Clinical trial NCT03712124
Conditions: Gastroparesis
Sponsor: PTC Therapeutics
Start date: 2019-02-27; Completion date: 2019-10-08
Enrollment: 21 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study evaluates CNSA-001 (sepiapterin) in the treatment of women with moderate to severe diabetic gastroparesis. Participants will be randomized in a ratio of 1:1 to receive CNSA-001 20 (milligrams) mg/kilogram (kg)/day or placebo. All participants will receive the standard of care for diabetic gastroparesis.

Detailed description:
Nerves throughout the luminal gastrointestinal (GI) tract express neuronal nitric oxide synthase (nNOS), which generates nitric oxide (NO), a key neurotransmitter in the regulation of GI motility. Several co-factors are known to be important for nNOS activity, including nicotinamide adenine dinucleotide phosphate hydrogen (NADPH), calcium, and tetrahydrobiopterin (BH4). The homodimeric conformation of all 3 isoforms of nitric oxide synthase (NOS) is regulated by BH4. In the absence of BH4, uncoupling of NO production occurs and leads to super oxide production, resulting in further impaired nNOS bioactivity.

CNSA-001 is a new chemical entity that is an endogenous, naturally occurring precursor of BH4 via the pterin salvage pathway. Oral administration of CNSA-001 will result in increases in both intracellular and circulating BH4 concentrations. Increased BH4 concentration is hypothesized to improve nNOS function resulting in a positive effect on gastric accommodation and emptying.

Arms: arm 1: Participants will receive CNSA-001 20 mg/kg/day (10 mg/kg twice daily \[BID\]) as an oral suspension for 14 days. arm 2: Participants will receive placebo matching to CNSA-001 BID for 14 days.
Interventions: intervention 1: CNSA-001 intervention 2: Placebo
Intervention descriptions: intervention 1: CNSA-001 Powder for Suspension intervention 2: Placebo Suspension

Protocol documents:
Prot_000.pdf: 
CNSA-001 (sepiapterin)         
     Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001         
      Page 1 
FINAL 06SEP2018 
CONFIDENTIAL 
CLINICAL TRIAL PROTOCOL 
Study Title: 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Pilot Study of 
CNSA-001 in Women With Moderate to Severe Diabetic Gastroparesis 
Study Number: 
GAS-001 
Study Phase: 
2 Pilot 
Product Name: 
CNSA-001 (sepiapterin)  
Dosage Form:  
Oral powder for suspension 
Indication: 
Treatment of women with moderate to severe diabetic gastroparesis 
Investigators: 
Multicenter study  
Sponsor: 
Censa Pharmaceuticals 
65 William Street 
Wellesley, MA 02481 
Sponsor Contact: 
 
Medical Monitor: 
 
Date 
Original Protocol: 
06 September 2018 
Confidentiality Statement 
The confidential information in this document is provided to you as an Investigator or consultant for 
review by you, your staff, and the applicable Institutional Review Board/Independent Ethics 
Committee. Your acceptance of this document constitutes agreement that you will not disclose the 
information contained herein to others without written authorization from the Sponsor.  
NCT03712124




CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 3 
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INVESTIGATOR’S SIGNATURE 
Study Title: 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Pilot Study 
of CNSA-001 in Women With Moderate to Severe Diabetic 
Gastroparesis 
Study Number: 
GAS-001 
Final Date: 
06 September 2018 
I have read the protocol described above. I agree to comply with all applicable regulations 
and to conduct the study as described in the protocol. 
 
 
 
Signature 
 
Date (DD Month YYYY) 
 
 
 
Printed Name, Credentials 
 
 
 
 
 
Affiliation 
 
 
 
 
 
Address 
 
 
 
 
 
Phone Number 
 
 
 
 
 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 4 
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SYNOPSIS 
Sponsor: 
Censa Pharmaceuticals 
Name of Finished Product: 
CNSA-001 
Name of Active Ingredient: 
Sepiapterin 
Name of Inactive Ingredients: 
Microcrystalline cellulose, colloidal silicon dioxide, croscarmellose, and ascorbic acid 
Study Title: 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Pilot Study of CNSA-001 in Women 
With Moderate to Severe Diabetic Gastroparesis 
Study Number: 
GAS-001 
Study Phase: Phase 2 pilot 
Primary Objective: 
 
To assess the impact of CNSA-001 on gastric accommodation, as measured by nutrient 
satiety testing, in women with moderate to severe diabetic gastroparesis 
Secondary Objectives: 
In women with moderate to severe diabetic gastroparesis: 
 
To evaluate improvement of gastroparesis symptoms measured by global assessment of 
symptoms and symptom severity (Gastroparesis Cardinal Symptom Index [GCSI]) 
(Section 6.8, Appendix 2) 
 
To evaluate patient-reported outcomes (PROs) as measured by the quality of life 
questionnaire Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity 
(PAGI-SYM) (Section 6.9, Appendix 2)  
 
To evaluate the emptying of the stomach as measured by the Gastric Emptying Breath Test 
(GEBT) 
 
To assess the safety and tolerability of CNSA-001 20 mg/kg/day 
Study Design: 
This is a Phase 2, randomized, double-blind, placebo-controlled pilot study of multiple doses of 
CNSA-001 (sepiapterin) powder for suspension administered orally in women with moderate to 
severe diabetic gastroparesis. Patients will be randomized in a ratio of 1:1 to receive CNSA-001 
20 mg/kg/day or placebo, each dosed twice a day (BID); each group will consist of 10 patients. All 
patients will receive the standard of care for diabetic gastroparesis. Approximately 4 centers will 
participate in this study. The study design is summarized in the study schema below. A schedule of 
study events is provided in Appendix 1. 
All study clinic visits will be outpatient visits.  
Patients will continue their usual diet without modification throughout the study. Patients are required 
to have been fasting overnight for the following assessments:  
 
Clinical laboratory, including glycosylated hemoglobin A1c (HbA1c), tests  
 
The nutrient satiety test 
 
The GEBT  


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 5 
FINAL 06SEP2018 
 
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Screening Period (Day -28 Through Day 1 Predose): 
An informed consent form (ICF) must be signed before any study-related procedures are performed. 
After providing consent, patients will undergo Screening procedures to determine study eligibility, as 
indicated in Appendix 1. Patients who are eligible based on Screening evaluations will undergo 
baseline evaluations before initiation of study drug (CNSA-001 or placebo), be randomized, and 
proceed to the Treatment Period.  
Treatment Period (Day 1 Through Day 14) 
Following the Screening Period and completion of baseline evaluations, all randomized patients will 
take their first dose of study drug (CNSA-001 or placebo) on Day 1 while in the clinic. Patients will 
undergo procedures during the Treatment Period as indicated in Appendix 1. 
End of Treatment Period (Day 14 Through Day 15 Evaluations) 
Patients will undergo End of Treatment (EOT) evaluations on Day 14 and Day 15 as indicated in 
Appendix 1. Preliminary efficacy will be assessed by the changes from Day 1 in the nutrient satiety 
test on Day 14. The GCSI (Section 6.8, Appendix 2) and PAGI-SYM (Section 6.9, Appendix 2) will 
also be administered on Day 14 (+1 day), and the GEBT will be conducted on Day 15. 
End of Study Period (Day 15 After Evaluations Through Day 28 [±1 Day] Evaluations) 
Patients will undergo End of Study evaluations on Day 28 (±1 day) as indicated in Appendix 1. 
Preliminary efficacy will be assessed by the changes from Day 1 in the nutrient satiety test on Day 28. 
The GCSI (Section 6.8, Appendix 2) and PAGI-SYM (Section 6.9, Appendix 2) will also be 
administered on Day 28 ±1, and the GEBT will be conducted on Day 27 or Day 29. 
Follow-up Period (Day 28 [±1 Day] After Evaluations Through Day 44 [±3 Days]) 
Patients will undergo telephone Follow-up on Day 44 ±3 days as indicated in Appendix 1.  


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 6 
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Number of Patients: 
Up to 20 women ≥18 and ≤65 years of age will be enrolled in this study and randomized in a ratio of 
1:1 to receive CNSA-001 or placebo.  
Main Criteria for Inclusion and Exclusion: 
Patients are eligible to participate if they meet all the following inclusion criteria: 
1. Informed consent 
2. Females ≥18 and ≤65 years of age 
3. Diagnosis of diabetes mellitus  
4. Documentation of delayed gastric emptying on gastric emptying scintigraphy (within 1 year of 
enrollment) 
5. Symptoms of gastroparesis for at least 6 months with GCSI (Section 6.8, Appendix 2) score 
>21 indicating moderate to severe symptoms 
6. Gastric accommodation, as measured by nutrient satiety testing, of ≤600 mL 
7. Negative upper endoscopy or upper gastrointestinal (GI) series within 3 years of enrollment 
(no evidence of mechanical obstruction or peptic ulcer disease) 
8. Either postmenopausal for ≥1 year or surgically sterile (having undergone tubal ligation, 
hysterectomy, or bilateral oophorectomy) for at least 6 months or, if of childbearing potential 
and not abstinent, willing to use a highly effective method of contraception throughout the 
study such as 1 of the following: 
 
Hormonal contraception (stable dose for 3 months) 
 
