title: Liprotamase long-term safety and support of nutritional status in pancreatic-insufficient cystic fibrosis.
abstract: OBJECTIVE
  Patients with cystic fibrosis (CF) who have exocrine pancreatic insufficiency (EPI) require treatment with pancreatic enzyme replacement therapy (PERT) to maintain adequate nutrition and age-appropriate growth and weight gain. Liprotamase, a nonporcine, highly purified biotechnology-derived PERT, has demonstrated significant efficacy in fat and protein malabsorption in patients with EPI compared to placebo. This study of liprotamase is the first ever long-term trial of a PERT to evaluate safety and nutritional parameters.
  
  
  METHODS
  This phase III 12-month open-label trial assessed the safety, tolerability, and long-term nutritional effects of liprotamase treatment in patients with CF and EPI 7 years and older. All of the patients were required to discontinue their long-term use of porcine PERTs at the time of enrollment. Dosing started at 1 capsule of liprotamase (32,500 US Pharmacopoeia (USP) units crystallized cross-linked lipase, 25,000 USP units crystallized protease, and 3,750 USP units amorphous amylase) per meal or snack; dose could be increased based on protocol-defined parameters.
  
  
  RESULTS
  A total of 215 subjects were enrolled and 214 received at least 1 dose of liprotamase (mean 5.5 capsules per day). During the study period, height, weight, and body mass index z scores and lung function as measured by forced expiratory volume in 1 second were stable. There were no clinically meaningful changes in laboratory tests, including levels of fat-soluble vitamins. Liprotamase was well tolerated without any significant safety concerns. Adverse events, primarily gastrointestinal, led to treatment discontinuation for 36 subjects (16.8%), most within the first 3 months.
  
  
  CONCLUSIONS
  Treatment with a mean of 5.5 capsules of liprotamase per day, during meals and snacks, for up to 12 months was safe, well tolerated, and associated with age-appropriate growth and weight gain or weight maintenance in subjects with CF-related EPI.
authors.affiliation: Division of Pediatric Pulmonology, Women and Children's Hospital of Buffalo, State University of New York at Buffalo, NY 14222, USA. dborowitz@upa.chob.edu
authors.forename: Drucy
authors.initials: D
authors.lastname: Borowitz
authors.forename: Christopher
authors.initials: C
authors.lastname: Stevens
authors.forename: Lee R
authors.initials: LR
authors.lastname: Brettman
authors.forename: Marilyn
authors.initials: M
authors.lastname: Campion
authors.forename: Michael
authors.initials: M
authors.lastname: Wilschanski
authors.forename: Henry
authors.initials: H
authors.lastname: Thompson
mesh_terms: D000293:Adolescent; D000328:Adult; D000681:Amylases / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D003550:Cystic Fibrosis / Q000150:complications*; D004334:Drug Administration Schedule; D056947:Enzyme Replacement Therapy / Q000009:adverse effects; D010188:Exocrine Pancreatic Insufficiency / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D006801:Humans; D008049:Lipase / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015596:Nutrition Assessment; D009752:Nutritional Status; D010447:Peptide Hydrolases / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D008049:Lipase; D000681:Amylases; D010447:Peptide Hydrolases