Cystic Fibrosis
Conditions
Keywords
Pancreatic exocrine insufficiency, Cystic Fibrosis
Brief summary
This study will assess the effect of pancrelipase delayed release 24,000 unit capsules on fat and nitrogen absorption in subjects with PEI due to Cystic Fibrosis.
Interventions
24000 unit Capsule
DRUGPlacebo Comparator
Placebo
Sponsors
Solvay Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed CF diagnosis by two positive chloride sweat tests or gene analysis * Confirmed PEI by historical CFA \< 70% without supplementation or current or historical fecal elastase \< 50µg/g stool (within the last 12 months) * Subjects of 12 years or older * 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 * Females of child-bearing potential must agree to continue using a medically acceptable method of birth control
Exclusion criteria
* Ileus or acute abdomen * History of fibrosing colonopathy * 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 |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Hungary, Israel, South Africa, Spain, United States
Participant flow
Recruitment details
Subjects were recruited in 10 centers in US between November 2007 and January 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. Subjects were to take 4000 lipase units/g fat intake during both cross-over periods.
Pre-assignment details
Two subjects prematurely withdrew before the randomization (1 withdrew consent and 1 for protocol violation). 32 subjects were randomly allocated to pancrelipase/placebo or placebo/pancrelipase. 1 subject did not complete the second period of the treatment. 1 subject was randomized twice and only the second randomization was used for analyses.
Participants by arm
| Arm | Count |
|---|---|
| Placebo/Pancrelipase | 16 |
| Pancrelipase/Placebo | 16 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Wash-out Period | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo/Pancrelipase | Pancrelipase/Placebo | Total |
|---|---|---|---|
| Age Continuous | 22.2 years STANDARD_DEVIATION 7.8 | 22.8 years STANDARD_DEVIATION 6.5 | 22.5 years STANDARD_DEVIATION 7.1 |
| Region of Enrollment United States | 16 participants | 16 participants | 32 participants |
| Sex: Female, Male Female | 4 Participants | 7 Participants | 11 Participants |
| Sex: Female, Male Male | 12 Participants | 9 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 14 / 32 | 20 / 31 |
| serious Total, serious adverse events | 0 / 32 | 0 / 31 |
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 |
|---|---|---|---|
| Pancrelipase | Coefficient of Fat Absorption (%) | 88.62 Percentage | Standard Deviation 6.62 |
| Placebo | Coefficient of Fat Absorption (%) | 49.78 Percentage | Standard Deviation 18.33 |
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 |
|---|---|---|---|
| Pancrelipase | Coefficient of Nitrogen Absorption (%) | 85.06 Percentage | Standard Deviation 6.38 |
| Placebo | Coefficient of Nitrogen Absorption (%) | 49.99 Percentage | Standard Deviation 17.14 |
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 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 |
|---|---|---|---|
| Pancrelipase | Percentage of Days With no Abdominal Pain. | 90.3 Percentage of days | Standard Deviation 16.8 |
| Placebo | Percentage of Days With no Abdominal Pain. | 59.1 Percentage of days | Standard Deviation 43.2 |
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 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 |
|---|---|---|---|
| Pancrelipase | Percentage of Days With no Flatulence. | 41.6 Percentage of days | Standard Deviation 41.9 |
| Placebo | Percentage of Days With no Flatulence. | 23.1 Percentage of days | Standard Deviation 35.1 |
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: 0.013ANOVA
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 |
|---|---|---|---|
| Pancrelipase | Stool Frequency | 1.75 Number per day | Standard Deviation 0.81 |
| Placebo | Stool Frequency | 2.88 Number per day | Standard Deviation 1.18 |
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 |
|---|---|---|---|
| Pancrelipase | Total Fat Excretion (Grams) | 57.7 Grams | Standard Deviation 46.1 |
| Placebo | Total Fat Excretion (Grams) | 243.2 Grams | Standard Deviation 112.7 |
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 |
|---|---|---|---|
| Pancrelipase | Total Stool Weight (Grams) | 630.1 Grams | Standard Deviation 306.9 |
| Placebo | Total Stool Weight (Grams) | 1582.5 Grams | Standard Deviation 664.5 |
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
Other Pre-specified
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 |
|---|---|---|---|
| Pancrelipase | Percentage of Days With Formed/Normal Stools. | 75.0 Percentage of days | Standard Deviation 30 |
| Placebo | Percentage of Days With Formed/Normal Stools. | 23.9 Percentage of days | Standard Deviation 27.8 |
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