Intrauterine device/Intrauterine Hormone-releasing System 
 
Barrier contraceptive method (diaphragm, cervical cap, contraceptive sponge, condom) 
Patients who are abstinent will not be required to use a contraceptive method unless they 
become sexually active. 
9. If on analgesics, including narcotics; promotility agents, including metoclopramide, or 
neuromodulators, including tricyclic antidepressants, gabapentin, and pregabalin, doses are 
stable for >30 days before randomization and the patient is not expected to require dose 
changes during the study through the EOT 
10. Have not used tobacco (e.g., cigarettes, e-cigarettes, cigars, smokeless tobacco, nicotine 
replacement) for 2 weeks prior to Day 1 and willingness to abstain from these products during 
the study through the EOT 
Patients are not eligible to participate if they meet any of the following exclusion criteria:  
1. Male gender 
2. Normal gastric emptying  
3. Gastroparesis from postsurgical etiologies 
4. Another active disorder that could, in the opinion of the Investigator, explain symptoms  
5. Weight >100 kg 
6. Alanine aminotransferase > 2× upper limit of normal (ULN) 
7. Pregnant, breastfeeding, or considering pregnancy 
8. Clinically significant cardiac arrhythmia at Screening 
9. QT interval corrected for heart rate (QTc) ≥480 msec (based on triplicate measurements taken 
at Screening)  
10. Recent clinically GI significant bleeding 
11. Taking levodopa or domperidone within 30 days before randomization or expected to require 
domperidone during the study through the EOT 
12. Taking erythromycin within 30 days before randomization or expected to require erythromycin 
within 30 days before randomization or expected to require erythromycin during the study 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 7 
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CONFIDENTIAL 
through the EOT; if a patient is taking erythromycin and is otherwise eligible to participate in 
the study, following signing the ICF, the patient may go through an erythromycin washout 
period of 30 days before randomization 
13. Taking any fundic-relaxing agents including, but not limited to, buspirone, clonidine, nitrates, 
phosphodiesterase inhibitors (i.e., sildenafil citrate [Viagra®]) and triptan-containing 
medications, within 30 days before randomization or expected to require any of these agents 
during the study through the EOT 
14. Taking any systemic antifolates, including, but not limited to, methotrexate, pemetrexed, and 
trimetrexate or expected to require any systemic antifolates during the study through the EOT 
(topical antifolates [e.g., cream, ointment, gel] or eye drops with antifolates are allowed) 
15. Pulmonary dysfunction (e.g., chronic obstructive pulmonary disease) 
16. Surgery for placement of a gastric stimulator within the past 6 months (patients postoperative 
>6 months with persistent symptoms and delayed gastric emptying are eligible) 
17. Gastrointestinal disease (such as irritable bowel syndrome, inflammatory bowel disease, 
chronic gastritis, peptic ulcer disease, small bowel malabsorption) that could affect the 
absorption of study drug or contraindicate undergoing the GEBT 
18. History of gastric surgery, including Roux-en-Y gastric bypass surgery or an antrectomy with 
vagotomy, or gastrectomy 
19. History of allergies or adverse reactions to tetrahydrobiopterin or related compounds, to any 
excipients in the study drug formulation, or to egg, wheat, or algae (Spirulina)  
20. Inability to tolerate oral medication 
21. Current participation in any other investigational drug study or use of any investigational agent, 
investigational device, or approved therapy for investigational use within 30 days or 
5 half-lives (whichever is longer) before Screening 
22. Any clinically significant laboratory abnormality; in general, each laboratory value from 
Screening and baseline chemistry and hematology panels should fall within the limits of the 
normal laboratory reference range unless deemed not clinically significant by the Investigator 
23. Major surgery within the previous 90 days  
24. The patient, in the opinion of the Investigator, is unwilling or unable to adhere to the 
requirements of the study 
25. History of alcohol or drug abuse within 6 months prior to Screening or current evidence of 
substance dependence as determined by the Investigator 
26. Episodes of ketoacidosis or hypoglycemia that are frequent as defined by the Investigator 
27. Any other conditions, including diabetic comorbidities, that, in the opinion of the Investigator 
or Sponsor, would interfere with the patient’s ability to participate in the study or increase the 
risk of participation for that patient 
Test Product, Dose, and Mode of Administration: 
The test product is CNSA-001 (sepiapterin) oral powder for suspension. CNSA-001 will be 
suspended in Medisca® Oral Mix prior to dispensing to the patient. Patients randomized to receive 
CNSA-001 will receive CNSA-001 20 mg/kg/day (i.e., 10 mg/kg BID) for 14 days. 
Reference Therapy; Dose; and Mode of Administration: 
The reference product is placebo. The placebo is a ready-made suspension containing 
microcrystalline cellulose, colloidal silicon dioxide, croscarmellose, ascorbic acid, and colorant 
(Yellow No. 6) that is suspended in Medisca® Oral Mix.  
Duration of Treatment: 
Patients will be treated for a total of 14 days.  


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 8 
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Criteria for Evaluation: 
Safety: 
Safety and tolerability of CNSA-001 as measured by severity and number of treatment-emergent 
adverse events (TEAEs), including assessment of severity of TEAEs, and changes in clinical 
laboratory and HbA1c tests, vital signs, and physical examinations 
Efficacy: 
The primary efficacy measure will be the change in maximal tolerated volume consumed during the 
nutrient satiety test from Day 1 to Day 14 and Day 1 to Day 28. 
Secondary efficacy measures will consist of changes in the following from baseline to Day 14 and 
baseline to Day 28 (±1 day):  
 
GCSI (Section 6.8, Appendix 2) PAGI-SYM (Section 6.9, Appendix 2) subscale 
(heartburn/regurgitation, fullness/early satiety, nausea/vomiting, bloating, upper abdominal 
pain, and lower abdominal pain) scores 
 
Gastric emptying as measured by the GEBT  
Statistical Methods: 
The following study populations will be analyzed: 
 
Safety population: all patients who were randomized and received any amount of study drug 
(CNSA-001 or placebo) 
 
Efficacy population: all patients who were randomized, received any amount of study drug 
(CNSA-001 or placebo), and had available Day 1 and Day 14 nutrient satiety test maximum 
tolerated volume results  
Safety will be assessed in the Safety population. Adverse events (AEs) will be coded using the 
Medical Dictionary for Regulatory Activities (MedDRA®). The number and percentage of patients 
with TEAEs will be tabulated by system organ class, preferred term, and treatment group. Severity of 
AEs and serious adverse events (SAEs) will be summarized similarly. Those AEs leading to 
premature discontinuation from the study drug and the serious TEAEs will be presented in a table or a 
listing. Clinical laboratory and HbA1c test results and vital signs will be summarized at each visit as 
will changes from baseline for each treatment group. A frequency distribution of abnormal physical 
examination results will be provided. 
Efficacy will be assessed in the Efficacy population. The changes from Day 1 to Day 14 and from 
Day 1 to Day 28 in maximal tolerated volume consumed during the nutrient satiety test will be 
compared between treatment groups using a student’s t-test. Results from the nutrient satiety test 
through Day 14 and Day 28, the GEBT through Day 15 and Day 27 or Day 29, and the GCSI 
(Section 6.8, Appendix 2) and PAGI-SYM (Section 6.9, Appendix 2) through Day 14 (+1) and 
through Day 28 (±1) will be summarized using summary statistics (number of patients, mean, 
standard deviation, median, and range) at each visit as well as changes from baseline within each 
treatment group. The 95% confidence intervals for the changes from baseline will be provided. 
Additional analyses may be conducted, and details will be provided in the statistical analysis plan. 
Date of Original Protocol: 06 September 2018 
 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 9 
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CONFIDENTIAL 
TABLE OF CONTENTS 
CLINICAL TRIAL PROTOCOL ..............................................................................................1 
SPONSOR SIGNATURES ........................................................................................................2 
INVESTIGATOR’S SIGNATURE ...........................................................................................3 
SYNOPSIS .................................................................................................................................4 
TABLE OF CONTENTS ...........................................................................................................9 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ..........................................12 
1 
INTRODUCTION .................................................................................................15 
1.1 
Diabetic Gastroparesis .....................................................................................15 
1.2 
Impaired Gastric Accommodation in Gastroparesis ........................................16 
1.3 
Current Treatment of Diabetic Gastroparesis ..................................................16 
1.4 
CNSA-001 (Sepiapterin) ..................................................................................17 
1.5 
Rationale for Study ..........................................................................................17 
2 
STUDY OBJECTIVES ..........................................................................................19 
2.1 
Primary Objective ............................................................................................19 
2.2 
Secondary Objectives.......................................................................................19 
3 
INVESTIGATIONAL PLAN ................................................................................20 
3.1 
Overall Study Design and Plan ........................................................................20 
3.2 
Rationale for Study Design and Control Group ...............................................21 
3.3 
Study Duration and Dates ................................................................................22 
4 
STUDY POPULATION SELECTION .................................................................23 
4.1 
Study Population ..............................................................................................23 
4.2 
Inclusion Criteria .............................................................................................23 
4.3 
Exclusion Criteria ............................................................................................24 
5 
STUDY TREATMENTS .......................................................................................26 
5.1 
Description of Treatments................................................................................26 
5.1.1 
Test Product .........................................................................................26 
5.1.2 
Placebo Control ....................................................................................26 
5.2 
Treatments Administered .................................................................................26 
5.3 
Selection and Timing of Dose for Each Patient ...............................................26 
5.4 
Method of Assigning Patients to Treatment Groups........................................27 
5.5 
Blinding............................................................................................................27 
5.6 
Concomitant Therapy.......................................................................................27 
5.7 
Restrictions ......................................................................................................28 
5.7.1 
Prior Therapy and Concomitant Therapy ............................................28 
5.7.2 
Food Intake ..........................................................................................29 
5.7.3 
Total Blood Volume ............................................................................29 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 10 
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5.7.4 
Patient Activity and Tobacco Restrictions ...........................................29 
5.8 
Treatment Compliance .....................................................................................29 
5.8.1 
Dosing Diary ........................................................................................29 
5.9 
Packaging and Labeling ...................................................................................30 
5.10 
Storage and Accountability ..............................................................................30 
5.11 
Investigational Product Retention at Study Site ..............................................30 
6 
STUDY PROCEDURES .......................................................................................31 
6.1 
Informed Consent.............................................................................................31 
6.2 
Medical History and Demographic Data .........................................................31 
6.3 
Vital Signs, Weight, and Height ......................................................................31 
6.4 
Physical Examination.......................................................................................31 
6.5 
Clinical Laboratory Tests and Glycosylated Hemoglobin A1c .......................31 
6.6 
Electrocardiogram ............................................................................................32 
6.7 
Nutrient Satiety Test ........................................................................................33 
6.8 
Gastroparesis Cardinal Symptom Index ..........................................................33 
6.9 
Patient Assessment of Upper Gastrointestinal Disorders-Symptom 
Severity ............................................................................................................33 
6.10 
Gastric Emptying Breath Test ..........................................................................33 
6.11 
Dispensing Study Drug ....................................................................................34 
6.12 
Adverse Events Assessments ...........................................................................34 
6.12.1 
Reporting Timelines.............................................................................34 
6.12.2 
Severity ................................................................................................36 
6.12.3 
Relationship .........................................................................................36 
6.12.4 
Expectedness ........................................................................................37 
6.12.5 
Clinical Laboratory Adverse Events ....................................................38 
6.12.6 
Serious Adverse Events .......................................................................38 
6.12.7 
Treatment-Emergent Adverse Events ..................................................39 
6.13 
Prior and Concomitant Medication Assessments ............................................40 
6.14 
Removal of Patients From the Trial or Study Drug .........................................40 
6.14.1 
Early Discontinuation From Study Drug Administration ....................40 
6.14.2 
Withdrawal From the Study .................................................................41 
6.14.3 
Study Stopping Criteria........................................................................41 
6.15 
Appropriateness of Measurements ...................................................................41 
7 
STUDY ACTIVITIES ...........................................................................................44 
7.1 
Screening Procedures (Day –28 to Day -1) .....................................................44 
7.2 
Day 1 Predose ..................................................................................................45 
7.3 
Day 1 After Baseline Evaluations Through Day 13 ........................................45 
7.3.1 
Day 1 ....................................................................................................45 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 11 
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7.4 
Early Termination Procedures .........................................................................46 
7.5 
End of Treatment Visits (Day 14 and Day 15) ................................................46 
7.6 
End of Study (Day 28 ±1 Day) ........................................................................47 
7.7 
Telephone Follow-up Day 44 (±3 Days) (30 ±3 Days After Last Dose) .........48 
8 
QUALITY CONTROL AND ASSURANCE .......................................................49 
9 
PLANNED STATISTICAL METHODS ..............................................................50 
9.1 
General Considerations ....................................................................................50 
9.2 
Determination of Sample Size .........................................................................50 
9.3 
Analysis Populations ........................................................................................50 
9.4 
Demographics, Baseline Characteristics, Enrollment, Protocol Deviations, 
and Patient Disposition ....................................................................................50 
9.5 
Statistical Analysis of Efficacy Variables ........................................................50 
9.6 
Safety Analysis ................................................................................................51 
10 
ADMINISTRATIVE CONSIDERATIONS ..........................................................52 
10.1 
Investigators and Study Administrative Structure ...........................................52 
10.2 
Institutional Review Board Approval ..............................................................52 
10.3 
Ethical Conduct of the Study ...........................................................................52 
10.4 
Patient Information and Consent .....................................................................52 
10.5 
Confidentiality .................................................................................................53 
10.6 
Study Monitoring .............................................................................................53 
10.7 
Case Report Forms and Study Records ...........................................................54 
10.8 
Protocol Violations/Deviations ........................................................................54 
10.9 
Access to Source Documentation ....................................................................55 
10.10 
Data Generation and Analysis .........................................................................55 
10.11 
Retention of Data .............................................................................................55 
10.12 
Financial Disclosure.........................................................................................56 
10.13 
Publication and Disclosure Policy ...................................................................56 
11 
REFERENCE LIST ...............................................................................................57 
Appendix 1 
Schedule of Events ...............................................................................60 
Appendix 2 
GCSI and PAGI-SYM Assessment Instruments..................................63 
LIST OF TABLES 
Table 1: 
Administrative Structure for GAS-001 Study............................................52 
LIST OF FIGURES 
Figure 1: 
Study Schema.............................................................................................21 
 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 12 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
AE 
Adverse event 
ALB 
Albumin  
ALT 
Alanine aminotransferase (serum glutamic pyruvic transaminase [SGPT]) 
AP 
Alkaline phosphatase 
AST 
Aspartate aminotransferase (serum glutamic oxaloacetic transaminase [SGOT]) 
AUC0-last 
Area under the concentration time curve from 0 to the last measurement 
BH4 
Tetrahydrobiopterin 
BID 
Twice a day 
BUN 
Blood urea nitrogen 
13C 
Carbon-13 
Ca 
Calcium  
CFR 
Code of Federal Regulations 
Cl 
Chloride 
Cmax 
Maximum concentration 
CO2 
Carbon dioxide  
12CO2 
Carbon-12 dioxide 
13CO2 
Carbon-13 dioxide 
CRO 
Contract Research Organization 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EOS 
End of Study 
EOT 
End of Treatment 
FDA 
United States Food and Drug Administration 
GCP 
Good Clinical Practice 
GCSI 
Gastroparesis Cardinal Symptom Index 
GEBT 
Gastric Emptying Breath Test 
GGT 
Gamma glutamyl transferase 
GI 
Gastrointestinal 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 13 
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GLP 
Good Laboratory Practice 
HbA1c 
Glycosylated hemoglobin A1c  
HCG 
Human chorionic gonadotropin 
HCT 
Hematocrit 
HEENT 
Head, eyes, ears, nose, and throat 
HGB 
Hemoglobin 
ICF 
Informed consent form 
ICH 
International Council on Harmonisation  
IRB 
Institutional Review Board 
K 
Potassium 
kPCD 
the Gastric Emptying Breath Test metric; “k” is a multiplier of 1000, and 
“PCD” is an acronym for percent carbon-13 dose excreted (as carbon-13 
dioxide)  
LAR 
legally authorized representative 
LDH 
Lactate dehydrogenase 
MedDRA® 
Medical Dictionary for Regulatory Activities 
Na 
Sodium  
NADPH 
nicotinamide adenine dinucleotide phosphate hydrogen 
nNOS 
Neuronal nitric oxide synthase 
NO 
Nitric oxide 
NOS 
Nitric oxide synthase 
PAGI-QOL 
Upper Gastrointestinal Disorders-Quality of Life 
 
 
PAGI-SYM 
Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity 
PRO 
Patient-reported outcome 
QTc  
QT interval corrected for heart rate 
RBC 
Red blood cell 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SUSAR 
Suspected unexpected serious adverse reaction 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 14 
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TEAE 
Treatment-emergent adverse event 
ULN 
Upper limit of normal 
WBC 
White blood cell 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 15 
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1 
INTRODUCTION 
1.1 
Diabetic Gastroparesis  
Gastroparesis is characterized by delayed gastric emptying in the absence of mechanical 
obstruction; symptoms are chronic with episodic symptom exacerbation (Parkman et al, 
2004). Gastroparesis affects women 4 times more than men (Soykan, et al, 1998). Idiopathic 
gastroparesis accounts for most cases, but gastroparesis is frequently associated with diabetes 
(diabetic gastroparesis) (Soykan, et al, 1998; Karamanolis et al, 2007). Several 
cross-sectional studies have found delayed gastric emptying of solids and/or liquids in 30% 
to 50% of patients with Type 1 or Type 2 diabetes (Horowitz et al, 2002). Patients with 
diabetes mellitus commonly experience gastric and intestinal dysfunction (Feldman and 
Schiller, 1983).  
The actual mechanism of diabetic gastroparesis is not well known. Vagal nerve dysfunction 
and/or damage, interstitial cells of Cajal loss, and smooth muscle and enteric neuron 
dysfunction have all been implicated in the pathogenesis of diabetic gastroparesis (Stacher, 
2001; Parkman et al, 2004). In addition, acute hyperglycemia has the potential to slow gastric 
emptying (Camilleri et al, 2013).  
At a molecular level, attention has been devoted to the potential role of altered nitrergic 
signaling in the enteric nervous system. Gastric motility is regulated in large part by neurons 
of the enteric nervous system located in the muscle wall (Wood et al, 1999). These neurons 
are either excitatory (releasing acetylcholine) or inhibitory (releasing nitric oxide [NO] and 
vasoactive intestinal peptide). Nerves throughout the luminal gastrointestinal (GI) tract 
express neuronal nitric oxide synthase (nNOS), which generates NO, a key neurotransmitter 
in the regulation of GI motility (Takahashi, 2003); it is the principal nonadrenergic 
noncholinergic inhibitory neurotransmitter in the GI tract. In diabetic rats, which serve as a 
model for type 1 diabetes, nNOS expression was found to be impaired. This impairment in 
nNOS messenger RNA expression was associated with impaired smooth muscle relaxation in 
response to electrical stimulation of circular muscle fibers obtained from the proximal 
stomach of these rats (Takahashi et al, 1997). It has been demonstrated that female diabetic 
rats had slower gastric emptying than age matched diabetic male rats, female control rats had 
greater nitrergic relaxation of circular antral muscle strips compared to male controls, and 
nitrergic relaxation was impaired in diabetic female rats but not matched diabetic male rats 
(Gangula et al, 2007). 
The core signs and symptoms of gastroparesis by incidence are nausea (92% to 96%), 
vomiting (68% to 88%), postprandial fullness (54% to 77%), early satiety (42% to 60%), and 
upper abdominal pain (36% to 85%) (Soykan et al, 1998; Hoogerwerf et al, 1999; Anaparthy 
et al, 2009). Patients may experience any combination of signs and symptoms with varying 
degrees of severity. Pain is less prevalent in diabetic gastroparesis than idiopathic 
gastroparesis. Patients with diabetic gastroparesis may experience further derangement of 
glucose control because of unpredictable gastric emptying and altered absorption of orally 
administered hypoglycemic drugs, which may, in turn, affect measurement of core signs and 
symptoms. Severe signs and symptoms may cause complications such as malnutrition, 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 16 
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esophagitis, and Mallory-Weiss tears. Gastroparesis adversely affects the lives of patients 
with the disease, resulting in decreased social interaction, poor work functionality, and 
development of anxiety or depression (Soykan et al, 1998; Parkman et al, 2004). 
1.2 
Impaired Gastric Accommodation in Gastroparesis 
Patients with diabetic gastroparesis have also been shown to have gastric hypersensitivity, 
especially in the postprandial state, and impairment of the postprandial accommodation 
response. (Kumar et al, 2008). The stomach functions as 2 separate regions: the fundus acts 
as a reservoir accommodating a meal without a significant increase in intragastric pressure, 
and the distal stomach/antrum triturates gastric contents. Receptive relaxation or 
accommodation is vagally mediated resulting in the release of NO and activation of nitrergic 
myenteric neurons. Nitrergic signaling is responsible for gastric accommodation and pyloric 
relaxation in response to a meal (Ishiguchi et al, 2001). 
Impaired accommodation has been associated with symptoms of early satiety and weight loss 
in patients with idiopathic gastroparesis (Karamanolis et al, 2007). A study of patients with 
diabetic gastroparesis found that 90% of patients had impaired gastric accommodation to a 
nutrient meal (Kumar et al, 2008). In the distal stomach, NO is required for the propulsive 
contractions that triturate gastric contents and control of pyloric closure; lack of NO can lead 
to delayed gastric emptying and impaired gastric accommodation (Gangula et al, 2007). 
Several co-factors are known to be important for nNOS activity, including nicotinamide 
adenine dinucleotide phosphate hydrogen (NADPH), calcium, and tetrahydrobiopterin (BH4) 
(Werner et al, 2003). The homodimeric conformation of all 3 isoforms of nitric oxide 
synthase (NOS) is regulated by BH4 (Werner et al, 2003). In the absence of BH4, uncoupling 
of NO production occurs and leads to super oxide production, resulting in further impaired 
nNOS bioactivity. 
1.3 
Current Treatment of Diabetic Gastroparesis  
Therapies for gastroparesis have been targeted at accelerating gastric emptying or controlling 
symptoms. Available therapies for accelerating gastric emptying are limited in number and 
efficacy. These include metoclopramide (Snape et al, 1982), erythromycin (Arts et al, 2005), 
and domperidone (not available in the United States [US]) (Prakash and Wagstaff, 1998). 
There is also poor correlation between gastric emptying and baseline symptom severity 
(Karamanolis et al, 2007; Talley et al, 2001) and in response to therapeutic intervention. In 
part, as a result of lack of understanding of the underlying pathogenesis that leads to 
alterations in GI motility and sensation, medical therapies have not been targeted at the 
underlying pathophysiology of gastroparesis.  
The first-line medical therapy for patients with diabetic gastroparesis is generally a 
combination of an antiemetic agent in addition to the promotility drug. Unfortunately, many 
patients with diabetic gastroparesis will not experience adequate symptom relief despite 
first-line therapy. For patients with refractory disease, options include combination prokinetic 
therapy, psychotropic medications, pyloric botulinum toxin injection, and gastric electric 
stimulation (Fass, 2010; Camilleri et al, 2013). 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 17 
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1.4 
CNSA-001 (Sepiapterin) 
Sepiapterin is 2-amino-6-[(2S)-2-hydroxypropanoyl]-7,8-dihydro-1H-pteridin-4-one with a 
molecular weight of 237.2 and a molecular formula of C9H11 N5O3. 
The chemical structure of sepiapterin is: 
 
