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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1, Open-Label Study to Examine the Effect of Ciprofloxacin, Itraconazole, and Rifampin on the Pharmacokinetics of Lumacaftor in Combination With Ivacaftor in Healthy Adult Subjects

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Lumacaftor
* Drug: Ivacaftor
* Drug: Ciprofloxacin
* Drug: Itraconazole
* Drug: Rifampin


Participation Criteria
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Eligibility Criteria
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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)

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group (Cohort 1)<br>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. | Drug: Lumacaftor<br>* tablet, 200mg taken every 12 hours<br>* Other names: VX-809;Drug: Ivacaftor<br>* tablet, 250mg taken every 12 hours<br>* Other names: VX-770;Drug: Ciprofloxacin<br>* 750 mg taken every 12 hours<br>|
| Experimental: Treatment Group (Cohort 2)<br>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. | Drug: Lumacaftor<br>* tablet, 200mg taken every 12 hours<br>* Other names: VX-809;Drug: Ivacaftor<br>* tablet, 250mg taken every 12 hours<br>* Other names: VX-770;Drug: Itraconazole<br>* 200mg taken once daily<br>|
| Experimental: Treatment Group (Cohort 3)<br>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. | Drug: Lumacaftor<br>* tablet, 200mg taken every 12 hours<br>* Other names: VX-809;Drug: Ivacaftor<br>* tablet, 250mg taken every 12 hours<br>* Other names: VX-770;Drug: Rifampin<br>* 600mg taken once daily<br>|
| Experimental: Treatment Group (Cohort 4)<br>Subjects will take a single dose of lumacaftor in combination with ivacaftor on 3 occasions separated by 7 days. | Drug: Lumacaftor<br>* tablet, 200mg taken every 12 hours<br>* Other names: VX-809;Drug: Ivacaftor<br>* tablet, 250mg taken every 12 hours<br>* Other names: VX-770;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Cohort 4: Change in lung function from before treatment with lumacaftor/ivacaftor to after treatment with lumacaftor/ivacaftor. |  | up to 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |