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.
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BibTeX
@article{ahrens2026efficacy,
title = {{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}},
author = {Richard Ahrens and Daniel Layish and Lino Rodrigues and Steven Boas and Chris Landon and Kimberly McBennett and Rebekah F. Brown and Kevin J. Gleason and Tingting Yi},
journal = {Trials},
year = {2026},
month = oct,
doi = {10.1186/s13063-026-09946-3},
url = {https://link.springer.com/article/10.1186/s13063-026-09946-3},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - 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
AU - Richard Ahrens
AU - Daniel Layish
AU - Lino Rodrigues
AU - Steven Boas
AU - Chris Landon
AU - Kimberly McBennett
AU - Rebekah F. Brown
AU - Kevin J. Gleason
AU - Tingting Yi
PY - 2026
DA - 2026/10/14
JO - Trials
DO - 10.1186/s13063-026-09946-3
UR - https://link.springer.com/article/10.1186/s13063-026-09946-3
AB - 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.
SN - 1745-6215
ER -