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

NCT ID: NCT02373215

Last Updated: 2025-05-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2013-11-30

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.

Detailed Description

The PK of nalbuphine hemodialysis (HD) patients is unknown and will be investigated under controlled dialysis conditions in the proposed clinical PK study.

Nalbuphine is a small molecular weight, water-soluble molecule with low protein binding (approximately 50%) and a large volume of distribution. In addition, its disposition is perfusion-rate limited. In the end-stage renal disease (ESRD) patients on HD, nalbuphine plasma clearance may be impacted, although it is predominantly hepatically cleared in the feces.

A dose-escalation design was selected to mimic nalbuphine use in uremic pruritus (UP) patients in subsequent clinical efficacy studies whereby patients will start at a low dose to minimize the AEs such as nausea and vomiting and allow the patients to develop some tolerance to these particular AEs.

Conditions

Uremic Pruritus

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1 - Groups 1-3

HD patients dosing up to 180mg BID

Group Type: EXPERIMENTAL

Nalbuphine HCL ER

Intervention Type: DRUG

Nalbuphine HCL extended release tablet

Cohort 1 - Group 4

HD patients dosing up to 240mg BID

Group Type: EXPERIMENTAL

Nalbuphine HCL ER

Intervention Type: DRUG

Nalbuphine HCL extended release tablet

Cohort 2

Healthy patients dosing up to 180mg BID

Group Type: EXPERIMENTAL

Nalbuphine HCL ER

Intervention Type: DRUG

Nalbuphine HCL extended release tablet

Interventions

Nalbuphine HCL ER

Nalbuphine HCL extended release tablet

Intervention Type: DRUG

Other Intervention Names

Nalbuphine

Eligibility Criteria

Inclusion Criteria

For Hemodialysis Patients Only

1. 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).

2. Subjects who experience at least mild intermittent pruritus.

3. Non-reactive serology for hepatitis B, hepatitis C, and human immunodeficiency virus (HIV) antibody screens.

4. Adequate venous access.

5. Hemoglobin concentration at Screening > 9 g/dL.

For Healthy Subjects Only

1. Subjects are demographically comparable to the ESRD subjects.

1. Gender matched 100%

2. Age ± 10 years

3. Body mass index (BMI) ± 15%

2. Clinical chemistry within normal range.

For Hemodialysis Patients and Healthy Subjects

1. Written informed consent must be obtained before any assessment is performed.

2. Male or female between the ages of 18 and 70 years, inclusive.

Exclusion Criteria

For Hemodialysis Patients Only

1. Patients who had a significant alteration in dialysis regimen within 2 weeks of the Screening Visit.

2. An alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) concentration > 2x the upper limit of the normal range (ULN) at Screening.

3. A serum total bilirubin > 1.8x ULN.

4. Patients who require peritoneal dialysis.

5. Patients who received daily or when necessary (PRN) barbiturates, amphetamines, or opiates within 7 days prior to Check-in.

For Healthy Subjects Only

1. 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

1. Subjects with a positive drug screen at Screening and Day -1 without a prescription.

2. Known hypersensitivity or allergy to nalbuphine or vehicle components.

3. Known drug allergy to opioids.

4. History of drug dependency, opioid abuse, or emotional instability deemed clinically significant per investigator review.

5. Women with a positive pregnancy test

6. Lactating females.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Davita Clinical Research

INDUSTRY

Sponsor Role: collaborator

Trevi Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chief Development Officer

Role: STUDY_DIRECTOR

Trevi Therapeutics

References

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.

Reference Type: DERIVED

PMID: 36680419 (View on PubMed)

Other Identifiers

TR01

Identifier Type: -

Identifier Source: org_study_id