Absorption and Safety With Sustained Use of RELiZORB Evaluation (ASSURE) Study in Patients With Cystic Fibrosis Receiving Enteral Feeding
Phase: NA
Conditions: Cystic Fibrosis
Sponsor: Alcresta Therapeutics, Inc.

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 1 of 47 
 
  
 
Protocol T
itle 
Absorption and Safety with Sustained Use of Relizorb™ 
Evaluation (ASSURE) Study in Patients With Cystic Fibrosis 
Receiving Enteral Feeding 
 
 
Protocol Number 0000498 
Indication 
Exocrine Pancreatic Insufficiency 
Date of Protocol 07 March 2016 
Revision Date 
NA 
Sponsor 
Alcresta Pharmaceuticals, Inc. 
One Newton Executive Park, Suite 100 
Newton, MA 02462 
 
Email:  
Phone:  
 
This document contains information that is confidential and proprietary to Alcresta Pharmaceuticals, 
Inc. (“Alcresta”). This information must be treated by you as confidential and is being provided for the 
sole purpose of your participation in conducting a research study with RelizorbTM immobilized lipase 
(iLipase
TM) cartridge, also know as the enteral feeding in-line cartridge (EFIC). This information may 
not be used for any other purpose and may not be disclosed to third parties except as provided 
below. Contents of this protocol may be disclosed to study personnel under your supervis
ion who 
need to know the contents for this purpose, to the Institutional Review Board or Independent Ethics 
Committee subject to the following: the contents of this protocol may not be used for any other 
research study and may not be disclosed to any other person or entity without the prior written 
permission of Alcresta. This does not apply to disclosure required by governmental regulatory or 
laws. However, prompt notice must be given to Alcresta of any such disclosure. Supplemental 
information and amendments that may be added to this document are also confidential and 
proprietary to Alcresta and subject to the same considerations as described herein. 
 
 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 2 of 47 
 
 
 
PROTOCOL AGREEMENT 
Protocol Title 
Absorption and Safety with Sustained Use of Relizorb™ 
Evaluation (ASSURE) Study in Patients With Cystic Fibrosis 
Receiving Enteral Feeding 
Protocol Number 0000498 
Investigational 
Device 
Relizorb™ immobilized lipase (iLipase
TM) cartridge 
Indication 
Exocrine Pancreatic Insufficiency 
Protocol Date 
07 March 2016 
Revision Date 
NA 
I have read this protocol and agree to conduct this research study as outlined herein. 
I will ensure that all subinvestigators and other study staff members have been 
trained and understand all aspects of this protocol. I agree to cooperate fully with 
Alcresta Pharmaceuticals, Inc. or any third parties utilized during the study. I will 
adhere to all Food and Drug Administration and other applicable regulations and 
guidelines regarding research studies during and after study completion. 
Principal Investigator ________________________________________ 
Printed Name 
________________________________________ 
Signature 
________________________________________ 
Date (ddmmmyyyy) 
________________________________________ 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 3 of 47 
STUDY SYNOPSIS 
Title 
Absorption and Safety with Sustained Use of Relizorb™ Evaluation 
(ASSURE) Study in Patients With Cystic Fibrosis Receiving Enteral 
Feeding 
Sponsor 
Alcresta Pharmaceuticals, Inc., One Newton Executive Park, Suite 100, 
Newton, MA 02462 
Sponsor 
Contacts 
Name 
Title 
Phone 
 
Chief Medical 
Officer 
 
 
Director, Clinical 
Operations 
 
Investigational 
Device 
Background 
The Relizorb™ digestive enzyme cartridge is a single-use, point-of-care 
device that connects in-line with existing enteral pump feed sets and 
pump extension sets. Relizorb is designed to hydrolyze fats contained in 
the enteral formulas, mimicking the function of the digestive enzyme 
lipase that is normally secreted by the pancreas. By hydrolyzing fats from 
enteral formula, Relizorb allows for the delivery of absorbable fatty acids 
and monoglycerides for patients who receive enteral nutrition and cannot 
hydrolyze fats normally.  
 
The active component in Relizorb is the digestive enzyme lipase, which is 
covalently attached to polymeric beads; the lipase-bead complex is called 
iLipase
TM. As the enteral formula passes through Relizorb during a tube 
feeding, it makes contact with the iLipase and the fat in the formula is 
hydrolyzed into its absorbable forms (fatty acids and monoglycerides) 
prior to ingestion. The iLipase remains in the cartridge and is not 
ingested. 
Indication and 
Classification 
The proposed indication is for use in children and adults to hydrolyze fats 
in enteral formula. 
The lipase used in Relizorb is designated by the US Food and Drug 
Administration (FDA) as generally recognized as safe (GRAS 000216). 
The FDA Center for Food Science and Applied Nutrition (CFSAN) 
cleared iLipase as a Food Contact Substance under the Food Contact 
Notification process on January 20, 2015 (FCN 1498). RELIZORB was 
cleared by the FDA Center for Devices and Radiological Health (CDRH) 
as a Class II low-risk device through a de novo application on November 
20, 2015 (DEN150001) and is indicated for use in adults to hydrolyze fats 
in enteral formula.  
Number of 
Patients 
Approximately 35 male and female patients with cystic fibrosis (CF) and 
exocrine pancreatic insufficiency (EPI) will be enrolled in Protocol 
0000498 with the intention of obtaining at least 30 evaluable subjects 
who complete the study. Subjects must be ≥4 years of age, with no upper 
age limit. Since the inclusion/exclusion criteria for this study is similar to 
Protocol 0000497, patients who participated in Protocol 0000497 will be 
eligible to participate in this study after they have completed participation 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 4 of 47 
in Protocol 0000497. 
Sites 
Approximately 10 sites in the United States will participate in this study. 
Sites that are actively enrolling patients for Protocol 0000497 will 
preferentially participate in this study.   
Objective 
The overall objective of the study is to assess safety and tolerability and 
demonstrate improved fat absorption with sustained use of Relizorb in 
patients with CF who have EPI and are receiving enteral nutrition as part 
of their total nutritional therapy.  In this study, subjects will be receiving a 
semi-elemental formula containing pre-hydrolyzed protein that has a high 
content of long chain triglycerides (Impact® Peptide 1.5) and will be using 
Relizorb during their enteral feeding in place of other therapies currently 
used to aid in fat digestion and absorption, such as pancreatic enzyme 
replacement therapy (PERT).  Plasma concentration of long-chain 
polyunsaturated fatty acids (LCPUFAs) such as docosahexaenoic acid 
(DHA; C:22:6n-3) and eicosapentaenoic acid (EPA; C20:5n-3) will be 
measured as biomarkers of fat absorption. Tissue accretion of LCPUFAs 
assessed through measurement of erythrocyte membrane concentrations 
of LCPUFAs such as DHA and EPA, as well as determination of the 
profile of fatty acids in plasma will also be evaluated as additional 
biomarkers of fat absorption. Plasma fat-soluble vitamin and serum 
protein concentrations will also be measured as indicators of 
effectiveness. All fatty acid, fat-soluble vitamin, and protein 
concentrations will be assessed in relation to values obtained at the 
beginning of the run-in period (Day -7), at baseline (Day 0), and during 
Relizorb use (Days 30, 60, and 90). Safety and tolerability of sustained 
use of Relizorb will be assessed during use and compared with 
gastrointestinal symptoms recorded during the observation phase of the 
study (Day -14 through Day -7).  
Efficacy  
• Evaluate effect of sustained Relizorb use during enteral feedings on fat 
absorption through serial measurements of plasma and tissue 
(erythrocyte membrane) concentrations of physiologically relevant 
LCPUFAs such as DHA & EPA as well as serial determinations of the 
plasma fatty acid profile changes as biomarkers of fat absorption 
• Evaluate effect of sustained Relizorb use during enteral feedings on 
plasma fat-soluble vitamin concentrations  
• Evaluate effect of sustained Relizorb use on the ratio of omega-6 to 
omega-3 fatty acids as a potential indicator of immunomodulation 
• Evaluate effect of sustained Relizorb use on urinary leukotriene levels 
• Evaluate effect of sustained Relizorb use on serum protein levels 
• Evaluate effect of sustained Relizorb use on growth 
Safety 
• Evaluate the safety and tolerability of sustained use of Relizorb as part 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 5 of 47 
of an enteral feeding regimen.  
Endpoints 
Efficacy 
• Change over time in plasma concentrations of omega-3 fatty acids 
such as DHA and EPA  
• Change over time in tissue (erythrocyte membrane) fatty acid 
concentrations such as DHA and EPA 
• Change over time in the plasma fatty acid profile 
• Change over time in the ratio of omega-6 to omega-3 fatty acids 
• Change over time in plasma concentrations of fat soluble vitamins A, 
D, and E 
• Change over time in serum protein concentrations (total protein, 
prealbumin, albumin, transferrin) 
• Change over time in markers of inflammation (urinary leukotrienes) 
• Change over time in weight and body mass index (BMI) and weight 
and BMI z-scores 
 
Safety 
• Frequency and severity of adverse events and unanticipated adverse 
device effects (UADEs) 
• Evaluation of clinical and laboratory findings  
• Concomitant medication assessment 
• Frequency and severity of gastrointestinal signs and symptoms 
(abdominal pain, vomiting, loss of appetite, bloating, flatulence and 
steatorrhea) 
Study Duration The duration of the study is approximately 7-8 months. Three and a half 
months will be allocated for patient enrollment. Patient time in study will 
be at least three and a half months (1 week observation period, 1 week 
run in, 3 months treatment), and UADEs that occur towards the end of 
the study may require another 30 days of follow up.   
Study Design  Protocol 0000498 is a multicenter open label study to evaluate the effect 
of sustained Relizorb use during enteral feeding on fat absorption, as well 
as safety and tolerability of sustained Relizorb use, in patients with CF 
and EPI who are receiving enteral tube feeding.  
At study entry (Day -14), blood and urine will be collected as part of the 
screening evaluation and to assess baseline plasma and erythrocyte 
membrane concentrations of LCPUFAs such as DHA and EPA, plasma 
concentrations of other long chain fatty acids, plasma concentrations of 
fat-soluble vitamins, serum protein concentrations, and urinary 
leukotriene concentrations. Body weight, height, and BMI will be 
recorded, as well as historical quantification of use of PERT with daytime 
meals and with enteral feeding. During an initial 7 day observation  period 
subjects will receive their usual enteral nutrition regimen. If subjects use 
PERT with their enteral nutrition, this will continue through the 
observation period, and PERT use will be recorded. The subject will also 
record gastrointestinal symptoms during the observation week in a 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 6 of 47 
gastrointestinal symptom diary. During a 7-day run in period Day -7 to 
Day -1), subjects will use a standard enteral formula that contains a 
prehydrolyzed protein (Peptamen
® 1.5) at their normal volume of 
administration from 500 mL up to a maximum volume of 1000 mL per 
feeding. If subjects use PERT with their enteral nutrition, this will continue 
through the run in period, and PERT use will be recorded. Throughout 
the study, individualized patient standard use of PERT with daily meals 
and snacks will continue.  
Following the run in period, subjects will receive an enteral formula 
similar to Peptamen 1.5 that has a higher long chain triglyceride to 
medium chain triglyceride ratio (Impact
® Peptide 1.5) at their normal 
volume of administration from 500 mL up to a maximum volume of 1000 
mL per feeding using Relizorb in line for the 90 day treatment period.  
During the 90-day treatment period, individualized patient standard use of 
oral PERT is allowed with daily meals, but use of therapeutic agents 
currently used to aid in fat absorption, such as PERT, will not be used 
with Relizorb during enteral feedings.  
Serial measurements (Days 0, 30, 60, and 90) of plasma concentrations 
and erythrocyte levels of LCPUFAs such as DHA and EPA, plasma 
concentrations of other long chain fatty acids, plasma concentrations of 
fat soluble vitamins, serum protein and concentrations, urinary 
leukotriene concentrations, and body weight and BMI will be obtained 
and compared with each other as well as with values obtained at study 
entry (Day -14).  
Safety and tolerability will be assessed using a gastrointestinal symptom 
diary, as well as recording adverse events (AEs), and unanticipated 
adverse device effects (UADEs). 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in Patients With Cystic Fibrosis Receiving 
Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 7 of 47 
STUDY SCHEMATIC 
Table 1: Schedule of Events 
 
Evaluation 
Visit 1 
Visit 2 
Visit 3 
Visit 4  
Visit 5 * 
Day -14 
Study Entry 
Day 0 
Baseline 
Day 30 
Treatment 
Day 60 
Treatment 
Day 90 
End of Study 
Informed Consent 
X 
 
 
 