Sepiapterin serves as a substrate for BH4 synthesis via the pterin salvage pathway (Mayer 
and Werner, 1995). Oral administration of sepiapterin was shown to be more potent (>2 fold) 
than oral administration of BH4 in increasing intracellular BH4 in normal mice (Sawabe et 
al, 2002). Translation of this finding to humans has been confirmed in a Phase 1 study, 
PKU-001, conducted by Censa Pharmaceuticals.  
1.5 
Rationale for Study 
BH4 biosynthesis is impaired in chronic diabetes. The mechanism of impairment is not well 
understood but is thought to be a result of hyperglycemia-induced proteasome-mediated 
degradation of GTP-cyclohydrolase, the rate-limiting enzyme in the synthesis pathway for 
BH4 (Xu et al, 2007).  
CNSA-001 is the first viable formulation of sepiapterin, shown to increase intracellular BH4 
(Section 1.4), intended for the treatment of female patients with diabetic gastroparesis. 
CNSA-001 was studied in a single and multiple ascending-dose study in healthy volunteers, 
the Phase 1 study, Study PKU-001. Part A of this study assessed the safety and 
pharmacokinetics of CNSA-001 at 6 dose levels inclusive of an assessment of food effect 
(i.e., 2.5 mg/kg, 7.5 mg/kg, 20 mg/kg, 40 mg/kg, 80 mg/kg, and 10 mg/kg [to assess food 
effect]). Additionally, Kuvan® (sapropterin dihydrochloride), a synthetic BH4 commercially 
available product, was administered at equivalent doses for the first 3 dose levels (2.5 mg/kg, 
7.5 mg/kg, and 20 mg/kg). Dose-dependent correlations between CNSA-001 and plasma 
BH4 concentrations were observed with each successive dose level. Dose proportionality was 
observed between the top 2 dose levels (40 mg/kg and 80 mg/kg) and resultant BH4 
concentrations. Administration with a standard high-fat (approximately 50 percent of total 
caloric content of the meal) and high calorie (approximately 800 to 1000 calories) meal 
resulted in approximately 80% higher plasma BH4 concentrations (area under the 
concentration time curve from 0 to the last measurement [AUC0-last] and maximum 
concentration [Cmax]) than in subjects who had fasted before receipt of CNSA-001. 
Treatment-emergent adverse events (TEAEs) in Part A of Study PKU-001 were reported in 
26 subjects (44.1%, 26/59). The TEAEs for CNSA-001 were generally mild and consistent 
with reported adverse events (AEs) for Kuvan® and placebo. The frequency of TEAEs did 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 18 
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not appear to increase with increasing dose. The TEAEs that were judged to be related to 
study treatment were reported in 17 subjects: 11 subjects (26.2%, 11/42) who received 
CNSA-001, 4 subjects (44.4%, 4/9) who received Kuvan®, and 2 subjects (25.0%, 2/8) who 
received placebo. No TEAEs were severe or serious or led to discontinuation of study drug. 
Headache and dizziness were the most common TEAEs , but these TEAEs occurred at a 
similar frequency as with placebo. 
Part B of Study PKU-001 assessed multiple ascending doses CNSA-001 in healthy 
volunteers. Data indicate CNSA-001 was well tolerated following daily doses of 5, 20, and 
60 mg/kg/day for 7 days and that TEAEs were reported in 14 subjects (58.3%, 14/24). The 
TEAEs in subjects who received CNSA 001 were mild or moderate and consistent with the 
TEAEs in subjects who received placebo: TEAEs were experienced by 10 subjects (55.6%, 
10/18) who received CNSA-001 at doses from 5 mg/kg to 60 mg/kg daily for 7 days and by 
4 subjects (66.7%, 4/6) who received placebo. No TEAEs were severe, serious, or led to 
discontinuation. Of the 10 TEAEs reported in subjects who received CNSA-001, only 4 were 
judged to be related to study drug, and, of the 4 TEAEs reported in subjects who received 
placebo, only 1 was judged to be related to study drug. Somnolence, fatigue, headache, and 
procedural pain (secondary to performance of 2 sequential lumbar punctures 7 days apart) 
were the most common TEAEs reported, and they occurred at a similar frequency when 
compared with placebo with the exception of fatigue and headache, which were each 
reported in 2 subjects who received CNSA-001 (11.1%, 2/18). 
This Phase 2 pilot study will assess CNSA-001 doses of 20 mg/kg/day administered as 
10 mg/kg twice a day (BID) in comparison to placebo administered BID in female patients 
with diabetic gastroparesis. This study will help support the design of future Phase 2/3 
studies in patients with diabetic gastroparesis.  


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 19 
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2 
STUDY OBJECTIVES 
2.1 
Primary Objective 
The primary objective of this study is to assess the impact of CNSA-001 on gastric 
accommodation, as measured by nutrient satiety testing (Section 6.7), in women with 
moderate to severe diabetic gastroparesis. 
2.2 
Secondary Objectives 
The secondary objectives of this study are, in women with moderate to severe diabetic 
gastroparesis: 
• To evaluate improvement of gastroparesis symptoms measured by global assessment of 
symptoms and symptom severity (Gastroparesis Cardinal Symptom Index [GCSI]) 
(Section 6.8, Appendix 2) 
• To evaluate patient-reported outcomes (PROs) as measured by the quality of life 
questionnaire Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity 
(PAGI-SYM) (Section 6.9, Appendix 2)  
• To evaluate the emptying of the stomach, as measured by the Gastric Emptying Breath 
Test (GEBT) (Section 6.10) 
• To assess the safety and tolerability of CNSA-001 20 mg/kg/day 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 20 
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3 
INVESTIGATIONAL PLAN 
3.1 
Overall Study Design and Plan 
Study GAS-001 is a Phase 2, randomized, double-blind, placebo-controlled pilot study of 
multiple doses of CNSA-001 (sepiapterin) powder for suspension administered orally in 
women with moderate to severe diabetic gastroparesis. This is an outpatient study in which 
up to 20 patients will be enrolled at approximately 4 centers. 
The Schedule of Events is provided in Appendix 1. The study schema is displayed in Figure 
1.  
Screening Period (Day -28 Through Day 1 Predose) 
An informed consent form (ICF) must be signed before any study-related procedures are 
performed. After providing consent, patients will undergo Screening procedures to determine 
study eligibility, as indicated in Appendix 1. Patients who are eligible based on Screening 
evaluations will undergo baseline evaluations before initiation of study drug (CNSA-001 or 
placebo), be randomized, and proceed to the Treatment Period.  
Treatment Period (Day 1 Through Day 14) 
Following the Screening Period and completion of baseline evaluations, all randomized 
patients will take their first dose of study drug (CNSA-001 or placebo) on Day 1 while in the 
clinic. Patients will undergo procedures during the Treatment Period as indicated in 
Appendix 1. 
Study drug may be prematurely discontinued for safety reasons, as described in 
Section 6.14.1. Patients may also withdraw from the study for any reason, as described in 
Section 6.14.2. If a patient discontinues study drug early, the patient should return to the 
study site within 24 hours of withdrawal and complete all of the procedures outlined for the 
End of Treatment (EOT) (Section 7.5, Appendix 1). If a patient withdraws early from the 
study before undergoing EOT evaluations, the patient will be asked to return to the study site 
within 24 hours of withdrawal and complete all of the procedures outlined for the EOT 
(Section 7.5, Appendix 1). If a patient withdraws from the study before undergoing End of 
Study (EOS) evaluations, the patient will be asked to return to the study site within 24 hours 
of withdrawal and complete all of the procedures outlined for the EOS (Section 7.6, 
Appendix 1).  
End of Treatment Period (Day 14 Through Day 15 Evaluations) 
Patients will undergo EOT evaluations on Day 14 and Day 15 as indicated in Appendix 1. 
Preliminary efficacy will be assessed by the changes from Day 1 in the nutrient satiety test 
(Section 6.7) on Day 14. The GCSI (Section 6.8, Appendix 2) and PAGI-SYM (Section 6.9, 
Appendix 2) will also be administered on Day 14 (+1 day), and the GEBT (Section 6.10) will 
be conducted on Day 15. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 21 
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End of Study Period (Day 15 After Evaluations Through Day 28 [±1 Day] Evaluations) 
Patients will undergo EOS evaluations on Day 28 (±1 day) as indicated in Appendix 1. 
Preliminary efficacy will be assessed by the changes from Day 1 in the nutrient satiety test 
(Section 6.7) on Day 28. The GCSI (Section 6.8, Appendix 2) and PAGI-SYM (Section 6.9, 
Appendix 2) will also be administered on Day 28 ±1, and the GEBT (Section 6.10) will be 
conducted on Day 27 or Day 29. 
Follow-up Period (Day 28 [±1 Day] After Evaluations Through Day 44 [±3 Days]) 
Patients will undergo telephone Follow-up on Day 44 ±3 days as indicated in Appendix 1.  
Figure 1: 
Study Schema  
 
