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document
Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation . 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 . ( Funded by Vertex Pharmaceuticals and others ; ClinicalTrials.gov number , NCT00457821 . ) .
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Intervention_Pharmacological
VX-770
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Intervention_Pharmacological
oral VX-770
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Intervention_Pharmacological
VX-770
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Intervention_Control
placebo
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Outcome_Physical
nasal potential difference
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Outcome_Physical
level of sweat chloride
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Outcome_Physical
forced expiratory volume
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Outcome_Adverse-effects
severe adverse events
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Outcome_Adverse-effects
diffuse macular rash
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Outcome_Physical
elevated blood and urine glucose levels
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Outcome_Physical
diabetes
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Outcome_Other
safety
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Outcome_Adverse-effects
adverse-event profile
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Outcome_Physical
CFTR
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Outcome_Physical
lung function