Conditions: Exocrine Pancreatic Insufficiency Cystic Fibrosis
Keywords: exocrine pancreatic insufficiency cystic fibrosis pancreatic enzyme replacement therapy
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 25
Healthy volunteers: no

Brief summary:
Liprotamase consists of 3 soluble, non-porcine digestive enzymes, lipase, protease, and amylase, combined in a fixed ratio. Liprotamase is stable in the stomach and can be formulated without enteric coating for administration either as a capsule or as a dosing solution dissolved in water or juice.

Detailed description:
The purpose of the present study is to evaluate the safety of long-term use of liprotamase in the management of cystic fibrosis-related exocrine pancreatic insufficiency

Arms:
arm 1: Oral, soluble, non-enterically coated, non-porcine, pancreatic enzyme replacement

Interventions: intervention 1: Liprotamase
Intervention descriptions: intervention 1: Oral, soluble, non-enterically coated, non-porcine, pancreatic enzyme replacement

Protocol document:
Prot_SAP_000.pdf: 
PROTOCOL SYNOPSIS 
Sponsor:   
Anthera Pharmaceuticals, Inc. 
Product Name: 
Liprotamase 
Indication: 
Cystic Fibrosis-Related Exocrine Pancreatic Insufficiency 
Protocol Title:   
An Open-Label Study Evaluating the Efficacy and Safety of 
Liprotamase in Subjects with Exocrine Pancreatic Insufficiency due to 
Cystic Fibrosis 
Study Name: 
 EASY:  Extended Access to Sollpura over Years 
Planned Study Centers: 
Centers having participated in Study AN-EPI3331 or participating in 
Study AN-EPI3333 
Treatment Duration: 
Until the first commercial authorization of liprotamase or until the 
Sponsor discontinues the study. 
Number of Subjects: 
Approximately 50: Subjects with a diagnosis of Cystic Fibrosis-Related 
EPI who completed Study AN-EPI3331 or Study AN-EPI3333 and were 
receiving liprotamase may be eligible to enroll. 
Objectives:   
To evaluate the safety of long-term use of liprotamase in the 
management of Cystic Fibrosis-Related Exocrine Pancreatic 
Insufficiency (EPI) 
Study Schematic: 
 
 
 
 
 
 


Study Design:   
• 
This is a multi-center, open-label study in which subjects who 
received liprotamase and completed Study AN-EPI3331 (the 
SOLUTION Study) or who completed AN-EPI3333 (the RESULT 
Study) at a lipase-CLEC dose of >10,000 U lipase-CLEC/kg/day and 
CFA of at least 80% may continue to receive liprotamase to evaluate 
the safety of long-term use of liprotamase in the management of EPI 
due to CF.   
• 
Subjects will be assessed approximately every 3 months throughout 
this study for safety and control of nutritional status. 
• 
Throughout this study, subjects should continue to receive the 
pre-study background medications for treatment of CF, including 
approved potentiators or modulators of the Cystic Fibrosis 
Transmembrane Conductance Regulator (CFTR), and gastric acid 
suppression medication.   
• 
Upon enrollment into the EASY Study, all subjects will receive 
liprotamase at the dose they were receiving in the prior study.  
Subsequent dose adjustments are allowed at any time based on 
Investigator assessment of nutritional status, food consumption, age, 
weight, fat intake, and clinical signs of malabsorption, as long as the 
protocol-defined maximum dose is not exceeded.  The maximum 
allowed doses of study drug are defined as follows:  
o 
For all subjects regardless of age, dose increases up to 
10,000 U lipase-CLEC/kg/day and 2,500 U lipase-CLEC/kg 
per meal or snack can be made irrespective of pre-study 
lipase dose, per CFF guidelines. 
o 
For subjects who enrolled from the RESULT Study, their final, 
optimized liprotamase dose from the RESULT Study is their 
maximum allowed dose in the EASY study.   
• 
The liprotamase dose may be adjusted, within the above constraints, 
at any time during the EASY Study by the Investigator based on 
clinically-observed symptoms of malabsorption or as-reported by the 
subject and/or parent/caregiver.  It is recommended that all subjects 
enrolled in this study follow the nutritional recommendations from the 
Cystic Fibrosis Foundation (Stallings 2008, Borowitz 2009). 
Inclusion Criteria:   
Subjects are eligible for enrollment if they meet the following inclusion 
criteria:  
1. Male or female subjects who received liprotamase and completed 
Study AN-EPI3331, or who completed Study AN-EPI3333 at a 
liprotamase dose >10,000 U lipase-CLEC/kg/day and CFA ≥80%  
2. Signed informed consent by subject and/or subject’s legally 
authorized representative  


