Cystic Fibrosis, Exocrine Pancreatic Insufficiency
Conditions
Keywords
Exocrine Pancreatic Insufficiency, Cystic Fibrosis, Steatorrhea, Malabsorption, Malnutrition
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.
Interventions
DRUGPanzytrat® 25,000
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.
DRUGKreon® 25,000
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.
Sponsors
Forest Laboratories
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
7 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Coefficient of Fat Absorption (CFA) | Day 12 up to Day 15 in first and second treatment periods | 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Stools With Normal Consistency | Day 12 up to Day 15 in first and second treatment periods | 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 | Day 12 up to Day 15 in first and second treatment periods | Mean total weight of stools was calculated for Day 12 to Day 15 in first and second treatment periods. |
| Mean Weight Per Stool Sample | Day 12 up to Day 15 in first and second treatment periods | 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 | Day 1 up to Day 15 in first and second treatment periods | 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 | Day 1 up to Day 15 in first and second treatment periods | 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) | Day 12 up to Day 15 in first and second treatment periods | 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. |
| Mean Daily Number of Stools | Day 12 up to Day 15 in first and second treatment periods | 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. |
| Nutritional Status as Assessed by Body Weight | Baseline, end of treatment (within 3 days after Day 15 of first and second treatment periods) or early discontinuation | 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) | Baseline, end of treatment (within 3 days after Day 15 of first and second treatment periods) or early discontinuation | 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 | Baseline, end of treatment (within 3 days after Day 15 of first and second treatment periods) or early discontinuation | 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 | Baseline, end of treatment (within 3 days after Day 15 of first and second treatment periods) or early discontinuation | 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 | Baseline, end of treatment (within 3 days after Day 15 of first and second treatment periods) or early discontinuation | 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). |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) | Baseline up to 30 days after last dose | 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. |
Countries
Germany, Poland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes randomized participants who received Panzytrat® 25,000 first and Kreon® 25,000 first. | 87 |
| Total | 87 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Second Treatment Period | Adverse Event | 1 | 1 |
| Second Treatment Period | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Continuous | 13.6 years STANDARD_DEVIATION 6.14 |
| Nutritional status as assessed by Vitamin A and E level Vitamin A (n=87) | 1.403 micromole/liter (mcmol/L) STANDARD_DEVIATION 0.5329 |
| Nutritional status as assessed by Vitamin A and E level Vitamin E (Alpha-Tocopherol) (n=87) | 18.554 micromole/liter (mcmol/L) STANDARD_DEVIATION 8.9713 |
| Nutritional status as assessed by Vitamin A and E level Vitamin E (Beta-Gamma-Tocopherol) (n=83) | 1.231 micromole/liter (mcmol/L) STANDARD_DEVIATION 2.0781 |
| Nutritional status as assessed by Vitamin D level | 55.4 nanomole/L (nmol/L) STANDARD_DEVIATION 33.24 |
| Sex: Female, Male Female | 34 Participants |
| Sex: Female, Male Male | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 32 / 86 | 20 / 85 |
| serious Total, serious adverse events | 0 / 86 | 0 / 85 |
Outcome results
Primary
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.
Time frame: Day 12 up to Day 15 in first and second treatment periods
Population: Per protocol population included all randomized participants who completed both treatment periods and had all bowel movements appropriately collected with no major protocol violations/deviations or other events considered to potentially bias the study evaluations.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Panzytrat® | Percent Coefficient of Fat Absorption (CFA) | 78.27 percent CFA | Standard Error 1.033 |
| Kreon® | Percent Coefficient of Fat Absorption (CFA) | 80.35 percent CFA | Standard Error 1.033 |
Comparison: Mixed model analysis method was used for comparison using log-transformed percent CFA as the response variable, fixed effect factors for treatment, period, treatment sequence and pooled site and participant within treatment sequence as a random effect.p-value: 0.45995% CI: [-7.23, 4.02]Mixed Models Analysis
Secondary
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.
Time frame: Day 12 up to Day 15 in first and second treatment periods
Population: Intent-to-treat (ITT) population included all randomized participants. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Panzytrat® | Mean Daily Number of Stools | 4.5 stools per day | Standard Deviation 2.43 |
| Kreon® | Mean Daily Number of Stools | 4.2 stools per day | Standard Deviation 2.14 |
Secondary
Mean Weight Per Stool Sample
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
Population: ITT population included all randomized participants. Here, 'N' (number of participants analyzed) signifies those participants who had 1 or more bowel movements over the 72-hour collection period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Panzytrat® | Mean Weight Per Stool Sample | 131.7 gram | Standard Deviation 79.67 |
| Kreon® | Mean Weight Per Stool Sample | 124.0 gram | Standard Deviation 81.71 |
Secondary
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.
