Randomised clinical trial: the efficacy and safety of pancreatin enteric-coated minimicrospheres (Creon 40000 MMS) in patients with pancreatic exocrine insufficiency due to chronic pancreatitis--a double-blind, placebo-controlled study.

Background Pancreatic exocrine insufficiency (PEI) results in maldigestion, leading to abdominal pain, steatorrhoea, malnutrition and weight loss. Aim To assess the efficacy and safety of pancreatin (Creon 40000 MMS) in treating PEI due to chronic pancreatitis (CP). Methods This was a 1-week, double-blind, randomised, placebo-controlled, parallel-group, multicentre study in India. Men and women =18 years of age with proven CP and PEI [defined as a coefficient of fat absorption (CFA) =80% during run-in phase] were randomised 1:1 to pancreatin or placebo (two capsules orally per main meal, one with snacks). The primary outcome measure was change in CFA from baseline to end of double-blind treatment (analysis of covariance). Results Of 62 patients randomised (34 pancreatin, 28 placebo), 61 completed treatment; one patient in the placebo arm withdrew consent before completion. Patient characteristics were similar in both groups except for the proportion of men (pancreatin 82% vs. placebo 68%). Patients receiving pancreatin had a statistically significant greater improvement in fat absorption from baseline to the end of double-blind treatment compared with those receiving placebo, with a least squares mean change (95% CI) in CFA of 18.5% (15.821.2) vs. 4.1% (1.07.2), respectively. This resulted in a treatment difference of 14.4% (10.318.5); P = 0.001. Patients receiving pancreatin also had a statistically significant greater improvement in nitrogen absorption and greater reductions in mean stool fat, stool frequency and stool weight compared with those receiving placebo. Treatment-emergent adverse events occurred in 12 patients on pancreatin and in seven on placebo; none led to study discontinuation. Conclusions The results provide evidence for the efficacy of pancreatin (Creon 40000 MMS) in patients with pancreatic exocrine insufficiency due to chronic pancreatitis, and confirm that this formulation is well tolerated, with a good safety profile, at the dose administered.