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

Sponsor

Vertex Pharmaceuticals Incorporated (Industry)

Overall Status

Completed

CT.gov ID

NCT01768663

Collaborator

(none)

Enrollment

Location

Arms

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: Lumacaftor Drug: Ivacaftor Drug: Ciprofloxacin Drug: Itraconazole Drug: Rifampin	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

80 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 2013

Actual Primary Completion Date :

Sep 1, 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Evansville	Indiana	United States

Sponsors and Collaborators

Vertex Pharmaceuticals Incorporated

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Vertex Pharmaceuticals Incorporated

ClinicalTrials.gov Identifier:

NCT01768663

Other Study ID Numbers:

VX12-809-009

First Posted:

Jan 15, 2013

Last Update Posted:

Nov 15, 2013

Last Verified:

Nov 1, 2013

Additional relevant MeSH terms:

Study Results

No Results Posted as of Nov 15, 2013