search
Back to results

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

Primary Purpose

Uremic Pruritus

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Nalbuphine HCL ER
Sponsored by
Trevi Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Uremic Pruritus

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Experimental

    Arm Label

    Cohort 1 - Groups 1-3

    Cohort 1 - Group 4

    Cohort 2

    Arm Description

    HD patients dosing up to 180mg BID

    HD patients dosing up to 240mg BID

    Healthy patients dosing up to 180mg BID

    Outcomes

    Primary Outcome Measures

    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
    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.

    Secondary Outcome Measures

    VAS measurement of anti-pruritic effects
    Visual Analogue Scale (VAS) itch measurement of anti-pruritic effects of nalbuphine HCl ER tablets in HD subjects with pruritus

    Full Information

    First Posted
    February 13, 2015
    Last Updated
    July 30, 2020
    Sponsor
    Trevi Therapeutics
    Collaborators
    Davita Clinical Research
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT02373215
    Brief Title
    Phase 1 Study of Nalbuphine HCl ER Tablets in Hemodialysis Patients With Uremic Pruritus
    Official Title
    A Phase 1, Open-Label, Non-Randomized, Parallel-Group Study to Characterize and Compare the Pharmacokinetics, Safety, and Tolerability of Escalating Oral Doses of Nalbuphine Hydrochloride Extended Release Tablets in End-Stage Renal Disease Patients on Hemodialysis and Matched Healthy Control Subjects
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2020
    Overall Recruitment Status
    Completed
    Study Start Date
    April 2013 (undefined)
    Primary Completion Date
    November 2013 (Actual)
    Study Completion Date
    November 2013 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Trevi Therapeutics
    Collaborators
    Davita Clinical Research

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Uremic Pruritus

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    22 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Cohort 1 - Groups 1-3
    Arm Type
    Experimental
    Arm Description
    HD patients dosing up to 180mg BID
    Arm Title
    Cohort 1 - Group 4
    Arm Type
    Experimental
    Arm Description
    HD patients dosing up to 240mg BID
    Arm Title
    Cohort 2
    Arm Type
    Experimental
    Arm Description
    Healthy patients dosing up to 180mg BID
    Intervention Type
    Drug
    Intervention Name(s)
    Nalbuphine HCL ER
    Other Intervention Name(s)
    Nalbuphine
    Intervention Description
    Nalbuphine HCL extended release tablet
    Primary Outcome Measure Information:
    Title
    Steady state PK of nalbuphine HCl ER tablets as a function of dose
    Description
    Steady state PK of nalbuphine HCl ER tablets following escalating repeated oral doses in ESRD patients receiving HD therapy relative to healthy subjects
    Time Frame
    Day -1 to 14 Cohort 1 Groups 1-3 and Cohort 2; Day -1 to 17 Cohort 1 Group 4
    Title
    Extent of extraction of nalbuphine by measuring nalbuphine in plasma and dialysate during dialysis
    Description
    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.
    Time Frame
    Day -1 to 14 Cohort 1 Groups 1-3; Day -1 to 17 Cohort 1 Group 4
    Secondary Outcome Measure Information:
    Title
    VAS measurement of anti-pruritic effects
    Description
    Visual Analogue Scale (VAS) itch measurement of anti-pruritic effects of nalbuphine HCl ER tablets in HD subjects with pruritus
    Time Frame
    Day -1 to 19-21 Cohort 1 Groups 1-3; Day -1 to 22-24 Cohort 1 Group 4

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: 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. Exclusion Criteria: 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 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 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.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Thomas Sciascia
    Organizational Affiliation
    Trevi Therapeutics
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Learn more about this trial

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

    We'll reach out to this number within 24 hrs