Abbreviations: BID = twice a day.  
 
3.2 
Rationale for Study Design and Control Group 
CNSA-001 (sepiapterin) is a new chemical entity that is an endogenous, naturally occurring 
precursor of BH4 via the pterin salvage pathway. Animal studies and data from a Phase 1 
single and multiple ascending-dose study in healthy volunteers conducted by Censa 
Pharmaceuticals indicate rapid intracellular conversion of sepiapterin to BH4. It is expected 
that oral administration of CNSA-001 to women with diabetic gastroparesis will result in 
increases in both intracellular and circulating BH4 concentrations. In chronic diabetes, BH4 
biosynthesis is impaired (Xu et al, 2007). 
CNSA-001 was studied in two 14-day Good Laboratory Practice (GLP) toxicity studies, as 
described in Section 5.3, and in a single and multiple ascending-dose study in healthy 
volunteers, Study PKU-001, as described in Section 1.5.  
Because all patients will receive the standard of care for diabetic gastroparesis in addition to 
their assigned study drug, the study design of a randomized study of CNSA-001 versus 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 22 
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placebo in female patients with diabetic gastroparesis will not expose patients to the risk of 
no treatment.  
This study has a double-blind design intended to reduce bias. 
3.3 
Study Duration and Dates 
The study duration for each patient will be up to 75 days, extending from Screening (Day -28 
through Day -1) through the final assessments on Day 44 (±3 days).  


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 23 
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4 
STUDY POPULATION SELECTION 
4.1 
Study Population 
Approximately 4 study centers will enroll up to 20 women with moderate to severe diabetic 
gastroparesis this study.  
4.2 
Inclusion Criteria 
Patients are eligible to participate in this study if they meet all the following inclusion 
criteria: 
1. Informed consent 
2. Females ≥18 and ≤65 years of age 
3. Diagnosis of diabetes mellitus  
4. Documentation of delayed gastric emptying on gastric emptying scintigraphy (within 
1 year of enrollment) 
5. Symptoms of gastroparesis for at least 6 months with GCSI (Section 6.8, Appendix 2) 
score >21 indicating moderate to severe symptoms 
6. Gastric accommodation, as measured by nutrient satiety testing, of ≤600 mL 
7. Negative upper endoscopy or upper GI series within 3 years of enrollment (no evidence 
of mechanical obstruction or peptic ulcer disease) 
8. Either postmenopausal for ≥1 year or surgically sterile (having undergone tubal ligation, 
hysterectomy, or bilateral oophorectomy) for at least 6 months or, if of childbearing 
potential and not abstinent, willing to use a highly effective method of contraception 
throughout the study such as 1 of the following: 
 Hormonal contraception (stable dose for 3 months) 
 Intrauterine device/Intrauterine Hormone-releasing System 
 Barrier contraceptive method (diaphragm, cervical cap, contraceptive sponge, 
condom) 
Patients who are abstinent will not be required to use a contraceptive method unless they 
become sexually active 
9. If on analgesics (including narcotics), promotility agents (including metoclopramide), or 
neuromodulators (including tricyclic antidepressants, gabapentin, and pregabalin), doses 
are stable for >30 days before randomization and the patient is not expected to require 
dose changes during the study through the EOT 
10. Have not used tobacco (e.g., cigarettes, e-cigarettes, cigars, smokeless tobacco, nicotine 
replacement) for 2 weeks prior to Day 1 and willingness to abstain from these products 
during the study through the EOT 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 24 
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4.3 
Exclusion Criteria 
Patients are not eligible to participate in this study if they meet any of the following 
exclusion criteria: 
1. Male gender 
2. Normal gastric emptying  
3. Gastroparesis from postsurgical etiologies 
4. Another active disorder that could, in the opinion of the Investigator, explain symptoms  
5. Weight >100 kg 
6. Alanine aminotransferase > 2× upper limit of normal (ULN) 
7. Pregnant, breastfeeding, or considering pregnancy 
8. Clinically significant cardiac arrhythmia at Screening 
9. QT interval corrected for heart rate (QTc) ≥480 msec (based on triplicate measurements 
taken at Screening)  
10. Recent clinically significant GI bleeding 
11. Taking levodopa or domperidone within 30 days before randomization or expected to 
require domperidone during the study through the EOT 
12. Taking erythromycin within 30 days before randomization or expected to require 
erythromycin within 30 days before randomization or expected to require erythromycin 
during the study through the EOT; if a patient is taking erythromycin and is otherwise 
eligible to participate in the study, following signing the ICF, the patient may go through 
an erythromycin washout period of 30 days before randomization 
13. Taking any fundic-relaxing agents including, but not limited to, buspirone, clonidine, 
nitrates, phosphodiesterase inhibitors (i.e., sildenafil citrate [Viagra®]) and 
triptan-containing medications, within 30 days before randomization or expected to 
require any of these agents during the study through the EOT 
14. Taking any systemic antifolates, including, but not limited to, methotrexate, pemetrexed, 
and trimetrexate or expected to require any systemic antifolates during the study through 
the EOT (topical antifolates [e.g., cream, ointment, gel] or eye drops with antifolates are 
allowed) 
15. Pulmonary dysfunction (e.g., chronic obstructive pulmonary disease) 
16. Surgery for placement of a gastric stimulator within the past 6 months (patients 
postoperative >6 months with persistent symptoms and delayed gastric emptying are 
eligible) 
17. Gastrointestinal disease (such as irritable bowel syndrome, inflammatory bowel disease, 
chronic gastritis, peptic ulcer disease, small bowel malabsorption) that could affect the 
absorption of study drug or contraindicate undergoing the GEBT (Section 6.10)  


