Safety Study of Ivacaftor in Subjects With Cystic Fibrosis

Vertex Pharmaceuticals

Status and phase

Completed

Phase 2

Conditions

Cystic Fibrosis

Treatments

Drug: Ivacaftor 150 mg or 250 mg

Drug: Ivacaftor 25 mg/75 mg

Drug: Ivacaftor 75 mg/150 mg

Drug: Placebo

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00457821

VX06-770-101

Details and patient eligibility

About

The purpose of this study was to evaluate the safety and tolerability of ivacaftor in patients with cystic fibrosis (CF) who were aged 18 years or older and have a G551D mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Ivacaftor is a potent and selective CFTR potentiator of wild-type, G551D, F508del, and R117H forms of human CFTR protein. Potentiators are pharmacological agents that increase the chloride ion transport properties of the channel in the presence of cyclic AMP-dependent protein kinase A (PKA) activation.

Full description

This was a double-blind, placebo-controlled, cross-over, multiple dose study of up to 28 days of dosing, in subjects with cystic fibrosis (CF) who have a G551D-CTFR gene mutation. Enrollment of 39 subjects occurred at 15 centers in the US, Canada, and Germany.

The study was conducted in 2 parts:

Part 1 consisted of Group A and Group B. Subjects in Group A (10 subjects) were randomized to receive 25 mg of ivacaftor every 12 hours [q12h] (4 subjects), 75 mg of ivacaftor q12h (4 subjects), or placebo (2 subjects) for 14 days. Following a 7- to 28-day washout period, subjects who received active study drug crossed over to the alternate dose strength of ivacaftor for an additional 14 days. Placebo subjects continued to receive placebo for an additional 14 days. Subjects in Group B (10 subjects) were randomized to receive 75 mg of ivacaftor q12h (4 subjects), 150 mg of ivacaftor q12h (4 subjects), or placebo (2 subjects) for 14 days. Following a 7- to 28-day washout period, the subjects who received active study drug crossed over to the alternate dose strength of ivacaftor for an additional 14 days. Placebo subjects continued to receive placebo for an additional 14 days.
Part 2 consisted of Group C; these subjects did not participate in Part 1. Subjects were randomized to receive 150 mg of ivacaftor q12h (7 subjects), 250 mg of ivacaftor q12h (7 subjects), or placebo (4 subjects) for a total of 28 days. Ivacaftor doses studied in Part 2 were selected following an interim pharmacokinetic/pharmacodynamic (PK/PD) and statistical analyses of data from Part 1. The 2 doses selected for Part 2 were anticipated to enable better definition of the optimal therapeutic dose.

Enrollment

39 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Weighing at least 40 kg
Confirmed diagnosis of cystic fibrosis (CF) and G551D mutation in at least 1 allele
Forced expiratory volume in 1 second (FEV1) of at least 40% of predicted normal for age, gender, and height
Willing to remain on stable medication regimen for the duration of study participation
No significant clinical laboratory abnormalities, not pregnant, and willing to use at least 2 highly effective birth control methods during Part 1 and 1 highly effective birth control method during Part 2 of the study
No clinically significant abnormalities that would have interfered with the study assessments, as judged by the investigator

Exclusion criteria

History of any illness or condition that might confound the results of the study or pose an additional risk in administering study drug to the subject
Ongoing acute respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 14 days of Day 1 of the study
History of alcohol, medication or illicit drug abuse within one year prior to Day 1
Abnormal liver function ≥ 3x the upper limit of normal
History of abnormal renal function (creatinine clearance < 50 mL/min using Cockcroft-Gault equation)
History of solid organ or hematological transplantation
Pregnant or breast-feeding (for women)
Ongoing participation in another therapeutic clinical trial, or prior participation in an investigational drug study without appropriate washout
Concomitant use of any inhibitors or inducers of cytochrome P450 3A4 (CYP3A4)

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Crossover Assignment

Masking

Quadruple Blind

39 participants in 4 patient groups, including a placebo group

Ivacaftor Group A

Experimental group

Description:

Subjects in Part 1 who first received 25 mg or 75 mg of ivacaftor every 12 hours (q12h) for 14 days, then crossed over to receive the alternate dose for another 14 days.

Treatment:

Drug: Ivacaftor 25 mg/75 mg

Ivacaftor Group B

Experimental group

Description:

Subjects in Part 1 who first received 75 mg or 150 mg of ivacaftor q12h for 14 days then crossed over to receive the alternate dose for another 14 days.

Treatment:

Drug: Ivacaftor 75 mg/150 mg

Ivacaftor Group C

Experimental group

Description:

Subjects in Part 2 who received 150 mg or 250 mg of ivacaftor q12h for 28 days.

Treatment:

Drug: Ivacaftor 150 mg or 250 mg

Placebo

Placebo Comparator group

Description:

Subjects who received placebo in Part 1 and subjects who received placebo in Part 2.