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

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: NCT02373215
Recruitment Status : Completed
First Posted : February 26, 2015
Last Update Posted : August 3, 2020
Sponsor:
Collaborator:
Davita Clinical Research
Information provided by (Responsible Party):
Trevi Therapeutics

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.

Condition or disease Intervention/treatment Phase
Uremic Pruritus Drug: Nalbuphine HCL ER Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : April 2013
Actual Primary Completion Date : November 2013
Actual Study Completion Date : November 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Dialysis Itching

Arm Intervention/treatment
Experimental: Cohort 1 - Groups 1-3
HD patients dosing up to 180mg BID
Drug: Nalbuphine HCL ER
Nalbuphine HCL extended release tablet
Other Name: Nalbuphine

Experimental: Cohort 1 - Group 4
HD patients dosing up to 240mg BID
Drug: Nalbuphine HCL ER
Nalbuphine HCL extended release tablet
Other Name: Nalbuphine

Experimental: Cohort 2
Healthy patients dosing up to 180mg BID
Drug: Nalbuphine HCL ER
Nalbuphine HCL extended release tablet
Other Name: Nalbuphine




Primary Outcome Measures :
  1. Steady state PK of nalbuphine HCl ER tablets as a function of dose [ Time Frame: Day -1 to 14 Cohort 1 Groups 1-3 and Cohort 2; Day -1 to 17 Cohort 1 Group 4 ]
    Steady state PK of nalbuphine HCl ER tablets following escalating repeated oral doses in ESRD patients receiving HD therapy relative to healthy subjects

  2. Extent of extraction of nalbuphine by measuring nalbuphine in plasma and dialysate during dialysis [ Time Frame: Day -1 to 14 Cohort 1 Groups 1-3; Day -1 to 17 Cohort 1 Group 4 ]
    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 :
  1. VAS measurement of anti-pruritic effects [ Time Frame: Day -1 to 19-21 Cohort 1 Groups 1-3; Day -1 to 22-24 Cohort 1 Group 4 ]
    Visual Analogue Scale (VAS) itch measurement of anti-pruritic effects of nalbuphine HCl ER tablets in HD subjects with pruritus



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

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): NCT02373215


Sponsors and Collaborators
Trevi Therapeutics
Davita Clinical Research
Investigators
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Study Director: Thomas Sciascia Trevi Therapeutics
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Responsible Party: Trevi Therapeutics
ClinicalTrials.gov Identifier: NCT02373215    
Other Study ID Numbers: TR01
First Posted: February 26, 2015    Key Record Dates
Last Update Posted: August 3, 2020
Last Verified: July 2020
Additional relevant MeSH terms:
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Pruritus
Skin Diseases
Skin Manifestations
Nalbuphine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents