A Double-blind, Randomized, Multicenter, Cross-over Study to Compare the Effect of Creon N and Creon® on Fat Digestion in Subjects ≥ 12 Years of Age With Pancreatic Exocrine Insufficiency Due to Cystic Fibrosis

Study Overview
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Brief Summary
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maldigestion of dietary macronutrients (pancreas not producing enough enzymes for digestion of fat, sugars and proteins) in Cystic Fibrosis

Official Title
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A Double-blind, Randomized, Multicenter, Cross-over Study to Compare the Effect of Creon N and Creon® on Fat Digestion in Subjects ≥ 12 Years of Age With Pancreatic Exocrine Insufficiency Due to Cystic Fibrosis

Conditions
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Pancreatic Exocrine Insufficiency Due to Cystic Fibrosis

Intervention / Treatment
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* Drug: Creon®
* Drug: Creon N


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent given by the subject, or the parents, or a legally acceptable representative. If required by the Institutional Review Board/Ethics Committee (IRB/IEC), assent will be given by the subject Age ≥ 12 years Subjects who are able to swallow capsules with each meal and snacks Diagnosis of Cystic Fibrosis (CF) confirmed by two positive chloride sweat tests or gene analysis Diagnosis of pancreatic exocrine insufficiency proven by: Coefficient of fat absorption (CFA) < 70% without supplementation or Human fecal elastase < 50 μg/g stool Currently receiving treatment with a commercially available pancreatic enzyme product and on a continuous dose of this product for more than 3 months Clinically stable condition without evidence of acute respiratory disease within 1 month of enrollment Stable body weight defined as no more than a 5% decline within 3 months of enrolment Females of child-bearing potential should agree to continue using a medically acceptable method of birth control throughout the study and for 30 days immediately after the last dose of study drug. Medically acceptable methods of birth control include bilateral tubal ligation or the use of either a contraceptive implant, a contraceptive injection (Depo-Provera™), an intrauterine device, or an oral contraceptive taken within the past 3 months where the subject agrees to continue using during the study or to adopt another birth control method, or a double-barrier method which consists of a combination of any two of the following: diaphragm, cervical cap, condom, or spermicide. Exclusion Criteria: Evidence of cardiovascular, respiratory, urogenital, gastrointestinal/hepatic (except underlying disease), hematologic/immunologic, head, ears, eyes, nose, throat, dermatologic/connective tissue, musculoskeletal, metabolic/nutritional (except underlying disease), endocrine (except diabetes mellitus), neurologic/psychiatric, allergy, recent major surgery, or other relevant diseases as revealed by history, physical examination and/or laboratory assessments, which could limit participation in or completion of the study History of acute abdomen History of fibrosing colonopathy History of distal intestinal obstruction syndrome (DIOS) within 6 months prior to enrollment Solid organ transplant or surgery affecting the large bowel other than appendectomy Small bowel surgery that significantly affected absorptive capacity (e.g. gastrectomy or pancreatectomy) Pregnancy or lactation Any type of malignancy involving the digestive tract in the last 5 years Celiac disease or Crohn's disease Known allergy to pancreatin or inactive ingredients (excipients) of pancreatin capsules Suspected non-compliance or non-cooperation Intake of experimental drugs within 30 days prior to study start Mental disability or any other lack of fitness, in the Investigator's opinion, to preclude subject's participation in or ability to complete the study Diagnosis of human immunodeficiency virus in medical history.

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: Creon N, then Creon®<br>Subjects first received Creon N for 5 days. After a washout period of 3 to 14 days, they received Creon® for 5 days. The Investigator calculated the total number of capsules per day needed to treat the subject with 8000 to <10000 lipase units per kg body weight and day, Capsules of both Creon N and Creon® contain 25000 lipase units. | Drug: Creon®<br>* active comparator<br>|
| Experimental: Creon® , then Creon N<br>Subjects first received Creon® for 5 days. After a washout period of 3 to 14 days, they received Creon N for 5 days. The Investigator calculated the total number of capsules per day needed to treat the subject with 8000 to <10000 lipase units per kg body weight and day, Capsules of both Creon N and Creon® contain 25000 lipase units. | Drug: Creon N<br>* experimental drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Coefficient of Fat Absorption (CFA) | CFA is calculated from fat intake and fat excretion, according to the formula: CFA (%) = 100 [fat intake - fat excretion] / fat intake | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Coefficient of Nitrogen Absorption (CNA). | CNA is calculated from nitrogen intake and nitrogen excretion, according to the formula: CNA (%) = 100 [nitrogen intake - nitrogen excretion] / nitrogen intake) | 5 days | 
| Total Fat Excretion | Total amount of fat excreted during the stool collection period in grams. | 5 days | 
| Stool Frequency | Stool frequency is the average of the daily number of stools recorded during the treatment period | 5 days | 
| Percentage of Days With no Flatulence | The percentage of days with no flatulence is calculated from the diary during the treatment period: 100*(number of days with no flatulence/number of days recorded in diary). | 5 days | 
| Percentage of Days With no Abdominal Pain | The percentage of days with no abdominal pain is calculated from the diary during the treatment period: 100*(number of days with no abdominal pain/ number of days recorded in diary). | 5 days | 
| Percentage of Days With Formed/Normal Stools | The percentage of days with formed/normal stools is calculated from the diary during the treatment period: 100*(number of days with formed/normal stools/ number of days recorded in diary). | 5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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maldigestion of dietary macronutrients (pancreas not producing enough enzymes for digestion of fat, sugars and proteins) in Cystic Fibrosis