Cystic Fibrosis, Pancreatic Insufficiency
Conditions
Keywords
Cystic Fibrosis, Pancreatic insufficiency, Steatorrhea, Children 7 to 11 years, Pancreatic enzyme
Brief summary
This is a Phase III, multicenter, open-label study, that will evaluate the improvement of nutrient absorption when participants will receive Ultrase® MT20. This study is sponsored by Aptalis (formerly Axcan). This study is performed in children from 7 to 11 years old.
Detailed description
This is a Phase III, multicenter, open-label study, which will quantify the improvement of nutrient absorption when participants are receiving Ultrase® MT20. The improvement will be demonstrated by comparing the CFA percent (%) and CNA% obtained during a washout of enzyme with the CFA% and CNA% obtained during a period of treatment with Ultrase® MT20. The study is also designed to obtain safety data in CF children suffering also from PI taking Ultrase® MT20. The total duration for the participation of children in this study will be approximately up to 38 days and will include 3 phases: screening phase, the washout phase and treatment phase. Screening phase: this phase will last 15 days and all participants will take Ultrase® MT20 as per investigator's discretion during this period. During the last 4 days, participants will be stabilized on a high fat diet and with Ultrase® MT20. The individual 'stabilized dose' of Ultrase® MT20 capsules will be determined for each participant based on the average number of capsules of Ultrase® MT20 taken during last 4 days. Washout phase: this phase will last 6 to 7 days. The participants will continue the high-fat diet but will refrain from taking Ultrase® MT20 or any other enzymes. A 72-hour stool collection will be performed and all food consumed by the participants will be recorded to assess the CFA% and CNA%. Treatment phase: this phase will last 7 to 11 days. The participants will continue the high-fat diet and will take the 'stabilized dose' of Ultrase® MT20 established during screening. Another 72-hour stool collection will be performed and all food consumed by the participants will be recorded to assess the CFA% and CNA%.
Interventions
DRUGUltrase® MT20
Ultrase® MT20 capsules will be administered orally with each meal during Day 1 to 15 in screening phase at a dose based on investigator's discretion. During Day 12 to 15, participants will receive high-fat diet and Ultrase® MT20 dose will be adjusted depending on symptoms of steatorrhea. This will be followed by a washout phase of 6 to 7 days, in which participants will receive only high-fat diet; then stabilized dose of Ultrase® MT20 capsule (as identified during screening phase) will be administered orally for 7 to 11 days during treatment phase. The stabilized dose should not to exceed 2500 lipase units per kilogram body weight per meal (lipase units/kg/meal).
Sponsors
Forest Laboratories
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
7 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* After a full explanation of the study, participants or their legally authorized representative must have signed the informed consent or assent form along with a parental form * Participants must have a confirmed diagnosis of CF based on one or more clinical features consistent with the CF phenotype, and one of the following: * A genotype with two identifiable mutations consistent with CF * A sweat chloride test greater that 60 millimole per liter (mmol/L) by quantitative pilocarpine iontophoresis * Participants must have PI as demonstrated by a fecal elastase-1 (FE-1) concentration less than 100 microgram per gram (mcg/g) of stools (ScheBo test) and requiring pancreatic enzyme supplementation * Participants must be clinically stable according to the physician's judgment by: * Medical and medication history * Baseline physical examination including vital signs and laboratory analyses * Participants must be 7 to 11 years of age * Participants must have an adequate nutritional status based on body mass index (BMI) greater than or equal to fifth percentile * Participants must be on an optimal clinical dose of pancreatic enzymes (Ultrase® MT12 , MT18 or MT20 or other pancreatic enzyme preparations) prior to entry in the study and must tolerate this medication in the opinion of the investigator * Participants must be able to be able to swallow capsules and eat a high-fat diet calculated as 2 gram fat per kilogram (g fat/kg) of body weight per day * Participants must be, in the opinion of the investigator, able and willing to complete the study * Female participants should be premenarcheal. Otherwise, a female participant of childbearing potential (WOCBP) must not be pregnant and must have practiced an acceptable method of contraception for at least 1 month prior to the study entry
Exclusion criteria
