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

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

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Lumacaftor; Drug: Ivacaftor; Drug: Ciprofloxacin; Drug: Itraconazole; Drug: Rifampin

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Evansville, Indiana, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: January 11, 2013
• First Submitted That Met QC Criteria: January 11, 2013
• First Posted (Estimate): January 15, 2013

Study Record Updates

• Last Update Posted (Estimate): November 15, 2013
• Last Update Submitted That Met QC Criteria: November 14, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Cystic Fibrosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Membrane Transport Modulators; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Leprostatic Agents; Hormone Antagonists; Cytochrome P-450 Enzyme Inducers; Antifungal Agents; Steroid Synthesis Inhibitors; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; 14-alpha Demethylase Inhibitors; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Cytochrome P-450 CYP1A2 Inhibitors; Chloride Channel Agonists; Rifampin; Ciprofloxacin; Itraconazole; Ivacaftor
• Other Study ID Numbers: VX12-809-009