<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> < 0.0001),
body mass index
<i>z</i> score (+0.15; 95% CI, 0.08 to 0.22;
<i>P</i> < 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>