Abstract | RATIONALE: 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).
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Authors | Jane C Davies, Claire E Wainwright, Gerard J Canny, Mark A Chilvers, Michelle S Howenstine, Anne Munck, Jochen G Mainz, Sally Rodriguez, Haihong Li, Karl Yen, Claudia L Ordoñez, Richard Ahrens, VX08-770-103 (ENVISION) Study Group |
Journal | American journal of respiratory and critical care medicine
(Am J Respir Crit Care Med)
Vol. 187
Issue 11
Pg. 1219-25
(Jun 01 2013)
ISSN: 1535-4970 [Electronic] United States |
PMID | 23590265
(Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Aminophenols
- CFTR protein, human
- Quinolones
- Cystic Fibrosis Transmembrane Conductance Regulator
- ivacaftor
- DNA
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Topics |
- Administration, Oral
- Alleles
- Aminophenols
(administration & dosage, therapeutic use)
- Child
- Cystic Fibrosis
(drug therapy, genetics, metabolism)
- Cystic Fibrosis Transmembrane Conductance Regulator
(genetics, metabolism)
- DNA
(genetics)
- Dose-Response Relationship, Drug
- Double-Blind Method
- Forced Expiratory Volume
- Humans
- Lung
(physiopathology)
- Mutation
- Quinolones
(administration & dosage, therapeutic use)
- Respiratory Function Tests
- Treatment Outcome
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