 
Inclusion / Exclusion Criteria 
X 
 
 
 
 
Demograph
ics 
X 
 
 
 
 
Medical History a 
X 
 
 
 
 
Physical Examination 
X 
 
 
 
X  
Height, Weight, Body Mass Index b 
X  
X 
X 
X 
X  
Vital Signs c 
X 
X 
X 
X 
X 
Hematology d 
X 
 
 
 
X 
Clinical Chemistry e 
X 
 
 
 
X 
Urinalysis f 
X 
 
 
 
X 
Blood Lipids g  
X 
X 
X 
X 
X 
Serum Proteinsh  
X 
X 
X 
X 
X 
Serum Pregnancy Test (β-hCG) i 
X 
 
 
 
 
Urinary Leukotrienes 
X 
X 
X 
X 
X 
7-Day Gastrointestinal Symptom Diary  
X 
X 
X 
X 
X 
Plasma Fatty Acid Samples j 
X 
X 
X 
X 
X 
Vitamins A, D, and Ek 
X 
X 
X 
X 
X 
Peptamen® 1.5 500 to 1000 mLl 
X 
 
 
 
 
Impact
® Peptide 500 to 1000 mL 
 
X 
X 
X 
X 
Relizorb Administration  
 
X  
Relizorb Accountability Log 
 
X 
Unanticipated Adverse Device Effects 
 
X 
 
Note:  Tests and procedures should be performed according to the above schedule but changes in scheduled study vis
its (±4 days) are allowed 
with permission from the site for holidays, vacations, etc. The amount of blood taken from subjects will be limited to no more than 3 mL/kg in 
24 hours and no more than 7 mL/kg over the course of the study. 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in Patients With Cystic Fibrosis Receiving 
Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 8 of 47 
* If any Unanticipated Adverse Device Event (UADE) is reported on Day 90, then a safety follow-up telephone call will occur on Day 
91, and the subject will be followed until either resolution of the event or for 30 days, whichever is shorter. 
a. A complete medical history will be obtained. 
b. Height and weight will be measured and recorded, and BMI will be calculated and recorded at each study visit. Four weight and 
BMI measurements recorded at 3 month intervals over the previous 12 months before Day -14 will be obtained from the medical 
record. 
c. Vital signs will include blood pressure, pulse rate, respiratory rate and oral/tympanic temperature and will be obtained on in-clinic 
days. 
d. Hematology includes complete blood count and white blood cell differential. 
e. Clinical chemistry includes albumin, alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), 
bicarbonate, blood urea nitrogen, calcium, chloride, cholesterol, creatine phosphokinase, creatinine, glucose, lactate 
dehydrogenase, magnesium, phosphorus, potassium, prealbumin, sodium, total and direct bilirubin, total protein, uric acid and 
A1C levels. 
f. Urinalysis to include bilirubin, blood, glucose, ketones, leukocyte esterase, pH, protein, specific gravity, urinary creatinine and uric 
acid. 
g. Blood lipids will include total cholesterol, triglycerides (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL).  
h. Serum proteins include total protein, prealbumin, albumin, and transferrin. 
i. A serum Beta-Human Chorionic Gonadotropin (β-hCG) pregnancy test will be performed only for females of childbearing potential. 
Results must be available prior to Day 1. 
j. Blood samples will be obtained for plasma and red blood cell fatty acid analysis. 
k. Blood samples will be collected to measure levels of Vitamins A, D, and E. 
l. Peptamen 1.5 will be administered as the enteral formula during the run in phase from Day -7 through Day -1. 
 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 9 of 47 
TABLE OF CONTENTS 
PROTOCOL AGREEMENT 
................................................................................................................... 2 
STUDY SYNOPSIS 
.................................................................................................................................. 3 
STUDY SCHEMATIC 
.............................................................................................................................. 7 
LIST OF TABLES 
.................................................................................................................................. 
11 
LIST OF FIGURES ................................................................................................................................ 
11 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
..................................................... 
12 
1.0 STUDY OVERVIEW 
................................................................................................................ 
14 
2.0 SCIENTIFIC AND CLINICAL BACKGROUND 
................................................................... 
14 
 
Description of Relizorb 
................................................................................................................. 
16 
 
Active Component and Mechanism of Action ............................................................................. 
17 
 
Clinical Labeling 
............................................................................................................................ 
18 
 
Storage Conditions 
....................................................................................................................... 
18 
 
Study Rationale and Purpose 
....................................................................................................... 
18 
 
Potential Benefits and Risks 
......................................................................................................... 
19 
3.0 STUDY OBJECTIVES AND ENDPOINTS............................................................................ 
21 
 
Objectives 
..................................................................................................................................... 
21 
 
Endpoints 
...................................................................................................................................... 
21 
4.0 STUDY DESIGN AND PROCEDURES 
................................................................................. 
22 
 
Enrollment Goals 
.......................................................................................................................... 
22 
 Representative Age Groups 
...................................................................................................... 
22 
 
Study Duration.............................................................................................................................. 
23 
 
Study Periods 
................................................................................................................................ 
23 
 
Selection of Patients 
..................................................................................................................... 
25 
 Inclusion Criteria ...................................................................................................................... 
25 
 Exclusion Criteria 
...................................................................................................................... 
26 
 
Patient Enrollment and Replacement Criteria 
............................................................................. 
27 
 
Allowed Concomitant Medications 
.............................................................................................. 
28 
 
Prohibited Medications 
................................................................................................................ 
28 
 
Safety Monitoring 
......................................................................................................................... 
28 
 Study Safety Procedures 
........................................................................................................... 
28 
 
Study Procedures ......................................................................................................................... 
29 
 Informed Consent 
..................................................................................................................... 
29 
 Inclusion and Exclusion Criteria................................................................................................ 
29 
 Demographics 
.......................................................................................................................... 
29 
 Medical History 
........................................................................................................................ 
29 
 Physical Examination ............................................................................................................... 
29 
 Height, Weight, and BMI.......................................................................................................... 
29 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 10 of 47 
 Vital Signs 
................................................................................................................................. 
29 
 Clinical Laboratory Tests 
.......................................................................................................... 
30 
 Pregnancy Test 
......................................................................................................................... 
30 
 Enteral Tube Feeding 
........................................................................................................... 
30 
 Gastrointestinal Symptom Diary.......................................................................................... 
31 
 Plasma and Tissue Fatty Acid Samples 
................................................................................ 
32 
 Fat Soluble Vitamin Samples ............................................................................................... 
32 
 Serum Protein Samples 
........................................................................................................ 
32 
 Removal of Subjects from the Study 
............................................................................................ 
32 
5.0 DATA ACQUISITION, TRANSFER AND ANALYSIS........................................................ 
32 
 
Data Acquisition ........................................................................................................................... 
32 
 
Data Transfer 
................................................................................................................................ 
33 
 
Analysis of Fatty Acid Absorption 
................................................................................................. 
33 
6.0 SAFETY OVERVIEW 
.............................................................................................................. 
33 
 
Monitoring of Adverse Events 
...................................................................................................... 
33 
 
Adverse Events 
............................................................................................................................. 
33 
 Causal Relationship 
.................................................................................................................. 
34 
 Anticipated Adverse Events in Subjects.................................................................................... 
34 
 
Unanticipated Adverse Device Effects 
......................................................................................... 
34 
 
Reporting Unanticipated Adverse Device Effects ........................................................................ 
35 
7.0 STATISTICAL PROCEDURES AND DATA ANALYSIS 
................................................... 
36 
 
General Considerations 
................................................................................................................ 
36 
 
Determination of Sample Size 
...................................................................................................... 
36 
 Stopping Rules 
.......................................................................................................................... 
36 
 
Randomization.............................................................................................................................. 
37 
 
Populations for Analysis 
............................................................................................................... 
37 
 Per Protocol Population ........................................................................................................... 
37 
 Safety Population 
..................................................................................................................... 
37 
 
Procedures for Handling Missing, Unused and Spurious Data .................................................... 
38 
 
Demographics and Baseline Characteristics ................................................................................ 
38 
 
Safety Analysis 
.............................................................................................................................. 
38 
 
Efficacy Analysis............................................................................................................................ 
39 
8.0 STUDY COORDINATION AND MONITORING 
................................................................ 
40 
 
Site Principal Investigators and Study Administrative Structure 
................................................. 
40 
 
Institutional Review Board / Independent Ethics Committee 
..................................................... 
40 
 
Study Monitoring 
.......................................................................................................................... 
40 
 
Onsite Audits 
................................................................................................................................ 
41 
 Study Device Accountability 
..................................................................................................... 
41 
 
Patient Information and Informed Consent 
................................................................................. 
41 
 
Patient Confidentiality.................................................................................................................. 
42 
 
Investigator Compliance 
............................................................................................................... 
42 
9.0 STUDY COMPLETION PROCEDURES 
............................................................................... 
42 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 11 of 47 
 
Completion of Study 
..................................................................................................................... 
42 
 
Records Retention 
........................................................................................................................ 
43 
 
Communication of Study Results 
................................................................................................. 
43 
 
Ethics ............................................................................................................................................ 
43 
10.0 REFERENCES 
........................................................................................................................... 
44 
11.0 APPENDICES ........................................................................................................................... 
46 
 Peptamen® 1.5 Nutrition Information - Unflavored (Nestle Health Science) .............................. 
46 
 Impact Peptide 1.5 Nutrition Information - Unflavored (Nestlé Healthcare Nutrition) 
.............. 
47 
 
 
LIST OF TABLES 
Table 1: Schedule of Events 
............................................................................................ 
7 
Table 2: Clinical Laboratory Tests 
................................................................................. 
31 
 
LIST OF FIGURES 
Figure 1: Relizorb Device .............................................................................................. 
16 
Figure 2: Enzyme Hydrolysis 
......................................................................................... 
17 
 
 
 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 12 of 47 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
AA 
Arachidonic Acid 
AE 
Adverse Event 
ALCT-460 
Rhizopus Oryzae Lipase (synonymous with FCS/enzyme)  
ALCT-463 
Enteral Feeding In-line Cartridge 
ALT 
Alanine Aminotransferase 
AST 
Aspartate Aminotransferase 
β-hCG 
BMI 
Beta Human Chorionic Gonadotropin 
Body Mass Index 
CF 
Cystic Fibrosis 
CFRD 
Cystic Fibrosis Related Diabetes 
DHA 
Docosahexaenoic acid 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EFIC 
Enteral Feeding In-line Cartridge 
EPA 
Eicosapentaenoic acid 
EPI 
Exocrine Pancreatic Insufficiency 
FA 
Fatty Acid 
FCS/Enzyme Complex Food Contact Substance/enzyme complex 
FDA 
Food and Drug Administration 
fND 
Fortified Nutritional Drink 
GCMS 
Gas Chromatography Mass Spectrometry 
GI 
Gastrointestinal 
GRAS 
Generally Recognized As Safe 
G-tube 
Gastrostomy Feeding Tube 
HDL 
High-Density Lipoprotein 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IEC 
IFU 
Independent Ethics Committee 
Instructions for Use 
IRB 
Institutional Review Board 
kcal 
Kilocalorie 
LA 
Linoleic Acid 
LCPUFA 
Long-Chain Polyunsaturated Fatty Acid 
LCT 
Long-Chain Triglyceride 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 13 of 47 
LDL 
Low-Density Lipoprotein 
MS/MS 
Mass Spectrometry/Mass Spectrometry 
PERT 
Pancreatic Enzyme Replacement Therapy 
PfND 
 
PI 
Pre-hydrolyzed Fortified Nutritional Drink (Post exposure to 
ALCT-460) 
Principal Investigator 
RBC 
Red Blood Cells 
RD 
Registered Dietitian 
RO 
Rhizopus oryzae 
SAE 
Serious Adverse Event 
TG  
UADE 
Triglycerides 
Unanticipated Adverse Device Effects 
ULN 
Upper Limit of Normal 
UPLC-MS/MS 
Ultra-high Performance Liquid Chromatography–Tandem 
Spectrometer  
 
