期刊
NEW ENGLAND JOURNAL OF MEDICINE
卷 363, 期 21, 页码 1991-2003出版社
MASSACHUSETTS MEDICAL SOC
DOI: 10.1056/NEJMoa0909825
关键词
-
资金
- Vertex Pharmaceuticals
- Cystic Fibrosis Foundation Therapeutics
- Food and Drug Administration Office of Orphan Products Development [FD-R-003432-01]
- National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (NIH) [K23 DK075788]
- Cystic Fibrosis Foundation Therapeutics [CLANCY05Y2, DURIE06A0, RAMSEY03Y0]
- National Center for Research Resources of the NIH [UL1 RR025005, GCRC M01 RR00070, CTSA 1UL1 RR025744, UL1 RR024989, M01 RR02172, CTSA UL1 RR025014, K23 RR018611-05, CTSA UL1 RR025780, CTSA UL 1RR025747, CTSA UL1 RR024153, CTSA UL1 RR024134]
- National Heart, Lung, and Blood Institute of the NIH [U01 HL081335]
- Inspire
- PTC Therapeutics
- Digestive Care
- Gilead
- Vertex
- Altus
- KaloBios
- Axcan Pharma
- Yasoo Health
- INO Therapeutics
- Mpex
- Genentech
- Transave
- MedImmune
- Novartis
- Bayer
- Roche
- Liquidia Technologies
- Pfizer
- Boehringer Ingelheim
- Ovation
- CSL Bering
- NanoBio
- Nektar
- Solvay
- Aridis
- AOP/Lantibio
- Johnson Johnson
- 23andMe
- Uluer
- Education Development Center
- Pharmaxis
- Hood Foundation
- Gerber Foundation
- Merck
- AlgiPharma
- Aradigm
- CSL Behring
- Eurand
- GlaxoSmithKline
- N30 Pharmaceuticals
- Seed-One Ventures
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据