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

Phase 1

Completed

Interventions: Drug: Digoxin
Drug: Caffeine
Drug: Rosuvastatin
Drug: Atorvastatin
Drug: Simvastatin

Brief Summary: 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

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Cenicriviroc	Atorvastatin	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.
Cenicriviroc	Simvastatin	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.
Group 1 (Digoxin)	Digoxin	Group 1 (12 subjects) will receive Digoxin on Days 1 and 13.
Group 1 (Caffeine)	Caffeine	Group 1 (12 subjects) will receive Caffeine on Days 1 and 13.
Group 1 (Rosuvastatin)	Rosuvastatin	Group 1 (12 subjects) will receive Rosuvastatin on Days 1 and 13.
Cenicriviroc	Rosuvastatin	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.
Cenicriviroc	Digoxin	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.
Group 2 (Atorvastatin)	Atorvastatin	Group 2 (12 subjects) will receive Atorvastatin on Days 1 and 13.
Group 3 (Simvastatin)	Simvastatin	Group 3 (12 subjects) will receive Simvastatin on Days 1 and 12.
Cenicriviroc	Caffeine	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.

Primary Outcome Measures

Name	Time	Method
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 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 area under the plasma concentration-time curve (AUC)	Days 1 and 13
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 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 ROS, ATO and Digoxin alone and in the presence of CVC, as measured by maximum plasma concentration (Cmax)	Days 1 and 13

Secondary Outcome Measures

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