 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 14 of 47 
1.0 
STUDY OVERVIEW 
This is a multicenter open label study to evaluate the effect of sustained RelizorbTM use 
during enteral tube feeding on fat absorption, as well as safety and tolerability of 
sustained Relizorb use, in patients with cystic fibrosis (CF) with exocrine pancreatic 
insufficiency (EPI) who are receiving enteral nutrition as part of their nutrition care plan. 
An estimated 35-40 male and female subjects will be recruited to yield 30 evaluable 
subjects who complete the study through at least Visit 4 at 60 days.  Subjects must be 
≥4 years of age but there is no upper age limit. After a 7 day observation period when 
subjects will follow their usual care plan, subjects will begin a 7 day run in period when 
they will receive a standard semi-elemental formula (Peptamen® 1.5) and use of 
pancreatic enzyme replacement therapy (PERT) with enteral tube feeding will be 
recorded. Following the run in period, subjects will use Relizorb while receiving a semi-
elemental formula (Impact
® Peptide 1.5) with a relatively increased ratio of long chain 
triglycerides (LCT) to medium chain triglycerides (MCT) for 90 days. Use of PERT in 
conjunction with enteral tube feeding will be discontinued during this 90 day period. 
Plasma concentration of relevant long-chain polyunsaturated fatty acid (LCPUFA) such 
as docosahexaenoic acid (DHA; C:22:6n-3) and eicosapentaenoic acid (EPA; C20:5n-
3) w
ill be measured as a biomarker of fat absorption, along with  tissue accretion of 
DHA and EPA assessed by measurement of erythrocyte membrane levels, 
determination of  changes in the plasma fatty acid profile, plasma fat soluble vitamin 
and serum protein concentrations, at study entry (Day -14), at baseline (Day 0), and 
during Relizorb use at 30 day intervals (Days 30, 60, and 90). 
2.0  SCIENTIFIC AND CLINICAL BACKGROUND 
A decrease in pancreatic lipase secretion associated w
ith impaired exocrine pancreatic 
function results in maldigestion and malabsorption of fats
 and reduced total calorie 
intake.
1 EPI includes acute conditions or chronic diseases, such as CF, pancreatitis, 
pancreatic cancer as well as in elderly patients and preterm infants.
2,3,4,5 
 
Compromised exocrine pancreatic output leads to a lack of pancreatic enzymes, 
including but most notably lipase. Lipase function is considered critical to maintain 
caloric intake, since 9 kcal of energy is derived per gram of fat, versus 4 kcal of energy 
per gram of protein or carbohydrate. Fats varying in fatty acid carbon chain lengths are 
hydrolyzed (digested) and metabolized differently. Short chain triglycerides (C:2 – C:4) 
and MCTs (C:6-C:12)  are absorbed directly through the villi of the intestinal mucosa. 
MCTs can be readily absorbed due to their shorter chain-length and the residual 
activity of gastric lipase, even in pancreatic compromised patients. LCTs have fatty 
acids of >12 carbons (C:14-C:24). LCTs are not directly absorbed but instead must first 
be hydrolyzed into fatty acids and monoglycerides by pancreatic lipase before 
absorption can take place in the small intestine. Once fatty acids and monoglycerides 
are absorbed, they are transported to the liver and, ultimately, to tissues in the body for 
various physiological purposes.6 Since long chain fatty acids, in particular LCPUFAs, 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 15 of 47 
are the most difficult to digest and absorb, plasma concentrations and tissue accretion 
of LCPUFAs are informative biomarkers of fat absorption in general in people w
ith fat 
malabsorption such as patients with CF and EPI. DHA in particular is known to be 
deficient in people with cystic fibrosis, leading to an imbalance of the omega-6 to 
omega-3 ratio.  
 
It is important to note that fatty acids with different carbon chain lengths have different 
impacts on physiologically functions.
7 While both LCTs and MCTs provide calories, 
only long chain fatty acids from LCTs such as omega-3 fatty acids DHA and 
eicosapentaenoic acid (EPA) and omega-6 fatty acid arachidonic acid (AA) are 
structural components of membranes and also biological mediators involved in the 
regulation of various physiological functions. MCTs, when substituted for LCTs, have 
been shown to increase energy expenditure and satiety leading to reduced overall 
caloric intake and reduced body fat mass, making them a poor long-term energy 
source for nutritionally compromised patients.8 LCPUFAs have been recommended for 
management of people with pancreatic insufficiency due to specific deficiencies. 4,9 
 
Reduced digestion and absorption of LCPUFA results in lower baseline serum levels 
and altered metabolism of some important omega-3 and omega-6 fats, such as DHA, 
EPA and AA.  These fatty acids have a critical role in the composition, development 
and function of heart, liver, and neural (retina and brain) tissues and inflammatory and 
immunological systems.
6 Proper tissue levels of LCPUFAs, such as DHA and EPA, 
have been linked to optimal brain and vision development, cognition improvement, 
improved immunity and cardiac health.
9,10 LCPUFAs, and omega-3 fatty acids DHA 
and EPA in particular, have been shown to have important anti-inflammatory properties 
by suppressing inflammatory cytokines.
10 
 
Specific fatty acid alterations, imbalances and deficiencies have been identified in the 
blood and tissues of people with CF with decreased levels of DHA as well the essential 
long-chain fatty acid linoleic acid (LA), and increased levels of AA, as well as elevated 
levels of MCTs.
11 Fatty acid imbalances in the omega-3 (DHA, EPA) to the omega-6 
(AA) ratio may contribute to the inflammatory characteristics of CF lung disease and 
gastrointestinal pathology.
12,13 Improving dietary fat intake or reducing fat 
malabsorption with pancreatic enzymes has failed to normalize the deficiency of DHA. 
While most people with CF seem to achieve adequate protein intake and absorption, 
they have significant deficiencies in the absorption of beneficial long-chain fatty acids 
that are important for achieving adequate weight gain and critical to correcting fatty 
acid imbalances, as well as maintaining good overall health.11,12,13 
 
To improve caloric intake and avoid malnutrition, many individuals with EPI utilize 
enteral feeding as a supplement to daily dietary intake. Due to incomplete fat 
hydrolysis, current enteral feeding practice relies on large volumes (1,000 mL or more) 
of high calorie, nutrient-dense liquid formula delivered over 8-16 hours or longer. The 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 16 of 47 
large volume requirements, coupled w
ith poor fat hydrolysis and absorption, causes 
bloating in the morning that results in poor caloric intake at breakfast. The high volume 
of enteral formula also adds a significant carbohydrate load (~200 g of carbohydrates 
for typical 1,000 mL of enteral formula) that may contribute to the development or 
exacerbation of CF related diabetes (CFRD).  
 
For patients with EPI who receive enteral nutrition, proteins can be provided pre-
hydrolyzed in easily absorbed peptide form in semi-elemental formulas. Unfortunately, 
fatty acids are inherently unstable, so fat in enteral formulas are provided in the stable 
triglyceride form. As previously noted, LCTs must be hydrolyzed by lipase to form 
monoglycerides and fatty acids, before normal absorption and utilization in the body.
  
 
Alcresta Pharmaceuticals, Inc. (Alcresta) has developed Relizorb to consistently and 
efficiently hydrolyze the fats in enteral tube feeding in order to provide the benefit of 
readily absorbable fats from a given enteral formula, in their fatty acid and 
monoglyceride form, to patients with EPI or lipid malabsorption. Relizorb is a 
single-use, ex-vivo, point-of-care device designed to mimic the function of pancreatic 
lipase by pre-hydrolyzing fats from their natural triglyceride form, as contained in 
enteral formula, into their absorbable free fatty acid and monoglyceride forms, 
minimizing the burden of enteral feeding to caregivers and patients. 
  
 
Description of Relizorb 
Relizorb is a single-use, point-of-care digestive enzyme cartridge that connects in-line 
with existing enteral pump feed sets and pump extension sets. Relizorb is designed to 
hydrolyze fats contained in the enteral formulas. By hydrolyzing fats from enteral 
formulas, Relizorb allows for the delivery of absorbable fatty acids and monoglycerides 
for patients who rely on supplemental enteral (tube) feeding. 
 
Figure 1:  Relizorb Device 
 
 
Relizorb (center) connecting with a pump feed tube (left) and the tube to the patient (right). 
he 
ended 
ys
tem. 
 the 
o not 
B (before 
ect the 
ction 
the 
ing 
e 
cture 
ce. The 
ined 
and 
e  
 
othe pouch sea
l is
 broken
 
othe RELIZORB is
 damaged
 
othe RELIZORB has
 been previous
ly used
3. 
from the pump tubing into the inlet of the RELIZORB with a twis
ting and pushing 
motion until secure.
 1
 2
REL
IZORB
Tube from
 Pump
In
let
Ou
t
let
F
IGURE
 3:
4. Follow the pump manufacturer’
s
 ins
tructions
 to prime the feeding formula through 
to the outlet of the RELIZORB.
5. 
that connects
 to the patient.
    
Tube to Pat
ient
In
let
Ou
t
let
 1
 2
REL
IZORB
F
IGURE
 4
6. Follow the pump manufacturer’
s
 ins
tructions
 to prime the feeding formula to the 
end of the pump extens
ion set.
7. 
with feeding.
WARNING:
they mus
t be introduced AFTER
 REL
IZORB (i.e. between REL
IZORB and the patient). They may 
patient as
 shown be
low.
REL
IZORB
Pa
t
ien
t
Pump
Y-connec
tor
Ex
tens
ion
 Se
t
Downs
t
ream
Med
ica
t
ions
 or
 
Othe
r
 So
lu
t
ions
May
 Be
 Added
 He
re
F
IGURE
 5: Medications
 may be added between REL
IZORB and patient.
RELIZORB has
 been sho
when tes
ted with 500 m
Comparable or improve
with entera
l feeding pu
TABLE
 1: Fat hydrolys
is
 f
120 mL
/hour
PRODUCT
F
NUTREN® 2.0 
TWOCAL® HN
IMP
ACT®  
PEPTIDE
 1.5
PEPTAMEN® 1.5^
PEPTAMEN AF® ^
VITAL AF
  
1.2 CAL™^
PEPTAMEN®^
NUTREN® 1.0
* % fat hydrolys
is
 is
 es
tim
§ Based upon tes
ting from
** MCT = medium cha
in t
Fat hydrolys
is
 rates
 may
For a more deta
iled lis
ti
with a summary of the h
 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 17 of 47 
Relizorb is comprised of a clear cylindrical, plastic cartridge with a single inlet 
connection port and a single purple outlet connection port (Figure 1). The inlet and 
outlet ports of Relizorb are intended to connect in-line with enteral pump feed sets and 
pump extension sets. Inside the cartridge, there are small white beads. The digestive 
enzyme, lipase, is covalently bound to polymeric beads. The lipase-bead complex, 
iLipase
TM (immobilized lipase), is retained within the cartridge during use by filters on 
both ends of the cartridge. The fat in enteral formulas is hydrolyzed as it comes in 
contact with iLipase as the formula passes through the cartridge. The iLipase is 
retained w
ithin the cartridge and it is important to note that only minute quantities of the 
lipase have the potential to exit Relizorb. Relizorb was cleared by the US Food and 
Drug Administration (FDA) Center for Devices and Radiological Health (CDRH) as a 
Class 2 low
-risk device and is indicated for use in adults to hydrolyze fats in enteral 
formula.  
 
Active Component and Mechanism of Action 
The active component of Relizorb is a lipase enzyme that is immobilized on polymeric 
beads, collectively called iLipase. 
 
A volume of 500 mL of enteral formula used for overnight feeding will typically 
provide 600 kilocalories and 27 g of fat. Relizorb is designed to consistently and 
efficiently hydrolyze approximately 90% of available fats into absorbable fatty acids 
and monoglycerides.  
 
A sensitive enzyme-based free fatty acid quantification assay for detecting medium 
and long-chain free fatty acids was used to measure fatty acid release resulting from 
the action of Relizorb over a range of conditions. Based on this method, in vitro 
analysis demonstrates that for most enteral formula tested, approximately >90% of fat 
will be hydrolyzed after passing through Relizorb. 
 
Figure 2: Enzyme Hydrolysis 
 
 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 18 of 47 
 
Clinical Labeling 
One Relizorb is packaged in a single foil pouch with an investigational use label 
customized to this study. Each subject and/or parent/caregiver w
ill receive Instructions 
For Use (IFU) that provides detailed instructions on the operational setup and use of 
Relizorb. 
   
 
Storage Conditions 
Storage conditions require temperatures of 2 °C to 27 °C (36 °F to 80 °F) according to 
product labeling. Relizorb is not to be frozen (-20 °C or -4 °F). Specifications regarding 
storage conditions are included in the IFU.  
 