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 25 
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18. History of gastric surgery, including Roux-en-Y gastric bypass surgery or an antrectomy 
with vagotomy, or gastrectomy 
19. History of allergies or adverse reactions to BH4 or related compounds, to any excipients 
in the study drug formulation, or to egg, wheat, or algae (Spirulina)  
20. Inability to tolerate oral medication 
21. Current participation in any other investigational drug study or use of any investigational 
agent, investigational device, or approved therapy for investigational use within 30 days 
or 5 half-lives (whichever is longer) before Screening 
22. Any clinically significant laboratory abnormality; in general, each laboratory value from 
Screening and baseline chemistry and hematology panels should fall within the limits of 
the normal laboratory reference range unless deemed not clinically significant by the 
Investigator 
23. Major surgery within the previous 90 days  
24. The patient, in the opinion of the Investigator, is unwilling or unable to adhere to the 
requirements of the study 
25. History of alcohol or drug abuse within 6 months prior to Screening or current evidence 
of substance dependence as determined by the Investigator 
26. Episodes of ketoacidosis or hypoglycemia that are frequent as defined by the Investigator 
27. Any other conditions, including diabetic comorbidities, that, in the opinion of the 
Investigator or Sponsor, would interfere with the patient’s ability to participate in the 
study or increase the risk of participation for that patient 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 26 
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5 
STUDY TREATMENTS 
5.1 
Description of Treatments 
5.1.1 
Test Product 
The test product is CNSA-001 (sepiapterin) oral powder for suspension. CNSA-001 contains 
the new chemical entity, sepiapterin. Sepiapterin is 2-amino-6-[(2S)-2-hydroxypropanoyl]-
7,8-dihydro-1H-pteridin-4-one with a molecular weight of 237.2 and a molecular formula of 
C9H11 N5O3. Inactive ingredients in CNSA-001 include microcrystalline cellulose, colloidal 
silicon dioxide, croscarmellose, and ascorbic acid. CNSA-001 will be suspended in Medisca® 
Oral Mix prior to dispensing it to the patient.  
5.1.2 
Placebo Control 
The placebo is a ready-made suspension containing microcrystalline cellulose, colloidal 
silicon dioxide, croscarmellose, ascorbic acid, and colorant (Yellow No. 6) that is suspended 
in Medisca® Oral Mix.  
5.2 
Treatments Administered 
Patients will be randomized in a ratio of 1:1 to the following treatment groups:  
• CNSA-001 20 mg/kg/day (10 mg/kg BID) for 14 days 
• Placebo BID for 14 days 
Dosing of CNSA-001 is based on the patient’s weight. The weight obtained on Day -1 will 
be used to calculate the exact amount (mg) of CNSA-001 active ingredient (sepiapterin) 
required for each patient’s daily dose.  
The placebo is formulated as ready-made suspension. The placebo will be administered in the 
same manner (volume) as CNSA-001. 
Details on preparation of study drug and dosing guidelines will be provided in a pharmacy 
manual for the site and an instruction guide for patients.  
5.3 
Selection and Timing of Dose for Each Patient 
All patients will be randomly assigned in a ratio of 1:1 to receive CNSA-001 20 mg/kg/day 
(10 mg/kg BID) or placebo BID.  
The CNSA-001 dose was selected following completion of two 14-day GLP toxicity studies 
in the rat and marmoset. The no observed adverse effect level from both studies was set at 
1000 mg/kg/day, which represents a human equivalent dose of 161.3 mg/kg/day based on 
allometric scaling. Consequently, the proposed dose of 20 mg/kg/day represents an 8.1-fold 
safety margin. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 27 
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Study drug will be dispensed on Day 1 (Section 6.11) with a dosing diary in which patients 
will record all doses taken and times they were taken (Section 5.8.1). The first dose on Day 1 
will be taken in the clinic after patients undergo the nutrient satiety test (Section 6.7). 
If a patient vomits after taking a dose of study drug, the patient should wait until the next 
scheduled timepoint to take another dose. A missed dose should be taken as soon as possible, 
but >2 doses should not be taken on the same day. 
5.4 
Method of Assigning Patients to Treatment Groups 
Patients who fulfill the eligibility criteria and provide informed consent will be randomized 
in a ratio of 1:1 to the CNSA-001 or placebo group via the randomization scheme generated 
for the study. Patients who are randomized will be considered to be enrolled.  
5.5 
Blinding 
This study has a double-blind design. The Investigator, study personnel, and patients will not 
make any effort to determine which study drug is being received. Unblinded pharmacy (or 
other qualified site) personnel will be utilized in this study to prepare the study drug. 
Patients will be blinded to study drug assignment. Only in an emergency, when knowledge of 
the study drug is essential for the clinical management or welfare of a specific patient, may 
the Investigator unblind a patient’s study drug assignment. Copies of the randomization 
sequence and treatment codes will be kept in the pharmacy at the sites. If emergency 
unblinding is required, the Investigator will have immediate access to individual sealed codes 
containing treatment allocations. However, before any unblinding occurs, the Investigator is 
strongly advised to discuss options with the Sponsor’s Medical Monitor or appropriate 
Sponsor study personnel. As soon as possible and without revealing the patient’s study drug 
assignment (unless important to the safety of patients remaining in the study), the 
Investigator must notify the Sponsor if the blind is broken for any reason and the Investigator 
was unable to contact the Sponsor prior to the unblinding. The Investigator will record in 
source documentation the date and reason for revealing the blinded study drug assignment 
for any patient and the names and roles of personnel unblinded. 
5.6 
Concomitant Therapy 
Patients will be permitted to take:  
 Analgesics, including narcotics, if the patient has been on a stable dose of the 
medication for >30 days before randomization; dose escalation is NOT permitted 
during the study through the EOT 
 Promotility agents, including metoclopramide if the patient has been on a stable dose 
of the medication >30 days before randomization; dose changes are NOT permitted 
during the study through the EOT 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 28 
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 Neuromodulators, including any tricyclic antidepressant, gabapentin, and pregabalin, 
if the patient has been on a stable dose >30 days before randomization; dose changes 
are NOT permitted during the study through the EOT 
 Rescue medications that patients would usually take, including ondansetron 
(Zofran®), promethazine (Phenergan®) or prochlorperazine (Compazine®) for nausea 
and tramadol (Ultram®), if symptoms related to gastroparesis require further 
treatment during the study through the EOT 
All prescription and over-the-counter medications (including herbal medications) that the 
patient took within 30 days before Screening though the EOT should be recorded.  
5.7 
Restrictions 
5.7.1 
Prior Therapy and Concomitant Therapy 
The following are prohibited: 
 Any investigational agent, investigational device, or approved therapy for 
investigational use within 30 days or 5 half-lives (whichever is longer) before 
Screening  
 Domperidone within 30 days before randomization or expected to require 
domperidone during the study through the EOT 
 Dose escalation of analgesic or promotility agents or neuromodulators within 30 days 
before randomization or during the study through the EOT 
 Erythromycin within 30 days before randomization or during the study through the 
EOT; if a patient is taking erythromycin and is otherwise eligible to participate in the 
study, following signing the ICF, the patient may go through an erythromycin 
washout period of 30 days before randomization 
 Systemic antifolates, including, but not limited to, methotrexate, pemetrexed, and 
trimetrexate or expected to require any systemic antifolates during the study through 
the EOT (topical antifolates [e.g., cream, ointment, gel] or eye drops with antifolates 
are allowed) 
 Fundic-relaxing agents, including, but not limited to, buspirone, clonidine, nitrates, 
phosphodiesterase inhibitors (i.e., sildenafil citrate [Viagra®]) and triptan-containing 
medications, within 30 days before randomization or expected to require any of these 
agents during the study through the EOT 
 Medications that can alter GI sensation or accommodation or gastric emptying 
overnight before the nutrient satiety test (Section 6.7) 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 29 
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5.7.2 
Food Intake 
Patients will continue their usual diet without modification throughout the study. Patients are 
required to have been fasting overnight for the following assessments: 
 Clinical laboratory, including glycosylated hemoglobin A1c (HbA1c), tests 
 The nutrient satiety test (Section 6.7), which requires the consumption of Ensure™ 
(Abbott Laboratories, Abbott Park, IL, USA)  
 The GEBT (Section 6.10), which requires consumption of a standardized 230 kCal 
meal, consisting of a standardized carbon-13 (13C)-labeled egg component and 
6 saltine crackers, with 6 ounces of water 
5.7.3 
Total Blood Volume 
The total volume of blood obtained from an individual study patient is expected to be 
approximately 40 mL, for clinical laboratory tests inclusive of the HbA1c test. 
5.7.4 
Patient Activity and Tobacco Restrictions 
Patients will not be confined during the study and will not require any activity restrictions. 
Patients must abstain from tobacco use (e.g., cigarettes, e-cigarettes, cigars, smokeless 
tobacco, nicotine replacement) for 2 weeks before Day 1 and during the study through the 
EOT. 
5.8 
Treatment Compliance 
Patients will be instructed to return all used (empty containers) and unused study drug on 
Day 14 if the patient takes the last dose of study drug on Day 14 while in the clinic or, if the 
patient takes the last dose of study drug on Day 14 after leaving the clinic, on Day 15 or Day 
28 (±1 day). Compliance with the dosing regimen will be assessed by reconciliation of used 
and unused study drug. The quantities dispensed, returned, used, and lost will be recorded on 
the dispensing log provided for the study.  
5.8.1 
Dosing Diary 
Patients will be provided with a dosing diary on Day 1 along with instructions for recording 
all doses of study drug and times they were taken. The dosing diary will be collected on 
Day 14 if the patient takes the last dose of study drug on Day 14 while in the clinic or, if the 
patient takes the last dose of study drug on Day 14 after leaving the clinic, on Day 15 or 
Day 28 (±1 day), and the Investigator (or designee) will transcribe all entries into the 
electronic case report form (eCRF).  


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 30 
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5.9 
Packaging and Labeling 
CNSA-001 Oral Powder for Suspension is packaged in 10 mL amber glass vials with black 
child proof caps. Each glass vial contains 175 mg of sepiapterin.  
Each vial of CNSA-001 Oral Powder for Suspension will contain the product name, strength, 
content, expiry/retest date, and company name. Each vial label will contain the words, 
“Caution: Investigational medicine for clinical trial use only.” 
CNSA-001 PLACEBO suspension is packaged in 500 mL bottles. Each bottle of CNSA-001 
PLACEBO suspension will contain the content and company name as well as “CNSA-001 
PLACEBO” on its label. 
The suspending vehicle, Medisca® Oral Mix, is commercially available and will be provided 
separately. 
5.10 
Storage and Accountability 
All drug product required for completion of this study will be provided by Censa 
Pharmaceuticals. It is the responsibility of the pharmacy staff or study staff to ensure that a 
current record of drug inventory and drug accountability is maintained. Inventory and 
accountability records must be readily available for inspection by the study monitor and are 
open to inspection at any time by applicable regulatory authorities. 
CNSA-001 Oral Powder for Suspension (non-reconstituted) may be stored frozen at -20°C or 
at refrigerated conditions (2 to 8°C). If not administered on the same day of suspending, 
CNSA-001 suspension should be stored at refrigerated conditions (2 to 8°C) until time of 
dosing. Once suspended, CNSA-001 is stable for 14 days.  
CNSA-001 PLACEBO suspension may be stored refrigerated at 2 to 8°C.  
5.11 
Investigational Product Retention at Study Site 
Upon completion of the study and once inventoried by the study site, all used (empty) 
containers of study drug will be destroyed. Any unused containers of study drug may be 
either destroyed or returned to the Sponsor following discussion with the Sponsor. If study 
drug is destroyed, a certificate of destruction will be provided to the Sponsor by the 
appropriate facility performing the destruction. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 31 
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6 
STUDY PROCEDURES 
6.1 
Informed Consent 
Consent forms describing in detail the study drug, study procedures, and risks are given to 
the patient, and written documentation of informed consent is required prior to conducting 
study-related procedures. See Section 10.4 for more information on the informed consent 
process. 
6.2 
Medical History and Demographic Data 
A detailed medical/surgical history will be obtained at Screening. The history will include 
specific information related to any prior or existing medical conditions or surgical procedures 
involving the following systems: dermatologic; head, eyes, ears, nose, and throat (HEENT); 
lymphatic; cardiovascular; respiratory; GI; musculoskeletal; and neurological. The medical 
history will be updated on Day 1 before the start of study drug. 
Demographic data obtained at Screening will include age, gender, and self-reported 
race/ethnicity. 
6.3 
Vital Signs, Weight, and Height 
Vital signs, including blood pressure, pulse, respiratory rate, and temperature, will be 
measured at Screening, Day 1 (predose and 2 hours postdose), and at the EOT and EOS 
visits. Vital signs will be measured prior to collection of laboratory samples and after patients 
have rested for 5 minutes  in the supine position. For timepoints other than Day 1, vital signs 
will be taken at any time during the visit after resting and laboratory sample collection.  
Weight will only be collected at Screening as necessary to determine the response to 
Exclusion Criterion #5 (Section 4.3) and on Day -1. Height will only be collected at 
Screening. 
6.4 
Physical Examination 
A complete physical examination will be performed at Screening, on Day 1 before start of 
study drug and at the EOT and EOS visits. The examination will assess general appearance, 
as well as dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, 
musculoskeletal, and neurological parameters.  
6.5 
Clinical Laboratory Tests and Glycosylated Hemoglobin A1c 
Clinical laboratory tests will be performed by qualified local laboratories. Blood and urine 
samples for clinical chemistry, hematology, and urinalysis will be collected at Screening, 
Day 1 (predose), and at the EOT and EOS visits. Patients should fast overnight prior to 
collection of blood samples (minimum of 8 hours before blood sample collection). Blood 
samples for HbA1c will be collected at Screening and at the EOT and EOS visits. Clinically 
significant laboratory abnormalities should be followed to a satisfactory resolution, as 
determined by the Investigator. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 32 
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The following clinical laboratory and other laboratory parameters will be assessed: 
Hematology: 
Hematocrit (HCT) 
Hemoglobin (HGB) 
Platelet count 
Red blood cell (RBC) count 
White blood cell (WBC) count with differential 
(neutrophils, eosinophils, basophils, 
lymphocytes, and monocytes) 
Urinalysis: 
Bilirubin 
Glucose 
Ketones 
Occult blood 
pH 
Protein 
Specific gravity 
Urobilinogen  
Microscopy: 
WBCs 
RBCs 
Epithelial cells 
Pregnancy Testing: a 
Serum human chorionic gonadotropin (HCG) 
at Screening 
Urine HCG Day 1 (predose) and Day 14 (±1 
day) 
Serum Chemistry: 
Albumin (ALB) 
Alkaline phosphatase (AP) 
Alanine aminotransferase (ALT; serum 
glutamic pyruvic transaminase [SGPT]) 
Aspartate aminotransferase (AST; serum 
glutamic oxaloacetic transaminase [SGOT]) 
Blood urea nitrogen (BUN) 
Calcium (Ca) 
Carbon dioxide (CO2) 
Chloride (Cl) 
Creatinine 
Gamma glutamyl transferase (GGT) 
Glucose 
Lactate dehydrogenase (LDH) 
Phosphorus 
Potassium (K) 
Sodium (Na) 
Total bilirubin 
Direct bilirubin 
Total cholesterol 
Total protein 
Uric acid 
Other: 
Glycosylated hemoglobin A1(HbA1c) 
a 
Required for all women who are of childbearing potential. Any positive urine pregnancy test should be 
confirmed by a serum pregnancy test. 
 
