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

NCT01768663 | Completed Phase 1

• 1 other identifier: VX12-809-009
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• 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

Study Arms (4)

Treatment Group (Cohort 1)

EXPERIMENTAL

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; Drug: Ivacaftor; Drug: Ciprofloxacin

Treatment Group (Cohort 2)

EXPERIMENTAL

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; Drug: Ivacaftor; Drug: Itraconazole

Treatment Group (Cohort 3)

EXPERIMENTAL

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; Drug: Ivacaftor; Drug: Rifampin

Treatment Group (Cohort 4)

EXPERIMENTAL

Subjects will take a single dose of lumacaftor in combination with ivacaftor on 3 occasions separated by 7 days.

Drug: Lumacaftor; Drug: Ivacaftor

Interventions

Lumacaftor DRUG

tablet, 200mg taken every 12 hours

Also known as: VX-809

Treatment Group (Cohort 1); Treatment Group (Cohort 2); Treatment Group (Cohort 3); Treatment Group (Cohort 4)

Ivacaftor DRUG

tablet, 250mg taken every 12 hours

Also known as: VX-770

Treatment Group (Cohort 1); Treatment Group (Cohort 2); Treatment Group (Cohort 3); Treatment Group (Cohort 4)

Ciprofloxacin DRUG

750 mg taken every 12 hours

Treatment Group (Cohort 1)

Itraconazole DRUG

200mg taken once daily

Treatment Group (Cohort 2)

Rifampin DRUG

600mg taken once daily

Treatment Group (Cohort 3)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead

Study Sites (1)

Unknown Facility

Evansville, Indiana, United States

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

lumacaftor; ivacaftor; Ciprofloxacin; Itraconazole; Rifampin

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Piperazines; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2013
• First Posted: January 15, 2013
• Study Start: January 1, 2013
• Primary Completion: September 1, 2013
• Last Updated: November 15, 2013

Record last verified: 2013-11

Locations

US (1)