Efficacy and safety of ataluren in patients with nonsense-mutation cystic fibrosis not receiving chronic inhaled aminoglycosides: The international, randomized, double-blind, placebo-controlled Ataluren Confirmatory Trial in Cystic Fibrosis (ACT CF).
Administration, Oral
Codon, Nonsense
Cystic Fibrosis
/ drug therapy
Cystic Fibrosis Transmembrane Conductance Regulator
/ genetics
Double-Blind Method
Drug Monitoring
/ methods
Female
Forced Expiratory Volume
Humans
Male
Oxadiazoles
/ administration & dosage
Respiratory Function Tests
/ methods
Symptom Flare Up
Treatment Outcome
Ataluren
Clinical trial
Cystic fibrosis
Journal
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
ISSN: 1873-5010
Titre abrégé: J Cyst Fibros
Pays: Netherlands
ID NLM: 101128966
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
15
01
2020
accepted:
17
01
2020
pubmed:
28
1
2020
medline:
14
9
2021
entrez:
28
1
2020
Statut:
ppublish
Résumé
Ataluren was developed for potential treatment of nonsense-mutation cystic fibrosis (CF). A previous phase 3 ataluren study failed to meet its primary efficacy endpoint, but post-hoc analyses suggested that aminoglycosides may have interfered with ataluren's action. Thus, this subsequent trial (NCT02139306) was designed to assess the efficacy and safety of ataluren in patients with nonsense-mutation CF not receiving aminoglycosides. Eligible subjects with nonsense-mutation CF (aged ≥6 years; percent predicted (pp) FEV 279 subjects were enrolled; 138 subjects in the ataluren arm and 136 in the placebo arm were evaluable for efficacy. Absolute ppFEV Neither ppFEV
Sections du résumé
BACKGROUND
Ataluren was developed for potential treatment of nonsense-mutation cystic fibrosis (CF). A previous phase 3 ataluren study failed to meet its primary efficacy endpoint, but post-hoc analyses suggested that aminoglycosides may have interfered with ataluren's action. Thus, this subsequent trial (NCT02139306) was designed to assess the efficacy and safety of ataluren in patients with nonsense-mutation CF not receiving aminoglycosides.
METHODS
Eligible subjects with nonsense-mutation CF (aged ≥6 years; percent predicted (pp) FEV
FINDINGS
279 subjects were enrolled; 138 subjects in the ataluren arm and 136 in the placebo arm were evaluable for efficacy. Absolute ppFEV
INTERPRETATION
Neither ppFEV
Identifiants
pubmed: 31983658
pii: S1569-1993(20)30030-8
doi: 10.1016/j.jcf.2020.01.007
pmc: PMC9167581
mid: NIHMS1808323
pii:
doi:
Substances chimiques
Codon, Nonsense
0
Oxadiazoles
0
Cystic Fibrosis Transmembrane Conductance Regulator
126880-72-6
ataluren
K16AME9I3V
Banques de données
ClinicalTrials.gov
['NCT02139306']
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
595-601Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK072482
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002548
Pays : United States
Informations de copyright
Copyright © 2020. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of Competing Interest JM is an employee of PTC Therapeutics, the funder of this clinical trial, and holds financial interests in the company. MWK, SMR, and DRV received compensation for consultant services from PTC Therapeutics prior to and/or during this study. EK, MW, IS-G, and KDB received compensation for travel expenses for meetings related to the study. All other authors declare no competing interests.
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