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Clinical Trial
. 2021 May;20(3):499-505.
doi: 10.1016/j.jcf.2020.12.006. Epub 2020 Dec 24.

VO2max as an exercise tolerance endpoint in people with cystic fibrosis: Lessons from a lumacaftor/ivacaftor trial

John Wilson  1 , Xiaojun You  2 , Matt Ellis  3 , Don S Urquhart  4 , Lokesh Jha  2 , Margaret Duncan  5 , Simon Tian  6 , Ryan A Harris  7 , Tom Kotsimbos  8 , Dominic Keating  9
Affiliations
Free article
Clinical Trial

VO2max as an exercise tolerance endpoint in people with cystic fibrosis: Lessons from a lumacaftor/ivacaftor trial

John Wilson et al. J Cyst Fibros. 2021 May.
Free article

Abstract

Background: The impact of lumacaftor/ivacaftor on exercise tolerance in people with cystic fibrosis (CF) has not been thoroughly studied.

Methods: We conducted a multisite Phase 4 trial comparing the impact of lumacaftor/ivacaftor on exercise tolerance with that of placebo in participants ≥ 12 years of age with CF homozygous for F508del-CFTR. The primary endpoint was relative change from baseline in maximum oxygen consumption (VO2max) during cardiopulmonary exercise testing (CPET) at Week 24. The key secondary endpoint was relative change from baseline in exercise duration during CPET at Week 24. Other secondary endpoints included changes in other indices of exercise tolerance and changes in CF assessments; safety and tolerability were assessed as an endpoint.

Results: Seventy participants were randomized to receive lumacaftor/ivacaftor (n = 34) or placebo (n = 36). The least-squares mean difference for lumacaftor/ivacaftor versus placebo in relative change in VO2max from baseline at Week 24 was -3.2% (95% CI: -9.2, 2.9; P=0.3021); the least-squares mean difference in relative change from baseline in exercise duration at Week 24 was -3.2% (95% CI: -8.0, 1.6). Safety results were consistent with the known lumacaftor/ivacaftor safety profile.

Conclusions: Definitive conclusions regarding the impact of lumacaftor/ivacaftor on exercise tolerance cannot be drawn from these results; however, multicenter studies using CPETs can be reliably performed with multiple time points and conventional methods, provided that calibration can be achieved. Future studies of exercise tolerance may benefit from lessons learned from this study. NCT02875366.

Keywords: Cystic fibrosis; Exercise duration; Exercise tolerance; Ivacaftor; Lumacaftor; Maximum oxygen consumption.

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Conflict of interest statement

Declaration of Competing Interest All authors received nonfinancial support (assistance with manuscript preparation) from ArticulateScience LLC, which received funding from Vertex Pharmaceuticals Incorporated. DK: personal fees (core laboratory overreading) from Vertex Pharmaceuticals Incorporated during the conduct of the study and personal fees (speaker fees) from Vertex Pharmaceuticals Incorporated outside the submitted work. DSU, ME, and RAH have nothing further to disclose. JW: grants and personal fees from Vertex Pharmaceuticals Incorporated outside the submitted work. LJ is a former employee of Vertex Pharmaceuticals Incorporated and owns stocks in Vertex Pharmaceuticals Incorporated. MD and ST are employees of Vertex Pharmaceuticals Incorporated and may own stock or stock options in Vertex Pharmaceuticals Incorporated. TK: personal fees (consulting fees) from Vertex Pharmaceuticals Incorporated during the conduct of the study. XY is a former employee of Vertex Pharmaceuticals Incorporated and may own stock or stock options in Vertex Pharmaceuticals Incorporated.

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