A randomised, double blind, active-controlled, two-treatment, crossover multinational, multicentre trial to compare two pancreatic enzyme products in the treatment of exocrine pancreatic insufficiency in subjects with cystic fibrosis - ND

INTERVENTION: Trade Name: ZENPEP Pharmaceutical Form: Capsule, soft INN or Proposed INN: Multienzymes (lipase, protease etc.) Concentration unit: U unit(s) Concentration type: equal Concentration number: 10000‐ Trade Name: CREON 10000 Capsules Pharmaceutical Form: Capsule, soft INN or Proposed INN: Multienzymes (lipase, protease etc.) Concentration unit: U unit(s) Concentration type: equal Concentration number: 10000‐ CONDITION: exocrine pancreatic insufficiency (EPI) associated with cystic fibrosis (CF) ; MedDRA version: 9.1 Level: HLGT Classification code 10015674 ; MedDRA version: 9.1 Level: LLT Classification code 10011762 PRIMARY OUTCOME: Main Objective: The primary objective of the study is to evaluate the safety and efficacy of EUR‐1008 as compared to Creon in the treatment of EPI associated with CF in subjects 12 years of age and older, and able to swallow the capsules whole. Primary end point(s): The primary efficacy variable is the coefficient of fat absorption (CFA‐72h) calculated at the end of each treatment period. CFA will be calculated from stools collected during the last 3 days (72 hours) of each treatment period. The collection will be performed during hospitalization or stay in a specialized center enabling supervised dietary intake and quantitative stool collection. Secondary Objective: To evaluate the effects of EUR‐1008 as compared to Creon:1)in controlling signs and symptoms of EPI such as: stool frequency, consistency, oil/blood in stool and abdominal pain,bloating and flatulence (as recorded in the subject diary) 2)on change in body weight 3)on total cholesterol, calculated low‐density lipoprotein cholesterol (LDL‐C), high density lipoprotein cholesterol(HDL‐C), fat soluble vitamins A, D, and E 4)on the coefficient of nitrogen absorption (CNA) 5)on the impact on overall health, daily life, perceived wellbeing and symptoms using the Cystic Fibrosis Questionnaire(CFQ), administered at baseline and at the end of each treatment period 6)on the safety of EUR‐1008 in terms of treatment‐emergent adverse events (AEs), clinical laboratory evaluations and vital signs INCLUSION CRITERIA: 1.Definitive diagnosis of CF based on the following: o 1 clinical feature consistent with CF and o Either a genotype with 2 identifiable mutations known to cause CF or a sweat chloride concentration that is greater than 60 mEq/L by quantitative pilocarpine iontophoresis; 2.Pancreatic insufficiency documented by a monoclonal fecal elastase (FE) < 50 ?g/g stool at screening (test results within the previous 12 months are acceptable); 3.Currently receiving pancreatic enzyme treatment; 4.Adequate nutritional status based on the following: Body Mass Index (BMI) > 19 kg/m2 in adult subjects or a BMI percentile greater than or equal to the 10th percentile for age in adolescent subjects; 5.Are clinically stable with no evidence of concomitant illness or acute upper or lower respiratory tract infection during the 7‐ day interval prior to screening and preceding accession into this clinical study; 6.Willing to be switched from existing pancreatic enzyme