A Phase 1 Study to Examine the Drug-Drug Interaction of Ciprofloxacin, Itraconazole, and Rifampin on the Combination of Lumacaftor With Ivacaftor in Healthy Adult Subjects
Phase 1
Completed
- Conditions
- Cystic Fibrosis
- Interventions
- Registration Number
- NCT01768663
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- Brief Summary
The purpose of this study is to examine the drug-drug interaction effects of ciprofloxacin, itraconazole, and rifampin on the pharmacokinetics of lumacaftor in combination with ivacaftor as well as to evaluate the potential effects of lumacaftor in combination with ivacaftor on lung function.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 80
Inclusion Criteria
- Male and female subjects must be between the ages of 18 and 55 years, inclusive
- Body mass index (BMI) of 18 to 31 kg/m2, inclusive, and a total body weight >50 kg.
Exclusion Criteria
- History of any illness that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug(s) to the subject. This may include, but is not limited to, a history of relevant drug or food allergies; history of cardiovascular or central nervous system disease; history or presence of clinically significant pathology; or history of mental disease.
- History of febrile illness within 5 days before the first dose.
- History of Gilbert's syndrome
- Abnormal renal function as defined at screening
- Blood donation of approximately 1 pint (500 mL) within 56 days before study drug administration
- Treatment with an investigational drug within 30 days or 5 half-lives (or as determined by the local requirements, whichever is longer) preceding the first dose of study drug
- Known hypersensitivity or prior adverse reaction to ciprofloxacin, or any member of the quinolone class of antimicrobial agents (Cohort 1 only); itraconazole, or to any of the other azoles (Cohort 2 only); rifampin, or to any of the rifamycins (Cohort 3 only)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment Group (Cohort 1) Lumacaftor Subjects will take lumacaftor in combination with ivacaftor for 14 days. Beginning on Day 15, subjects will take lumacaftor in combination with ivacaftor and ciprofloxacin through Day 21. Treatment Group (Cohort 2) Lumacaftor Subjects will take lumacaftor in combination with ivacaftor for 14 days. Beginning on Day 15, subjects will take lumacaftor in combination with ivacaftor and itraconazole through Day 21. Treatment Group (Cohort 3) Lumacaftor Subjects will take lumacaftor in combination with ivacaftor for 14 days. Beginning on Day 15, subjects will take lumacaftor in combination with ivacaftor and rifampin through Day 24. Treatment Group (Cohort 1) Ivacaftor Subjects will take lumacaftor in combination with ivacaftor for 14 days. Beginning on Day 15, subjects will take lumacaftor in combination with ivacaftor and ciprofloxacin through Day 21. Treatment Group (Cohort 1) Ciprofloxacin Subjects will take lumacaftor in combination with ivacaftor for 14 days. Beginning on Day 15, subjects will take lumacaftor in combination with ivacaftor and ciprofloxacin through Day 21. Treatment Group (Cohort 2) Ivacaftor Subjects will take lumacaftor in combination with ivacaftor for 14 days. Beginning on Day 15, subjects will take lumacaftor in combination with ivacaftor and itraconazole through Day 21. Treatment Group (Cohort 2) Itraconazole Subjects will take lumacaftor in combination with ivacaftor for 14 days. Beginning on Day 15, subjects will take lumacaftor in combination with ivacaftor and itraconazole through Day 21. Treatment Group (Cohort 4) Ivacaftor Subjects will take a single dose of lumacaftor in combination with ivacaftor on 3 occasions separated by 7 days. Treatment Group (Cohort 3) Ivacaftor Subjects will take lumacaftor in combination with ivacaftor for 14 days. Beginning on Day 15, subjects will take lumacaftor in combination with ivacaftor and rifampin through Day 24. Treatment Group (Cohort 4) Lumacaftor Subjects will take a single dose of lumacaftor in combination with ivacaftor on 3 occasions separated by 7 days. Treatment Group (Cohort 3) Rifampin Subjects will take lumacaftor in combination with ivacaftor for 14 days. Beginning on Day 15, subjects will take lumacaftor in combination with ivacaftor and rifampin through Day 24.
- Primary Outcome Measures
Name Time Method Cohort 4: Change in lung function from before treatment with lumacaftor/ivacaftor to after treatment with lumacaftor/ivacaftor. up to 21 days Cohorts 1-3: PK parameters including Cmax, and AUC from time of dosing to time tau of lumacaftor and ivacaftor in the absence and presence of ciprofloxacin, itraconazole, and rifampin up to 24 days
- Secondary Outcome Measures
Name Time Method Cohorts 1-4: Safety and tolerability as measured by adverse events (AEs) and changes in laboratory test values (serum chemistry, hematology, coagulation, and urinalysis), vital signs, standard 12 lead electrocardiograms (ECGs), and spirometry up to 31 days Cohort 4: PK parameters, including Cmax of lumacaftor/ivacaftor, and lung function 16 days