Journal Article

Efficacy and Safety of Ivacaftor in Patients Aged 6 to 11 Years with Cystic Fibrosis with a G551D Mutation

Ordoñez, Claudia L., Rodriguez, Sally, Li, Haihong, Mainz, Jochen G., Canny, Gerard J., Chilvers, Mark A., Howenstine, Michelle S., Wainwright, Claire E., Yen, Karl, Munck, Anne, Ahrens, Richard, Davies, Jane C.

2013

Overview

Abstract Rationale Ivacaftor (VX-770), a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, has been shown to improve lung function, pulmonary exacerbation rate, respiratory symptoms, and weight gain compared with placebo in patients with cystic fibrosis aged 12 years or older with a G551D-CFTR mutation. Objectives This randomized, double-blind, placebo-controlled trial evaluated ivacaftor in patients with cystic fibrosis aged 6–11 years with a G551D-CFTR mutation on at least one allele. Methods Patients were randomly assigned to receive ivacaftor administered orally at 150 mg (n = 26) or placebo (n = 26) every 12 hours for 48 weeks in addition to existing prescribed cystic fibrosis therapies. Measurements and Main Results Despite near-normal mean baseline values in FEV1, patients receiving ivacaftor had a significant increase in percent predicted FEV1 from baseline through Week 24 versus placebo group (treatment effect, 12.5 percentage points; P < 0.001). Effects on pulmonary function were evident by 2 weeks, and a significant treatment effect was maintained through Week 48. Patients treated with ivacaftor gained, on average, 2.8 kg more than those receiving placebo at Week 48 (P < 0.001). The change from baseline through Week 48 in the concentration of sweat chloride, a measure of CFTR activity, with ivacaftor was −53.5 mmol/L (P < 0.001) versus placebo. The incidence of adverse events was similar in the two groups. Conclusions In patients who are younger and healthier than those in previously studied populations, ivacaftor demonstrated a significant improvement in pulmonary function, weight, and CFTR activity compared with placebo. Clinical trial registered with www.clinicaltrials.gov (NCT00909727).

• Publisher: Oxford University Press,American Thoracic Society
• Subject: Administration, Oral / Alleles / Aminophenols - administration & dosage / Aminophenols - therapeutic use / Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy / Biological and medical sciences / Child / Chloride / Cystic fibrosis / Cystic Fibrosis - drug therapy / Cystic Fibrosis - genetics / Cystic Fibrosis - metabolism / Cystic Fibrosis Transmembrane Conductance Regulator - genetics / Cystic Fibrosis Transmembrane Conductance Regulator - metabolism / DNA - genetics / Dose-Response Relationship, Drug / Double-Blind Method / Errors of metabolism / Forced Expiratory Volume / Humans / Intensive care medicine / Lung - physiopathology / Medical sciences / Metabolic diseases / Miscellaneous hereditary metabolic disorders / Mutation / Patients / Pneumology / Proteins / Quinolones - administration & dosage / Quinolones - therapeutic use / Respiratory Function Tests / Treatment Outcome