SOLUTION: Study of Oral Liprotamase Unit-Matched Therapy Of Non-Porcine Origin in Patients With Cystic Fibrosis

Study Overview
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Brief Summary
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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
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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).

Official Title
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A Phase 3, Randomized, Open-Label, Assessor-Blind, Noninferiority, Active-Comparator Study Evaluating the Efficacy and Safety of Liprotamase in Subjects With Cystic Fibrosis-Related Exocrine Pancreatic Insufficiency

Conditions
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Exocrine Pancreatic Insufficiency, Cystic Fibrosis

Intervention / Treatment
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* Drug: Liprotamase
* Drug: porcine (pig) PERT


Participation Criteria
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Eligibility Criteria
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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%

Ages Eligible for Study
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Minimum Age: 7 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liprotamase<br>Individually-optimized dose to be administered orally | Drug: Liprotamase<br>* oral, soluble, non-enterically coated, non-porcine, pancreatic enzyme replacement<br>|
| Active Comparator: porcine (pig) PERT<br>Individually-optimized dose to be administered orally | Drug: porcine (pig) PERT<br>* oral, enterically-coated, pancreatic replacement enzymes prepared from a porcine source<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Baseline, 7 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Coefficient of Fat Absorption (CFA) | Change from baseline in coefficient of fat absorption | Baseline, 7 weeks | 
| Coefficient of Nitrogen Absorption (CNA) | Change from baseline in coefficient of nitrogen absorption | Baseline, 7 weeks |