Cystic Fibrosis, Exocrine Pancreatic Insufficiency
Conditions
Brief summary
Liprotamase powder is a non-porcine, soluble and stable mixture of three digestive enzymes including lipase, protease, and amylase. The purpose of the present study is to provide additional efficacy and safety data compared to approved, porcine-derived, enterically-coated and encapsulated pancreatic enzyme replacement therapy. The primary efficacy endpoint of the study will be comparative efficacy measured as the change in the coefficient of fat absorption (CFA) in Cystic Fibrosis patients with exocrine pancreatic insufficiency (EPI). Liprotamase is stable in stomach and digestive fluids allowing administration in a variety of convenient formulations and with a number of foods without enteric coating.
Detailed description
Porcine derived enzymes are used for pancreatic enzyme replacement therapy in patients with cystic fibrosis (CF). Liprotamase is a biotechnology-derived enzyme replacement without enteric coating. This is an open-label, assessor blind, parallel group, multicenter, international trial to evaluate the noninferiority of liprotamase and pancrelipase in CF patients aged ≥7 years with pancreatic insufficiency. Subjects were randomized to liprotamase or pancrelipase, dose-matched to pre-study lipase doses. The lower bound of the 95% confidence interval (CI) for noninferiority was -15% for treatment difference in change from baseline coefficient of fat absorption (CFA).
Interventions
DRUGLiprotamase
oral, soluble, non-enterically coated, non-porcine, pancreatic enzyme replacement
DRUGporcine (pig) PERT
oral, enterically-coated, pancreatic replacement enzymes prepared from a porcine source
Sponsors
Anthera Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
7 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Cystic Fibrosis based on presentation, genotype and/or sweat chloride * Fecal elastase \<100 mcg/g stool * Minimum Coefficient of Fat (CFA) at screening while on stable PERT therapy * Good nutritional status
Exclusion criteria
* History or diagnosis of fibrosing colonopathy * Distal intestinal obstruction syndrome in 6 months prior to screening * Receiving enteral tube feedings * Chronic diarrheal illness unrelated to pancreatic insufficiency * Liver abnormalities, or liver or lung transplant, or significant bowel resection * Forced expiratory volume in 1 second (FEV1) \<30%
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Difference in Coefficient of Fat Absorption (CFA) Change From Baseline | Baseline, 7 weeks | The primary endpoint evaluates the difference between treatment arms in change from baseline in coefficient of fat absorption (CFA). As such, descriptive statistics for individual treatment arms are not provided in this measure, but are reported in the secondary endpoints |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Coefficient of Fat Absorption (CFA) | Baseline, 7 weeks | Change from baseline in coefficient of fat absorption |
| Coefficient of Nitrogen Absorption (CNA) | Baseline, 7 weeks | Change from baseline in coefficient of nitrogen absorption |
Countries
Canada, Czechia, Hungary, Israel, Poland, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Liprotamase Individually-optimized dose to be administered orally
Liprotamase: oral, soluble, non-enterically coated, non-porcine, pancreatic enzyme replacement | 65 |
| Porcine (Pig) PERT Individually-optimized dose to be administered orally
porcine (pig) PERT: oral, enterically-coated, pancreatic replacement enzymes prepared from a porcine source | 63 |
| Total | 128 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Lack of Efficacy | 4 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Undefined | 2 | 1 |
| Overall Study | Withdrawal by Subject | 9 | 2 |
Baseline characteristics
| Characteristic | Liprotamase | Porcine (Pig) PERT | Total |
|---|---|---|---|
| Age, Continuous | 22.5 years STANDARD_DEVIATION 8.54 | 21.0 years STANDARD_DEVIATION 8.95 | 21.8 years STANDARD_DEVIATION 8.74 |
| Coefficient of fat absorption (CFA) | 88.7 fat absorbed as percent of fat ingested | 89.4 fat absorbed as percent of fat ingested | 89.1 fat absorbed as percent of fat ingested |
| Coefficient of nitrogen absorption (CNA) | 96.9 % of nitrogen ingested | 97.3 % of nitrogen ingested | 97.1 % of nitrogen ingested |
| pre-randomization enzyme dose | 6299 lipase units/kg/day | 6264 lipase units/kg/day | 6282 lipase units/kg/day |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) White | 63 Participants | 61 Participants | 124 Participants |
| Sex: Female, Male Female | 30 Participants | 31 Participants | 61 Participants |
| Sex: Female, Male Male | 35 Participants | 32 Participants | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 65 | 0 / 63 |
| other Total, other adverse events | 41 / 65 | 38 / 63 |
| serious Total, serious adverse events | 7 / 65 | 6 / 63 |
Outcome results
Primary
Treatment Difference in Coefficient of Fat Absorption (CFA) Change From Baseline
The primary endpoint evaluates the difference between treatment arms in change from baseline in coefficient of fat absorption (CFA). As such, descriptive statistics for individual treatment arms are not provided in this measure, but are reported in the secondary endpoints
Time frame: Baseline, 7 weeks
Population: Analysis population evaluates all subjects who received at least one dose of study drug. Missing Visit 7 CFA values were multiply imputed using baseline CFA, baseline BMI, sex, age, acid suppression usage, and region.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment Difference | Treatment Difference in Coefficient of Fat Absorption (CFA) Change From Baseline | -11.852 percent change from baseline |
Secondary
Coefficient of Fat Absorption (CFA)
Change from baseline in coefficient of fat absorption
Time frame: Baseline, 7 weeks
Population: Analysis population evaluates observed case data without multiple imputation for missing values
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Difference | Coefficient of Fat Absorption (CFA) | 76.5 fat absorbed as % of fat ingested | Standard Deviation 16.13 |
| Porcine (Pig) PERT | Coefficient of Fat Absorption (CFA) | 89.5 fat absorbed as % of fat ingested | Standard Deviation 5.84 |
Secondary
Coefficient of Nitrogen Absorption (CNA)
Change from baseline in coefficient of nitrogen absorption
Time frame: Baseline, 7 weeks
Population: Analysis population evaluates observed case data without multiple imputation for missing values
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Difference | Coefficient of Nitrogen Absorption (CNA) | 95.8 percent of nitrogen ingested | Standard Deviation 2.46 |
| Porcine (Pig) PERT | Coefficient of Nitrogen Absorption (CNA) | 97.5 percent of nitrogen ingested | Standard Deviation 1.21 |