240 A randomized, double-blind, multicentre, multinational crossover comparison of the pancreatic enzyme product (PEP) APT-1008 (ZENPEP®) to KREON® in the treatment of exocrine pancreatic insufficiency (EPI) associated with cystic fibrosis (CF) in patients ≥12 years of age

Abstract

Objectives An investigational PEP (APT-1008, to be marketed in Europe as ENZEPI®) was compared to KREON® in the treatment of EPI associated with CF. Methods This was a randomized, double-blind, active-controlled, 2-arm crossover, multinational, multicentre study comparing APT-1008 (APT) to KREON in the treatment of EPI in patients ≥12 years of age with CF. Patients were stabilized on their current PEP treatment during screening followed by randomization to APT or KREON for 28 days; then switched without washout to the opposite treatment with the same treatment schedule. The primary efficacy endpoint was the coefficient of fat absorption over 72 hours (CFA-72h) at the end of each period. Secondary endpoints included the coefficient of nitrogen absorption over 72 hours, clinical signs and symptoms of EPI, and quality of life. Safety assessments included adverse events (AE), laboratory tests and vital signs. Results 96 patients were randomized into 2 treatment sequences (APT/KREON or KREON/APT) with 83 completers comprising the efficacy population. APT demonstrated both non-inferiority and equivalence to KREON in fat absorption (LS mean CFA-72h: APT 84.08% [SE 1.109] vs. KREON 85.33% [SE 1.109]). Efficacy results of APT and KREON were generally similar for the secondary endpoints. The most frequent AEs were gastrointestinal, in 8.7% and 11.1% of patients on APT and KREON, respectively; no treatment-related serious AEs occurred. APT demonstrated safety and tolerability similar to KREON. Conclusions This study demonstrated that APT has comparable efficacy and safety to KREON in the treatment of adolescents and adult patients with EPI associated with CF.