 
Study Rationale and Purpose 
Enteral nutrition supplements, usually delivered as a nocturnal tube feeding, are 
provided for nutritionally challenged patients with EPI to support nutritional status and 
maintain or gain weight. There are well-accepted benefits associated with enteral 
nutrition, especially in CF, but use varies dramatically among centers, ranging from 0% 
to 33% of patients utilizing enteral nutrition to supplement daily caloric intake. Current 
enteral nutrition practice relies on large volumes of a nutrient dense liquid formula 
delivered over 8 to >12 hours. Common chal
lenges in the current practice include 
duration of feeding, clogging of lines resulting in pump alarms, sleep interruption, the 
inability to administer PERT during continuous overnight delivery of the enteral 
formula. PERT is sometimes administered before, during, and/or after enteral tube 
feeding sessions. However, it is impractical to administer PERT products overnight that 
would provide for adequate hydrolysis of fat. Moreover, the efficacy and safety of 
PERT product use in conjunction w
ith enteral nutrition has not been established. PERT 
product manufacturer prescribing information warns against crushing the product or 
adding it to formula, and the FDA advises that pancreatic enzyme products are not 
approved for administration via gastrostomy tubes. Symptoms of fat malabsorption 
such as nausea, bloating and steatorrhea due to incomplete hydrolysis of fats are often 
reported to be increased in patients with CF who receive enteral nutrition.  
 
Some macronutrients in enteral formulas, such as protein, can be prepared pre-
hydrolyzed in a peptide form that is stable and available to be readily absorbed. In 
addition, hydrolysis of protein occurs in the stomach independent of pancreatic 
enzymes. Therefore, patients with EPI theoretically should not need protease to 
achieve adequate absorption of peptides and amino acids in enteral formulas, although 
this has not been investigated. Due to poor stability of fatty acids, no enteral formula 
containing hydrolyzed fat has been manufactured to date. However, hydrolyzing fats at 
the time of consumption (point-of-care) avoids this problem. Thus, the intended benefit 
of this point-of-care approach w
ith Relizorb is that fats in enteral formula, including 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 19 of 47 
LCTs, are pre-hydrolyzed ex-vivo just before ingestion and provided in a form readily 
available for absorption in individuals who lack pancreatic lipase or the physiological 
capacity to digest fat. 
 
The objectives of this study are as follows: 
 
1. Demonstrate that sustained use of Relizorb in conjunction with enteral tube 
feeding w
ithout concomitant use of PERT results in an increase in fat absorption 
as evidenced by increased plasma concentrations of LCPUFAs such as DHA 
and EPA, tissue accretion (RBC) of omega-3 fatty acids such as DHA and EPA, 
and increased concentrations of fat soluble vitamins; 
2. Show that serum protein levels are maintained despite withdrawal of PERT use 
associated with enteral tube feeding with sustained use of Relizorb in 
conjunction with enteral tube feeding using a semi-elemental formula; 
3. Demonstrate the safety and tolerability of sustained use of Relizorb in 
conjunction with enteral tube feeding; 
4. Explore the potential immunomodulatory effect of increased plasma 
concentrations of DHA and EPA as evidenced by changes in the omega-6 to 
omega-3 fatty acid ratio and urinary leukotriene concentrations. 
 
 
Potential Benefits and Risks 
This open-label study is the companion study to Protocol 0000497, an ongoing study 
enrolling patients from the same population.  In both studies it is expected that, w
ith 
Relizorb use, patients will experience a decrease in symptoms associated with fat 
malabsorption, improved fat absorption and calorie intake, and uptake of 
physiologically relevant fatty acids like DHA and EPA. Since fat hydrolysis occurs 
ex-vivo in-line with the enteral feeding circuit, patients will not be exposed to the 
enzyme but only to formula, with fat in a readily absorbable form (fatty acids and 
monoglycerides). 
 
The porcine model of EPI is a well-established surgical model where ligation of 
pancreatic ducts causes a total lack of pancreatic enzymes, including lipase, 
diminished levels of bicarbonate, and reduced pH in the duodenum. Like EPI in 
humans, residual gastric lipase remains. EPI pigs have steatorrhea, arrested growth, 
fatty acid deficiencies, as well as common gastrointestinal symptoms seen in people 
with pancreatic insufficiency.17 In four pre-clinical studies using this model, use of 
Relizorb and its prototypes was associated with improved growth as well as laboratory 
nutritional parameters. Improved total and LCPUFA fat absorption was demonstrated, 
especially increases in plasma and tissue levels of omega-3 and omega-6 fats, 
normalization of blood fat profile and increases in other nutritional parameters (e.g., fat 
soluble vitamins, proteins). There was also a decrease in signs of malabsorption in 
animals treated with Relizorb, and there were no observed adverse events associated 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 20 of 47 
with Relizorb use. There were no observed adverse events associated w
ith use of the 
Relizorb.
17, 18  
 
The safety and tolerability of iLipase is also supported by two clinical studies.  In a 
study in normal, healthy volunteers, subjects orally consumed a single bottle of 
BOOST® Original fortified with 10 mL of algae oil, either as a pre-hydrolyzed drink 
(PfND) after exposure to iLipase contained within a mesh bag or as a non-hydrolyzed 
nutritional drink (fND). No serious adverse events occurred when a single PfND and 
fND were consumed. Adverse events were similar among the two groups; one mild 
headache (≤24h) in the fND group, and three unrelated study events (dental infection-
1, headache-1, vomiting-1) in the PfND group. Compliance with the protocol was 100% 
with both nutritional drinks consumed w
ithin two minutes. No subsequent GI issues 
were reported at the 24h safety follow-up call in either group. 
 
In a second study, patients with presumed EPI orally consumed a single bottle of 
BOOST® Original fortified with 10 mL of algae oil, either as a pre-hydrolyzed drink 
(PfND) after exposure to iLipase contained within a mesh bag or as a non-hydrolyzed 
nutritional drink (fND). There was 100% compliance, with all subjects consuming the 
full volume of PfND and fND. The hydrolyzed drink and non-hydrolyzed drink were both 
well tolerated by all subjects. There was no difference in palatability between 
hydrolyzed and non-hydrolyzed drink.   Three subjects experienced a study event 
following consumption of fND and 3 subjects experienced a study event after 
consumption of PfND. Headache occurred in one subject in each treatment group.  
One instance each of fatigue, dizziness and nausea were reported.  Two study events 
were considered treatment-related: abdominal pain (fND) and throat irritation (PfND). 
There were no SAEs in the study. 
 
To date, the observed risks of Relizorb use are determined to be low based on 
preclinical validation, including safety evaluation in animal models as well as clinical 
studies in healthy volunteers and people w
ith EPI. Relizorb is cleared by the FDA as a 
Class II (low risk) device for use in adults to hydrolyze fats in enteral formula. 
Nonclinical data is available in the Investigator’s Brochure in Section 11.0 that supports 
continuation of further studies. 
 
In summary, the potential benefits of participation in this open label study include the 
possibility of improved fat absorption and decrease in gastrointestinal symptoms 
related to fat malabsorption. Based on available preclinical and clinical data, the risk 
profile associated with participation in this open label study is low. 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 21 of 47 
3.0 STUDY OBJECTIVES AND ENDPOINTS 
 
Objectives 
The overall objective of the study is to demonstrate improved fat absorption w
ith 
sustained use of Relizorb in patients with CF who have EPI and are receiving enteral 
tube feeding.  In this study, subjects will be receiving an enteral formula that has a high 
content of long chain triglycerides (Impact® Peptide 1.5) and will be using Relizorb 
during their enteral feeding in place of other therapies currently used to aid in fat 
absorption, such as pancreatic enzyme replacement therapy (PERT).  Plasma 
concentration of relevant LCPUFAs such as DHA and EPA w
ill be measured as a 
biomarker of fat absorption. Tissue accretion of fatty acids DHA and EPA assessed by 
measurement of erythrocyte membrane levels and the plasma fatty acid profile will be 
evaluated as additional biomarkers of fat absorption. Plasma fat-soluble vitamin and 
serum protein concentrations will also be measured. All fatty acid, fat-soluble vitamin, 
and protein concentrations w
ill be assessed in relation to values obtained at study 
entry (Day -14), at baseline (Day 0), and during Relizorb use (Days 30, 60, and 90). 
Safety and tolerability of sustained use of Relizorb will also be assessed during use 
and compared with gastrointestinal symptoms recorded during the observation phase 
of the study (Day -14 through Day -8).  
Efficacy  
• Evaluate effect of sustained Relizorb use during enteral feedings on fat absorption 
through serial measurements of plasma and tissue (erythrocyte membrane) 
concentrations of physiologically relevant LCPUFAs such as DHA and EPA, as well 
as the plasma fatty acid profile changes, as biomarkers of fat absorption. 
• Evaluate effect of sustained Relizorb use during enteral feedings on plasma 
fat-soluble vitamin concentrations.  
• Evaluate effect of sustained Relizorb use on the ratio of omega-6 to omega-3 fatty 
acids as a potential indicator of immunomodulation  
• Evaluate effect of sustained Relizorb use on urinary leukotriene levels 
• Evaluate effect of sustained Relizorb use on serum protein levels 
• Evaluate effect of sustained Relizorb use on growth. 
 
Safety 
• Evaluate the safety and tolerability of sustained use of Relizorb as part of a enteral 
feeding regimen.  
 
 
Endpoints 
Efficacy 
• Change over time in plasma concentrations of LCPUFAs such as DHA and EPA 
• Change over time in tissue (erythrocyte membrane) fatty acid concentrations such 
as DHA and EPA  

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 22 of 47 
• Change over time in plasma fatty acid profile of LCPUFAs 
• Changes over time in the ratio of omega-6 to omega-3 fatty acids in plasma and in 
tissue (erythrocyte membrane) levels 
• Change over time in plasma concentrations of fat soluble vitamins 
• Change over time in body weight, BMI, and weight and BMI standard scores 
• Change over time in serum protein concentrations (total protein, prealbumin, 
albumin, transferrin) 
• Change over time in markers of inflammation (urinary leukotrienes) 
 
Safety 
• Frequency and severity of adverse events and unanticipated adverse device effects 
(UADEs) 
• Evaluation of clinical and laboratory findings  
• Concomitant medication assessment 
• Frequency and severity of gastrointestinal signs and symptoms (abdominal pain, 
vomiting, loss of appetite, bloating, flatulence and steatorrhea) 
 
4.0 STUDY DESIGN AND PROCEDURES 
 
Enrollment Goals 
Male and female patients with CF and EPI will be screened for the study from 
approximately 10 investigative centers in the United States. Approximately 35 subjects 
will be enrolled in the study with the goal of having at least 30 evaluable subjects 
completing the study through at least Visit 4 (Day 60).   
 
 
Representative Age Groups 
 
This study will enroll patients with CF who are 4 years of age or older w
ithout an upper 
age limit. Since median predicted survival age for patients with CF is approximately 40 
years, it is expected that the majority of patients enrolled will be less than 40 years old.  
 
To obtain a diverse age range in the study population, the PIs will be encouraged to 
recruit patients along the age continuum. Since study sites are pediatric centers, it is 
expected that the majority of subjects will be in the pediatric age range. However, PIs 
at study sites will be encouraged to collaborate with affiliated adult CF centers to allow 
for the recruitment of adult patients with CF. 
 
Subjects discontinuing study participation may need to be replaced to achieve the 
minimum total number of 30. All available data for subjects who were enrolled and 
discontinued w
ill be captured in data reports. Patients who participated in Protocol 
0000497 and considered to be protocol compliant will be eligible for enrollment in 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 23 of 47 
Protocol 0000498. In addition, Relizorb naïve patients that meet eligibility criteria may 
enroll. It is anticipated that active enrollment will last approximately three and a half 
months. 
 
 
Study Duration 
The anticipated study duration is approximately 104 days. This includes a 7 day 
observation period when the subject is maintaining their usual care routine, a 7 day run 
in period, and a 90 day open label treatment period. Subjects who experience a UADE 
during the last 29 days of the open label period w
ill be followed for 30 days following 
the occurrence of the UADE or until resolution, whichever comes first.  
 
 
Study Periods 
The study will have three periods: a 7 day observation period that w
ill establish a 
baseline, a 7 day run in period that will normalize the enteral formula type and volume 
of the feeding, and a 90 day treatment period. Study visits and the attendant tests and 
procedures should be performed according to schedule. However, changes in 
scheduled study visits are allowed with permission from the site for holidays, vacations, 
etc. For these exceptions, the study visit should occur within 4 days (4) of the 
scheduled day. There will be five study visits as described below: 
 
Visit 1:  Study Entry (Day -14) 
 
On Visit 1 (Day -14), subjects (or legally authorized parent or guardian) will sign a 
written informed consent, or assent when applicable. Baseline procedures will include 
evaluation of eligibility criteria and recording or obtaining demographics, medical 
history, physical examination, height, weight, body mass index, vital signs, standard 
clinical laboratory tests (hematology, clinical chemistry, urinalysis), blood lipids, urine 
sample for urinary leukotriene evaluation, plasma fatty acid sample, pregnancy test for 
childbearing females and concomitant medications.  Collected results on Day -14 w
ill 
be used to screen patients for eligibility and characterize the study population. Study 
staff will also review the medical records and obtain up to four body weight 
measurements recorded at 3 month intervals over the previous 12 months.  Historical 
average daily PERT use with meals and snacks and w
ith enteral nutrition will be 
recorded. Study staff will provide detailed instructions for subjects to maintain a 
gastrointestinal symptom diary for 7 consecutive days. 
 
