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
Overview
- Phase
- Phase 1
- Intervention
- Rosuvastatin
- Conditions
- Healthy
- Sponsor
- Tobira Therapeutics, Inc.
- Enrollment
- 36
- Primary Endpoint
- Pharmacokinetic Assessment of SIM alone and in the presence of CVC, as measured by maximum plasma concentration (Cmax)
- Status
- Completed
- Last Updated
- 8 years ago
Overview
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
Investigators
Eligibility Criteria
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/m
- •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.
Arms & Interventions
Group 1 (Rosuvastatin)
Group 1 (12 subjects) will receive Rosuvastatin on Days 1 and 13.
Intervention: Rosuvastatin
Group 1 (Digoxin)
Group 1 (12 subjects) will receive Digoxin on Days 1 and 13.
Intervention: Digoxin
Group 1 (Caffeine)
Group 1 (12 subjects) will receive Caffeine on Days 1 and 13.
Intervention: Caffeine
Group 2 (Atorvastatin)
Group 2 (12 subjects) will receive Atorvastatin on Days 1 and 13.
Intervention: Atorvastatin
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.
Intervention: Rosuvastatin
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.
Intervention: Atorvastatin
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.
Intervention: Simvastatin
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.
Intervention: Digoxin
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.
Intervention: Caffeine
Group 3 (Simvastatin)
Group 3 (12 subjects) will receive Simvastatin on Days 1 and 12.
Intervention: Simvastatin
Outcomes
Primary Outcomes
Pharmacokinetic Assessment of SIM alone and in the presence of CVC, as measured by maximum plasma concentration (Cmax)
Time Frame: Days 1 and 12
Pharmacokinetic Assessment of SIM alone and in the presence of CVC, as measured by minimum plasma concentration (Cmin)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: Days 1 and 13
Pharmacokinetic Assessment of Caffeine alone and in the presence of CVC, as measured by maximum plasma concentration (Cmax)
Time Frame: Days 1 and 13
Pharmacokinetic Assessment of Caffeine alone and in the presence of CVC, as measured by minimum plasma concentration (Cmin)
Time Frame: 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)
Time Frame: Days 1 and 13
Secondary Outcomes
- Changes from Baseline in 12-lead ECGs(Baseline and 23 days)
- Evaluation of Adverse Events(23 days)
- Changes from Baseline in Clinical Laboratory Tests(Baseline and 23 days)
- Changes from Baseline in Vital Signs(Baseline and 23 days)
- Changes from Baseline in Physical Examinations(Baseline and 23 days)