6.6 
Electrocardiogram 
At Screening, 12-lead electrocardiograms (ECGs) will be obtained in triplicate, with 
1 minute separating the first and second recordings and 1 minute separating second and third 
recordings. The following ECG parameters will be collected and recorded in the eCRF: RR, 
PR, QRS, QT, and QTc intervals. In addition, the ECG tracing should be reported as normal, 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 33 
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abnormal clinically significant, or abnormal not clinically significant. If abnormalities are 
noted on the ECG, these should be recorded in the eCRF. 
6.7 
Nutrient Satiety Test  
For the nutrient satiety test, patients consume 120 mL of Ensure™ every 4 minutes. At 
5-minute intervals, patients score their fullness using a rating scale that combines verbal 
descriptors on a scale graded 0 to 5 (0: no symptoms, 1: first sensation of fullness [threshold], 
2: mild, 3: moderate, 4: severe and 5: maximum or unbearable fullness). Patients are told to 
stop when a score of 5 is obtained. The actual volume of Ensure™ consumed at this point is 
the maximum tolerated volume. Symptoms are measured 30 minutes after completing the test 
with patients scoring each symptom of bloating, fullness, nausea and pain on a visual 
analogue scale with 100-mm lines and the words “unnoticeable” and “unbearable” as 
anchors. The sum of the four 100-mm visual analogue scales provides an aggregate symptom 
score (Park, 2011). 
The nutrient satiety test will be administered in the clinic at Screening, on Day 1 (predose), 
and on Day 14 and Day 28 after overnight fasts and after any medications that can alter GI 
sensation or accommodation or gastric emptying have been held overnight. A nutrient satiety 
test volume of ≤600 mL at Screening is required for patients to participate in this study. 
6.8 
Gastroparesis Cardinal Symptom Index 
The GCSI (Appendix 2) consisting of a subset of items from the PAGI-SYM instrument 
(Section 6.9, Appendix 2), will be administered in the clinic at Screening and on Day 1 
(predose), Day 14 (+1 day), and Day 28 (±1 day). A GCSI score >21 at Screening, indicating 
moderate to severe symptoms, is required for patients to participate in this study. 
6.9 
Patient Assessment of Upper Gastrointestinal Disorders-Symptom 
Severity 
The PAGI-SYM (Appendix 2) is a 20-item upper GI symptom severity instrument with 
6 subscales: heartburn/regurgitation, fullness/early satiety, nausea/vomiting, bloating, upper 
abdominal pain, and lower abdominal pain. It will be administered in the clinic on Day 1 
(predose) and on Day 14 (+1 day), and Day 28 (±1 day).  
6.10 
Gastric Emptying Breath Test 
The GEBT, which is a nonradioactive noninvasive test, will be administered in the clinic on 
Day -1, Day 15, and Day 27 or Day 29 after the patient has fasted overnight (a minimum of 
8 hours before test administration with the exception of 4 ounces of water up to 1 hour before 
the test). At the clinic, the patient provides baseline (premeal) breath samples and then 
consumes a standardized 230 kCal meal, consisting of a proprietary standardized 13C-labeled 
egg component (which is rehydrated and then microwaved for 1.5 minutes) and 6 saltine 
crackers, accompanied by 6 ounces of water. The meal is to be consumed within 10 minutes. 
Single postmeal breath samples are collected in capped glass tubes at 45, 90, 120, 150, 180, 
and 240 minutes after the meal is consumed and sent to the specified local laboratory for 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 34 
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analysis by Gas Isotope Ratio Mass Spectrometry. By adding 13C to the test meal, the GEBT 
can determine how fast the stomach empties the meal by measuring the rate of carbon-13 
dioxide (13CO2) excretion arising from the digested test meal. The rate of 13CO2 excretion 
found in the patient’s breath is proportional to the patient’s rate of gastric emptying. The 
patient’s 13CO2 excretion rate at each breath collection time is reported using the GEBT 
metric “kPCD.” The “k” is a multiplier of 1000, and “PCD” is an acronym for percent 13C 
dose excreted (as 13CO2). The test should not be administered to patients with a known 
allergy to egg, wheat, or algae (Spirulina) (Cairn Diagnostics™; Sutton et al, 2015; GEBT 
package insert, 2015; United States Food and Drug Administration, 2015).  
6.11 
Dispensing Study Drug  
Study drug will be dispensed on Day 1 along with a dosing diary to record all doses taken 
and times they were taken. A sufficient supply of study drug will be dispensed for dosing 
through Day 14. Details on the preparation of study drug, dosing guidelines, and storage will 
be provided in a pharmacy manual for the site and an instruction guide for patients. 
6.12 
Adverse Events Assessments 
An AE is defined as any untoward medical occurrence associated with the use of an 
intervention in humans, whether or not considered intervention-related. 
The occurrence of an AE or serious adverse event (SAE) (Section 6.12.6) may come to the 
attention of study personnel during study visits and interviews of a study patient presenting 
for medical care, or upon review by a study monitor. All AEs including local and systemic 
reactions not meeting the criteria for SAEs will be captured on the appropriate eCRF. 
Information to be collected includes, but is not limited to, the event description, time of 
onset, clinician’s assessment of severity, relationship to study drug (assessed only by those 
with the training and authority to make a diagnosis), and date of resolution/stabilization of 
the event. Action taken regarding study medication (e.g., drug withdrawn, interrupted) will 
also be collected in the eCRF. All AEs that start during the study must be documented 
appropriately regardless of relationship. All treatment-related AEs or AEs leading to 
discontinuation will be followed to an adequate resolution, as determined by the Investigator. 
Any medical condition that is present at the time that the patient is screened will be 
considered as medical history and not reported as an AE. However, if the patient’s condition 
deteriorates at any time during the study, it will be recorded as an AE. 
Changes in the severity of an AE will be documented to allow an assessment of the duration 
of the event at each level of severity to be performed. The AEs characterized as intermittent 
require documentation of onset and duration of each episode. 
6.12.1 
Reporting Timelines 
The Investigator will record all reportable events with start dates occurring any time after 
informed consent and continue through clinical study completion or, in the case of 
withdrawal, until the outcome is determined. The AEs will be assessed at each visit and/or 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 35 
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through telephone contact with the patient. A neutral question, such as “How have you been 
feeling since your last visit?” may be asked.  
All SAEs should be reported after the patient signs the informed consent and followed until 
resolution, stabilization, or until the Investigator provides sufficient evidence that no further 
information can be obtained. 
All SAEs and pregnancies (in a patient or partner of a male patient) occurring while the 
patient is on the study or within 30 (±3) days after the patient received the last dose of study 
drug must be reported within 24 hours of the knowledge of the event by study personnel 
whether or not considered to be related to study drug. 
Deaths that occur ≥30 (±3) days after the patient’s last study dose must be reported within 
24 hours of knowledge of the event, if deemed related to study drug by the Investigator. 
Although pregnancy is not considered an AE or SAE by regulatory definition, for this study 
pregnancies must be processed following SAE timelines (e.g., within 24 hours of knowledge 
of the pregnancy) for data transmission purposes. In the event that a pregnancy complication 
occurs, or elective termination of a pregnancy is required for medical reasons, then the 
complication will be recorded as an AE or SAE, as appropriate. 
While elective and uncomplicated induced abortion not required for medical reasons does not 
constitute an AE or SAE (even if the patient or patient’s partner is hospitalized to undergo 
abortion), spontaneous abortion is considered a fatal event and must be reported as an AE 
and SAE, as appropriate. 
Any pregnancy and/or suspected pregnancy that occurs during the study in a female patient 
should be reported using Pregnancy Reporting Form within 24 hours of knowledge of the 
event by study personnel. Any pregnancy and/or suspected pregnancy will be followed for 
outcome. 
If the patient has received the investigational drug prior to becoming pregnant, the patient 
will continue the efficacy assessment and Follow-up periods and measures of safety and 
efficacy will be obtained. 
The patient will be followed until the outcome of the pregnancy is determined. It is the 
responsibility of the Investigator to obtain and document pregnancy information on the most 
recent Pregnancy Report Form. Furthermore, any SAE occurring as an outcome of the 
pregnancy must be reported according to the procedures outlined for SAE reporting. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 36 
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6.12.2 
Severity 
The intensity of each AE will be graded as follows: 
Mild: 
Events require minimal or no treatment and do not interfere with the patient’s 
daily activities.  
Moderate: 
Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning.  
Severe: 
Events interrupt a patient’s usual daily activity and may require systemic 
drug therapy or other treatment. Severe events are usually potentially 
life-threatening or incapacitating.  
 