During the observation period (Day -14 to Day -8), subjects will maintain their usual 
care plan. The brand, volume, and administration rate of the enteral formula used in 
the enteral feeding will be recorded, along with the usual dose of PERT use associated 
with the enteral feeding. Crushing of PERT products and adding to the enteral feeding 
bag is prohibited. Subjects will make entries into a 7-day gastrointestinal symptom 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 24 of 47 
diary each day. PERT use with meals and snacks and with enteral tube feeding will be 
recorded each day by the subject. 
 
During the run in period (Day -7 to Day -1), subjects will maintain their usual enteral 
feeding volume up to a maximum volume of 1000 mL and administration rate using 
Peptamen 1.5 for at least 5 days preceding the treatment period between Day -7 and 
Day -1. The usual dose of PERT use associated with the enteral feeding will be 
allowed, but crushing of PERT products and adding to the enteral feeding bag is 
prohibited. Subjects w
ill make entries into a 7-day gastrointestinal symptom diary each 
day. PERT use with meals and snacks and with enteral tube feeding will be recorded 
each day by the subject. Peptamen 1.5 for use during the run in period w
ill be shipped 
to the subject’s home prior to Day -7. 
Visit 2: Baseline (Day 0) 
 
During Visit 2, as well as each subsequent visit, the study staff will collect the 
completed gastrointestinal symptom diary. Blood samples will be collected for fatty 
acid, protein, and fat-soluble vitamin analysis during these visits. In addition, a urine 
sample will be collected for urinary leukotriene analysis. Body weight and height w
ill be 
measured and recorded, and BMI will be calculated and recorded. Each subject and/or 
parent(s) will receive verbal instructions on the temperature storage, setup and 
operation of Relizorb with Impact Peptide 1.5. Study staff will physically demonstrate 
setup and operation of Relizorb so that subjects/parents receive hands-on training prior 
to leaving the clinic. Study staff will instruct subjects/parents/caregivers on recording 
the use of Relizorb between study visits. Subjects and parents w
ill have the opportunity 
to ask questions to ensure familiarity with the principles of operation. This will ensure 
that subjects/parents are knowledgeable regarding the proper use of formula with 
either the Covidien Kangaroo™ ePump or MOOG Enteral Lite® Infinity
® pumps. 
Instructions For Use (IFU) will be provided to subjects/parents to take home.  
 
Impact Peptide 1.5 is the only enteral formula allowed for use for enteral tube feedings 
in this part of the study. Subjects will maintain their usual enteral feeding volume up to 
a maximum volume of 1000 mL and administration rate using Impact Peptide 1.5.  
Study staff will inform subjects/parents that any use of PERT in association with the 
enteral tube feeding is strictly prohibited. 
 
On or before Day 0, all subjects will receive outpatient study supplies, such as the 
Relizorb investigational device, Impact Peptide 1.5, Relizorb Accountability Log, 7-day 
gastrointestinal diary and specific written instructions. Subjects/parents/caregivers will 
be informed that they should start a 7-day gastrointestinal diary one week before the 
next study visit so it is completed the day before the next study visit. Subjects will be 
instructed to maintain their normal CF treatment regimen and usual diet throughout the 
study. No dietary restrictions exist during the outpatient period. Subjects should follow 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 25 of 47 
dietary recommendations from their registered dietitian (RD), nutritionist or healthcare 
professional. 
 
Visits 3, 4, and 5: Treatment Period (Days 30, 60, and 90) 
 
Approximately one week before visits 3, 4, and 5, study staff will contact 
subjects/parents/caregivers and remind them to start a 7-day gastrointestinal diary 
such that it is completed the day before the study visit, and also remind them to bring 
the completed diary with them to the clinic visit along w
ith all used and unused Relizorb 
cartridges. During these visits study staff will collect the completed 7-day 
gastrointestinal symptom diary. Blood samples w
ill be collected for fatty acid, protein, 
and fat-soluble vitamin analysis during these visits. In addition, a urine sample will be 
collected for urinary leukotriene analysis. Body weight and height will be measured and 
recorded, and BMI will be calculated and recorded. Study staff will assess UADEs and 
concomitant procedures and medication use.  
 
Study staff will review the Relizorb Accountability Log for completeness, collect all 
used Relizorb cartridges, and provide subjects with additional unused Relizorb 
cartridges for at home use until the next scheduled visit. Concomitant medications and 
UADEs will be assessed.  
 
Subjects who experienced a new or ongoing UADE within the previous 29 days will 
receive a follow-up safety contact until 30 days after the occurrence of the UADE or 
until the UADE has resolved, whichever comes first. Therefore the duration of the 
study may be extended if a subject has a new or ongoing UADE between Day 60 and 
Day 90. 
 
On the final clinic visit (Day 90), the majority of baseline procedures will be repeated. 
End of study procedures w
ill include standard laboratory testing (clinical chemistry, 
hematology and urinalysis), blood lipids, vital signs, weight, and height measurement, 
and BMI calculation. 
 
Subjects will be instructed to bring to the clinic all used and unused devices to enable 
study staff to check administration compliance. All used and unused cartridges w
ill be 
inventoried and returned to the Sponsor, unless destruction at the study site is 
authorized.  
 
 
Selection of Patients 
 
Inclusion Criteria 
 
Each patient must meet all of the following inclusion criteria to be enrolled in the study: 
 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 26 of 47 
1. Male or female patients 4 years of age or older 
2. Confirmed diagnosis of CF defined as two clinical features consistent with CF 
and have either:  
a. Genotype with two identifiable mutations consistent with CF, determined 
using diagnostic devices that have been cleared by the US FDA (the FDA 
clearance requirement does not apply if the test was performed prior to 
2005, the year the US FDA first started evaluating genetic tests for CF), or 
b. Sweat chloride >60 mEq/L by quantitative pilocarpine iontophoresis 
3. Documented history of exocrine pancreatic insufficiency due to CF (e.g., 
historical fecal elastase test, genotype consistent with exocrine pancreatic 
insufficiency, etc.) 
4. Enteral formula user a minimum of four to five times per week, using PERT, 
consuming an unrestricted fat diet, and willing to use Peptamen 1.5 and Impact 
Peptide 1.5 
5. Clinically stable with no significant changes in health status within 14 days of 
Day -14  
6. Written informed consent obtained from patient, or, if the patient is a minor, from 
the patient’s legal representative with assent from the minor when applicable. 
 
 
Exclusion Criteria 
 
Each patient who meets any of the following exclusion criteria will be excluded from the 
study: 
 
1. Uncontrolled diabetes mellitus 
2. Signs and symptoms of liver cirrhosis or portal hypertension (e.g., 
splenomegaly, ascites, esophageal varices) or significant liver disease. 
Significant liver disease is defined as liver transaminases >3x upper limit of 
normal (ULN) or total bilirubin 1.5x ULN at baseline (or based upon the 
discretion of the Principal Investigator (PI) 
3. Lung or liver transplant 
4. Active cancer disease currently receiving cancer treatment 
5. Known small intestinal inflammatory diseases such as Crohn’s or Celiac 
disease, or diarrheal illness unrelated to EPI (e.g., infectious gastroenteritis, 
sprue, lactose intolerance, inflammatory bowel disease) 
6. History of fibrosing colonopathy or recurring distal intestinal obstructive 
syndrome (e.g. more than three occurrences per year) 
7. CF respiratory exacerbations within 2 weeks prior to study entry 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 27 of 47 
8. Oral glucocorticoid therapy or intravenous glucocorticoids within 2 weeks prior 
to baseline; patients who are receiving low dose alternate day corticosteroid 
therapy for lung disease may be enrolled in the study subject to consultation 
between the site PI and the Alcresta Chief Medical Officer 
9. Major surgery or serious lung infection within 2 weeks prior to study entry 
10. 
Acute life-threatening or uncontrolled medical illness 
11. 
Known alcohol, drug or medication abuse 
12. 
Any condition, in the judgment of the site PI, which would interfere with the 
intent of the study or make participation not in the best interest of the patient 
13. 
For females of childbearing potential:  
a. Positive pregnancy test at study entry 
b. Lactating 
c. Unwilling to use an effective medically acceptable form of contraception 
(e.g., prescription oral contraceptives, contraceptive injections, 
contraceptive patch, an intrauterine device, NuVaRing®, diaphragm with 
spermicide or abstinence) from baseline to the end of the study. 
14. 
Treatment with investigational study agents (drug, biologic or device) other than 
Relizorb within 30 days of study entry 
15. 
Adult subjects who lack the capacity to provide individual informed consent. 
 
 
Patient Enrollment and Replacement Criteria 
Approximately 30 to 35 patients will be enrolled in the study. Protocol compliant 
patients from Protocol 0000497 are eligible for this study, unless clinical changes have 
occurred in which the patient no longer meets the initial eligibility criteria. All eligible 
patients willing to continue in this study will be accepted. Every reasonable attempt 
should be made by study staff to assist eligible patients interested in participating in 
this study. 
 
Any subject who withdraws from the study before Study Visit 3 on Day 30 will be 
replaced by an eligible patient.  
 
Any subject who withdraws from the study before Study Visit 4 on Day 60 must be 
replaced by an eligible patient.  
 
Any subject who withdraws from the study before Study Visit 5 on Day 90 may be 
replaced by an eligible patient unless the sum of completed subjects and currently 
enrolled and active subjects is greater than 30, in which case the subject will not be 
replaced unless the sum of completed subjects and currently enrolled and active 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 28 of 47 
subjects drops below 30 before the thirtieth enrolled and active subject completes 
Study Visit 4 on Day 60 with the intention of finishing the study out to Day 90.  
 
Every effort should be made to collect information regarding UADEs from subjects who 
drop out or are removed or excluded from the study. Data collected up to the point of 
withdrawal will be used in the analysis of the appropriate time point but will not be 
carried forward. 
 
 
Allowed Concomitant Medications 
Subjects should continue all prescribed medications and supportive therapies. 
Concomitant medications taken for current medical history and birth control are all 
allowed. Prescription and over-the-counter medications for the treatment of AE/UADEs 
are permitted. 
 
All supportive therapies and concomitant medications taken by the subject will be 
recorded in the source documents and entered on the electronic case report form 
(eCRF). Any dosage changes to concomitant medications required during the study 
must be recorded in the eCRF. 
 
 
Prohibited Medications 
There are currently no known interactions to other medications with Relizorb. 
Treatments with any investigational drug, biologic or medical device are prohibited 
during the study.  
 
Subjects may use oral PERT with meals and snacks during the day but are prohibited 
from using PERT or any other medication intended to hydrolyze fat if associated with 
administration of enteral tube feeding.  
 
 
Safety Monitoring  
 
Study Safety Procedures 
 
Safety data will be monitored on a continual basis throughout the study and clinical 
changes evaluated. Safety monitoring will include safety follow-up contacts, monitoring 
AE/UADE, subject withdrawals and safety data. The site monitor will advise the Chief 
Medical Officer of the frequency and severity of UADEs. The Alcresta Chief Medical 
Officer will evaluate all UADEs within 24 hours of notification.   
 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 29 of 47 
 
Study Procedures 
Table 1 lists the timing of assessments and study procedures. If a subject misses a 
scheduled study visit within the ±4 day window, the visit should be rescheduled as 
soon as possible. 
 
 
Informed Consent 
 
Each patient must provide written informed consent, as well as assent, when 
applicable, before any study-related procedure is conducted. 
 
 
Inclusion and Exclusion Criteria 
 
The inclusion and exclusion criteria will be reviewed to determine patient eligibility. 
 
 
Demographics 
 
Subject demographics will document age, gender, and ethnicity. 
 
 
Medical History 
 
On Day -14, a relevant medical history dating back at least 1 year will be obtained. The 
medical history will emphasize CF disease characteristics, prior therapy, surgery, 
allergies and assess the patient for any disqualifying medical conditions as specified in 
the exclusion criteria. 
 
 
Physical Examination 
 
Complete physical examinations are required for all patients entering the study. A 
qualified member of the study staff (e.g., physician, physician’s assistant) will perform a 
complete physical examination.  
 
 
Height, Weight, and BMI 
 
Height, weight and BMI will be assessed at the time points outlined in Table 1. In 
addition, study staff will review the medical record and record up to 4 body weights at 3 
month intervals recorded over the previous12 months. 
 
