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      Lumacaftor/Ivacaftor in Patients Aged 6–11 Years with Cystic Fibrosis and Homozygous for F508del-CFTR

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          Abstract

          <p class="first" id="d12500761e233"> <b>Rationale:</b> Combination lumacaftor/ivacaftor has been shown to improve lung function and other endpoints in patients aged 12 years and older with cystic fibrosis and homozygous for <i>F508del-CFTR</i>, but it has not been assessed in younger patients. </p><p id="d12500761e241"> <b>Objectives:</b> In this open-label phase III trial, we evaluated the safety, tolerability, pharmacodynamics, and efficacy of lumacaftor/ivacaftor combination therapy in patients aged 6–11 years with cystic fibrosis who were homozygous for <i>F508del-CFTR</i>. </p><p id="d12500761e249"> <b>Methods:</b> Patients (N = 58) received 200 mg lumacaftor/250 mg ivacaftor orally every 12 hours for 24 weeks in addition to their existing cystic fibrosis medications. </p><p id="d12500761e254"> <b>Measurements and Main Results:</b> Lumacaftor/ivacaftor was well tolerated; the safety profile was generally similar to that observed in larger lumacaftor/ivacaftor trials with older patients. Four patients discontinued (two because of drug-related adverse events: elevated liver transaminases, n = 1; rash, n = 1). No safety concerns were associated with spirometry. No significant changes in percent predicted FEV <sub>1</sub> were observed (change from baseline at Week 24, +2.5 percentage points; 95% confidence interval [CI], −0.2 to 5.2; <i>P</i> = 0.0671). At Week 24, significant improvements from baseline were observed in sweat chloride (−24.8 mmol/L; 95% CI, −29.1 to −20.5; <i>P</i> &lt; 0.0001), body mass index <i>z</i> score (+0.15; 95% CI, 0.08 to 0.22; <i>P</i> &lt; 0.0001), Cystic Fibrosis Questionnaire-Revised respiratory domain score (+5.4; 95% CI, 1.4 to 9.4; <i>P</i> = 0.0085), and lung clearance index based on lung volume turnover required to reach 2.5% of starting N <sub>2</sub> concentration (−0.88; 95% CI, −1.40 to −0.37; <i>P</i> = 0.0018). </p><p id="d12500761e284"> <b>Conclusions:</b> Lumacaftor/ivacaftor was well tolerated in this young population; no new safety concerns were identified. Improvements in lung clearance index, sweat chloride, nutritional status, and health-related quality of life were observed after 24 weeks of treatment. </p><p id="d12500761e289">Clinical trial registered with <a data-untrusted="" href="http://www.clinicaltrials.gov" id="d12500761e291" target="xrefwindow">www.clinicaltrials.gov</a> (NCT01897233). </p>

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          Author and article information

          Journal
          American Journal of Respiratory and Critical Care Medicine
          Am J Respir Crit Care Med
          American Thoracic Society
          1073-449X
          1535-4970
          April 2017
          April 2017
          : 195
          : 7
          : 912-920
          Article
          10.1164/rccm.201608-1754OC
          5440888
          27805836
          2c46604e-8100-404d-8ae6-e00a6b25fe3c
          © 2017
          History

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