Cystic Fibrosis, Pancreatic Exocrine Insufficiency
Conditions
Keywords
Cystic Fibrosis, Pancreatic Exocrine Insufficiency
Brief summary
This study will assess the effect of pancrelipase delayed release 12,000 unit capsules on fat and nitrogen absorption in subjects 7 - 11 with pancreatic exocrine insufficiency due to Cystic Fibrosis.
Interventions
12,000 unit Capsules, dosed individually based on fat intake.
DRUGPlacebo Comparator
Placebo
Sponsors
Solvay Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
7 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed CF diagnosis by two positive chloride sweat tests or gene analysis * Confirmed PEI by historical Coefficient of fat Absorption \< 70% without supplementation or current or historical fecal elastase \< 50µg/stool (within the last 12 months) * Currently receiving treatment with a commercially available pancreatic enzyme product on a stable dose for more than 3 months * Clinically stable condition without evidence of acute respiratory disease or any other acute condition * Stable body weight and agrees to abstain from sexual activity
Exclusion criteria
* Ileus or acute abdomen * History of fibrosing colonopathy, celiac disease, gastrectomy, Crohn´s disease and small bowel surgery other than minor resection due to meconium ileus without resulting in malabsorption syndrome * History of distal ileal obstruction syndrome within 6 months of enrollment * Use of an immunosuppressive drug * Any type of malignancy involving the digestive tract in the last 5 years * Known infection with HIV
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Coefficient of Fat Absorption (%) | 5 days | This coefficient is calculated from fat intake and fat excretion : 100\*\[fat intake-fat excretion\]/fat intake. Stools were collected on 3 days during the 5 days treatment period. Higher values indicate a better response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Fat Excretion (Grams) | 5 days | Total amount of fat excreted during the stool collection period. Stools were collected on 3 days during the 5 days treatment period. Lower values indicate a better response. |
| Total Stool Weight (Grams) | 5 days | Total weight of the stools collected during the stool collection period. Stools were collected on 3 days during the 5 days treatment period. Lower values indicate a better response. |
| Stool Frequency | 5 days | Stool frequency is the average of the daily number of stools recorded during the treatment period. Lower values indicate a better response. |
| Coefficient of Nitrogen Absorption (%) | 5 days | This coefficient is calculated from nitrogen intake and nitrogen excretion : 100\*\[nitrogen intake-nitrogen excretion\]/nitrogen intake. Stools were collected on 3 days during the 5 days treatment period. Higher values indicate a better response. |
| Percentage of Days With Formed/Normal Stools. | 5 days | 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 with any stool). Higher values indicate a better response. |
| Percentage of Days With no Abdominal Pain. | 5 days | 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). Higher values indicate a better response. |
| Percentage of Days With no Flatulence. | 5 days | 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). Higher values indicate a better response. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited in 10 centers in US between June 2008 and October 2008. Before the randomization, subjects were evaluated for eligibility. They underwent a short period of up to 14 days on their usual pancreatic enzyme supplementation.
Pre-assignment details
Twenty three subjects had given their consent and 17 subjects were randomly allocated to pancrelipase/placebo or placebo/pancrelipase. One subject did not complete the first period of the treatment (consent withdrawal).
Participants by arm
| Arm | Count |
|---|---|
| Placebo/Pancrelipase Placebo period followed by Pancrelipase delayed release 12000 units period | 8 |
| Pancrelipase/Placebo Pancrelipase delayed release 12000 units period followed by Placebo period | 9 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo/Pancrelipase | Pancrelipase/Placebo | Total |
|---|---|---|---|
| Age Continuous | 8.9 years STANDARD_DEVIATION 1.1 | 8.7 years STANDARD_DEVIATION 1.4 | 8.8 years STANDARD_DEVIATION 1.3 |
| Region of Enrollment United States | 8 participants | 9 participants | 17 participants |
| Sex: Female, Male Female | 1 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 16 | 5 / 17 |
| serious Total, serious adverse events | 0 / 16 | 0 / 17 |
Outcome results
Primary
Coefficient of Fat Absorption (%)
This coefficient is calculated from fat intake and fat excretion : 100\*\[fat intake-fat excretion\]/fat intake. Stools were collected on 3 days during the 5 days treatment period. Higher values indicate a better response.
Time frame: 5 days
Population: The analysis was done on the Full Analysis Sample defined as the randomized subjects with at least one post-baseline efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Coefficient of Fat Absorption (%) | 47.41 Percentage | Standard Deviation 16.84 |
| Pancrelipase | Coefficient of Fat Absorption (%) | 82.81 Percentage | Standard Deviation 8.29 |
Comparison: The parameter was analyzed using an analysis of variance (ANOVA) including treatment, sequence and period as fixed effect and subject within sequence as a random effect.p-value: <0.001ANOVA
Secondary
Coefficient of Nitrogen Absorption (%)
This coefficient is calculated from nitrogen intake and nitrogen excretion : 100\*\[nitrogen intake-nitrogen excretion\]/nitrogen intake. Stools were collected on 3 days during the 5 days treatment period. Higher values indicate a better response.