* Participants with a known contraindication, sensitivity or hypersensitivity to Ultrase® MT20 or any porcine protein * Participants with a known allergy to the food, drug and cosmetic (FD&C) Blue No. 2 dye indicator (stool marker) * Participants who are not willing to stop the prohibited medications or products at study entry and throughout the study * Participants who use narcotics chronically and bowel stimulants and/or laxatives on a regular basis * Participants with acute pancreatitis or acute exacerbation of chronic pancreatic disease * Participants with an acute pulmonary infection * Participants with a history of bowel resection * Participants suffering from any dysmotility disorders * Participants with chronic or severe abdominal pain * Participants receiving enteral tube feeding and not willing to stop during the course of the study * Participants with a significant medical disease that would compromise their welfare or confound the study results * Participants with a history of or a current diagnosis of clinically significant portal hypertension * Participants who have a condition known to increase fecal fat loss including celiac's disease, biliary cancer, biliary stricture, cholelithiasis, Crohn's disease, ulcerative colitis, pancreas cancer, radiation enteritis, tropical sprue, Whipple's disease, lactose intolerance, pseudomembranous colitis * Participants with a current diagnosis or a history of complete distal intestinal obstruction syndrome (DIOS) in the past 6 months; or, participants who had 2 or more episodes of DIOS in the past year * Participants with poorly controlled diabetes according to the investigator's opinion * Female participants who are pregnant or lactating * Participants who received an investigational drug within 30 days prior to entry into the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Coefficient of Fat Absorption (CFA) | Day 3 to Day 5 or Day 6 during washout phase and treatment phase | Percent CFA was calculated as (\[fat intake - fat excretion\]/fat intake)\*100, determined by the stools collected during the 72-hour period in either washout phase or treatment phase. Mean percent CFA was calculated for Day 3 to Day 5 or Day 6 of the respective phase. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Coefficient of Nitrogen Absorption (CNA) | Day 3 to Day 5 or Day 6 during washout phase and treatment phase | Percent CNA was calculated as \[(nitrogen intake-nitrogen excretion)/nitrogen intake\]\*100, determined by the stools collected during the 72- hour period in either washout phase or treatment phase. Nitrogen intake was calculated as protein intake/6.25. Nitrogen excretion was measured as total fecal nitrogen. Mean percent CNA was calculated for Day 3 to Day 5 or Day 6 of the respective phase. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ultrase® MT20 Ultrase® MT20 capsules orally with each meal during Day 1 to 15 in screening phase at a dose based on investigator's discretion. During Day 12 to 15, participants received high-fat diet and Ultrase® MT20 dose was adjusted depending on symptoms of steatorrhea. This was followed by a washout phase of 6 to 7 days, in which participants received only high-fat diet. Then the treatment phase was started which consisted of a stabilized dose of Ultrase® MT20 capsule (as identified during screening phase) orally for 7 to 11 days. The stabilized dose not to exceed 2500 lipase units per kilogram body weight per meal (lipase units/kg/meal). | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Washout Phase | Adverse Event | 2 |
Baseline characteristics
| Characteristic | Ultrase® MT20 |
|---|---|
| Age, Continuous | 9.8 years STANDARD_DEVIATION 1.64 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 9 | 6 / 9 | 2 / 7 |
| serious Total, serious adverse events | 0 / 9 | 0 / 9 | 0 / 7 |
Outcome results
Primary
Percent Coefficient of Fat Absorption (CFA)
Percent CFA was calculated as (\[fat intake - fat excretion\]/fat intake)\*100, determined by the stools collected during the 72-hour period in either washout phase or treatment phase. Mean percent CFA was calculated for Day 3 to Day 5 or Day 6 of the respective phase.
Time frame: Day 3 to Day 5 or Day 6 during washout phase and treatment phase
Population: Intent-to-treat (ITT) population included all the participants who took at least 1 dose of Ultrase® MT20 and had completed at least 1 phase (washout or treatment phase) evaluating primary and secondary efficacy parameters.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ultrase® MT20 Washout Phase | Percent Coefficient of Fat Absorption (CFA) | 34.5 Percent CFA | Standard Deviation 21.35 |
| Ultrase® MT20 Treatment Phase | Percent Coefficient of Fat Absorption (CFA) | 82.7 Percent CFA | Standard Deviation 13.25 |
p-value: 0.0013t-test, 1 sided
Secondary
Percent Coefficient of Nitrogen Absorption (CNA)
Percent CNA was calculated as \[(nitrogen intake-nitrogen excretion)/nitrogen intake\]\*100, determined by the stools collected during the 72- hour period in either washout phase or treatment phase. Nitrogen intake was calculated as protein intake/6.25. Nitrogen excretion was measured as total fecal nitrogen. Mean percent CNA was calculated for Day 3 to Day 5 or Day 6 of the respective phase.
Time frame: Day 3 to Day 5 or Day 6 during washout phase and treatment phase
Population: Intent-to-treat (ITT) population included all the participants who took at least 1 dose of Ultrase® MT20 and had completed at least 1 phase (washout or treatment phase) evaluating primary and secondary efficacy parameters.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ultrase® MT20 Washout Phase | Percent Coefficient of Nitrogen Absorption (CNA) | 33.4 Percent CNA | Standard Deviation 20.06 |
| Ultrase® MT20 Treatment Phase | Percent Coefficient of Nitrogen Absorption (CNA) | 79.5 Percent CNA | Standard Deviation 10.56 |
p-value: 0.0009t-test, 1 sided