Back to resultsControl of Steatorrhea in Participants With Cystic Fibrosis and Exocrine Pancreatic Insufficiency
Primary Purpose
Exocrine Pancreatic Insufficiency, Cystic Fibrosis
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Panzytrat® 25,000
Kreon® 25,000
Sponsored by
About this trial
This is an interventional treatment trial for Exocrine Pancreatic Insufficiency focused on measuring Exocrine Pancreatic Insufficiency, Cystic Fibrosis, Steatorrhea, Malabsorption, Malnutrition
Eligibility Criteria
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
Sites / Locations
- Klinikum-Bochum
- Universitätsklinikum Carl Gustav Carus
- Universitaetsklinikum Erlangen
- Jena University Hospital, Universitaetsklinikum Jena
- Klinikum der Universitat Munchen Medizinische Klinik-Innenstadt
- University Children's Clinic Tubingen
- Specjalistyczny Zespół Opieki Zdrowotnej nad Matką i Dzieckiem Poradnia Leczenia Mukowiscydozy
- Wojewodzki Specjalistityczny Szpital Dziect Im Sw Ludwika
- Dziecięcy Szpital Kliniczny im. Prof. Antoniego Gębali
- Szpital Kliniczny im Karola Jonschera
- NZOZ Sanatorium Cassia Villa Medica
- NZOZ Podkarpacki Osrodek Pulmonologii i Alergologii
- Children's Health Memorial Institute
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Panzytrat® 25,000
Kreon® 25,000
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
Total Weight of Stools
Mean total weight of stools was calculated for Day 12 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.
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).
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).
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.
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.
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).
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).
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).
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).
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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01327703
Brief Title
Control of Steatorrhea in Participants With Cystic Fibrosis and Exocrine Pancreatic Insufficiency
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2014
Overall Recruitment Status
Completed
Study Start Date
April 2011 (undefined)
Primary Completion Date
May 2012 (Actual)
Study Completion Date
May 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Forest Laboratories
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Exocrine Pancreatic Insufficiency, Cystic Fibrosis
Keywords
Exocrine Pancreatic Insufficiency, Cystic Fibrosis, Steatorrhea, Malabsorption, Malnutrition
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
87 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Panzytrat® 25,000
Arm Type
Experimental
Arm Title
Kreon® 25,000
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Panzytrat® 25,000
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Kreon® 25,000
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percent Coefficient of Fat Absorption (CFA)
Description
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.
Time Frame
Day 12 up to Day 15 in first and second treatment periods
Secondary Outcome Measure Information:
Title
Mean Daily Number of Stools
Description
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.
Time Frame
Day 12 up to Day 15 in first and second treatment periods
Title
Percentage of Stools With Normal Consistency
Description
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.
Time Frame
Day 12 up to Day 15 in first and second treatment periods
Title
Total Weight of Stools
Description
Mean total weight of stools was calculated for Day 12 to Day 15 in first and second treatment periods.
Time Frame
Day 12 up to Day 15 in first and second treatment periods
Title
Mean Weight Per Stool Sample
Description
Mean weight per stool sample was calculated for Day 12 to Day 15 in first and second treatment periods.
Time Frame
Day 12 up to Day 15 in first and second treatment periods
Title
Relative Frequency of Days With Abdominal Symptoms
Description
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).
Time Frame
Day 1 up to Day 15 in first and second treatment periods
Title
Percentage of Participants With Abdominal Distension
Description
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).
Time Frame
Day 1 up to Day 15 in first and second treatment periods
Title
Percent Coefficient of Fat Absorption (CFA) Based on Concomitant Use of Proton Pump Inhibitors (PPIs)
Description
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.
Time Frame
Day 12 up to Day 15 in first and second treatment periods
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs)
Description
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.
Time Frame
Baseline up to 30 days after last dose
Title
Nutritional Status as Assessed by Body Weight
Description
Mean body weight was calculated at end of treatment (within 3 days after Day 15 of first and second treatment periods).
Time Frame
Baseline, end of treatment (within 3 days after Day 15 of first and second treatment periods) or early discontinuation
Title
Nutritional Status as Assessed by Body Mass Index (BMI)
Description
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).
Time Frame
Baseline, end of treatment (within 3 days after Day 15 of first and second treatment periods) or early discontinuation
Title
Nutritional Status as Assessed by Electrolytes Level
Description
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).
Time Frame
Baseline, end of treatment (within 3 days after Day 15 of first and second treatment periods) or early discontinuation
Title
Nutritional Status as Assessed by Albumin, Serum Transferrin and Hemoglobin Level
Description
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).
Time Frame
Baseline, end of treatment (within 3 days after Day 15 of first and second treatment periods) or early discontinuation
Title
Nutritional Status as Assessed by Hematocrit Level
Description
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).
Time Frame
Baseline, end of treatment (within 3 days after Day 15 of first and second treatment periods) or early discontinuation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
7 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aptalis Medical Information
Organizational Affiliation
Forest Laboratories
Official's Role
Study Director
Facility Information:
Facility Name
Klinikum-Bochum
City
Bochum
Country
Germany
Facility Name
Universitätsklinikum Carl Gustav Carus
City
Dresden
Country
Germany
Facility Name
Universitaetsklinikum Erlangen
City
Erlangen
Country
Germany
Facility Name
Jena University Hospital, Universitaetsklinikum Jena
City
Jena
Country
Germany
Facility Name
Klinikum der Universitat Munchen Medizinische Klinik-Innenstadt
City
München
Country
Germany
Facility Name
University Children's Clinic Tubingen
City
Tubingen
Country
Germany
Facility Name
Specjalistyczny Zespół Opieki Zdrowotnej nad Matką i Dzieckiem Poradnia Leczenia Mukowiscydozy
City
Gdansk
Country
Poland
Facility Name
Wojewodzki Specjalistityczny Szpital Dziect Im Sw Ludwika
City
Krakow
Country
Poland
Facility Name
Dziecięcy Szpital Kliniczny im. Prof. Antoniego Gębali
City
Lublin
Country
Poland
Facility Name
Szpital Kliniczny im Karola Jonschera
City
Poznan
Country
Poland
Facility Name
NZOZ Sanatorium Cassia Villa Medica
City
Rabka Zdrój
Country
Poland
Facility Name
NZOZ Podkarpacki Osrodek Pulmonologii i Alergologii
City
Rzeszow
Country
Poland
Facility Name
Children's Health Memorial Institute
City
Warszawa
Country
Poland
12. IPD Sharing Statement
Learn more about this trial
Control of Steatorrhea in Participants With Cystic Fibrosis and Exocrine Pancreatic Insufficiency
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