Exclusion Criteria: 
Subjects must NOT meet any of the following exclusion criteria: 
1. Any medical, psychological or social condition, or clinical or 
laboratory abnormality (in the previous study or currently) that, at the 
discretion of the Investigator, may put the subject at increased risk 
by participating in this study or confound interpretation of study 
results. 
2. Treatment with any PERT other than study drug, investigational 
drugs, or devices 
3. Females who are nursing, pregnant, intending to become pregnant, 
or intending to nurse during the time of the study, or who have a 
positive pregnancy test at Visit Day 1.  All sexually-active subjects of 
reproductive potential are required to remain on a reliable method of 
birth control.  Females and males are required to continue using a 
reliable method of birth control throughout the study, and for at least 
3 months following completion of study therapy.  A reliable method 
of birth control is defined as one of the following:  oral or injectable 
contraceptives, intrauterine device, contraceptive implants, tubal 
ligation, hysterectomy, or a double-barrier method (diaphragm with 
spermicidal foam or jelly, or a condom), abstinence or vasectomy.  
Periodic abstinence (calendar, symptothermal, or post-ovulation 
methods) is not an acceptable method of contraception.  The 
preferred and usual lifestyle of the subject must also be evaluated in 
determining if sexual abstinence is a reliable method of birth control.  
4. Known hypersensitivity to the study drug and/or the excipients. 
Test Product, Dose and 
Mode of Administration:  
Liprotamase is taken orally with meals and snacks.  Each dose of 
liprotamase contains 3 digestive biotechnology-derived enzymes 
formulated at a fixed ratio of lipase:protease:amylase activities of 1.0 : 
1.0 : 0.15, respectively.  Liprotamase will be supplied as capsules at 2 
dosage strengths:  
• 
Oral Capsule: 40,000 U Lipase cross-linked enzyme crystals 
(CLEC), 40,000 U Protease, 6,000 U Amylase. 
• 
Oral Capsule: 10,000 U Lipase-CLEC, 10,000 U Protease, 1,500 U 
Amylase. 
 
Subjects who have completed Study AN-EPI3331 will continue to receive 
open-label liprotamase, initially at the same dose which they were 
receiving at the time they completed the prior liprotamase study.  The 
Investigator may subsequently adjust the dose for any subject if judged 
clinically appropriate up to 10,000 U lipase CLEC/kg/day. For subjects 
who have completed Study AN-EPI3333 (RESULT), doses will remain 
the same during the EASY study, with the exception that they may be 
adjusted on an absolute (lipase Unit) basis to accommodate for changes 
in body weight. 
 
Instructions on dosing of liprotamase are provided in the Pharmacy 
Manual. 


Endpoints: 
The primary endpoint analysis will evaluate the long-term safety of 
liprotamase in qualifying adults and pediatric subjects from Studies 
AN-EPI3331 and AN-EPI3333.  Safety will be evaluated based on 
adverse events (AEs) and serious AEs (SAEs); including but not limited 
to abnormal laboratory results, abnormal findings in physical 
examinations and abnormal vital signs deemed clinically significant by 
the Investigator.   
The secondary endpoints will include: 
• 
Change in weight, height, and BMI from baseline. 
• 
Changes in measures of growth including weight, height, and 
BMI relative to population anthropomorphic measures. 
• 
Signs and symptoms of malabsorption including stool frequency, 
stool consistency, bloating, steatorrhea, abdominal pain, and 
flatulence compared with baseline.  
For efficacy analyses of change from baseline, baseline will be defined 
as the first observation in this study. 
Sample Size and 
Statistical Methods: 
No formal statistical hypothesis testing will be performed 
Procedures: 
Refer to Schedule of Assessments (Appendix A).