Phase 1 Study of Multiple-Dose Pharmacokinetics of Cenicriviroc in Subjects With Mild and Moderate Hepatic Impairment

Study Overview
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Brief Summary
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To determine whether CVC exposures are altered in subjects with impaired hepatic function, compared to subjects with normal hepatic function. The results will help guide the clinical use of CVC in patients with hepatic impairment, determine the extent of PK changes, if any, and identify the potential need for dose adjustments of CVC in this population.

Official Title
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An Open Label, Phase 1 Study to Evaluate the Effect of Mile and Moderate Hepatic Impairment on the Multiple-Dose Pharmacokinetics of Cenicriviroc (CVC)

Conditions
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Liver Insufficiency

Intervention / Treatment
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* Drug: Cenicriviroc in mild liver impaired
* Drug: Cenicriviroc in moderate liver impaired


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and non-pregnant, non-lactating females aged 18-65 Weight ≥ 50.0 kg BMI 18.0 - 40.0 kg/m2 Able to participate, and willing to give written informed consent and to comply with the study restrictions Subjects with hepatic impairment will have stable liver disease (Child Pugh A or Child Pugh B) Exclusion Criteria: Pregnant or lactating women and male partners of women who are pregnant or lactating Uncontrolled treated or untreated hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 105 mmHg) QTcF > 450 msec for males and > 470 msec for females at Screening or Day -1 Donation or loss of blood over 350 mL within 60 days prior to screening Any evidence of progressive liver disease within the last 4 weeks for subjects with hepatic impairment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cenicriviroc in mild liver impaired<br>Subjects with mild liver impaired will receive cenicriviroc, 1 tablet once daily, for 14 days. Matching healthy subjects will receive Cenicriviroc, 1 tablet once daily, for 14 days. | Drug: Cenicriviroc in mild liver impaired<br>* Subjects with mild hepatic impairment will receive CVC, 1 tablet once daily, for 14 days. Matching healthy subjects will receive CVC, 1 tablet once daily, for 14 days.<br>* Other names: CVC;|
| Experimental: Cenicriviroc in moderate liver impaired<br>Subjects with moderate liver impaired will receive cenicriviroc, 1 tablet once daily, for 14 days. Matching healthy subjects will receive Cenicriviroc, 1 tablet once daily, for 14 days. | Drug: Cenicriviroc in moderate liver impaired<br>* Subjects with moderate hepatic impairment will receive CVC, 1 tablet once daily, for 14 days. Matching healthy subjects will receive CVC, 1 tablet once daily, for 14 days.<br>* Other names: CVC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Multiple-dose pharmacokinetics of CVC | Intensive PK on Days 1 and 14. Trough PK on Days 3-13. Additional free (unbound) CVC will be assessed 2 hours and 24 hours postdose on Day 14. | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours postdose on Days 1 and 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability | Adverse events, concomitant medications, vital signs, 12-lead triplicate ECGs, clinical laboratory tests (chemistry, hematology, urinalysis) and physical examinations will be assessed. | Days 1 through 35 for hepatic impaired subjects and Days 1-28 for healthy matching subjects | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver Insufficiency, Hepatic impairment