Liprotamase long-term safety and support of nutritional status in pancreatic-insufficient cystic fibrosis

J Pediatr Gastroenterol Nutr. 2012 Feb;54(2):248-57. doi: 10.1097/MPG.0b013e31823315d1.


Objectives: 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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amylases / adverse effects
  • Amylases / therapeutic use*
  • Child
  • Cystic Fibrosis / complications*
  • Drug Administration Schedule
  • Enzyme Replacement Therapy* / adverse effects
  • Exocrine Pancreatic Insufficiency / drug therapy*
  • Exocrine Pancreatic Insufficiency / etiology
  • Female
  • Humans
  • Lipase / adverse effects
  • Lipase / therapeutic use*
  • Male
  • Middle Aged
  • Nutrition Assessment
  • Nutritional Status
  • Peptide Hydrolases / adverse effects
  • Peptide Hydrolases / therapeutic use*
  • Treatment Outcome
  • Young Adult


  • Lipase
  • Amylases
  • Peptide Hydrolases