Journal article
Effect of VX-770 in Persons with Cystic Fibrosis and the G551D-CFTR Mutation
The New England journal of medicine, Vol.363(21), pp.1991-2003
2010
DOI: 10.1056/NEJMoa0909825
PMCID: PMC3148255
PMID: 21083385
Abstract
BACKGROUND
A new approach in the treatment of cystic fibrosis involves improving the function of mutant cystic fibrosis transmembrane conductance regulator (CFTR). VX-770, a CFTR potentiator, has been shown to increase the activity of wild-type and defective cell-surface CFTR in vitro.
METHODS
We randomly assigned 39 adults with cystic fibrosis and at least one G551D-CFTR allele to receive oral VX-770 every 12 hours at a dose of 25, 75, or 150 mg or placebo for 14 days (in part 1 of the study) or VX-770 every 12 hours at a dose of 150 or 250 mg or placebo for 28 days (in part 2 of the study).
RESULTS
At day 28, in the group of subjects who received 150 mg of VX-770, the median change in the nasal potential difference (in response to the administration of a chloride-free isoproterenol solution) from baseline was −3.5 mV (range, −8.3 to 0.5; P=0.02 for the within-subject comparison, P=0.13 vs. placebo), and the median change in the level of sweat chloride was −59.5 mmol per liter (range, −66.0 to −19.0; P=0.008 within-subject, P=0.02 vs. placebo). The median change from baseline in the percent of predicted forced expiratory volume in 1 second was 8.7% (range, 2.3 to 31.3; P=0.008 for the within-subject comparison, P=0.56 vs. placebo). None of the subjects withdrew from the study. Six severe adverse events occurred in two subjects (diffuse macular rash in one subject and five incidents of elevated blood and urine glucose levels in one subject with diabetes). All severe adverse events resolved without the discontinuation of VX-770.
CONCLUSIONS
This study to evaluate the safety and adverse-event profile of VX-770 showed that VX-770 was associated with within-subject improvements in CFTR and lung function. These findings provide support for further studies of pharmacologic potentiation of CFTR as a means to treat cystic fibrosis.
Details
- Title: Subtitle
- Effect of VX-770 in Persons with Cystic Fibrosis and the G551D-CFTR Mutation
- Creators
- Frank J ACCURSO - University of Colorado Denver and Children's Hospital, Aurora, United StatesSteven M ROWE - University of Alabama at Birmingham, Birmingham, United StatesRichard B MOSS - Stanford University School of Medicine, Palo Alto, CA, United StatesJoseph M PILEWSKI - University of Pittsburgh, Pittsburgh, United StatesRonald C RUBENSTEIN - Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, United StatesAhmet Z ULUER - Children's Hospital Boston, United StatesMoira L AITKEN - University of Washington, United StatesSteven D FREEDMAN - Beth Israel Deaconess Medical Center, Boston, United StatesLynn M ROSE - University of Washington, United StatesNicole MAYER-HAMBLETT - University of Washington, United StatesQUNMING DONG - Vertex Pharmaceuticals, Cambridge, MA, United StatesJIUHONG ZHA - Vertex Pharmaceuticals, Cambridge, MA, United StatesJ. P CLANCY - University of Alabama at Birmingham, Birmingham, United StatesAnne J STONE - Vertex Pharmaceuticals, Cambridge, MA, United StatesEric R OLSON - Vertex Pharmaceuticals, Cambridge, MA, United StatesClaudia L ORDONEZ - Vertex Pharmaceuticals, Cambridge, MA, United StatesPreston W CAMPBELL - Cystic Fibrosis Foundation Therapeutics, Bethesda, MD, United StatesMelissa A ASHLOCK - Cystic Fibrosis Foundation Therapeutics, Bethesda, MD, United StatesBonnie W RAMSEY - Seattle Children's Hospital, Seattle, United StatesMichael P BOYLE - Johns Hopkins Medical Institutions, Baltimore, United StatesJordan M DUNITZ - University of Minnesota, Minneapolis, United StatesPeter R DURIE - Hospital for Sick Children and the University of Toronto, Toronto, CanadaScott D SAGEL - University of Colorado Denver and Children's Hospital, Aurora, United StatesDouglas B HORNICK - University of Iowa Carver College of Medicine, Iowa City, United StatesMichael W KONSTAN - Rainbow Babies and Children's Hospital and Case Western Reserve University School of Medicine, Cleveland, United StatesScott H DONALDSON - University of North Carolina at Chapel Hill, Chapel Hill, United States
- Resource Type
- Journal article
- Publication Details
- The New England journal of medicine, Vol.363(21), pp.1991-2003
- Publisher
- Massachusetts Medical Society
- DOI
- 10.1056/NEJMoa0909825
- PMID
- 21083385
- PMCID
- PMC3148255
- ISSN
- 0028-4793
- eISSN
- 1533-4406
- Language
- English
- Date published
- 2010
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984094760402771
Metrics
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