Control of Steatorrhea in Participants With Cystic Fibrosis and Exocrine Pancreatic Insufficiency

Study Overview
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Brief Summary
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This study by Aptalis (formerly Axcan) assesses the efficacy and safety of Panzytrat® 25,000 compared to Kreon® 25,000 in the control of steatorrhea in participants with cystic fibrosis (CF) and exocrine pancreatic insufficiency (EPI).

Detailed Description
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This is an open-label, Phase IV, multicenter, randomized, two-period cross-over study to compare the efficacy and safety of Panzytrat® 25,000 to Kreon® 25,000 in participants aged 7 years and older suffering from CF and EPI. The study consists of a qualification phase (5 to 15 days); two treatment periods of 14 days each (plus a 3-day window if needed) and a 3-day stool collection will be performed from Days 12 to 15. A safety follow-up phone call will be arranged 7-10 days after completion of the treatment phase or after an early discontinuation.

Official Title
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An Open-label, Multicenter, Randomized, Cross-over Study to Compare the Safety and Efficacy of PANZYTRAT® 25,000 to KREON® 25,000 in the Control of Steatorrhea in Subjects Aged 7 Years and Older With Cystic Fibrosis (CF) and Exocrine Pancreatic Insufficiency (EPI)

Conditions
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Exocrine Pancreatic Insufficiency, Cystic Fibrosis

Intervention / Treatment
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* Drug: Panzytrat® 25,000
* Drug: Kreon® 25,000


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant or his/her legal representative signed informed consent form (ICF) prior to starting any study procedures Participant with clinical diagnosis of CF based on one or more typical clinical features of CF phenotype, in addition to one of the following: a genotype that documents the presence of 2 CF-causing mutation, or a sweat chloride test greater than or equal to 60 millimole per liter (mmol/L) by quantitative pilocarpine iontophoresis on two separate occasions Participant with severe EPI confirmed by enzyme-linked immunosorbent assay (ELISA) measurement of fecal elastase-1 (FE-1) Male or female participant aged 7 years or older Participant currently receiving and has received a stable dose of lipase with either Panzytrat® 25,000 or Kreon® 25,000 for at least 30 days prior to ICF signature Participant generally in good health, except for the underlying symptoms associated with CF and EPI, and is clinically stable (no change in the last 30 days of physical examination) as evidenced by medical and medication histories, physical examination including vital signs during screening and laboratory tests Participant able to maintain a CF standardized diet with a lipid content customized to his/her needs during the study according to the qualification phase diary Women of childbearing potential must have a negative pregnancy test at study entry and must use a medically acceptable contraceptive method for the duration of the study Exclusion Criteria: Participant with known contraindication, sensitivity or hypersensitivity to Panzytrat® 25,000 or Kreon® 25,000, or to any porcine protein Participant who recently received treatment of an emergent acute infection with oral or intravenous (IV) antibiotics that was not stopped at least 14 days prior to randomization Participant with chronic use of narcotics that were not stopped at least 7 days prior to the qualification visit Participant using of any prohibited medications or products listed in the prohibited medication section of the protocol Participant with acute pancreatitis or exacerbation of chronic pancreatic disease Participant with history of significant bowel resection that could impair fat absorption Participant with any condition known to increase fecal fat loss including but not limited to: celiac disease, Crohn's disease, tropical sprue, bacterial bowel infection, liver disease, lactose intolerance, pseudomembranous colitis, biliary and pancreatic cancer, radiation enteritis, Whipple's disease, Whipple's procedure, etc Participant with any significant gastrointestinal dysmotility disorders Participant with chronic abdominal pain or severe abdominal pain at study entry Participant using enteral tube feeding over day and night Participant with history or presence of clinically significant portal hypertension Participant with history or presence of complete distal intestinal obstruction syndrome (DIOS) in the past 6 months, or 2 or more episodes of DIOS in the past year Participant with poorly controlled diabetes as per the investigator's opinion Female participants who are pregnant or breastfeeding Participant with any condition or history of any illness, or pre-study laboratory abnormality which, in the opinion of the investigator or sponsor, might put the participant at risk, prevent the participant from completing the study, or otherwise affect the outcome of the study Participant using any investigational drug within 30 days prior to the date of signature of the ICF

