 1

• 1 other identifier: TR01
• Study Type: interventional
• Target: 22
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a single-center clinical research study with the purpose to evaluate the safety, tolerability, and pharmacokinetics (PK) of nalbuphine HCl ER (extended release) tablets in end-stage renal disease (ESRD) patients receiving hemodialysis (HD) therapy and reporting pruritus.

Conditions

Uremic Pruritus

Outcome Measures

Primary Outcomes (2)

• Steady state PK of nalbuphine HCl ER tablets as a function of dose

  Steady state PK of nalbuphine HCl ER tablets following escalating repeated oral doses in ESRD patients receiving HD therapy relative to healthy subjects

  Day -1 to 14 Cohort 1 Groups 1-3 and Cohort 2; Day -1 to 17 Cohort 1 Group 4

• Extent of extraction of nalbuphine by measuring nalbuphine in plasma and dialysate during dialysis

  Extraction by dialysis was assessed by measuring nalbuphine concentrations in plasma during dialysis obtained from arterial (pre-dialyzer) and venous access ports (post-dialyzer) and by measuring the amount removed in the dialysate during dialysis in the dialysate as a function of dose.

  Day -1 to 14 Cohort 1 Groups 1-3; Day -1 to 17 Cohort 1 Group 4

Secondary Outcomes (1)

• VAS measurement of anti-pruritic effects

  Day -1 to 19-21 Cohort 1 Groups 1-3; Day -1 to 22-24 Cohort 1 Group 4

Study Arms (3)

Cohort 1 - Groups 1-3

EXPERIMENTAL

HD patients dosing up to 180mg BID

Drug: Nalbuphine HCL ER

Cohort 1 - Group 4

EXPERIMENTAL

HD patients dosing up to 240mg BID

Drug: Nalbuphine HCL ER

Cohort 2

EXPERIMENTAL

Healthy patients dosing up to 180mg BID

Drug: Nalbuphine HCL ER

Interventions

Nalbuphine HCL ER DRUG

Nalbuphine HCL extended release tablet

Also known as: Nalbuphine

Cohort 1 - Group 4; Cohort 1 - Groups 1-3; Cohort 2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For Hemodialysis Patients Only
• Patients with chronic renal failure who have been receiving chronic in-center HD on an average of 3 times a week for at least 3 months (with Kt/V \> 1.1).
• Subjects who experience at least mild intermittent pruritus.
• Non-reactive serology for hepatitis B, hepatitis C, and human immunodeficiency virus (HIV) antibody screens.
• Adequate venous access.
• Hemoglobin concentration at Screening \> 9 g/dL.
• For Healthy Subjects Only
• Subjects are demographically comparable to the ESRD subjects.
• Gender matched 100%
• Age ± 10 years
• Body mass index (BMI) ± 15%
• Clinical chemistry within normal range.
• For Hemodialysis Patients and Healthy Subjects
• Written informed consent must be obtained before any assessment is performed.
• Male or female between the ages of 18 and 70 years, inclusive.

You may not qualify if:

• For Hemodialysis Patients Only
• Patients who had a significant alteration in dialysis regimen within 2 weeks of the Screening Visit.
• An alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) concentration \> 2x the upper limit of the normal range (ULN) at Screening.
• A serum total bilirubin \> 1.8x ULN.
• Patients who require peritoneal dialysis.
• Patients who received daily or when necessary (PRN) barbiturates, amphetamines, or opiates within 7 days prior to Check-in.
• For Healthy Subjects Only
• \. Any clinically significant abnormality identified on the physical, ECG, vital sign measurements, or clinical laboratory examinations at Screening or Day -1.
• For Hemodialysis Patients and Healthy Subjects
• Subjects with a positive drug screen at Screening and Day -1 without a prescription.
• Known hypersensitivity or allergy to nalbuphine or vehicle components.
• Known drug allergy to opioids.
• History of drug dependency, opioid abuse, or emotional instability deemed clinically significant per investigator review.
• Women with a positive pregnancy test
• Lactating females.

Sponsors & Collaborators

• Trevi Therapeutics: lead
• Davita Clinical Research: collaborator

Related Publications (1)

• Eudy-Byrne R, Riggs M, Hawi A, Sciascia T, Rohatagi S. A population pharmacokinetic-pharmacodynamic model evaluating efficacy of nalbuphine extended-release in patients with prurigo nodularis. Br J Clin Pharmacol. 2023 Jul;89(7):2088-2101. doi: 10.1111/bcp.15663. Epub 2023 Feb 9.

  PMID: 36680419 DERIVED

MeSH Terms

Interventions

Nalbuphine

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Chief Development Officer

  Trevi Therapeutics

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: February 13, 2015
• First Posted: February 26, 2015
• Study Start: April 1, 2013
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: May 22, 2025

Record last verified: 2025-05