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

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

Study Overview

• Status: Completed
• Conditions: Pancreatic Exocrine Insufficiency Due to Cystic Fibrosis
• Intervention / Treatment: Drug: Creon®; Drug: Creon N

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 3

Contacts and Locations

Study Locations

• Hungary
  • Budapest, Hungary, 1122
    • Research facility ID ORG-000826
  • Debrecen, Hungary, 4031
    • Research facility ID ORG-000816
  • Kaposvár, Hungary, 7400
    • Research facility ID ORG-000827
  • Törökbálint, Hungary, 2045
    • Research facility ID ORG-000825
• Spain
  • Barcelona, Spain, 8035
    • Research facility ID ORG-000829
  • Sevilla, Spain, 41013
    • Research facility ID ORG-000828
  • Valencia, Spain, 46026
    • Research facility ID ORG-000815

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

  1. Coefficient of fat absorption (CFA) < 70% without supplementation
  2. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Creon N, then Creon®; 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®; active comparator
Experimental: Creon® , then Creon N; 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; experimental drug

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Abbott

Publications and helpful links

General Publications

• Somaraju URR, Solis-Moya A. Pancreatic enzyme replacement therapy for people with cystic fibrosis. Cochrane Database Syst Rev. 2020 Aug 5;8(8):CD008227. doi: 10.1002/14651858.CD008227.pub4.

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: February 12, 2014
• First Submitted That Met QC Criteria: May 9, 2014
• First Posted (Estimate): May 13, 2014

Study Record Updates

• Last Update Posted (Estimate): January 22, 2016
• Last Update Submitted That Met QC Criteria: January 21, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: maldigestion of dietary macronutrients (pancreas not producing enough enzymes for digestion of fat, sugars and proteins) in Cystic Fibrosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Gastrointestinal Agents; Pancrelipase; Pancreatin
• Other Study ID Numbers: PANC3004; 2013-002819-10 (EudraCT Number)