 
Vital Signs 
 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 30 of 47 
After a minimum resting period of 15 minutes, vital signs (heart rate, respiratory rate 
and sitting blood pressure) will be measured. Oral or tympanic temperature w
ill also be 
collected.  
 
 
Clinical Laboratory Tests 
 
Blood sample collections will be obtained at the time points outlined in Table 1. 
Subjects will be in a seated or supine position during blood sample collection.  
 
The clinical laboratory tests to be performed are listed in Table 2 (Clinical Laboratory 
Tests) below. Handling and shipment of clinical laboratory samples will be analyzed by 
a central laboratory and be outlined in the laboratory manual. 
 
 
Pregnancy Test 
 
A serum β-hCG pregnancy test will be performed only for females of childbearing 
potential. Negative results must be available four days prior to the first Relizorb usage 
on Day 0. If a female subject becomes pregnant while participating in the study, the 
site is responsible for notifying the Alcresta Chief Medical Officer as soon as possible. 
 
 Enteral Tube Feeding 
 
During the treatment period (Days 0 to 90), subjects will receive enteral feedings using 
the same enteral formula, Impact Peptide 1.5. The volume of enteral tube feeding 
should be 500 to 1000 mL; subjects who routinely receive more or less volume may be 
enrolled only if approved by the Alcresta Chief Medical Officer. The enteral formula 
should be delivered using a compatible pump that has a no flow/low flow alarm at a 
flow rate set between 24 and 120 mL. 
 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 31 of 47 
Table 2: Clinical Laboratory Tests 
Clinical Chemistry 
Hematology 
Lipids 
Urinalysis 
Albumin 
Complete blood count 
and white blood cell 
differential 
Total cholesterol 
Bi
lirubin 
Alkaline phosphatase 
Triglycerides 
Ketones 
ALT 
HDL 
Leukocyte esterase 
AST 
 
LDL 
pH 
Bicarbonate 
 
 
Protein 
BUN 
 
 
Specific gravity 
Calcium 
 
 
Urinary creatinine 
Chloride 
 
 
Urinary uric acid 
Cholesterol 
 
 
 
Creatine phosphokinase 
 
 
 
Creatinine 
 
 
 
Glucose 
 
 
 
Lactate dehydrogenase 
 
 
 
Magnesium 
 
 
 
Phosphorus 
 
 
 
Potassium 
 
 
 
Prealbumin 
 
 
 
Sodium 
 
 
 
Total and direct bilirubin 
 
 
 
Total protein 
 
 
 
Uric acid 
 
 
 
A1C levels 
 
 
 
Transferrin 
 
 
 
 
 Gastrointestinal Symptom Diary 
 
Detailed verbal instructions on how to record entries in the gastrointestinal symptom 
diary should be conducted by study staff on Day -14 and again as a subsequent 
reminder on Days 0, 30, and 60. The gastrointestinal symptom diary will also include a 
brief instruction.  Entries need to occur on a daily basis for 7 consecutive days. The 
completed symptom diary will be entered into the eCRF and regarded as a source 
document.  Diary data will be used for the primary safety study endpoint to determine 
the frequency and severity of gastrointestinal symptoms.   
  

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 32 of 47 
 Plasma and Tissue Fatty Acid Samples 
 
Blood samples will be collected on Day -14 and Day 0 as baseline measures of fatty 
acid levels. The other fatty acid blood samples will be obtained at the time points 
specified in Table 1. 
 
 Fat Soluble Vitamin Samples 
 
Blood samples will be collected on Day -14 and Day 0 to measure baseline fat-soluble 
vitamin (A, D, and E) levels. The other fat-soluble vitamin blood samples will be 
obtained at the time points specified in Table 1. 
  
 Serum Protein Samples 
 
Blood samples will be collected on Day -14 and Day 0 as baseline measures of serum 
protein (total protein, prealbumin, albumin, transferrin) levels. The other serum protein 
blood samples w
ill be obtained at the time points specified in Table 1.  
  
 
Removal of Subjects from the Study  
During the course of this study, subjects will be withdrawn and their participation 
terminated if any of the following occurs: 
• Any UADE severe enough in nature to warrant discontinuation in the study 
• Withdrawal of consent 
• The site PI, in consultation with the Alcresta Chief Medical Officer, believes the 
subject should be removed from the study for safety reasons 
• Subject is non-compliant with study requirements. 
 
5.0 DATA ACQUISITION, TRANSFER AND ANALYSIS 
 
Data Acquisition 
Electronic case report forms (eCRF) are considered confidential data. The Alcresta 
data management vendor w
ill provide user access and training to investigative sites on 
the use of the eCRF system. Subject data will be entered into the eCRF by site staff 
using a secure, web-based electronic data capture application. Clinical data required 
by the protocol w
ill be captured on the eCRF and supported by source documentation 
at site. The site PI will prepare and maintain adequate and accurate medical histories 
designed to record all observations and pertinent study data for each subject. 
 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 33 of 47 
To ensure data accuracy, eCRF entry for individual subjects should be completed as 
soon as possible after the study visit. Site staff should enter information on the eCRF 
according to the completion guidelines provided by the Alcresta data management 
vendor. The site PI is ultimately responsible for all information collected on enrolled 
subjects and must ensure data is reviewed and verified for completeness and 
accuracy. The signature of the site PI or subinvestigator indicates formal approval of all 
data entered on the eCRF. 
 
The Alcresta data management vendor will retain eCRF data and corresponding audit 
trails. A copy of the final archival eCRF in the form of a compact disk or other 
electronic media will be placed in the Investigator Site File.  
 
 
Data Transfer 
Alcresta, in collaboration with the data management vendor, will be responsible for the 
electronic transfer of external laboratory data according to fully executed data 
transmission agreements, data management plans or other study documentation.  
 
 
Analysis of Fatty Acid Absorption 
The concentration of LCPUFAs such as DHA and EPA in plasma is the primary 
determination supporting the primary endpoint of fat absorption and will be analyzed 
using UPLC-MS expressed as ug/mL. The relative levels of LCPUFAs such as DHA 
and EPA in erythrocyte membrane and the overall plasma fatty acid profile also 
support the primary endpoint and will be analyzed using GC/MS expressed as g/100 g 
FA.  
 
6.0 SAFETY OVERVIEW 
 
Monitoring of Adverse Events 
All study staff are responsible for ensuring that complete safety data has been 
recorded on the eCRF. Medical assessments must be performed during each 
scheduled study visit and serve as the primary basis for identifying an UADE. Although 
spontaneous or elicited medical complaints will likely constitute the majority of UADEs, 
any non-scheduled visit to a healthcare provider, or the initiation of a new medication, 
should trigger additional questioning as to the occurrence of an AE or UADE. 
 
 
Adverse Events 
An adverse experience (AE) is defined as any untoward medical occurrence in a 
subject, regardless of its causal relationship to the investigational device. An AE can 
therefore be any unfavorable and unintended sign (including abnormal laboratory 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 34 of 47 
findings), symptom or disease experienced w
ith use of the product, whether or not it is 
related to the product. This includes any newly occurring event or a previous condition 
that has increased in severity or frequency since the use of Relizorb. 
 
 
Causal Relationship 
 
All AE must be assessed for causality in reference to Relizorb use. When entering data 
for a reported AE, the site PI will be asked to assess the relationship of Relizorb use to 
the AE. Causality will be categorized according to the following criteria: 
 
Not Related: 
 There is no medical evidence to suggest the event may be 
 related to Relizorb use, or there is another more probable 
 medical explanation. 
 
Possibly Related: An event, including laboratory test abnormality, with a temporal 
relationship to Relizorb use that makes a causal relationship 
improbable and which other medications, events or underlying 
disease provide a plausible explanation.  
 
Probably Related: The event occurred within a reasonable time sequence to using 
Relizorb, but could be explained by concurrent disease or other 
medications or events.  
 
Related: 
There is strong medical evidence to suggest that the AE is related 
to Relizorb use. 
 
 
Anticipated Adverse Events in Subjects 
 
Due to the GI complications inherent in CF patients, the identified risks are upper 
abdominal pain, bloating, constipation, diarrhea, flatulence, heartburn, indigestion, 
nausea, steatorrhea (fatty stool), vomiting, weight decrease and headache. 
 
 
Unanticipated Adverse Device Effects  
An unanticipated adverse device effect (UADE) is any serious adverse effect on health 
or safety, any life-threatening problem or death caused by, or associated with a device, 
if that effect, problem, or death was not previously identified in nature, severity, or 
degree of incidence in the application; or any other unanticipated serious problem 
associated with a device that relates to the rights, safety, or welfare of subjects. 
 
An UADE is analogous to a serious adverse event (SAE), defined as any AE, occurring 
at any exposure to the therapeutic agent, that results in any of the following outcomes: 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 35 of 47 
death, life-threatening AE, inpatient hospitalization or prolonged existing 
hospitalization, a persistent or significant disability or incapacity or a congenital 
anomaly/birth defect. 
 
An UADE is defined as “any serious adverse effect on health or safety or any 
life-threatening problem or death caused by, or associated with, a device, if that effect, 
problem, or death, was not previously identified in a nature, severity or degree of 
incidence in the investigational plan or application (including a supplementary plan or 
application), or any other unanticipated serious problem associated with a device that 
relates to the rights, safety, or welfare of subjects” according to 21 Code of Federal 
Regulations Part 812.3. 
 
As provided by the International Conference of Harmonization (ICH) criteria, a serious 
adverse effect (event) is any clinical event or condition that is: 
• Fatal 
• Life-threatening 
(Note:  The term “life-threatening” refers to any AE that, as it occurs, puts the 
subject at immediate risk of death. It does not refer to an AE that hypothetically 
might have caused death if it were more severe.) 
• Requires hospitalization or prolonged current hospitalization (not including 
hospitalization for a pre-existing condition that has not increased in severity or 
frequency from the subject’s underlying medical condition prior to entry into the 
study) 
• Results in persistent or significant disability/incapacity 
• A congenital anomaly/birth defect 
• Judged to be medically significant by the Investigator 
(Note:  A medically significant AE is a medical event that may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject 
or require intervention to prevent one of the outcomes listed above). 
 
 
Reporting Unanticipated Adverse Device Effects 
A sponsor who conducts an evaluation of an UADE under §812.46(b) shall report the 
results of such evaluation to FDA and to all reviewing IRB
's and participating 
investigators within 10 business days after the sponsor first receives notice of the 
UADE. Thereafter the sponsor shall submit such additional reports concerning the 
effect as FDA requests. The site will complete an UADE event eCRF form within 24 
hours of the Investigator being notified of the UADE. The report will be scanned and 
emailed to clinical@alcresta.com and then forwarded for Alcresta Chief Medical Officer 
review.  
 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 36 of 47 
In addition, any event that results in a subject’s withdrawal from the study must be 
reported directly to the Alcresta Chief Medical Officer as soon as possible but no later 
than 24 hours. 
 
7.0 
STATISTICAL PROCEDURES AND DATA ANALYSIS 
 
General Considerations 
Data collected in this study will be presented using summary tables, subject data 
listings and figures. Summary tables will present data by subject and, if applicable, by 
study visit. Continuous variables w
ill be summarized using descriptive statistics, 
specifically the mean, median, standard deviation, minimum and maximum values. 
Categorical variables will be summarized by frequencies and percentages. Figures 
may be used to support the presentation of certain data. 
 
All available data w
ill be included in data listings.  No imputation of values for missing 
data w
ill be performed, unless otherw
ise specified.  The relevance of missing sample 
data w
ill be assessed. In the case of subject withdrawal from the study, data collected 
at the Day 30 and Day 60 time point will be employed in the analysis of that time point 
but those values w
ill not be carried forward. Data that are potentially spurious or 
erroneous will be examined according to data management standard operating 
procedures. 
 
Qualitative or descriptive data w
ill be analyzed to evaluate against safety and 
tolerability endpoints.  The potential influence of other covariates such as age, gender, 
ethnicity, height and weight will be examined. 
 
 
Determination of Sample Size 
The proposed study with 30 complete and evaluable subjects would have 80% power 
to detect a minimum effect size of 0.53. Based on literature reviews using 1.5% as the 
maximum standard deviation expected when measuring DHA levels, the study should 
be able to detect an absolute increase of at least 0.8% from the baseline DHA value 
after 90 days of Relizorb use (i.e., a change from 3.0% at baseline to 3.8% after 90 
administration days or a 27% relative increase). This sample size will be adequate to 
detect the desired 30% relative increase in DHA levels.  
 
