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

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Cenicriviroc
* Drug: Pioglitazone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 (Cenicriviroc, PGZ, CVC+PGZ)<br>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<br>* 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<br>* Other names: CVC 150 mg;|
| Experimental: Group 2 (Pioglitazone, CVC, CVC+PGZ)<br>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<br>* 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<br>* Other names: PGZ 45 mg;|

What is the study measuring?
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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 |