Study of Ivacaftor in Subjects With Cystic Fibrosis (CF) Who Have the R117H-CF Transmembrane Conductance Regulator (CFTR) Mutation (KONDUCT)

Vertex Pharmaceuticals

Status and phase

Completed

Phase 3

Conditions

Cystic Fibrosis

Treatments

Drug: Placebo

Drug: Ivacaftor

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01614457

VX11-770-110

Details and patient eligibility

About

The purpose of this study is to evaluate the efficacy and safety of ivacaftor in subjects with cystic fibrosis (CF) who have the R117H-CFTR mutation.

Full description

Ivacaftor is the first CFTR modulator to show an improvement in CFTR function and clinical benefit in subjects with CF. Results from Phase 3 studies (VX08-770-102 [Study 102] [NCT00909532] and VX08-770-103 [Study 103] [NCT00909727]) showed that ivacaftor is effective in the treatment of subjects with CF who have the G551D-CFTR mutation, as evidenced by sustained improvements in CFTR channel function (measured by reduction in sweat chloride concentration) and corresponding substantial, durable improvements in lung function, pulmonary exacerbations, respiratory symptoms, and weight gain. Ivacaftor was also well tolerated, as evidenced by the rates and reasons for premature discontinuation and results of safety assessments.

Ivacaftor (Trade Name Kalydeco; 150 mg tablets) was initially approved in the United States for the treatment of CF in subjects 6 years of age and older who have a G551D mutation in the CFTR gene.

Enrollment

70 patients

Sex

All

Ages

6+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Male or female with confirmed diagnosis of CF
Must have at least 1 allele of the R117H CFTR mutation
Percent predicted forced expiratory volume in 1 second (FEV1) 40 percent (%) to 90% (for subjects aged 12 years or older) or 40% to 105% (for subjects aged 6 to 11 years) predicted normal for age, sex, and height
6 years of age or older
Minimum weight of 15 kilogram (kg) at screening
Females of childbearing potential must not be pregnant
Willing to comply with contraception requirements

Exclusion criteria

CFTR gene mutation leading to CFTR channel with gating defect (that is, any 1 of the following mutations: G551D, G178R, G551S, S549N, S549R, G970R, G1244E, S1251N, S1255P, or G1349D)
History of any illness or condition that might confound the results of the study or pose an additional risk in administering ivacaftor to the subject
An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before the first dose of study drug
Abnormal liver function, at screening, defined as greater than or equal to (>=) 3 time upper limit of normal (ULN), of any 3 or more of the following: serum aspartate transaminase (AST), serum alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT), serum alkaline phosphatase (ALP), total bilirubin
Colonization with organisms associated with a more rapid decline in pulmonary status (for example, Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus) at screening
History of solid organ or hematological transplantation
History of alcohol, medication or illicit drug abuse within 1 year before the first dose of study drug
Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within 30 days before screening
Any "non-CF-related" illness within 2 weeks before Day 1 (first dose of study drug). "Illness" was defined as an acute (serious or non-serious) condition (for example, gastroenteritis)
Use of any inhibitors or inducers of cytochrome (CYP) P450 3A