We propose to test the effectiveness of the combination of CF pancreatic enzyme replacement therapy (PERT) on absorption of Ravicti® and subsequent restoration of nasal epithelial cystic fibrosis transmembrane conductance regulator (CFTR)-mediated chloride transport during the nasal potential difference (NPD) test. Funding source FDA Office of Orphan Products Development.
Name: Ravicti low dose
Name: Ravicti high dose
Name: Placebo
Description: chloride and sodium transport in nasal epithelium
Measure: The primary biological endpoint will be the change in average measurement of nasal potential difference between day 7 and baseline. Time: 7 daysDescription: change between date and baseline in sodium and chloride transport
Measure: Change in other NPD measures from baseline and Days 4, 7, and 14 to include baseline PD, change in amiloride, low chloride, and low chloride plus isoproterenol. Time: 14 daysDescription: change between study time point and baseline in sweat chloride
Measure: Change in average sweat chloride measurement between days 4, 7, 14 and baseline. Time: 14 daysDescription: standard safety and tolerability lab values
Measure: Safety and tolerability. Time: 14 daysDescription: quantification of exogenous pancreatic enzyme effects on release of active drug from the pro-drug triglyceride form
Measure: Efficacy of PERT on absorption of Ravicti®. Time: 14 daysDescription: blood pharmacokinetics
Measure: Plasma will be sampled for pharmacokinetics (PK) studies Time: 14 daysDescription: blood counts, metabolic measures, CRP
Measure: Safety labs: hematology, complete metabolic panel (CMP), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), uric acid. Sputum microbiology and spirometry will be performed. Time: 14 daysAllocation: Randomized
Parallel Assignment
There is one SNP
In the ensuing years, Vertex Pharmaceuticals, Inc. has had success with the development of ivacaftor3;3;4 (VX-770) as a potentiator of G551D CFTR and has studied the drug alone and in combination with their corrector lumacaftor5 (VX-809) and VX-661. --- G551D ---