Time frame: Baseline up to 30 days after last dose
Population: Safety population included all randomized participants who received at least 1 dose of study medication. Here, 'N' (number of participants analyzed) specifies number of participants who were evaluable for this measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Panzytrat® | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) | AEs | 32 participants |
| Panzytrat® | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Kreon® | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) | AEs | 20 participants |
| Kreon® | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) | SAEs | 0 participants |
Secondary
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).
Time frame: Baseline, end of treatment (within 3 days after Day 15 of first and second treatment periods) or early discontinuation
Population: Safety population included all randomized participants who received at least 1 dose of study drug. Here, 'N' specifies number of participants who were evaluable for this outcome measure and 'n' specifies number of participants who were evaluable for specific categories at each time point for each arm group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Panzytrat® | Nutritional Status as Assessed by Albumin, Serum Transferrin and Hemoglobin Level | Hemoglobin: End of treatment (n=42, 42) | 137.935 gram/L (g/L) | Standard Deviation 11.4543 |
| Panzytrat® | Nutritional Status as Assessed by Albumin, Serum Transferrin and Hemoglobin Level | Albumin: Baseline (n=41, 42) | 40.553 gram/L (g/L) | Standard Deviation 11.3568 |
| Panzytrat® | Nutritional Status as Assessed by Albumin, Serum Transferrin and Hemoglobin Level | Albumin: End of treatment (n=41, 42) | 40.785 gram/L (g/L) | Standard Deviation 11.1893 |
| Panzytrat® | Nutritional Status as Assessed by Albumin, Serum Transferrin and Hemoglobin Level | Serum transferrin: Baseline (n=40, 41) | 2.877 gram/L (g/L) | Standard Deviation 0.9769 |
| Panzytrat® | Nutritional Status as Assessed by Albumin, Serum Transferrin and Hemoglobin Level | Serum transferrin: End of treatment (n=40, 41) | 2.916 gram/L (g/L) | Standard Deviation 0.9416 |
| Panzytrat® | Nutritional Status as Assessed by Albumin, Serum Transferrin and Hemoglobin Level | Hemoglobin: Baseline (n=42, 42) | 137.337 gram/L (g/L) | Standard Deviation 11.757 |
| Kreon® | Nutritional Status as Assessed by Albumin, Serum Transferrin and Hemoglobin Level | Serum transferrin: End of treatment (n=40, 41) | 2.626 gram/L (g/L) | Standard Deviation 1.1618 |
| Kreon® | Nutritional Status as Assessed by Albumin, Serum Transferrin and Hemoglobin Level | Hemoglobin: End of treatment (n=42, 42) | 141.263 gram/L (g/L) | Standard Deviation 11.4412 |
| Kreon® | Nutritional Status as Assessed by Albumin, Serum Transferrin and Hemoglobin Level | Serum transferrin: Baseline (n=40, 41) | 2.618 gram/L (g/L) | Standard Deviation 1.1857 |
| Kreon® | Nutritional Status as Assessed by Albumin, Serum Transferrin and Hemoglobin Level | Albumin: Baseline (n=41, 42) | 37.995 gram/L (g/L) | Standard Deviation 14.8405 |
| Kreon® | Nutritional Status as Assessed by Albumin, Serum Transferrin and Hemoglobin Level | Hemoglobin: Baseline (n=42, 42) | 141.118 gram/L (g/L) | Standard Deviation 11.4577 |
| Kreon® | Nutritional Status as Assessed by Albumin, Serum Transferrin and Hemoglobin Level | Albumin: End of treatment (n=41, 42) | 37.991 gram/L (g/L) | Standard Deviation 14.9636 |
Secondary
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).
Time frame: Baseline, end of treatment (within 3 days after Day 15 of first and second treatment periods) or early discontinuation
Population: Safety population included all randomized participants who received at least 1 dose of study drug. Here, 'N' specifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Panzytrat® | Nutritional Status as Assessed by Body Mass Index (BMI) | Baseline | 17.84 kg/m^2 | Standard Deviation 3.296 |
| Panzytrat® | Nutritional Status as Assessed by Body Mass Index (BMI) | End of treatment | 17.94 kg/m^2 | Standard Deviation 3.244 |
| Kreon® | Nutritional Status as Assessed by Body Mass Index (BMI) | Baseline | 17.90 kg/m^2 | Standard Deviation 3.264 |
| Kreon® | Nutritional Status as Assessed by Body Mass Index (BMI) | End of treatment | 18.01 kg/m^2 | Standard Deviation 3.24 |
Secondary
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).
