Safety and Efficacy Study of 2 Pancreatic Enzymes for Treatment of Exocrine Pancreatic Insufficiency in Cystic Fibrosis.

Study Overview
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Brief Summary
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The purpose of the study is to further evaluate the safety and efficacy of EUR-1008 as compared to Kreon® in the treatment of exocrine pancreatic insufficiency associated with Cystic Fibrosis in subjects 12 years of age and older.

Official Title
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A Randomised, Double-Blind, Active-Controlled, Two-Treatment, Crossover, Multinational, Multicentre Study to Compare Two Pancreatic Enzyme Products in the Treatment of Exocrine Pancreatic Insufficiency in Subjects With Cystic Fibrosis

Conditions
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Exocrine Pancreatic Insufficiency: Cystic Fibrosis

Intervention / Treatment
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* Drug: EUR-1008 25,000 Units
* Drug: Kreon 25,000 Units


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Definitive diagnosis of CF based on the following: One clinical feature consistent with CF and Either a genotype with 2 identifiable mutations known to cause CF or a sweat chloride concentration >60 mEq/L by pilocarpine iontophoresis Pancreatic insufficiency documented by a monoclonal faecal elastase (FE) 100 μg/g stool at screening (test results within the previous 12 months are acceptable) Currently receiving pancreatic enzyme replacement therapy Adequate nutritional status based on the following: body mass index (BMI) >19 kg/m2 in adult subjects or a BMI percentile 10th percentile for age in adolescent (12 to 17 years age group) subjects Are clinically stable with no evidence of concomitant illness or acute upper or lower respiratory tract infection that requires antibiotics during the 7-day interval prior to screening and preceding entry into this clinical study Exclusion Criteria: Age <12 years Known contraindication, hypersensitivity, or intolerance to pork or other porcine PEPs Current uncontrolled diabetes mellitus History of solid organ transplantation History of surgery affecting the bowel function and weight gain

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EUR-1008 then Kreon<br>EUR-1008 during Treatment Period 1 (29 days ±2 days) and Kreon during Treatment Period 2 (29 days ±2 days). | Drug: EUR-1008 25,000 Units<br>* EUR-1008 25,000 Units is a PEP with pancreas powder as the active ingredient.18 Pancreas powder contains various enzymes having proteolytic, lipolytic, and amylolytic activity. Each capsule contains approximately 25,000 Ph. Eur. lipase units. EUR-1008 25,000 consists of orally administered capsules containing enteric-coated beads.<br>* Other names: Zenpep;Drug: Kreon 25,000 Units<br>* Kreon 25,000 is a PEP consisting of porcine-derived pancreatic enzymes.18 Each capsule contains approximately 25,000 Ph. Eur. lipase units. Kreon 25,000 consists of orally administered capsules containing enteric-coated spheres.<br>* Other names: Kreon;|
| Experimental: Kreon then EUR-1008<br>Kreon during Treatment Period 1 (29 days ±2 days) and EUR-1008 during Treatment Period 2 (29 days ±2 days). | Drug: EUR-1008 25,000 Units<br>* EUR-1008 25,000 Units is a PEP with pancreas powder as the active ingredient.18 Pancreas powder contains various enzymes having proteolytic, lipolytic, and amylolytic activity. Each capsule contains approximately 25,000 Ph. Eur. lipase units. EUR-1008 25,000 consists of orally administered capsules containing enteric-coated beads.<br>* Other names: Zenpep;Drug: Kreon 25,000 Units<br>* Kreon 25,000 is a PEP consisting of porcine-derived pancreatic enzymes.18 Each capsule contains approximately 25,000 Ph. Eur. lipase units. Kreon 25,000 consists of orally administered capsules containing enteric-coated spheres.<br>* Other names: Kreon;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Coefficient of Fat Absorption over 72 hours (CFA-72h) | During the last 72 hours of each treatment period, the CFA-72h will be calculated using fat intake data from the diet and fat excretion data from stools. Fat intake will be calculated by the dietician in collaboration with the study investigator using a validated tool. | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body weight | Body weight at baseline (Visit 2 [Day 0]) and at the end of each treatment period. | 58 days. | 
| Coefficient of nitrogen absorption | Coefficient of nitrogen absorption at the end of each treatment period as assessed by a specialised central laboratory by means of Dumas combustion method. | 72 hours | 
| Control of signs and symptoms of EPI | Control of signs and symptoms of EPI (as recorded in subject diaries). The following will be captured: Stools frequency (number/day) Stools consistency (hard, formed/normal; soft, watery, overt diarrhoea) Fat or grease visible in stools (Yes/No) Abdominal pain (mild, moderate, severe) Bloating (mild, moderate, severe) Flatulence (mild, moderate, severe) | 2- 14 day periods | 
| Impact on overall health, daily life, perceived well-being, and symptoms | Impact on overall health, daily life, perceived well-being, and symptoms evaluated using the CFQ (administered by designated study personnel prior to randomisation and at the end of each treatment period). | 58 days | 
| Total cholesterol, calculated LDL-C, HDL-C | Total cholesterol, calculated LDL-C, HDL-C (sampling performed prior to randomisation and at the end of each treatment period). | 58 days | 
| Treatment Emergent Adverse Events | Frequency, duration, and severity of treatment-emergent adverse events (TEAEs); | 78 days | 
| Standard safety laboratory tests | Standard safety laboratory tests, analysed by central laboratory: Haematology: red blood cell count, haemoglobin, haematocrit, total leukocytes with diff count, and platelets Serum biochemistry: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total protein, albumin, total bilirubin, direct and indirect bilirubin, blood urea nitrogen, uric acid, creatinine, fasting plasma glucose, fasting cholesterol evaluations (total cholesterol, LDL-C, HDL-C, and triglycerides), fat-soluble vitamins (A, D, and E) and serum electrolytes | 58 days | 
| Vital signs | Vital signs including blood pressure, heart rate, respirations and body temperature. | 78 days | 
| Fat-soluble vitamins A, D, and E | Fat-soluble vitamins A, D, and E (sampling performed prior to randomisation and at the end of each treatment period). | 58 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exocrine Pancreatic Insufficiency, Cystic Fibrosis, Pancreatic Insufficiency