- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04020016
Nalbuphine ER Effects of Liver Disease on Pharmacokinetics and Itch
A Study of Nalbuphine Extended-release (NAL ER) Oral Tablets in Subjects With Impaired Hepatic Function Compared to Healthy Subjects and Exploratory Effect on Itch
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The study is a three-center study that will include both a single-ascending-dose (SAD) portion and a multiple-ascending dose (MAD) portion. The PK, safety, and tolerability of single ascending doses (SAD) of NAL ER (4 dose levels) will be evaluated in subjects with mild, moderate and severe hepatic impairment.
The purpose of the SAD will be to assess the safety and PK parameters of the given dose levels in hepatic impaired subjects relative to a selected healthy subject control population as part of the overall NAL ER development program. The SAD will also allow a better understanding of the safety, tolerability and expected steady state PK characteristics in mild and moderate hepatic impairment prior to undertaking safety and itch suppression efficacy studies in this patient population.
In the MAD portion of this study, PK assessment will be carried out at steady state at each respective dose level at steady state during the titration over 13 days up to the highest planned therapeutic dose of 162 mg. It is well documented, in clinical practice and the opiate literature, that gradually increasing the dose of drug with a structured titration can reduce the frequency and severity of the expected AEs associated with initiation of therapy. The NAL ER clinical program utilizes this type of structured titration strategy, starting with once per day dosing at the 27 mg dose of NAL ER, and increasing the dose in a stepwise manner over the next 13 days to the target investigational dose of 162 mg twice daily. Pharmacokinetic steady state is reached
Study Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Florida
-
Miami, Florida, United States, 33136
- 01
-
Miami, Florida, United States, 33146
- 02
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Orlando, Florida, United States, 32809
- 03
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
For Subjects with Hepatic Impairment (Cohort 1 to 4 and Cohort 6)
- Male or female with stable hepatic impairment, non-smoker and/or light smoker.
- Clinical diagnosis of liver cirrhosis
- Stable for study participation based upon medical history, physical examination, vital signs, ECGs, and screening clinical laboratory evaluations
Inclusion Criteria:
For Healthy Subjects (Cohort 5):
- Male or female, non-smoker and/or light smoker (up to 5 cigarettes or equivalent/day),
Healthy as defined by:
- Normal hepatic function
- The absence of clinically significant illness and surgery within 4 weeks prior to dosing.
Exclusion Criteria:
For Subjects with Hepatic Impairment (Cohort 1 to 4 and Cohort 6)
- Clinically significant unstable medical conditions
- Clinically significant abnormalities of laboratory, ECG, pulse oximetry, or clinical data that would preclude participation in the study.
- History of any illness that might confound the results of the study or pose an additional risk to the subject by participation in the study.
Exclusion Criteria
For Healthy Subjects (Cohort 5):
- Diagnosis of liver disease
- History of heart problems.
- History of significant alcohol abuse or drug abuse
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Part 1 Single Ascending Dose
Impaired liver function subjects and healthy liver subjects single ascending dosing up to 162 mg BID of Nalbuphine ER
|
Cohort 1: 6-8 subjects will receive 1 dose of 27mg and observed for 4 days.
Cohort 2: 6-7 subjects will receive 1 dose of 54 mg and observed for 4 days.
Cohort 3: 6-7 subjects will receive 1 dose of 108 mg and observed for 4 days.
Cohort 4: 6-8 subjects will receive 1 dose of 162 mg and observed for 4 days.
Cohort 5: 6-8 healthy subjects will receive dosing of NAL ER and observed for 4 days.
Other Names:
|
Experimental: Part 2 Multiple Ascending Dose
Impaired liver function subjects will receive multiple ascending dosing up to 162 mg BID of Nalbuphine ER
|
Cohort 6: • 6-8 subjects with mild hepatic impairment and 6-8 subjects with moderate hepatic impairment.
Doses will be subsequently escalated for each subject starting at 27 mg on Day 1 to twice daily, 12 hours apart, 27 mg, 54 mg, 108 mg, and 162 mg over 13 days.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Individual and mean plasma concentrations verses time curves will be evaluated as a function of dose
Time Frame: Day -1 to 14
|
The PK of NAL ER will be measured in hepatic impaired subjects steady state as a function of dose.
|
Day -1 to 14
|
Incidence of Treatment-Emergent Adverse Events as assessed by Pulse Oximetry and Electrocardiogram (ECG)
Time Frame: Day -1 to 14
|
Hepatic impaired subjects will be monitored for by pulse oximetry and ECG for Treatment-Emergent Adverse Events from dosing of NAL ER
|
Day -1 to 14
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Worst Itch Numerical Rating Scale (WI-NRS) measurement tool for rating of itch severity in the hepatic impaired population
Time Frame: Day -1 to Day 16
|
WI-NRS measure will be used to determine the severity of itch experienced by subjects with hepatic impairment (for Cohort 6 only) at screening.
Subjects will be completing the two forms (the "Night-time Itch" and the "Daytime Itch") at the same time during the screening visit and the average will be taken to determine the baseline severity.
The scale is a 0 to 10 rating scale with 10 being the most severe itch experienced and 0 being no itching experienced.
|
Day -1 to Day 16
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Thomas Sciascia, Trevi Therapeutics, Inc.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- Protocol 182018 (TR10)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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