 
Stopping Rules 
 
Relizorb is a low risk medical device, and the patient population under study is at 
relatively low risk for a severe adverse experience. Therefore, there are no prospective 
stopping rules for this study. 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 37 of 47 
 
The Alcresta Chief Medical Officer will review all UADEs as they occur. In addition, 
every 30 days all UADEs will be reviewed in aggregate starting from the first subject 
enrolled until the last subject has completed the study. Based on this planned 
surveillance, the Alcresta Chief Medical Officer will convene a teleconference w
ith the 
chair of the Data Safety Monitoring Board (DSMB) as soon as possible if any of the 
following occur: 
 
• Death of any subject in the study, regardless of causality, 
• Two occurrences of the same UADE where causality has been assigned to 
Relizorb use by the site PI, or more than three occurrences of the same UADE 
regardless of causality, 
• A trend emerges in the occurrence of similar UADEs. 
 
If either the Alcresta Chief Medical Officer or the chair of the DSMB has a concern 
regarding the safety of study subjects, the Chief Medical Officer will convene a 
teleconference with the DSMB and the site PIs as soon as possible to discuss the 
potential safety issue. Possible outcomes of the teleconference include: 
 
• Continuation of the study w
ith no change in study conduct if it is determined that 
there is no safety issue, 
• Placing the study on clinical hold until the study protocol can be modified to 
mitigate the safety issue, 
• Termination of the study. 
 
 
Randomization 
Randomization will not be used in this open label study. 
 
 
Populations for Analysis 
 
Per Protocol Population 
The per protocol population consists of all subjects who met the inclusion criteria, used 
Relizorb as stated in the protocol and IFU through at least Visit 3 (Day 30) and has not 
been the subject of any major protocol deviation. 
 
 
Safety Population 
The safety population includes all subjects who received at least one Relizorb 
exposure. For subjects who withdraw from the study, every effort will be made to 
retrieve all relevant safety information.  
 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 38 of 47 
 
Procedures for Handling Missing, Unused and Spurious Data 
All available safety and tolerability data will be presented in data listings and 
tabulations. No data imputation will be applied for missing values. The relevance of 
missing sample data will be assessed. Data that are potentially spurious or erroneous 
will be examined according to standard data management operating procedures. 
 
In the case of subject w
ithdrawal from the study, data collected at the Day 30 and Day 
60 time point will be employed in the analysis of that time point but those values will 
not be carried forward. 
 
 
Demographics and Baseline Characteristics 
Demographic and baseline characteristics will be summarized and presented overall. 
Demographic data to be evaluated w
ill include age, sex, ethnicity, height, weight and 
BMI. Demographic data will be presented in a by-subject listing. Age will be calculated 
from date of birth to date informed consent was obtained.  
 
 
Safety Analysis 
Safety will be assessed based on the incidence, severity, and type of AE and UADE, 
clinically significant changes or abnormalities in the subject’s clinical laboratory results 
and vital signs. For clinical laboratory tests, descriptive summaries of actual values and 
changes from the baseline will be presented. Descriptive statistics will be provided for 
vital sign measurements collected during clinic visits. 
 
AE and UADEs w
ill be recorded throughout the study and listed in summary tables in 
terms of severity and causal relationship to Relizorb use. Relationship assessments 
that indicate the AE is “Not Related” is an event related to etiology, rather than from 
Relizorb use. “Related” is defined as an association between the AE or UADE and 
Relizorb use. Other selections include “Possibly Related” and “Probably Related”. 
 
The gastrointestinal symptoms recorded in the 7 day gastrointestinal symptom diary 
during the run in period w
ill be compared with the symptoms recorded three separate 
times during the treatment period.  Each symptom will be categorized as a) occurring 
or not occurring b) rated as a 1,2, or 3 in severity, and lasting in duration for less than 
15 minutes, 15 to 30 minutes, 31 to 60 minutes, or greater than 60 minutes. 
   
For the comparison between symptoms recorded during the run in period and the 
treatment period, the following analyses will be performed: 
 
• Number of days where any symptom occurred; 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 39 of 47 
• Number of days each symptom occurred; 
• For each symptom, number of days when the severity was a 1, 2, and 3 
• For each symptom, number of days when the symptoms lasted in duration for 
less than 15 minutes, 15 to 30 minutes, 31 to 60 minutes, or greater than 60 
minutes. 
Comparison of these values during the run in and treatment periods w
ill be performed 
using analysis of variance (ANOVA). 
 
 
Efficacy Analysis 
The measurement of the absorption of fats is an important efficacy endpoint, using 
absorption of fatty acids as surrogate biomarkers for fat absorption. LCPUFA plasma 
concentrations such as DHA and EPA will be an outcome variable, along with tissue 
accretion of LCPUFAs, measured as relative levels in erythrocyte membrane, and the 
profile of fatty acids in plasma. The fatty acid profile will also be used to calculate the 
ratio of omega-6 to omega-3 fatty acids, another outcome variable. Fat-soluble vitamin 
(A, D, and E) concentration is an additional efficacy endpoint and will be used as a 
laboratory outcome variable. Serum protein (total protein, prealbumin, albumin, and 
transferrin) concentrations and urinary leukotriene concentrations are additional 
endpoints and also represent laboratory outcome variables. 
 
For all laboratory outcome variables, mean values from samples obtained on Day -14 
and Day 0 w
ill be compared using a two-sided test for comparison. The mean value 
from samples obtained on Day 0 will be used as the baseline for comparison with 
mean values from samples obtained on Days 30, 60, and 90 using ANOVA.  
 
Body weight, height, and BMI are endpoints and clinical outcome variables. Absolute 
change in body weight from Day 0 through Days 30, 60, and 90 w
ill be analyzed using 
ANOVA. To evaluate the effect of Relizorb use on weight and BMI, up to 4 weight and 
BMI recordings obtained from the medical record at 3 month intervals over the 
previous 12 months. The historical weight recordings will be used to calculate historical 
weight gain velocity, expressed as grams of body weight per kilogram of body weight 
per day. The study weight gain velocity will be similarly calculated by using the body 
weight values obtained on Days 0, 30, 60, and 90. The historical weight gain velocity 
will be compared to the study weight gain velocity using a two-sided test for 
comparison. In addition, the historical weight and BMI recordings, along with the weight 
and BMI values recorded on Day 0, will be used to calculate a standard score for 
weight and BMI values recorded on Days 30, 60, and 90. 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 40 of 47 
8.0 
STUDY COORDINATION AND MONITORING 
 
Site Principal Investigators and Study Administrative Structure 
The site PI will ensure that all persons assisting w
ith the study are adequately 
qualified, informed about the protocol and any amendments to the protocol, the study 
treatments and their study-related duties and functions. The site PI must maintain a list 
of subinvestigators and other appropriately qualified and trained individuals to whom 
significant study-related duties have been delegated. 
 
The site PI also certifies licensure to practice medicine in the state in which the study is 
conducted. Investigators are responsible for providing documentation of qualifications, 
GCP training, and current medical licensure and filing in a regulatory file. 
 
 
Institutional Review Board / Independent Ethics Committee 
The site PI will not begin the research study until the Institutional Review Board (IRB) 
or Independent Ethics Committee (IEC) that governs their participation has approved 
the protocol and ICF. The IRB/IEC will also review and approve all advertisements, if 
applicable. The site PI will forward a copy of the IRB/IEC approval document to 
Alcresta. Any protocol amendments must also be approved in writing by the IRB/IEC, 
prior to implementation by the site PI, except where necessary to eliminate an 
immediate hazard to study participants. 
 
The site PI will submit a progress report to the IRB/IEC at intervals of one year or less, 
as established by review committees. The site PI will retain a copy of this report in the 
Investigator’s Site File. 
 
 
Study Monitoring 
The monitoring plan and auditing procedures developed or approved by Alcresta will 
be followed to comply with current good clinical practices (cGCP) guidelines and 
applicable regulations. The site monitor will visit the site PI and study site at periodic 
intervals and maintain regular site communication. The site PI and study staff is 
expected to contact the site monitor directly, regarding clinical questions or clarification 
of protocol language. 
 
The site PI will prepare and maintain adequate and accurate source documents 
designed to record all observations and other pertinent data for each subject. The 
Investigator w
ill allow the Sponsor’s representatives, contract designees and 
authorized regulatory authority inspectors to have direct access to all source 
documents and medical records pertaining to the subject prior to and during the 
conduct period of the study. Access to patient records after participation in the study is 
complete may be required to follow resolution of AEs and UADEs. 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 41 of 47 
 
 
Onsite Audits 
Regulatory authorities, the IRB/IEC, and Alcresta (or Alcresta’s contract vendor) may 
request access to all source documents, eCRFs and other study documentation for on-
site audit or inspection. The site PI must guarantee direct access to these documents. 
Medical records and other study documents may be copied during an audit or 
inspection, provided that subject names are obliterated on the copies to ensure 
confidentiality. 
 
 
Study Device Accountability 
 
Alcresta or its contracted vendor will arrange for shipments of the investigational 
device to the study sites and Peptamen 1.5 and Impact Peptide 1.5 to the subject’s 
home. An inventory of package contents will accompany each shipment of clinical 
research materials and ancillary supplies. The study coordinator or designee must 
receive the study material delivery, review the inventory, complete the record of receipt 
and ensure clinical research materials are properly stored in a secure, controlled, 
environmentally appropriate location and safely handled. Copies of all shipping 
receipts and dispensing records for the cartridges must be retained at site as part of 
required device accountability. 
 
Accountability for the number of investigational devices dispensed at the study site is 
the responsibility of the site PI and study staff. Accountability records must indicate 
delivery to the site, a record of inventory, use by each subject and amount returned to 
Alcresta or designee. Study staff must provide the site monitor with records of the 
disposition of all investigational devices. The site monitor will account for the 
dispensation of clinical research study materials at the site and review Relizorb 
accountability. Accountability of all used and unopened Relizorb packages should 
occur on an ongoing basis. The site monitor will attempt to resolve any discrepancies 
of clinical research materials w
ith the study coordinator or designee. On-site disposal 
of Relizorb will not be permitted unless previously authorized by Alcresta. 
 
 
Patient Information and Informed Consent 
The site PI will obtain IRB/IEC written approval of the ICF (including approval of 
revisions) to be provided to the patients, inclusive of assent for minors 7 to 17 years of 
age. Prior to study entry, the site PI or an authorized staff member will inform patients 
about the nature of the study. Patients and/or parent/caregivers w
ill have the 
opportunity to inquire about details of the study and to decide on participation. Patients 
will be instructed that they are free to withdraw from study participation at any time, 
without penalty or loss of benefits to which they are otherw
ise entitled.  
 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 42 of 47 
Patients will also be given information regarding Health Insurance Portability and the 
Accountability Act, either in a separate consent form or as a separate section 
contained within the ICF. The Investigator w
ill inform patients of new information that 
may be relevant to their willingness to continue study participation. The Investigator will 
provide each patient with a copy of the signed and dated ICF and record it was given 
to the patient in the source documents. 
 
 
Patient Confidentiality 
To maintain patient privacy, all eCRFs, device accountability records, study reports 
and communications w
ill identify the patient by initials and assigned identification 
number. The patient’s confidentiality will be maintained and their identity will not be 
made publicly available, to the extent permitted by applicable laws and regulations.  
  
Patient data stored on a computer will be handled in accordance w
ith local data 
protection laws. Patients will be informed that representatives of the Sponsor, IRB/IEC, 
or regulatory authorities may inspect their medical records to verify information 
collected and that all personal information made available for inspection will be 
handled in strictest confidence and in accordance w
ith local data protection laws. 
 
 
Investigator Compliance 
The site PI will not alter/modify this clinical study protocol without obtaining appropriate 
prior written agreement from Alcresta and the IRB/IEC. In the event of an emergency, 
the site PI shall implement any medical procedures deemed appropriate. However, all 
such procedures must be promptly reported to the Sponsor and appropriately 
documented in the source documents for this study. 
 
By signing the Investigator’s Agreement page of this protocol, the site PI confirms in 
writing that he/she has read, understands and will strictly adhere to the study protocol, 
and will conduct the study in accordance w
ith ICH Guidelines for GCP and applicable 
regulatory requirements. By signing page 2, the site PI commits to ensuring that all site 
staff involved in the execution of this study are qualified and properly trained to perform 
their assigned responsibilities. 
 
9.0 STUDY COMPLETION PROCEDURES 
 
Completion of Study 
At the end of the study, Alcresta will provide written documentation to all investigative 
sites and central IRBs that the study is closed. The site monitor will conduct close-out 
visits and ensure that IRB/IEC are notified of study closure. 
 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 43 of 47 
 
Records Retention 
The site PI must maintain all study records, according to ICH-GCP, and applicable 
regulatory requirements. Records will be retained and preserved until: 
• At least two years after the last marketing application approval or Alcresta has 
discontinued research w
ith Relizorb or 
• At least two years since the formal discontinuation of clinical development of 
Relizorb. 
 
