An open-label extension study of ivacaftor in children with CF and a CFTR gating mutation initiating treatment at age 2-5 years (KLIMB).
Aminophenols
/ administration & dosage
Body Mass Index
Child, Preschool
Chloride Channel Agonists
/ administration & dosage
Cystic Fibrosis
/ diagnosis
Cystic Fibrosis Transmembrane Conductance Regulator
/ genetics
Female
Humans
Ion Channel Gating
/ genetics
Liver Function Tests
/ methods
Male
Pancreas
/ enzymology
Quinolones
/ administration & dosage
Sodium Chloride
/ analysis
Sweat
/ chemistry
Transaminases
/ blood
Treatment Outcome
Weight Gain
/ drug effects
(3–6 required): Cystic fibrosis
CFTR potentiator
Ivacaftor
KLIMB
Pediatrics
Safety
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:
11 2019
11 2019
Historique:
received:
29
01
2019
revised:
22
03
2019
accepted:
24
03
2019
pubmed:
6
5
2019
medline:
11
11
2020
entrez:
5
5
2019
Statut:
ppublish
Résumé
KIWI (NCT01705145) was a 24-week, single-arm, pharmacokinetics, safety, and efficacy study of ivacaftor in children aged 2 to 5 years with cystic fibrosis (CF) and a CFTR gating mutation. Here, we report the results of KLIMB (NCT01946412), an 84-week, open-label extension of KIWI. Children received age- and weight-based ivacaftor dosages for 84 weeks. The primary outcome was safety. Other outcomes included sweat chloride, growth parameters, and measures of pancreatic function. All 33 children who completed KIWI enrolled in KLIMB; 28 completed 84 weeks of treatment. Most adverse events were consistent with those reported during KIWI. Ten (30%) children had transaminase elevations >3 × upper limit of normal (ULN), leading to 1 discontinuation in a child with alanine aminotransferase >8 × ULN. Improvements in sweat chloride, weight, and body mass index z scores and fecal elastase-1 observed during KIWI were maintained during KLIMB; there was no further improvement in these parameters. Ivacaftor was generally well tolerated for up to 108 weeks in children aged 2 to 5 years with CF and a gating mutation, with safety consistent with the KIWI study. Improvements in sweat chloride and growth parameters during the initial 24 weeks of treatment were maintained for up to an additional 84 weeks of treatment. Prevalence of raised transaminases remained stable and did not increase with duration of exposure during the open-label extension.
Sections du résumé
BACKGROUND
KIWI (NCT01705145) was a 24-week, single-arm, pharmacokinetics, safety, and efficacy study of ivacaftor in children aged 2 to 5 years with cystic fibrosis (CF) and a CFTR gating mutation. Here, we report the results of KLIMB (NCT01946412), an 84-week, open-label extension of KIWI.
METHODS
Children received age- and weight-based ivacaftor dosages for 84 weeks. The primary outcome was safety. Other outcomes included sweat chloride, growth parameters, and measures of pancreatic function.
RESULTS
All 33 children who completed KIWI enrolled in KLIMB; 28 completed 84 weeks of treatment. Most adverse events were consistent with those reported during KIWI. Ten (30%) children had transaminase elevations >3 × upper limit of normal (ULN), leading to 1 discontinuation in a child with alanine aminotransferase >8 × ULN. Improvements in sweat chloride, weight, and body mass index z scores and fecal elastase-1 observed during KIWI were maintained during KLIMB; there was no further improvement in these parameters.
CONCLUSIONS
Ivacaftor was generally well tolerated for up to 108 weeks in children aged 2 to 5 years with CF and a gating mutation, with safety consistent with the KIWI study. Improvements in sweat chloride and growth parameters during the initial 24 weeks of treatment were maintained for up to an additional 84 weeks of treatment. Prevalence of raised transaminases remained stable and did not increase with duration of exposure during the open-label extension.
Identifiants
pubmed: 31053538
pii: S1569-1993(19)30061-X
doi: 10.1016/j.jcf.2019.03.009
pmc: PMC6821553
mid: NIHMS1033369
pii:
doi:
Substances chimiques
Aminophenols
0
Chloride Channel Agonists
0
Quinolones
0
Cystic Fibrosis Transmembrane Conductance Regulator
126880-72-6
ivacaftor
1Y740ILL1Z
Sodium Chloride
451W47IQ8X
Transaminases
EC 2.6.1.-
Banques de données
ClinicalTrials.gov
['NCT01946412']
Types de publication
Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
838-843Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK072482
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK089507
Pays : United States
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.
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