Back to resultsPhase 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
About this trial
This is an interventional treatment trial for Uremic Pruritus
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.
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
NCT ID
NCT02373215
First Posted
February 13, 2015
Last Updated
July 30, 2020
Sponsor
Trevi Therapeutics
Collaborators
Davita Clinical Research
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
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