Time frame: Baseline, end of treatment (within 3 days after Day 15 of first and second treatment periods) or early discontinuation
Population: Safety population included all randomized participants who received at least 1 dose of study drug. Here, 'N' specifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Panzytrat® | Nutritional Status as Assessed by Body Weight | Baseline | 40.82 kg | Standard Deviation 16.001 |
| Panzytrat® | Nutritional Status as Assessed by Body Weight | End of treatment | 41.22 kg | Standard Deviation 15.999 |
| Kreon® | Nutritional Status as Assessed by Body Weight | Baseline | 41.43 kg | Standard Deviation 15.861 |
| Kreon® | Nutritional Status as Assessed by Body Weight | End of treatment | 41.88 kg | Standard Deviation 15.886 |
Secondary
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).
Time frame: Baseline, end of treatment (within 3 days after Day 15 of first and second treatment periods) or early discontinuation
Population: Safety population included all randomized participants who received at least 1 dose of study drug. Here, 'N' specifies number of participants who were evaluable for this outcome measure and 'n' specifies number of participants who were evaluable for specific categories at each time point for each arm group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Panzytrat® | Nutritional Status as Assessed by Electrolytes Level | Sodium: Baseline (n=42, 43) | 138.41 millimole/L (mmol/L) | Standard Deviation 3.026 |
| Panzytrat® | Nutritional Status as Assessed by Electrolytes Level | Sodium: End of treatment (n=42, 43) | 139.11 millimole/L (mmol/L) | Standard Deviation 2.35 |
| Panzytrat® | Nutritional Status as Assessed by Electrolytes Level | Potassium: Baseline (n=42, 42) | 4.441 millimole/L (mmol/L) | Standard Deviation 0.4799 |
| Panzytrat® | Nutritional Status as Assessed by Electrolytes Level | Potassium: End of treatment (n=42, 42) | 4.322 millimole/L (mmol/L) | Standard Deviation 0.4113 |
| Panzytrat® | Nutritional Status as Assessed by Electrolytes Level | Chloride: Baseline (n=38, 40) | 102.08 millimole/L (mmol/L) | Standard Deviation 3.436 |
| Panzytrat® | Nutritional Status as Assessed by Electrolytes Level | Chloride: End of treatment (n=38, 40) | 102.13 millimole/L (mmol/L) | Standard Deviation 2.796 |
| Kreon® | Nutritional Status as Assessed by Electrolytes Level | Chloride: Baseline (n=38, 40) | 101.40 millimole/L (mmol/L) | Standard Deviation 3.193 |
| Kreon® | Nutritional Status as Assessed by Electrolytes Level | Sodium: Baseline (n=42, 43) | 138.54 millimole/L (mmol/L) | Standard Deviation 3.356 |
| Kreon® | Nutritional Status as Assessed by Electrolytes Level | Potassium: End of treatment (n=42, 42) | 4.344 millimole/L (mmol/L) | Standard Deviation 0.3506 |
| Kreon® | Nutritional Status as Assessed by Electrolytes Level | Sodium: End of treatment (n=42, 43) | 139.07 millimole/L (mmol/L) | Standard Deviation 2.466 |
| Kreon® | Nutritional Status as Assessed by Electrolytes Level | Chloride: End of treatment (n=38, 40) | 102.18 millimole/L (mmol/L) | Standard Deviation 2.541 |
| Kreon® | Nutritional Status as Assessed by Electrolytes Level | Potassium: Baseline (n=42, 42) | 4.371 millimole/L (mmol/L) | Standard Deviation 0.3721 |
Secondary
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).
Time frame: Baseline, end of treatment (within 3 days after Day 15 of first and second treatment periods) or early discontinuation
Population: Safety population included all randomized participants who received at least 1 dose of study drug. Here, 'N' specifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Panzytrat® | Nutritional Status as Assessed by Hematocrit Level | Baseline | 0.408 proportion of hematocrit | Standard Deviation 0.0324 |
| Panzytrat® | Nutritional Status as Assessed by Hematocrit Level | End of treatment | 0.409 proportion of hematocrit | Standard Deviation 0.0311 |
| Kreon® | Nutritional Status as Assessed by Hematocrit Level | Baseline | 0.417 proportion of hematocrit | Standard Deviation 0.0333 |
| Kreon® | Nutritional Status as Assessed by Hematocrit Level | End of treatment | 0.416 proportion of hematocrit | Standard Deviation 0.0328 |
Secondary
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).
Time frame: Day 1 up to Day 15 in first and second treatment periods
Population: ITT population included all randomized participants. Here, 'N' specifies number of participants who had abdominal distension assessment at screening and end of specified treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panzytrat® | Percentage of Participants With Abdominal Distension | 12.8 percentage of participants |
| Kreon® | Percentage of Participants With Abdominal Distension | 11.8 percentage of participants |
Secondary
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.
Time frame: Day 12 up to Day 15 in first and second treatment periods
Population: ITT population included all randomized participants. Here, 'N' (number of participants analyzed) specify signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Panzytrat® | Percentage of Stools With Normal Consistency | 0.644 percentage of stools | Standard Deviation 0.3442 |
| Kreon® | Percentage of Stools With Normal Consistency | 0.635 percentage of stools | Standard Deviation 0.3517 |
Secondary
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.
