Pharmacokinetic and Safety Study of Cenicriviroc and HMG-CoA Reductase Inhibitors, Caffeine and Digoxin

A Phase 1 Open-Label Study in Healthy Adult Subjects to Assess the Effect of Cenicriviroc Mesylate (CVC) on the Pharmacokinetics (PK) of HMG-CoA Reductase Inhibitors (Rosuvastatin, Atorvastatin and Simvastatin), Caffeine and Digoxin

This is a Phase 1, Open-Label, 3-Period, Single-sequence, Drug-drug Interaction Study in Healthy Subjects to Assess the Effect of Cenicriviroc on the Pharmacokinetics (PK) of HMG-CoA Reductase Inhibitors [Rosuvastatin (ROS), Atorvastatin (ATO) and Simvastatin (SIM)], Caffeine and Digoxin

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Rosuvastatin; Drug: Atorvastatin; Drug: Caffeine; Drug: Digoxin; Drug: Simvastatin

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Be informed of the nature of the study and have provided written informed voluntary consent.
• Have a BMI ≥ 18.0 and ≤ 35.0 kg/m2.
• Be in good general health with no clinically relevant abnormalities based on medical history, physical examination, clinical laboratory evaluations (clinical chemistry, hematology, urinalysis), and 12-lead ECG that, in the opinion of the Investigator, would affect subject safety.
• Be able to communicate effectively with the Investigator and other study center personnel and 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 cardiovascular, hematological, renal, hepatic, pulmonary, endocrine, gastrointestinal, immunological, dermatological, neurological, or psychiatric disease, as determined by the Investigator and, if necessary, the Sponsor's Medical Monitor.
• History of stomach or intestinal surgery, except for fully healed appendectomy and/or cholecystectomy which will be allowed.
• Clinically significant illness or clinically significant surgery within 4 weeks before the administration of study medication.
• History of GERD, heartburn, or nausea more than once a month, or any similar symptoms requiring the regular use of antacids, or any use of H2 histamine blockers or proton-pump inhibitors over the past 3 months.
• History of achlorhydria, pernicious anemia, or peptic ulcers over the past 6 months.
• Known or suspected hypersensitivity or allergic reaction to any of the components of CVC, ROS, ATO, SIM, Digoxin or Caffeine tablets.
• History of malignancy, with the exception of cured basal cell or squamous cell carcinoma of the skin.
• If female, is pregnant or breast feeding, or has a positive pregnancy test result prior to the first dose of study medication.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1 (Rosuvastatin); Group 1 (12 subjects) will receive Rosuvastatin on Days 1 and 13.	Drug: Rosuvastatin; Other Names: Rosuvastatin 20 mg
Active Comparator: Group 1 (Digoxin); Group 1 (12 subjects) will receive Digoxin on Days 1 and 13.	Drug: Digoxin; Other Names: Digoxin 0.25 mg
Active Comparator: Group 1 (Caffeine); Group 1 (12 subjects) will receive Caffeine on Days 1 and 13.	Drug: Caffeine; Other Names: Caffine 200 mg
Active Comparator: Group 2 (Atorvastatin); Group 2 (12 subjects) will receive Atorvastatin on Days 1 and 13.	Drug: Atorvastatin; Other Names: Atorvastatin 20 mg
Experimental: Cenicriviroc; Subjects in Group 1 and Group 2 will receive Cenicriviroc on Days 3-12. Subjects in Group 3 will receive Cenicriviroc on Days 2-12.	Drug: Rosuvastatin; Other Names: Rosuvastatin 20 mg; Drug: Atorvastatin; Other Names: Atorvastatin 20 mg; Drug: Caffeine; Other Names: Caffine 200 mg; Drug: Digoxin; Other Names: Digoxin 0.25 mg; Drug: Simvastatin; Other Names: Simvastatin 20 mg
Active Comparator: Group 3 (Simvastatin); Group 3 (12 subjects) will receive Simvastatin on Days 1 and 12.	Drug: Simvastatin; Other Names: Simvastatin 20 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic Assessment of ROS, ATO and Digoxin alone and in the presence of CVC, as measured by maximum plasma concentration (Cmax)	Days 1 and 13
Pharmacokinetic Assessment of SIM alone and in the presence of CVC, as measured by maximum plasma concentration (Cmax)	Days 1 and 12
Pharmacokinetic Assessment of Caffeine alone and in the presence of CVC, as measured by maximum plasma concentration (Cmax)	Days 1 and 13
Pharmacokinetic Assessment of ROS, ATO and Digoxin alone and in the presence of CVC, as measured by minimum plasma concentration (Cmin)	Days 1 and 13
Pharmacokinetic Assessment of ROS, ATO and Digoxin alone and in the presence of CVC, as measured by area under the plasma concentration-time curve (AUC)	Days 1 and 13
Pharmacokinetic Assessment of SIM alone and in the presence of CVC, as measured by minimum plasma concentration (Cmin)	Days 1 and 12
Pharmacokinetic Assessment of SIM alone and in the presence of CVC, as measured by area under the plasma concentration-time curve (AUC)	Days 1 and 12
Pharmacokinetic Assessment of Caffeine alone and in the presence of CVC, as measured by minimum plasma concentration (Cmin)	Days 1 and 13
Pharmacokinetic Assessment of Caffeine alone and in the presence of CVC, as measured by area under the plasma concentration-time curve (AUC)	Days 1 and 13

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of Adverse Events	Evaluate adverse events	23 days
Changes from Baseline in Clinical Laboratory Tests	Evaluate changes from baseline in clinical laboratory tests including serum chemistry, and hematology	Baseline and 23 days
Changes from Baseline in 12-lead ECGs	Evaluate changes from baseline in 12-lead ECGs	Baseline and 23 days
Changes from Baseline in Vital Signs	Evaluate changes from baseline in vital signs, including blood pressure and pulse rate	Baseline and 23 days
Changes from Baseline in Physical Examinations	Evaluate changes from baseline in physical examinations	Baseline and 23 days

Collaborators and Investigators

• Sponsor: Tobira Therapeutics, Inc.
• Investigators: Study Director: Millie Gottwald, PharmD, Tobira Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2016
• Primary Completion (Actual): February 23, 2016
• Study Completion (Actual): February 23, 2016

Study Registration Dates

• First Submitted: February 3, 2016
• First Submitted That Met QC Criteria: February 12, 2016
• First Posted (Estimate): February 18, 2016

Study Record Updates

• Last Update Posted (Actual): November 24, 2017
• Last Update Submitted That Met QC Criteria: November 21, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Enzyme Inhibitors; Purinergic Antagonists; Purinergic Agents; Antimetabolites; Protective Agents; Cardiotonic Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Digoxin; Atorvastatin; Rosuvastatin Calcium; Simvastatin; Caffeine
• Other Study ID Numbers: 652-124