Pancrelipase delayed-release capsules (CREON) for exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery: A double-blind randomized trial.
OBJECTIVE
Pancreatic-enzyme replacement therapy (PERT) is the standard of care to prevent maldigestion, malnutrition, and excessive weight loss in patients with exocrine pancreatic insufficiency (EPI) due to chronic pancreatitis (CP) or pancreatic surgery (PS). Our objective was to assess the efficacy and safety of a new formulation of pancrelipase (pancreatin) delayed-release 12,000-lipase unit capsules (CREON) in patients with EPI due to CP or PS.


METHODS
This was a double-blind, randomized, multicountry, placebo-controlled, parallel-group trial enrolling patients ≥18 years old with confirmed EPI due to CP or PS conducted in clinical research centers or hospitals. After a 5-day placebo run-in period (baseline), patients were randomized to pancrelipase (72,000 lipase units per meal; 36,000 per snack) or placebo for 7 days. All patients received an individually designed diet to provide at least 100 g of fat per day. The primary efficacy measure was the change in coefficient of fat absorption (CFA) from baseline to end of the double-blind period, analyzed using non-parametric analysis of covariance. Secondary outcomes included the coefficient of nitrogen absorption (CNA), clinical symptoms, and safety parameters.


RESULTS
In total, 25 patients (median age of 54 years, 76% male) received pancrelipase and 29 patients (median age of 50 years, 69% male) received placebo. Th e mean ± s.d. change from baseline in CFA was significantly greater with pancrelipase vs. placebo: 31.9 ± 18.6 vs. 8.7 ± 12.4 % ( P < 0.0001) [corrected]. Similarly, the mean ± s.d. change from baseline in CNA was greater for pancrelipase vs. placebo: 35.2 ± 29.1 vs. 8.9 ± 28.0 % ( P = 0.0005) [corrected].Greater improvements from baseline in stool frequency, stool consistency, abdominal pain, and flatulence were observed with pancrelipase vs. placebo. Treatment-emergent adverse events (TEAEs) were reported in five patients (20.0%) in the pancrelipase group and in six (20.7%) in the placebo group; the most common were gastrointestinal (GI) events and metabolism/nutrition disorders. There were no treatment discontinuations due to TEAEs.


CONCLUSIONS
Pancrelipase delayed-release 12,000-lipase unit capsules were effective in treating fat and nitrogen maldigestion with a TEAE rate similar to that of placebo in patients with EPI due to CP or PS.
Whitcomb
David C
DC
Department of Medicine, University of Pittsburgh, Pennsylvania, USA. whitcomb@pitt.edu
Lehman
Glen A
GA
Vasileva
Galina
G
Malecka-Panas
Ewa
E
Gubergrits
Natalya
N
Shen
Yannan
Y
Sander-Struckmeier
Suntje
S
Caras
Steven
S
D002214:Capsules; D016009:Chi-Square Distribution; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000627:therapeutic use; D004311:Double-Blind Method; D010188:Exocrine Pancreatic Insufficiency / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000601:surgery*; D010195:Pancreatitis / Q000150:complications* / Q000188:drug therapy; D020799:Pancrelipase / Q000008:administration & dosage* / Q000627:therapeutic use; D018579:Patient Selection; D016896:Treatment Outcome
D002214:Capsules; D003692:Delayed-Action Preparations; D005765:Gastrointestinal Agents; D020799:Pancrelipase