Time frame: Day 12 up to Day 15 in first and second treatment periods
Population: Per protocol population. Here, 'n' specifies number of participants who were evaluable for specific categories for each arm group, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Panzytrat® | Percent Coefficient of Fat Absorption (CFA) Based on Concomitant Use of Proton Pump Inhibitors (PPIs) | PPIs used (n=7, 7) | 79.66 percent CFA | Standard Error 1.071 |
| Panzytrat® | Percent Coefficient of Fat Absorption (CFA) Based on Concomitant Use of Proton Pump Inhibitors (PPIs) | PPIs not used (n=31, 31) | 80.89 percent CFA | Standard Error 1.037 |
| Kreon® | Percent Coefficient of Fat Absorption (CFA) Based on Concomitant Use of Proton Pump Inhibitors (PPIs) | PPIs used (n=7, 7) | 94.29 percent CFA | Standard Error 1.071 |
| Kreon® | Percent Coefficient of Fat Absorption (CFA) Based on Concomitant Use of Proton Pump Inhibitors (PPIs) | PPIs not used (n=31, 31) | 79.24 percent CFA | Standard Error 1.037 |
Secondary
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).
Time frame: Day 1 up to Day 15 in first and second treatment periods
Population: ITT population included all randomized participants. Here, 'N' specifies number of participants who were evaluable for this outcome measure and 'n' specifies the number of participants with at least one report of the symptom at that severity level during a treatment period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Panzytrat® | Relative Frequency of Days With Abdominal Symptoms | Abdominal pain (n=86, 85) | 0.227 days | Standard Deviation 0.25 |
| Panzytrat® | Relative Frequency of Days With Abdominal Symptoms | Mild abdominal pain (n=58, 57) | 0.302 days | Standard Deviation 0.244 |
| Panzytrat® | Relative Frequency of Days With Abdominal Symptoms | Moderate abdominal pain (n=37, 39) | 0.434 days | Standard Deviation 0.2496 |
| Panzytrat® | Relative Frequency of Days With Abdominal Symptoms | Severe abdominal pain (n=14, 12) | 0.429 days | Standard Deviation 0.2646 |
| Panzytrat® | Relative Frequency of Days With Abdominal Symptoms | Flatulence (n=86, 85) | 0.365 days | Standard Deviation 0.3215 |
| Panzytrat® | Relative Frequency of Days With Abdominal Symptoms | Mild flatulence (n=67, 61) | 0.467 days | Standard Deviation 0.2912 |
| Panzytrat® | Relative Frequency of Days With Abdominal Symptoms | Moderate flatulence (n=35, 40) | 0.351 days | Standard Deviation 0.2649 |
| Panzytrat® | Relative Frequency of Days With Abdominal Symptoms | Severe flatulence (n=20, 13) | 0.616 days | Standard Deviation 0.2959 |
| Kreon® | Relative Frequency of Days With Abdominal Symptoms | Severe flatulence (n=20, 13) | 0.554 days | Standard Deviation 0.1968 |
| Kreon® | Relative Frequency of Days With Abdominal Symptoms | Abdominal pain (n=86, 85) | 0.216 days | Standard Deviation 0.2251 |
| Kreon® | Relative Frequency of Days With Abdominal Symptoms | Flatulence (n=86, 85) | 0.329 days | Standard Deviation 0.329 |
| Kreon® | Relative Frequency of Days With Abdominal Symptoms | Mild abdominal pain (n=58, 57) | 0.308 days | Standard Deviation 0.2199 |
| Kreon® | Relative Frequency of Days With Abdominal Symptoms | Moderate flatulence (n=35, 40) | 0.577 days | Standard Deviation 0.2806 |
| Kreon® | Relative Frequency of Days With Abdominal Symptoms | Moderate abdominal pain (n=37, 39) | 0.374 days | Standard Deviation 0.2269 |
| Kreon® | Relative Frequency of Days With Abdominal Symptoms | Mild flatulence (n=67, 61) | 0.459 days | Standard Deviation 0.3018 |
| Kreon® | Relative Frequency of Days With Abdominal Symptoms | Severe abdominal pain (n=14, 12) | 0.400 days | Standard Deviation 0.2741 |
Secondary
Total Weight of Stools
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
Population: ITT population included all randomized participants. Here, 'N' (number of participants analyzed) signifies those participants who had 1 or more bowel movements over the 72-hour collection period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Panzytrat® | Total Weight of Stools | 521.6 gram | Standard Deviation 301.95 |
| Kreon® | Total Weight of Stools | 484.0 gram | Standard Deviation 326.81 |