title: Safety and preliminary clinical activity of a novel pancreatic enzyme preparation in pancreatic insufficient cystic fibrosis patients.
abstract: OBJECTIVE
  Currently available pancreatic enzyme products are crude porcine products with few data available regarding their efficacy, safety, and manufacture. We conducted a phase 1 study of a novel pancreatic enzyme product, TheraCLEC-Total (TCT), a proprietary formulation of microbial-derived lipase, protease, and amylase, to determine its safety and preliminary efficacy in cystic fibrosis.
  
  
  METHODS
  We conducted an open-label, dose-ranging study in 23 subjects diagnosed with pancreatic insufficiency with cystic fibrosis. The subjects received TCT containing lipase dose of 100, 500, 1000, 2500, or 5000 USP U/kg per meal with each meal or snack for 3 days. The clinical and laboratory parameters and adverse events (AEs) were monitored.
  
  
  RESULTS
  There were no serious AEs. Most AEs were mild, although gastrointestinal complaints were common. TCT increased the coefficient of fat and nitrogen absorption in all groups except in the low-dose group. At the other dosing levels, the mean coefficient of fat and nitrogen absorption increases were 19.1% +/- 24.9% and 17.8% +/- 13.6%, respectively, whereas the mean stool weight decreased by 517 +/- 362 g.
  
  
  CONCLUSIONS
  TCT was well tolerated in this short-term exposure study. The preliminary efficacy data demonstrate lipase and protease activity with little difference seen with lipase doses greater than 500 USP U/kg per meal. These data support a larger randomized phase 2 trial.
authors.affiliation: CF Therapeutics Development Network, Seattle, Wash, USA. dborowitz@upa.chob.edu
authors.forename: Drucy
authors.initials: D
authors.lastname: Borowitz
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Goss
authors.forename: Christopher
authors.initials: C
authors.lastname: Stevens
authors.forename: Denise
authors.initials: D
authors.lastname: Hayes
authors.forename: Laurie
authors.initials: L
authors.lastname: Newman
authors.forename: Anna
authors.initials: A
authors.lastname: O'Rourke
authors.forename: Michael W
authors.initials: MW
authors.lastname: Konstan
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wagener
authors.forename: Richard
authors.initials: R
authors.lastname: Moss
authors.forename: Leslie
authors.initials: L
authors.lastname: Hendeles
authors.forename: David
authors.initials: D
authors.lastname: Orenstein
authors.forename: Richard
authors.initials: R
authors.lastname: Ahrens
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Oermann
authors.forename: Moira L
authors.initials: ML
authors.lastname: Aitken
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Mahl
authors.forename: K Randall
authors.initials: KR
authors.lastname: Young
authors.forename: Jordan
authors.initials: J
authors.lastname: Dunitz
authors.forename: Frederick T
authors.initials: FT
authors.lastname: Murray
mesh_terms: D000293:Adolescent; D000328:Adult; D000681:Amylases / Q000008:administration & dosage* / Q000009:adverse effects; D003550:Cystic Fibrosis / Q000150:complications*; D010188:Exocrine Pancreatic Insufficiency / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D008049:Lipase / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D009584:Nitrogen / Q000378:metabolism; D010179:Pancreas / Q000201:enzymology*; D010447:Peptide Hydrolases / Q000008:administration & dosage*
chemical_list: D008049:Lipase; D000681:Amylases; D010447:Peptide Hydrolases; D009584:Nitrogen