An Open-Label, Phase 1 Study in Healthy Adult Subjects to Examine the Effects of Multiple-Dose Ciprofloxacin on Ivacaftor and VX-661 in Combination With Ivacaftor

An Open-Label, Phase 1 Study in Healthy Adult Subjects to Examine the Effects of Multiple-Dose Ciprofloxacin on the Multiple-Dose Pharmacokinetics of Ivacaftor and on the Multiple-Dose Pharmacokinetics of VX-661 Administered in Combination With Ivacaftor

To evaluate the effect of ciprofloxacin on the pharmacokinetics (PK) of ivacaftor and on the pharmacokinetics of VX-661 when administered in combination with ivacaftor

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: ivacaftor; Drug: ciprofloxacin; Drug: VX-661

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Willing and able to comply with scheduled visits, treatment plan, study restrictions,laboratory tests, contraception guidelines, and other study procedures
• Healthy subjects, as defined by no clinically relevant abnormalities identified by a detailed medical history and full physical examination, including blood pressure and heart rate measurement, standard 12-lead ECG, and clinical laboratory tests.
• Body mass index (BMI) of 18.0 to 31.0 kg/m2, inclusive, and a total body weight >50 kg
• Female subjects of childbearing potential must have a negative serum pregnancy test at screening and at the Day -1 Visit.

Exclusion Criteria:

• History of any illness, clinical condition, or other factor that, in the opinion of the investigator or the subject's general practitioner, might confound the results of the study or pose an additional risk in administering study drug(s) to the subject
• Inability to swallow capsules, or inadequate venous access.
• History of febrile illness within 5 days before the first study drug dose
• A screen positive for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus 1 or 2 antibodies.
• For female subjects: Pregnant or nursing subjects and female subjects of childbearing potential who are unwilling or unable to use an acceptable method of contraception as outlined in this protocol. For male subjects: Subject has a female partner who is pregnant, nursing, or planning to become pregnant during the study or within 120 days after the last study drug dose.
• Any condition possibly affecting drug absorption
• Abnormal renal function at screening

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cohort 1; participants in Cohort 1 will be administered ivacaftor alone followed by ivacaftor with concomitant ciprofloxacin.	Drug: ivacaftor; Drug: ciprofloxacin
Experimental: Cohort 2; Participants in Cohort 2 will be administered VX-661 in combination with ivacaftor followed by VX-661 in combination with ivacaftor and concomitant ciprofloxacin	Drug: ivacaftor; Drug: ciprofloxacin; Drug: VX-661

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK parameters of ivacaftor and metabolites following concomitant dosing with ciprofloxacin relative to ivacaftor administered alone	PK Parameters - maximum observed plasma concentrations (Cmax) and area under the concentration versus time curve (AUC),	Day 7, Day 14
PK parameters of VX-661 and metabolites when dosed in combination with ivacaftor and concomitant ciprofloxacin relative to VX-661 administered in combination with ivacaftor	PK parameters - maximum observed plasma concentrations (Cmax) and area under the concentration versus time curve (AUC),	Day 10, Day 20

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK parameters of ivacaftor and metabolites when administered in combination with VX-661, with and without concomitant ciprofloxacin	PK Parameters - maximum observed plasma concentrations (Cmax) and area under the concentration versus time curve (AUC),	Day 10, Day 20
Safety and tolerability, as assessed by adverse events (AEs), vital signs, ECGs and laboratory assessments		Day 1 through Day 21 (cohort 1) or Day 34 (cohort2)

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated
• Investigators: Study Director: Medical Monitor, Vertex Pharmaceutical Incorporated

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: December 9, 2013
• First Submitted That Met QC Criteria: December 12, 2013
• First Posted (Estimate): December 19, 2013

Study Record Updates

• Last Update Posted (Estimate): March 26, 2014
• Last Update Submitted That Met QC Criteria: March 25, 2014
• Last Verified: March 1, 2014

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; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Membrane Transport Modulators; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Chloride Channel Agonists; Ciprofloxacin; Ivacaftor
• Other Study ID Numbers: VX13-770-017