Impact of Severe Hepatic Impairment on Pharmacokinetics of Cenicriviroc and Its Metabolites

An Open-Label Study to Evaluate the Effect of Severe Hepatic Impairment on the Pharmacokinetics of Cenicriviroc and Its Metabolites Following Single Dose Administration

The objective of this study is to assess the pharmacokinetics (PK), safety, and tolerability profiles of cenicriviroc (CVC) and its metabolites (M-I and M-II) in participants with severely impaired hepatic function compared with matched healthy participants following single-dose administration

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: Cenicriviroc

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology of Miami
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria for all participants:

• Sign the ICF and have the mental capability to understand it
• If female, have a negative result from a serum pregnancy test at screening and a negative result from a serum or urine pregnancy test on Day -1
• If male, agree to use an effective method of contraception (ie, condom plus diaphragm with spermicide or condom plus spermicide) and not have their partners become pregnant for at least 30 days after dosing study treatment, or have been sterilized for at least 1 year
• If female of childbearing potential, agree to use an effective method of contraception (ie, condom plus diaphragm with spermicide, condom plus spermicide, or nonhormonal intrauterine device) and not become pregnant for at least 30 days after dosing study treatment. Females who are at least 2 years postmenopausal (with supporting documentation from an obstetrician/gynecologist) or who have had tubal ligation or hysterectomy (with supporting documentation from the physician who performed the surgery) will not be considered to be of childbearing potential
• Be nonsmoking (never smoked or have not smoked in the previous 2 years) or a light smoker (fewer than 10 cigarettes per day within 1 week prior to study treatment administration)
• Have a body mass index (BMI) ≥ 18 kg/m2 and ≤ 42 kg/m2

Inclusion Criteria for Participants with Severely Impaired Hepatic Function:

• Have chronic liver disease and/or cirrhosis documented by the presence of at least 1 of the following:

  1. Liver biopsy with histologic findings consistent with cirrhosis
  2. Computerized tomographic or ultrasonographic evidence of liver disease with or without portal hypertension
  3. Physical examination and clinical and laboratory evidence of chronic liver disease

  4. Colloid shift on a liver-spleen scan

     Exclusion Criteria for all participants:

• Known hypersensitivity to cenicriviroc and other chemokine receptor 2 and/or 5 (CCR2 and/or CCR5) antagonists such as maraviroc (CCR5 antagonist)
• History of substance abuse within the previous 2 years
• Dosing in any other clinical investigation using an experimental drug requiring repeated blood or plasma draws within 30 days of study treatment administration
• Participation in a blood or plasma donation program within 60 or 30 days, respectively, of study treatment administration
• Consumption of caffeine within 48 hours prior to dosing; consumption of grapefruit containing products, vegetables from the mustard green family (eg, kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, mustard), foods containing poppy seeds, and charbroiled meats within 14 days prior to dosing; or consumption of alcohol within 72 hours prior to dosing before study treatment administration
• Employee, or immediate relative of an employee, of the sponsor, any of its affiliates or partners, or the study center
• Previously taken cenicriviroc or previously participated in an investigational study of cenicriviroc
• Pregnant or breastfeeding (female participants)

Exclusion Criteria for Participants with Severely Impaired Hepatic Function:

• Have an acute exacerbation of liver disease as indicated by worsening clinical signs and/or laboratory tests within the 4 weeks before study treatment administration
• Have ascites that will require paracentesis within 1 week of dosing or during the study period
• Have gastrointestinal hemorrhage due to esophageal varices, peptic ulcers or Mallory Weiss Syndrome within 6 months before Day 1, unless banded and stable
• Have a Child-Pugh score of < 10
• Any clinical condition other than hepatic impairment or previous surgery that might affect the absorption, distribution, biotransformation, or excretion of cenicriviroc and its metabolites

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Severe hepatic impairment; Cenicriviroc tablet; single-dose oral administration	Drug: Cenicriviroc; 1 tablet; single-dose oral administration; Other Names: CVC
EXPERIMENTAL: Normal Hepatic function; Cenicriviroc tablet; single-dose oral administration	Drug: Cenicriviroc; 1 tablet; single-dose oral administration; Other Names: CVC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the plasma concentration versus time curve (AUC) from time 0 to time t (AUC0-t)	6 days (144 hours)
AUC from time 0 to infinity (AUC0-∞)	6 days (144 hours)
Maximum plasma drug concentration (Cmax)	6 days (144 hours)

Secondary Outcome Measures

Outcome Measure	Time Frame
Time of maximum plasma drug concentration (Tmax)	6 days (144 hours)
Terminal elimination rate constant	6 days (144 hours)
Terminal elimination half-life (T½)	6 days (144 hours)
Total body clearance of drug from plasma (CL/F for CVC only)	6 days (144 hours)
Volume of distribution during the terminal phase (Vz/F for CVC only)	6 days (144 hours)

Collaborators and Investigators

• Sponsor: Allergan
• Investigators: Study Director: Surya Ayalasomayajula, Allergan

Publications and helpful links

Helpful Links

• Additional information on study locations near you may be found at AllerganClinicalTrials.com. For any study not on AllerganClinicalTrials.com, please contact IR-CTRegistration@Allergan.com for assistance.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 6, 2017
• Primary Completion (ACTUAL): November 24, 2017
• Study Completion (ACTUAL): December 17, 2017

Study Registration Dates

• First Submitted: August 2, 2017
• First Submitted That Met QC Criteria: December 13, 2017
• First Posted (ACTUAL): December 19, 2017

Study Record Updates

• Last Update Posted (ACTUAL): January 11, 2018
• Last Update Submitted That Met QC Criteria: January 9, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Hepatic Impairment; Cenicriviroc; Liver insufficiency
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; CCR5 Receptor Antagonists; Cenicriviroc
• Other Study ID Numbers: 3152-102-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No