Uremic PruritusPhase 1NCT02373215
Phase 1 Study of Nalbuphine HCl ER Tablets in Hemodialysis Patients With Uremic Pruritus
A Phase 1 study testing Nalbuphine HCL ER in people with Uremic Pruritus, run by Trevi Therapeutics.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Uremic Pruritus
- What is being tested?
- Nalbuphine HCL ER
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- No sites listed yet
- Study dates
- Apr 2013to Nov 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Show all 15Show fewer
- 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.
Who cannot join
- 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.
Show all 15Show fewer
- 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.
About this study
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
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.
Read the 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
- Being tested
- Nalbuphine HCL ER
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nalbuphine HCL ERDrug
Also called Nalbuphine
Nalbuphine HCL extended release tablet
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 - Groups 1-3 | Experimental | HD patients dosing up to 180mg BID Receives: Drug: Nalbuphine HCL ER |
| Cohort 1 - Group 4 | Experimental | HD patients dosing up to 240mg BID Receives: Drug: Nalbuphine HCL ER |
| Cohort 2 | Experimental | Healthy patients dosing up to 180mg BID Receives: Drug: Nalbuphine HCL ER |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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
Visual Analogue Scale (VAS) itch measurement of anti-pruritic effects of nalbuphine HCl ER tablets in HD subjects with pruritus
Measured: Day -1 to 19-21 Cohort 1 Groups 1-3; Day -1 to 22-24 Cohort 1 Group 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2015 (estimated)
- Study startApr 2013
- Primary completionNov 2013
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Uremic PruritusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Trevi Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Davita Clinical Research
- Responsible party
- Sponsor
- Investigators
- Chief Development Officer, Study director, Trevi Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02373215
- Sponsor's protocol ID
- TR01
- Status last verified
- May 2025
- First submitted
- 13 Feb 2015
- Last updated
- 22 May 2025
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 36680419
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02373215
- Acronym / sponsor ID
- TR01
- Conditions
- Uremic Pruritus
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Trevi TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- Davita Clinical Research
- Study start
- Apr 2013
- Primary completion
- Nov 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 26 Feb 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 - Groups 1-3 | Experimental | Drug: Nalbuphine HCL ERHD patients dosing up to 180mg BID |
| Cohort 1 - Group 4 | Experimental | Drug: Nalbuphine HCL ERHD patients dosing up to 240mg BID |
| Cohort 2 | Experimental | Drug: Nalbuphine HCL ERHealthy patients dosing up to 180mg BID |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nalbuphine HCL ERAlso: NalbuphineNalbuphine HCL extended release tablet | Drug | Cohort 1 - Group 4, Cohort 1 - Groups 1-3, Cohort 2 |
Primary outcome
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
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.
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2025.
- Derived from this study: PubMed 36680419Eudy-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.
Related trials for Uremic Pruritus
Active, not recruitingObservational study
Cardiovascular and Bone Mineral Markers in Dialysis Patients and Healthy Controls
End-Stage Kidney Disease (ESKD), Hemodialysis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chief Development Officer study director
Trevi Therapeutics
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nalbuphine HCL ER in people with Uremic Pruritus, run by Trevi Therapeutics.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 May 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02373215, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2025.