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

• ClinicalTrials.gov Identifier: NCT02342067
• Recruitment Status: Completed
• First Posted: January 19, 2015
• Last Update Posted: May 12, 2015
• Sponsor: Tobira Therapeutics, Inc.
• Information provided by (Responsible Party): Tobira Therapeutics, Inc.

Tracking Information

• First Submitted Date: January 12, 2015
• First Posted Date: January 19, 2015
• Last Update Posted Date: May 12, 2015
• Study Start Date: December 2014
• Actual Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 14, 2015)

• Pharmacokinetic Assessment of CVC, as measured by Cmax, Cmin and AUC [ Time Frame: Predose (0 hours), 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours postdose on Days 10, 30 and 40 ]
  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.
• Pharmacokinetic Assessment of PGZ, as measured by Cmax, Cmin and AUC [ Time Frame: Predose (0 hours), 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours postdose on Days 10, 30 and 40 ]
  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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 16, 2015)

• Evaluation of Adverse Events [ Time Frame: 40 days ]
  Evaluate adverse events
• Changes from Baseline in Clinical Laboratory Tests [ Time Frame: 40 days ]
  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)
• Changes from Baseline in 12-lead ECGs [ Time Frame: 40 days ]
  Evaluate changes from baseline in 12-lead ECGs
• Changes from Baseline in Vital Signs [ Time Frame: 40 days ]
  Evaluate changes from baseline in vital signs, including blood pressure and pulse rate
• Changes from Baseline in Physical Examinations [ Time Frame: 40 days ]
  Evaluate changes from baseline in physical examinations

Original Secondary Outcome Measures (submitted: January 14, 2015)

• Evaluation of Adverse Events [ Time Frame: 40 days ]
  Evaluate adverse events
• Changes from Baseline in Clinical Laboratory Tests [ Time Frame: 40 days ]
  Evaluate changes from baseline in clinical laboratory tests (chemistry, hematology, urinalysis)
• Changes from Baseline in 12-lead ECGs [ Time Frame: 40 days ]
  Evaluate changes from baseline in 12-lead ECGs
• Changes from Baseline in Vital Signs [ Time Frame: 40 days ]
  Evaluate changes from baseline in vital signs
• Changes from Baseline in Physical Examinations [ Time Frame: 40 days ]
  Evaluate changes from baseline in physical examinations

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pharmacokinetic and Safety Study of Cenicriviroc and Pioglitazone, When Dosed Alone or in Combination
• Official Title: 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
• Brief Summary: 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

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
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Healthy

Intervention

• 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 Name: CVC 150 mg
• 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 Name: PGZ 45 mg

Study Arms

• 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
  Intervention: Drug: Cenicriviroc
• 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
  Intervention: Drug: Pioglitazone

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 14, 2015): 20
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: April 2015
• Actual Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02342067
• Other Study ID Numbers: 652-1-122
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Tobira Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Tobira Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Tobira Therapeutics, Inc.
• Verification Date: May 2015