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

NCT02685462 | Completed Phase 1

• 1 other identifier: 652-124
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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

Conditions

Healthy

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (5)

• Evaluation of Adverse Events

  23 days

• Changes from Baseline in Clinical Laboratory Tests

  Baseline and 23 days

• Changes from Baseline in 12-lead ECGs

  Baseline and 23 days

• Changes from Baseline in Vital Signs

  Baseline and 23 days

• Changes from Baseline in Physical Examinations

  Baseline and 23 days

Study Arms (6)

Group 1 (Rosuvastatin)

ACTIVE COMPARATOR

Group 1 (12 subjects) will receive Rosuvastatin on Days 1 and 13.

Drug: Rosuvastatin

Group 1 (Digoxin)

ACTIVE COMPARATOR

Group 1 (12 subjects) will receive Digoxin on Days 1 and 13.

Drug: Digoxin

Group 1 (Caffeine)

ACTIVE COMPARATOR

Group 1 (12 subjects) will receive Caffeine on Days 1 and 13.

Drug: Caffeine

Group 2 (Atorvastatin)

ACTIVE COMPARATOR

Group 2 (12 subjects) will receive Atorvastatin on Days 1 and 13.

Drug: Atorvastatin

Cenicriviroc

EXPERIMENTAL

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; Drug: Atorvastatin; Drug: Simvastatin; Drug: Digoxin; Drug: Caffeine

Group 3 (Simvastatin)

ACTIVE COMPARATOR

Group 3 (12 subjects) will receive Simvastatin on Days 1 and 12.

Drug: Simvastatin

Interventions

Rosuvastatin DRUG

Also known as: Rosuvastatin 20 mg

Cenicriviroc; Group 1 (Rosuvastatin)

Atorvastatin DRUG

Also known as: Atorvastatin 20 mg

Cenicriviroc; Group 2 (Atorvastatin)

Simvastatin DRUG

Also known as: Simvastatin 20 mg

Cenicriviroc; Group 3 (Simvastatin)

Digoxin DRUG

Also known as: Digoxin 0.25 mg

Cenicriviroc; Group 1 (Digoxin)

Caffeine DRUG

Also known as: Caffine 200 mg

Cenicriviroc; Group 1 (Caffeine)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tobira Therapeutics, Inc.: lead

Study Sites (1)

Unknown Facility

Miami, Florida, United States

Location

MeSH Terms

Interventions

Rosuvastatin Calcium; Atorvastatin; Simvastatin; Digoxin; Caffeine

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrroles; Azoles; Heptanoic Acids; Fatty Acids; Lipids; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Glycosides; Carbohydrates; Xanthines; Alkaloids; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Millie Gottwald, PharmD

  Tobira Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2016
• First Posted: February 18, 2016
• Study Start: January 31, 2016
• Primary Completion: February 23, 2016
• Study Completion: February 23, 2016
• Last Updated: November 24, 2017

Record last verified: 2017-11

Locations

US (1)