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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Rosuvastatin
* Drug: Atorvastatin
* Drug: Simvastatin
* Drug: Digoxin
* Drug: Caffeine


Participation Criteria
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Eligibility Criteria
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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.

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |