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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT01768663
First received: January 11, 2013
Last updated: November 14, 2013
Last verified: November 2013
  Purpose

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 Intervention Phase
Cystic Fibrosis
Drug: Lumacaftor
Drug: Ivacaftor
Drug: Ciprofloxacin
Drug: Itraconazole
Drug: Rifampin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Vertex Pharmaceuticals Incorporated:

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 [ Time Frame: up to 24 days ] [ Designated as safety issue: No ]
  • Cohort 4: Change in lung function from before treatment with lumacaftor/ivacaftor to after treatment with lumacaftor/ivacaftor. [ Time Frame: up to 21 days ] [ Designated as safety issue: No ]

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 [ Time Frame: up to 31 days ] [ Designated as safety issue: Yes ]
  • Cohort 4: PK parameters, including Cmax of lumacaftor/ivacaftor, and lung function [ Time Frame: 16 days ] [ Designated as safety issue: No ]

Enrollment: 80
Study Start Date: January 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: VX-809
Drug: Ivacaftor
tablet, 250mg taken every 12 hours
Other Name: 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 Name: VX-809
Drug: Ivacaftor
tablet, 250mg taken every 12 hours
Other Name: 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 Name: VX-809
Drug: Ivacaftor
tablet, 250mg taken every 12 hours
Other Name: 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 Name: VX-809
Drug: Ivacaftor
tablet, 250mg taken every 12 hours
Other Name: VX-770

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01768663

Locations
United States, Indiana
Evansville, Indiana, United States
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
  More Information

No publications provided

Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT01768663     History of Changes
Other Study ID Numbers: VX12-809-009
Study First Received: January 11, 2013
Last Updated: November 14, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Ciprofloxacin
Rifampin
Hydroxyitraconazole
Itraconazole
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antitubercular
Anti-Bacterial Agents
Antitubercular Agents
Leprostatic Agents
14-alpha Demethylase Inhibitors
Antifungal Agents

ClinicalTrials.gov processed this record on April 23, 2014