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

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

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.

Study Overview

• Status: Completed
• Conditions: Liver Insufficiency
• Intervention / Treatment: Drug: Cenicriviroc in mild liver impaired; Drug: Cenicriviroc in moderate liver impaired

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Fort Lauderdale, Florida, United States, 33014
      • Clinical Pharmacology of Miami, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cenicriviroc in mild liver impaired; 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; 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.; Other Names: CVC
Experimental: Cenicriviroc in moderate liver impaired; 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; 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.; Other Names: CVC

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Time Frame
Pro-inflammatory cytokines and biomarkers of bacterial translocation	28 days after receiving first dose of study drug

Collaborators and Investigators

• Sponsor: Tobira Therapeutics, Inc.
• Investigators: Principal Investigator: Kenneth C Lasseter, MD, Clinical Pharmacology of Miami, Inc.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: April 18, 2014
• First Submitted That Met QC Criteria: April 18, 2014
• First Posted (Estimate): April 22, 2014

Study Record Updates

• Last Update Posted (Estimate): August 21, 2014
• Last Update Submitted That Met QC Criteria: August 19, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: Hepatic impairment; Liver Insufficiency
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Liver Failure; Hepatic Insufficiency; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Hematinics; CCR5 Receptor Antagonists; Liver Extracts; Cenicriviroc
• Other Study ID Numbers: TBR 652-1-121