Pharmacokinetic and Safety Study of Cenicriviroc and Pioglitazone, When Dosed Alone or in Combination

A Phase 1, Multiple-Dose, Open-Label, Randomized, Crossover Study in Healthy Subjects to Assess the Effect of Pioglitazone (PGZ) on the Pharmacokinetics (PK) of Cenicriviroc Mesylate (CVC) and the Effect of CVC on the PK of PGZ

A single center, open-label, fixed sequence study to evaluate the pharmacokinetics (PK) of Cenicriviroc (CVC) administered with and without Pioglitazone (PGZ), and to evaluate the PK of PGZ administered with and without CVC.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Cenicriviroc; Drug: Pioglitazone

Detailed Description

This is a open-label, fixed-sequence, 3-period study being conducted in a single center to evaluate the following:

• PK of CVC administered with and without PGZ
• PK of PGZ administered with and without CVC
• Safety of CVC administered with and without PGZ
• Tolerability of CVC administered with and without PGZ

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Lakewood, Colorado, United States, 80228
      • Davita Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provide written informed consent
• BMI ≥ 18 and ≤ 35 kg/m2
• No clinically relevant abnormalities based on medical history, physical examination, clinical laboratory evaluations, and 12-lead ECG
• Agree to comply with the study procedures and restrictions

Exclusion Criteria:

• Any disease or condition that might affect drug absorption, metabolism, or excretion, or clinically significant conditions as determined by the investigator
• History of stomach or intestinal surgery, except for fully healed appendectomy and/or cholecystectomy
• Serum ALT, AST or bilirubin ≥ grade 1 (ALT and AST > ULN - 3.0 x ULN; bilirubin > ULN - 1.5 x ULN) at screening
• Positive for HIV, HBV or HCV infection
• Use of any prescription drugs or prohibited medications within 30 days from the first dose of the study medication
• Use of alcohol-containing or caffeine-containing foods or beverages within 72 hours prior to the first dose of study medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 (Cenicriviroc, PGZ, CVC+PGZ); Treatment A: CVC 150 mg QD for 10 days followed by 10-day washout Treatment B: PGZ 45 mg QD for 10 days Treatment C: co-administration of PGZ 45 mg QD + CVC 150 mg QD for 10 days	Drug: Cenicriviroc; CVC 150 mg QD on Days 1-10, washout on Days 11-20, PGZ 45 mg QD on Days 21-30, and CVC 150 mg QD + PGZ 45 mg QD on Days 31-40; Other Names: CVC 150 mg
Experimental: Group 2 (Pioglitazone, CVC, CVC+PGZ); Treatment B: PGZ 45 mg QD for 10 days followed by 10-day washout Treatment A: CVC 150 mg QD for 10 days Treatment C: co-administration of CVC 150 mg QD + PGZ 45 mg QD for 10 days	Drug: Pioglitazone; PGZ 45 mg QD on Days 1-10, washout on Days 11-20, CVC 150 mg QD on Days 21-30, and CVC 150 mg QD + PGZ 45 mg QD on Days 31-40; Other Names: PGZ 45 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Assessment of CVC, as measured by Cmax, Cmin and AUC	PK profile will be calculated based on CVC exposure. Trough (predose) CVC plasma samples will be obtained prior to dosing on Days 2-9, 22-29, and 32-39.	Predose (0 hours), 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours postdose on Days 10, 30 and 40
Pharmacokinetic Assessment of PGZ, as measured by Cmax, Cmin and AUC	PK profile will be calculated based on PGZ exposure. Trough (predose) CVC plasma samples will be obtained prior to dosing on Days 2-9, 22-29, and 32-39.	Predose (0 hours), 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours postdose on Days 10, 30 and 40

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of Adverse Events	Evaluate adverse events	40 days
Changes from Baseline in Clinical Laboratory Tests	Evaluate changes from baseline in clinical laboratory tests including serum chemistry (ALT, AST, BUN, cholesterol, glucose), hematology (hemoglobin, red blood cell count, white blood cell count and differential), urinalysis (pH, glucose, ketones, protein, urobilinogen)	40 days
Changes from Baseline in 12-lead ECGs	Evaluate changes from baseline in 12-lead ECGs	40 days
Changes from Baseline in Vital Signs	Evaluate changes from baseline in vital signs, including blood pressure and pulse rate	40 days
Changes from Baseline in Physical Examinations	Evaluate changes from baseline in physical examinations	40 days

Collaborators and Investigators

• Sponsor: Tobira Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: January 12, 2015
• First Submitted That Met QC Criteria: January 14, 2015
• First Posted (Estimate): January 19, 2015

Study Record Updates

• Last Update Posted (Estimate): May 12, 2015
• Last Update Submitted That Met QC Criteria: May 11, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; CCR5 Receptor Antagonists; Pioglitazone; Cenicriviroc
• Other Study ID Numbers: 652-1-122