BACKGROUND: Ivacaftor, a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, is approved for the treatment of patients with cystic fibrosis aged 6 years or older with Gly551Asp-CFTR. We assessed the safety and efficacy of ivacaftor during 96 weeks of PERSIST in patients with cystic fibrosis who completed a previous 48-week, placebo-controlled trial of the drug (STRIVE or ENVISION). METHODS: In this phase 3, open-label extension study, patients received ivacaftor 150 mg every 12 h in addition to their prescribed cystic fibrosis therapies. Patients who received placebo in their previous study initiated ivacaftor in this extension study. Patients were eligible if they had a Gly551Asp-CFTR mutation on at least one allele. The primary objective was to assess the long-term safety profile of ivacaftor as assessed by adverse events, clinical laboratory assessments, electrocardiograms, vital signs, and physical examination; secondary measures included change in forced expiratory volume in one second (FEV1), weight, and pulmonary exacerbations. This study is registered with ClinicalTrials.gov, number NCT01117012 and EudraCT, number 2009-012997-11. FINDINGS: Between July 8, 2010, and April 8, 2013, 144 adolescents/adults (≥12 years) from STRIVE and 48 children (6-11 years) from ENVISION were enrolled. Across both trials, 38 (20%) patients had a serious adverse event during the first 48 weeks and 44 (23%) during the subsequent 48 weeks. Two adults (1%) and one child (<1%) discontinued because of adverse events. The most common adverse events were pulmonary exacerbation, cough, and upper respiratory tract infection. Patients previously treated with ivacaftor had sustained improvements in FEV1, weight, and rate of pulmonary exacerbations for up to 144 weeks of treatment. Among adolescents/adults and children who previously received ivacaftor, absolute change in FEV1 at week 96 (144 weeks ivacaftor) was 9·4 and 10·3 % points and absolute increase in weight was 4·1 kg and 14·8 kg, respectively. For adolescents/adults only, the pulmonary exacerbation rate remained suppressed compared with that of patients who received placebo in the placebo-controlled study. INTERPRETATION: At 144 weeks of treatment, ivacaftor was well tolerated, with no new safety concerns. Ivacaftor also provided durable effects for 144 weeks in patients who had received active treatment in the placebo-controlled study. Those patients who previously received placebo had improvements comparable to those of patients treated with ivacaftor in the placebo-controlled study. FUNDING: Vertex Pharmaceuticals Inc.

Assistance Publique Hôpitaux de Paris Hôpital Robert Debré CF Centre Université Paris 7 Paris France

Assistance Publique Hôpitaux de Paris INSERM U 1151 Université Paris Sorbonne Paris France

Case Western Reserve University School of Medicine and Rainbow Babies and Children's Hospital Cleveland OH USA

Cork University Hospital University College Cork Ireland

Division of Respiratory Medicine Department of Pediatrics The Hospital for Sick Children Toronto ON Canada; University of Toronto Toronto ON Canada

Hauner Children's Hospital Munich Germany; Ludwig Maximillians University Munich Germany

Royal Brompton Hospital London UK

Royal Children's Hospital and Queensland Children's Medical Research Institute The University of Queensland Brisbane QLD Australia

St Vincent's University Hospital Dublin Ireland; University College Dublin School of Medicine Dublin Ireland

State University of New York at Buffalo Buffalo NY USA

University Hospital Motol and 2nd Faculty of Medicine Charles University Prague Czech Republic

Vertex Pharmaceuticals Inc Boston MA USA

Lancet Respir Med. 2014 Nov;2(11):863-865. doi: 10.1016/S2213-2600(14)70191-2. PubMed

Citace poskytuje Crossref.org

Paediatrics: messages from Munich

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ClinicalTrials.gov
NCT01117012

EudraCT
2009-012997-11