Time frame: 5 days
Population: The analysis was done on the Full Analysis Sample defined as the randomized subjects with at least one post-baseline efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Coefficient of Nitrogen Absorption (%) | 44.98 Percentage | Standard Deviation 20.47 |
| Pancrelipase | Coefficient of Nitrogen Absorption (%) | 80.33 Percentage | Standard Deviation 7.92 |
Comparison: The parameter was analyzed using an analysis of variance (ANOVA) including treatment, sequence and period as fixed effect and subject within sequence as a random effect.p-value: <0.001ANOVA
Secondary
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 with any stool). Higher values indicate a better response.
Time frame: 5 days
Population: The analysis was done on the Full Analysis Sample defined as the randomized subjects with at least one post-baseline efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percentage of Days With Formed/Normal Stools. | 38.9 Percentage of days | Standard Deviation 33 |
| Pancrelipase | Percentage of Days With Formed/Normal Stools. | 77.7 Percentage of days | Standard Deviation 27 |
Comparison: The parameter was analyzed using an analysis of variance (ANOVA) including treatment, sequence and period as fixed effect and subject within sequence as a random effect.p-value: 0.003ANOVA
Secondary
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). Higher values indicate a better response.
Time frame: 5 days
Population: The analysis was done on the Full Analysis Sample defined as the randomized subjects with at least one post-baseline efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percentage of Days With no Abdominal Pain. | 65.2 Percentage of days | Standard Deviation 28.9 |
| Pancrelipase | Percentage of Days With no Abdominal Pain. | 85.3 Percentage of days | Standard Deviation 21.1 |
Comparison: The parameter was analyzed using an analysis of variance (ANOVA) including treatment, sequence and period as fixed effect and subject within sequence as a random effect.p-value: 0.023ANOVA
Secondary
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). Higher values indicate a better response.
Time frame: 5 days
Population: The analysis was done on the Full Analysis Sample defined as the randomized subjects with at least one post-baseline efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percentage of Days With no Flatulence. | 36.3 Percentage of days | Standard Deviation 36.9 |
| Pancrelipase | Percentage of Days With no Flatulence. | 45.0 Percentage of days | Standard Deviation 42.1 |
Comparison: The parameter was analyzed using an analysis of variance (ANOVA) including treatment, sequence and period as fixed effect and subject within sequence as a random effect.p-value: 0.671ANOVA
Secondary
Stool Frequency
Stool frequency is the average of the daily number of stools recorded during the treatment period. Lower values indicate a better response.
Time frame: 5 days
Population: The analysis was done on the Full Analysis Sample defined as the randomized subjects with at least one post-baseline efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Stool Frequency | 3.46 Number per day | Standard Deviation 1.06 |
| Pancrelipase | Stool Frequency | 1.88 Number per day | Standard Deviation 0.82 |
Comparison: The parameter was analyzed using an analysis of variance (ANOVA) including treatment, sequence and period as fixed effect and subject within sequence as a random effect.p-value: <0.001ANOVA
Secondary
Total Fat Excretion (Grams)
Total amount of fat excreted during the stool collection period. Stools were collected on 3 days during the 5 days treatment period. Lower values indicate a better response.
Time frame: 5 days
Population: The analysis was done on the Full Analysis Sample defined as the randomized subjects with at least one post-baseline efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Total Fat Excretion (Grams) | 182.9 Grams | Standard Deviation 68 |
| Pancrelipase | Total Fat Excretion (Grams) | 58.1 Grams | Standard Deviation 27.5 |
Comparison: The parameter was analyzed using an analysis of variance (ANOVA) including treatment, sequence and period as fixed effect and subject within sequence as a random effect.p-value: <0.001ANOVA
Secondary
Total Stool Weight (Grams)
Total weight of the stools collected during the stool collection period. Stools were collected on 3 days during the 5 days treatment period. Lower values indicate a better response.
Time frame: 5 days
Population: The analysis was done on the Full Analysis Sample defined as the randomized subjects with at least one post-baseline efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Total Stool Weight (Grams) | 436.5 Grams | Standard Deviation 158.4 |
| Pancrelipase | Total Stool Weight (Grams) | 161.4 Grams | Standard Deviation 57.5 |
Comparison: The parameter was analyzed using an analysis of variance (ANOVA) including treatment, sequence and period as fixed effect and subject within sequence as a random effect.p-value: <0.001ANOVA