Jerry A Nick1, Connie St Clair2, Marion C Jones3, Lan Lan4, Mark Higgins5. 1. National Jewish Health, 1400 Jackson Street, Denver, CO 80206, United States. Electronic address: nickj@njhealth.org. 2. National Jewish Health, 1400 Jackson Street, Denver, CO 80206, United States. Electronic address: StClairC@njhealth.org. 3. National Jewish Health, 1400 Jackson Street, Denver, CO 80206, United States. Electronic address: JonesM@NJHealth.org. 4. Formerly of Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, United States. Electronic address: lan012345@yahoo.com. 5. Vertex Pharmaceuticals (Europe) Limited, 2 Kingdom Street, London, W2 6BD, United Kingdom. Electronic address: mark_higgins@vrtx.com.
Abstract
BACKGROUND:Ivacaftor shows benefit in patients with cystic fibrosis (CF) and CFTR mutations associated with residual CF transmembrane conductance regulator (CFTR) function. Here we further assess the effect of ivacaftor in such patients using an N-of-1 study design. METHODS:Patients aged ≥12 years with CF with clinical or molecular evidence of residual CFTR function were randomized to 1 of 4 treatment sequences for two 4-week, double-blind crossover cycles (each divided into 2 weeks of ivacaftor treatment and placebo) followed by 8 weeks of open-label ivacaftor treatment. The primary endpoint was absolute change from cycle baseline of percent predicted forced expiratory volume in 1 s (ppFEV1) after 2 weeks of treatment with ivacaftor relative to placebo. RESULTS:Absolute change (SD) from study baseline in ppFEV1 favored ivacaftor by 2.3 (1.0) percentage points (95% credible interval, 0.4-4.1) after 2 weeks of treatment. Absolute mean change (SD) from open-label baseline (defined as day 1 of the open-label ivacaftor treatment period) in ppFEV1 after 8 weeks of treatment was 4.7 (4.2) percentage points (P<.0001). Safety of ivacaftor was consistent with that observed in prior studies. CONCLUSIONS:Ivacaftor improved lung function during the double-blind and open-label treatment periods in patients with CF and CFTR mutations associated with residual CFTR function (ClinicalTrials.gov, NCT01685801).
RCT Entities:
BACKGROUND:Ivacaftor shows benefit in patients with cystic fibrosis (CF) and CFTR mutations associated with residual CF transmembrane conductance regulator (CFTR) function. Here we further assess the effect of ivacaftor in such patients using an N-of-1 study design. METHODS:Patients aged ≥12 years with CF with clinical or molecular evidence of residual CFTR function were randomized to 1 of 4 treatment sequences for two 4-week, double-blind crossover cycles (each divided into 2 weeks of ivacaftor treatment and placebo) followed by 8 weeks of open-label ivacaftor treatment. The primary endpoint was absolute change from cycle baseline of percent predicted forced expiratory volume in 1 s (ppFEV1) after 2 weeks of treatment with ivacaftor relative to placebo. RESULTS: Absolute change (SD) from study baseline in ppFEV1 favored ivacaftor by 2.3 (1.0) percentage points (95% credible interval, 0.4-4.1) after 2 weeks of treatment. Absolute mean change (SD) from open-label baseline (defined as day 1 of the open-label ivacaftor treatment period) in ppFEV1 after 8 weeks of treatment was 4.7 (4.2) percentage points (P<.0001). Safety of ivacaftor was consistent with that observed in prior studies. CONCLUSIONS:Ivacaftor improved lung function during the double-blind and open-label treatment periods in patients with CF and CFTR mutations associated with residual CFTR function (ClinicalTrials.gov, NCT01685801).
Authors: Meredith C Fidler; Alexandra Buckley; James C Sullivan; Marvin Statia; Sylvia F Boj; Robert G J Vries; Anne Munck; Mark Higgins; Matteo Moretto Zita; Paul Negulescu; Fredrick van Goor; Kris De Boeck Journal: Clin Transl Sci Date: 2020-12-06 Impact factor: 4.689
Authors: Eitan Kerem; Malena Cohen-Cymberknoh; Reuven Tsabari; Michael Wilschanski; Joel Reiter; David Shoseyov; Alex Gileles-Hillel; Thea Pugatsch; Jane C Davies; Christopher Short; Clare Saunders; Cynthia DeSouza; James C Sullivan; Jamie R Doyle; Keval Chandarana; Nils Kinnman Journal: Ann Am Thorac Soc Date: 2021-03