Efficacy and safety of pancrelipase delayed-release capsules (CREON®) from new manufacturing sites: a prospective, multicenter, randomized, double-blind, active-controlled, two-part, two-period, two-sequence, crossover, non-inferiority study

Abstract Background Pancreatic enzymes are approved for the treatment of exocrine pancreatic insufficiency (EPI) in adult and pediatric patients. The efficacy and safety of pancrelipase (CREON®; AbbVie Inc., North Chicago, IL) manufactured at one site utilizing a modernized drug product process (PANCRELIPASE-MP) and CREON® with drug substance from a second new site (PANCRELIPASE-AAPIS), compared with CREON® currently marketed in the US (PANCRELIPASE-MKT), were evaluated in patients with EPI due to cystic fibrosis (CF). Methods This was a prospective, multicenter, randomized, double-blind, active-controlled, two-part (Part 1: PANCRELIPASE-MP; Part 2: PANCRELIPASE-AAPIS), two-period, two-sequence, crossover, non-inferiority (NI) study in patients with CF aged ≥ 12 years with EPI and Fecal Elastase-1 < 15 μg/g. The primary endpoint was the coefficient of fat absorption (CFA). Secondary endpoints were the coefficient of nitrogen absorption (CNA), stool fat content, and stool weight. Adverse events (AEs) were recorded throughout. Results Twenty-six patients were randomized in Part 1 and 23 patients in Part 2. The mean CFA difference in Part 1 (PANCRELIPASE-MKT minus PANCRELIPASE-MP) was 0.94% (99% CI −2.370, 4.259); the mean CFA difference in Part 2 (PANCRELIPASE-MKT minus PANCRELIPASE-AAPIS) was −1.15% (99%CI −4.892, 2.602). Similar mean CNA, stool fat, and stool weight values were estimated for PANCRELIPASE-MKT, PANCRELIPASE-MP, or PANCRELIPASE-AAPIS. AEs were infrequent and similar between PANCRELIPASE-MP, PANCRELIPASE-AAPIS, and PANCRELIPASE-MKT. Conclusion Both PANCRELIPASE-MP and PANCRELIPASE-AAPIS demonstrated non-inferiority to marketed CREON®, with similar safety profiles. No new safety concerns were identified.