These documents will be retained for a longer period if required by the applicable 
regulatory requirements or the hospital, institution or private practice in which the study 
is being conducted. At the end of the above periods, the site PI will notify Alcresta in 
writing of the intent to destroy study records. Alcresta shall have 30 days to respond to 
the site PI
’s notification and may assume payment for continued record retention. 
 
Custody of the records may be transferred to another responsible site PI, deemed 
acceptable to Alcresta, who agrees to abide by the retention policies. Written notice of 
transfer must be submitted to the Sponsor and to the site’s IRB/IEC. The site PI must 
contact Alcresta prior to disposing of any study records. 
 
 
Communication of Study Results 
All information regarding use of Relizorb, the protocol and all other study materials are 
privileged and confidential information. The site PI agrees to use this information to 
execute the study and w
ill not use it for other purposes, without consent from Alcresta. 
 
It is anticipated that the results of this study will be presented at medical conferences 
and will be available in scientific publications or medical journals. 
 
Publication by the site of any data from this study is strictly prohibited. Any exceptions 
must be carried out in accordance with the Clinical Trial Agreement. 
  
 
Ethics 
This study will be conducted in accordance w
ith applicable standards of GCP (21 Code 
of Federal Regulations Part 812), in agreement w
ith the Declaration of Helsinki and in 
keeping with federal and local regulations. The IRB/IEC will review all appropriate 
study documentation to safeguard the rights, safety and well being of patients. This 
study will only be conducted at sites where IRB/IEC approvals have been obtained. 
The site PI will be thoroughly familiar with the proper use of Relizorb as described in 
the protocol, and the corresponding Investigator’s Brochure. 
 
 
 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 44 of 47 
10.0 REFERENCES 
1. Al-Kaade, S, et al. Exocrine pancreatic insufficiency. eMedicine Medscape. 
[Online] Jan 29, 2013. http://emedicine.medscape.com/article 
 
2. Zoppi G, et al. Exocrine pancreas function in premature and full term neonates. 
Pediatric Research 1972; 6:880-886 
 
3. Figarella C, et al. Congenital pancreatic lipase deficiency. The Journal of 
Pediatrics 1980; 96(3):412-416 
 
4. http://www.nim.nih.gov/medlineplus/pancreaticcancer.html 
 
5. Fleith M, et al. Dietary PUFA for preterm and term infants: review of clinical 
studies. Critical Reviews in Food Science and Nutrition 2005; 45(3):205-229 
 
6. Guyton A, Hall JE. Textbook of medical physiology. Edition 11, s.l.: Elsevier, 
2006; 808-819 
 
7. Russell, FD, et al. Distinguishing health benefits of eicosapentaenoic and 
docosahexaenoic. Marine Drugs 2012; 10:2535-2559 
 
8. M-P. St-Onge, P.J.H. Jones (2003). "Greater rise in fat oxidation with medium-
chain trigylceride consumption relative to long-chain triglyceride is associated 
with lower initial body weight and greater loss of subcutaneous adipose tissue". 
International Journal of Obesity 27 (12): 1565-1571 
 
9. Kidd, PM. Omega-3 DHA and EPA for cognition, behavior and mood: clinical 
findings and structural-functional synergies with cell membrane phospholipids. 
Alternative Med Review 2007; 12:3 
 
10. 
Kiecolt-Glaser JK. Stress, Food, and Inflammation: Psychoneuroimmunology 
and Nutrition at the Cutting Edge. Biol Psychiatry. 2014 Dec 8. pii: S0006-
3223(14) 00966-4 
 
11. 
Oliveira G. Serum phospholipid fatty acid profile and dietary intake in an adult 
Mediterranean population with cystic fibrosis. British Journal of Nutrition (2006), 
96, 343-349 
 
12. 
Lloyd-Still JD et al. Bioavailability and safety of a high dose of docosahexaenoic 
acid triacyglycerol of algal origin in cystic fibrosis patients: a randomized 
controlled study. Nutrition 22 (2006) 36-46 
 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization 
Page 45 of 47 
13. 
Kalivianaki M et al. Fat malabsorption in cystic fibrosis patients receiving 
enzyme replacement therapy is due to impaired intestinal uptake of long-chain 
fatty acids. Am J Clin Nutr 1999; 69:127-34 
 
14. 
Alcresta abstract. Novel immobilized lipase device (EFIC™) enhances the 
nutritional benefits of enteral feeding and provides greater flexibility for shorter 
duration feedings and reduced volumes. Abstract for ECSF 2015 accepted as 
oral presentation 
 
15. 
Alcresta report #0000452-03. 24h pharmacodynamic profile of total fat and fatty 
acid after single G-tube feeding with EFIC pre-hydrolyzed Peptamen AF, BF-03 
study 
 
16. 
Alcresta report #0000450-04. Long-term, 12 days efficiency study in EPI pigs 
fed w
ith G-tube EFIC pre-hydrolyzed Peptamen AF, BF-03 study 
 
17. 
Alcresta report #0000164-02. Testing the efficacy of microbial lipase for 
digestion of long-chain polyunsaturated fatty acid (LCPUFA) in the infant 
formula in young pigs with total pancreatic insufficiency, BF-02 study 
 
18. 
Alcresta report #0000134-01. Histopathology evaluation to Alcresta Inc. study   
number BF-02 2012 (Testing the efficacy of immobilised Rhizopus oryzae 
lipases for digestion of long chain polyunsaturated fatty acid (LCPUFA) in the 
infant formula fed young pigs with total pancreatic insufficiency BF-02 study 
 
19. 
Alcresta report #0000293-01. A Randomized, Double Blind Crossover Study in 
Healthy Adult Subjects to Evaluate Safety, Tolerability, and Rate and Extent of 
Absorption of Long-Chain Polyunsaturated Fatty Acids (LCPUFAs) from a 
Nutritional Drink Pre-hydrolyzed by Exposure to ALCT-460 
 
20. 
Alcresta report #0000749-01. Clinical Study Report: Protocol 0000135-07. A 
Randomized, Double-Blind Crossover Study to Evaluate Safety, Tolerability, 
and Rate and Extent of Absorption of Long-Chain Polyunsaturated Fatty Acids 
After Exposure to ALCT-460 in Pancreatic Insufficient Subjects 
 
 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
 
 Page 46 of 47 
11.0 APPENDICES 
 Peptamen® 1.5 Nutrition Information - Unflavored (Nestle Health 
Science) 
 
 
One bottle equals 250 mL (1Carton) 
Amount Per Serving 
Unit 
Amount Amount per Serving 
Unit 
Amount  
Calories 
Kcal 
375 
Total Fat * 
g 
14 
Sodium 
mg (mEq) 
 255 
(11.1) 
Potassium 
mg (mEq) 
465 (12) 
Total Carbohydrate 
G 
 46 
Protein 
g 
17 
Vitamin A** 
IU 
1615 
Vitamin C 
mg 
128 
Calcium 
Mg 
250 
Iron 
mg 
6.75 
Vitamin D 
IU 
200 
Vitamin E 
IU 
11.3 
Vitamin K 
Mcg 
30 
Thiamin 
mg 
0.75 
Riboflav
in 
Mg 
0.9 
Niacin 
mg 
10.5 
Vitamin B6 
Mg 
1.5 
Fol
ic Acid 
mcg 
200 
Vitamin B12 
Mcg 
3 
Biotin 
mcg 
150 
Pantothenic Acid 
Mg 
5.25 
Phosphorus 
mg 
250 
Iodine 
Mcg 
56 
Magnesium 
mg 
100 
Zinc 
Mg 
9 
Selenium 
mcg 
19 
Copper 
Mg 
0.75 
Manganese 
mg 
1 
Chromium 
Mcg 
15 
Molybdenum 
mcg 
45 
Chloride 
mg (mEq) 
435 (12.3) L-Carnitine 
mg 
37.5 
Taurine 
Mg 
37.5 
Choline 
mg 
170 
Water 
mL 
193 
 
 
 
*  
MCT provides 10 g/250 mL 
** Includes 37% of vitamin A activity from beta-carotene 
 
 
Ingredients of Peptamen
® 1.5 (Unflavored): 
Water, Maltodextrin, Enzymatically Hydrolyzed Whey Protein (from M
ilk), Medium Chain Triglycerides (from 
Coconut and/or Palm Kernel Oil), and less than 2% of Cornstarch, Soybean Oil, Soy Lecithin, Magnesium 
Chloride, Sodium Ascorbate, Sodium Phosphate, Calcium Phosphate, Guar Gum, Calcium Citrate, Choline 
Chloride, Potassium Chloride, Salt, Sodium Citrate, Taurine, L-Carnitine, Magnesium Oxide, Alpha-Tocopheryl 
Acetate, Zinc Sulfate, Ferrous Sulfate, Niacinamide, Calcium Pantothenate, Vitamin A Palmitate, Potassium 
Citrate, Manganese Sulfate, Pyridox
ine Hydrochloride, Vitamin D3, Copper Sulfate, Thiamine Mononitrate, 
Riboflavin, Beta Carotene, Folic Acid, Biotin, Citric Acid, Potassium Iodide, Chromium Chloride, Sodium 
Selenate, Sodium Molybdate, Phytonadione, Vitamin B12. 
 

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
 
 Page 47 of 47 
 Impact Peptide 1.5 Nutrition Information - Unflavored (Nestlé Healthcare 
Nutrition)  
 
 One bottle equals 250 mL (1 Carton is 8.45 ounces) 
Amount Per Serving 
Unit 
Amount 
Amount per Serving 
Unit 
Amount  
Calories 
cal 
375 
Total Fat * 
g 
15.9 
MCT 
g 
7.8 
MCT/LCT ratio 
50:50 
DHA+EPA 
g 
1.225 
Sodium 
mg 
292 
Potassium 
mg 
468 
Carbohydrate 
g 
35 
Protein 
g 
23.5 
Vitamin A 
IU 
3750 
Vitamin C  
mg 
250 
Calcium 
mg 
250 
Iron 
mg 
4.5 
Vitamin D 
IU 
200 
Vitamin E 
IU 
25 
Vitamin K 
mcg 
18.7 
Thiamine (Vitamin B1) 
mg 
0.75 
Riboflav
in (Vitamin B2) 
mg 
0.6 
Niacin 
mg 
7 
Vitamin B6 
mg 
1 
Vitamin B12 
mcg 
2 
Biotin 
mcg 
100 
Pantothenic Acid 
mg 
3.5 
Phosphorus 
mg 
250 
Iodine 
mcg 
40 
Magnesium 
mg 
105 
Zinc 
mg 
9 
Selenium 
mcg 
25 
Copper 
mg 
0.75 
Manganese 
mg 
1 
Chromium 
mcg 
35 
Molybdenum 
mcg 
55 
Chloride 
mg 
435 
Choline 
mg 
138 
Fol
ic Acid 
mcg 
135 
L-Carnitine 
mg 
37.5 
Taurine 
mg 
70 
 
 
 
Ingredients of Impact
® Peptide 1.5 (Unflavored): 
Water, Maltodextrin, Enzymatically Hydrolyzed Whey Protein (from Milk), Medium Chain 
Triglycerides (from Coconut and/or Palm Kernel Oil), contains less than 2% of L-Arginine 
Cornstarch, Refined Fish Oil (Anchovy, Sardine), Soybean Oil, Citric Acid, Calcium Citrate, 
Yeast Extract, Magnesium Chloride, Potassium Phosphate, Ascorbic Acid, Salt, Hdroxy
lated 
Soy Lecithin, Sodium Citrate, Choline Chloride, Guar Gum, Xanthan Gum, Potassium 
Citrate, Taurine, Magnesium Oxide, Sodium Ascorbate, Alpha-Tocophery
l Acetate, 
L-Carnitine, Zinc Sulfate, Ferrous Sulfate, Niacinamide, Vitamin A Palmitate, Calcium 
Pantothenate, Manganese Sulfate, Vitamin D3, Copper Sulfate, Pyridoxine Hydrochloride, 
Beta Carotene, Thiamine Mononitrate, Riboflavin, Folic Acid, Chromium Chloride, Biotin, 
Sodium Molybdate, Potassium Iodide, Sodium Selenate, Phytonadione and Vitamin B12.

Alcresta Pharmaceuticals, Inc. 
Document Number: 0000498 VER. 02 
Document Status: Approved/Effective 
Effective Date: 09-Mar-2016 
 
Title:  Absorption and Safety with Sustained Use of Relizorb™ Evaluation (Assure) Study in 
Patients With Cystic Fibrosis Receiving Enteral Feeding 
 
Confidential Information - Do Not Reproduce Without Authorization