Ages Eligible for Study
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Minimum Age: 7 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Panzytrat® 25,000<br> | Drug: Panzytrat® 25,000<br>* Panzytrat® 25,000 capsule will be given orally daily at a stabilized dose, as per investigator's discretion, for 14 days. Stabilized dose for a participant will be the optimal dose determined during a qualification phase that precedes the first treatment period and will be based upon the participant's usual lipase and lipid intake. Total dose will not exceed 10,000 European Pharmacopoeia (Ph.Eur.) units lipase/kilogram (kg) body weight/day in either first treatment period or second treatment period.<br>|
| Active Comparator: Kreon® 25,000<br> | Drug: Kreon® 25,000<br>* Kreon® 25,000 capsule will be given orally daily at a stabilized dose, as per investigator's discretion, for 14 days. Stabilized dose for a participant will be the optimal dose determined during a qualification phase that precedes the first treatment period and will be based upon the participant's usual lipase and lipid intake. Total dose will not exceed 10,000 Ph.Eur. units lipase/kg body weight/day in either first treatment period or second treatment period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Coefficient of Fat Absorption (CFA) | Percent CFA was calculated as ([fat intake - fat excretion]/fat intake)*100, determined in the stools which were collected over a 3-day period (Day 12 to morning of Day 15) during each treatment period. Least squares mean percent (%) CFA was calculated for Day 12 to Day 15 in first and second treatment periods. Percent CFA was based on log transformed data. | Day 12 up to Day 15 in first and second treatment periods | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Daily Number of Stools | Mean daily number of stools of each participant was calculated from frequency of stools by the participant per day. Mean daily number of stools during the collection period (Day 12 to Day 15 in first and second treatment periods) for total participants was summarized. | Day 12 up to Day 15 in first and second treatment periods | 
| Percentage of Stools With Normal Consistency | Normal consistency of stool was defined as formed hard, normal or soft stool and abnormal consistency was defined as loose and unformed, liquid stool and diarrhea. Percentage of stools with normal consistency of each participant was calculated as the number of stools with normal consistency relative to the total number of stools during the collection period. Mean percentage of stool with normal consistency during the collection period (Day 12 to Day 15 in first and second treatment periods) for total participants was summarized. | Day 12 up to Day 15 in first and second treatment periods | 
| Total Weight of Stools | Mean total weight of stools was calculated for Day 12 to Day 15 in first and second treatment periods. | Day 12 up to Day 15 in first and second treatment periods | 
| Mean Weight Per Stool Sample | Mean weight per stool sample was calculated for Day 12 to Day 15 in first and second treatment periods. | Day 12 up to Day 15 in first and second treatment periods | 
| Relative Frequency of Days With Abdominal Symptoms | Abdominal symptoms included abdominal pain and flatulence. Symptoms were classified by severity as mild (no impairment of daily activities), moderate (slight impairment of daily activities), or severe (unable to perform daily activities). For each type of abdominal symptom, the relative frequency of days with the symptom for each participant in a treatment period was calculated as the number of days in which the symptom was reported divided by the total number of days in which the abdominal symptom case report form (CRF) was completed. Mean relative frequency of days with abdominal symptoms was calculated during each treatment period (Day 1 to Day 15). | Day 1 up to Day 15 in first and second treatment periods | 
| Percentage of Participants With Abdominal Distension | Abdominal distension is a sense of increased abdominal pressure by the participant that involves an actual measurable change in the circumference of a participant's abdomen on physical examination. Percentage of participants with abdominal distension was calculated for each treatment period (Day 1 to Day 15). | Day 1 up to Day 15 in first and second treatment periods | 
| Percent Coefficient of Fat Absorption (CFA) Based on Concomitant Use of Proton Pump Inhibitors (PPIs) | Percent CFA was calculated as ([fat intake - fat excretion]/fat intake)*100, determined in the stools which were collected over a 3-day period (Day 12 to morning of Day 15) during each treatment period. Least squares mean percent (%) CFA was calculated for Day 12 to Day 15 in first and second treatment periods. Percent CFA was based on log transformed data. Percent CFA was calculated separately for participants who used and did not use acid suppressing therapy (PPIs) during the study. | Day 12 up to Day 15 in first and second treatment periods | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) | An AE was defined as any untoward medical occurrence regardless of its causal relationship to study drug. A TEAE was defined as any event not present prior to exposure to study drug or any event already present that worsens in either intensity or frequency following exposure to test drug. A SAE was defined as any event that results in death, is immediately life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect or is assessed as medically important. | Baseline up to 30 days after last dose | 
| Nutritional Status as Assessed by Body Weight | Mean body weight was calculated at end of treatment (within 3 days after Day 15 of first and second treatment periods). | Baseline, end of treatment (within 3 days after Day 15 of first and second treatment periods) or early discontinuation | 
| Nutritional Status as Assessed by Body Mass Index (BMI) | Nutritional status of participants was assessed by determining their BMI. BMI was calculated by dividing body weight (kg) by square of height in meter (m). Mean BMI was calculated at end of treatment (within 3 days after Day 15 of first and second treatment periods). | Baseline, end of treatment (within 3 days after Day 15 of first and second treatment periods) or early discontinuation | 
| Nutritional Status as Assessed by Electrolytes Level | Nutritional status of participants was assessed by determining their electrolytes (sodium, potassium and chloride) level. Mean electrolytes level was calculated at end of treatment (within 3 days after Day 15 of first and second treatment periods). | Baseline, end of treatment (within 3 days after Day 15 of first and second treatment periods) or early discontinuation | 
| Nutritional Status as Assessed by Albumin, Serum Transferrin and Hemoglobin Level | Nutritional status of participants was assessed by determining their albumin, serum transferrin and hemoglobin level. Mean albumin, serum transferrin and hemoglobin level was calculated at end of treatment (within 3 days after Day 15 of first and second treatment periods). | Baseline, end of treatment (within 3 days after Day 15 of first and second treatment periods) or early discontinuation | 
| Nutritional Status as Assessed by Hematocrit Level | Nutritional status of participants was assessed by determining their hematocrit level. Mean hematocrit level was calculated at end of treatment (within 3 days after Day 15 of first and second treatment periods). | Baseline, end of treatment (within 3 days after Day 15 of first and second treatment periods) or early discontinuation | 

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