It is important to distinguish between serious and severe AEs. Severity is a measure of 
intensity; however, an AE of severe intensity need not necessarily be considered serious. For 
example, nausea that persists for several hours may be considered severe nausea but may not 
be considered an SAE. Alternatively, a stroke that results in only a limited degree of 
disability may be considered only a mild stroke but would be considered an SAE. 
6.12.3 
Relationship 
The Investigator’s assessment of causality must be provided for all AEs (serious and 
nonserious). An Investigator’s causality assessment is the determination of whether there 
exists a reasonable possibility that the study drug caused or contributed to an AE. For 
purposes of consistency, guidelines for assessing causality are provided below: 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 37 
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Not Related 
The AE is completely independent of study drug administration, and/or 
evidence exists that the event is definitely related to another etiology. There 
must be an alternative, definitive etiology documented by the clinician. 
No relationship between the experience and the administration of study drug; 
related to other etiologies such as concomitant medications or patient’s 
clinical state. 
Unlikely to be 
Related 
A clinical event, including an abnormal laboratory test result, whose 
temporal relationship to drug administration makes a causal relationship 
improbable (e.g., the event did not occur within a reasonable time after 
administration of the trial medication) and in which other drugs or chemicals 
or underlying disease provides plausible explanations (e.g., the patient’s 
clinical condition, other concomitant treatments). 
Possibly 
Related 
There is some evidence to suggest a causal relationship (e.g., the event 
occurred within a reasonable time after administration of the trial 
medication). However, other factors may have contributed to the event 
(e.g., the patient’s clinical condition, other concomitant events). Although an 
AE may rate only as “possibly related” soon after discovery, it can be 
flagged as requiring more information and later be upgraded to “probably 
related” or “definitely related,” as appropriate. 
Probably 
Related 
There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely. The clinical event, including an abnormal laboratory test 
result, occurs within a reasonable time after administration of the drug, is 
unlikely to be attributed to concurrent disease or other drugs or chemicals, 
and follows a clinically reasonable response on withdrawal (dechallenge). 
Rechallenge information is not required to fulfill this definition.  
Definitely 
Related 
There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an 
abnormal laboratory test result, occurs in a plausible time relationship to drug 
administration and cannot be explained by concurrent disease or other drugs 
or chemicals. The response to withdrawal of the drug (dechallenge) should 
be clinically plausible. The event must be pharmacologically or 
phenomenologically definitive, with use of a satisfactory rechallenge 
procedure if necessary.  
 
These criteria, in addition to good clinical judgment, should be used as a guide for 
determining the causal assessment. If the event is believed to be unrelated to study drug 
administration, then an alternative explanation should be provided, if available. 
6.12.4 
Expectedness 
An AE or suspected adverse reaction is considered “unexpected” if it is not listed in the 
Investigators’ Brochure or is not listed at the specificity or severity that has been observed; 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 38 
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or, if an Investigators’ Brochure is not required or available, is not consistent with the risk 
information described in the general investigational plan or elsewhere in the protocol. 
The drug safety medical reviewer will be responsible for determining whether an AE is 
expected or unexpected. An AE will be considered unexpected if the nature, severity, or 
frequency of the event is not consistent with the risk information previously described for the 
study agent (e.g., Investigators’ Brochure). 
6.12.5 
Clinical Laboratory Adverse Events 
Laboratory abnormalities should not be recorded as AEs or SAEs unless they are associated 
with clinical signs or symptoms or require medical intervention, as determined by the 
Investigator. However, each laboratory abnormality (e.g., clinically significant changes 
detected in hematology, serum chemistry panel, urinalysis, urine microscopic, and HbA1c 
evaluations) independent from any underlying medical condition that requires medical or 
surgical intervention, or that leads to study drug interruption or discontinuation, must be 
recorded as an AE, or SAE if applicable. If the laboratory abnormality is part of a clinical 
condition or syndrome, it should be recorded as the syndrome or diagnosis rather than as the 
individual laboratory abnormality. In addition, laboratory abnormalities or other abnormal 
test assessments (e.g., vital signs) performed that are associated with signs or symptoms must 
be recorded as AEs or SAEs if they meet the definition of an AE (or SAE) as described 
below. 
6.12.6 
Serious Adverse Events 
6.12.6.1 
Definition 
An SAE is defined as an AE or suspected adverse reaction occurring at any dose that results 
in any of the following outcomes: death, life-threatening AE, inpatient hospitalization or 
prolongation of existing hospitalization, a persistent or significant disability/incapacity or a 
substantial disruption of the ability to conduct normal life functions, or a congenital 
anomaly/birth defect. 
An AE or suspected adverse reaction is considered ‘‘life-threatening’’ if, in the view of either 
the Investigator or Sponsor, its occurrence places the patient at immediate risk of death. It 
does not include an AE or suspected adverse reaction that, had it occurred in a more severe 
form, might have caused death. 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical judgment, 
they may jeopardize the patient and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. Examples of such medical events include 
allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of 
drug dependency or drug abuse. Medical and scientific judgment should be exercised in 
deciding whether expedited reporting is appropriate in these other situations. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 39 
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6.12.6.2 
Suspected Unexpected Serious Adverse Reaction (SUSAR) 
The Sponsor must submit a safety report for any suspected adverse reaction to study 
treatment that is both serious and unexpected. Before submitting a safety report, the Sponsor 
needs to ensure that the event meets all 3 of the definitions: 
 Suspected adverse reaction 
 Serious 
 Unexpected 
If the AE does not meet all 3 of the definitions, it should not be submitted as a safety report. 
6.12.6.3 
Reporting Serious Adverse Events 
The Investigator will report all SAEs to the designated drug safety team within 24 hours of 
knowledge of the event whether or not considered to be related to study drug using the SAE 
Report Form provided. 
Although not all information required for a complete SAE Report Form may be readily 
available at the time of the event, the Investigator must include sufficient information on the 
SAE Report Form to allow for a complete medical assessment. This should include at a 
minimum the patient number, site number, detailed description of the event, seriousness 
criteria, causality/relationship to study drug, and Investigator signature. 
The designated drug safety team will acknowledge the receipt of the SAE via email to the 
clinical site. After submission of the initial report, the Investigator will provide follow-up 
information to the drug safety team as requested (e.g., concomitant medications, hospital 
discharge summary) to further evaluate the event and assure that all appropriate information 
is received. Once all information is received and the SAE has been deemed appropriate for 
closure, the SAE Report Form must be signed and dated by the Investigator. 
The Investigator is responsible for informing the Institutional Review Board (IRB) of the 
SAE in accordance with institutional policies and procedures including relevant initial and 
follow-up information about the SAE. 
Treatment-related SAEs or events leading to discontinuation of study drug will be followed 
for outcome information until resolution or stabilization. Other supporting documentation of 
the event may be requested by Censa Pharmaceuticals (or designee) and should be provided 
as soon as possible. The Medical Monitor should be contacted when the Investigator 
considers an SAE to be treatment-related. 
6.12.7 
Treatment-Emergent Adverse Events 
Those AEs that start at the time of or after the first dose of study drug are TEAEs. Those AEs 
that worsen at or after the time of first dose of study drug are also considered 
treatment-emergent. All AEs that occur on or after the ICF has been signed, including all 
TEAEs, through Day 29 will be recorded in the eCRF. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 40 
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All SAEs through Day 44 ±3 days [30 ±3 days after the patient received last dose of study 
drug] will be recorded in the eCRF and reported as described in Section 6.12.6.3. 
6.13 
Prior and Concomitant Medication Assessments 
All prescription and over-the-counter medications (including herbal medications) taken by a 
patient starting from the 30-day period before Screening through Day 28 (±1 day) before the 
patient leaves the clinic after completion of all EOS evaluations will be recorded. Any 
concomitant medications added or discontinued during the study will be recorded at each 
visit. 
6.14 
Removal of Patients From the Trial or Study Drug 
6.14.1 
Early Discontinuation From Study Drug Administration 
Premature discontinuation of study drug administration is defined as the discontinuation of 
study drug for an individual patient before the required full course of study drug is 
completed. Reasons for premature discontinuation from study drug administration should be 
recorded on the appropriate page(s) of the eCRF and may include, but are not limited to the 
following: 
 Occurrence of an AE, SAE, or clinically significant laboratory abnormality that, in the 
opinion of the Investigator, warrants the patient’s permanent discontinuation from study 
drug administration 
 In the judgment of the Investigator, the patient experiences a general or specific 
change(s) that renders the patient unsuitable for continued study drug administration 
 There is a need for concomitant medication that makes the patient ineligible for further 
study drug administration 
 Pregnancy 
Given the requirement for pregnancy testing in women of childbearing potential at Screening 
and the requirement for highly effective methods of contraception during the study, it is 
unlikely that pregnancies will occur during study conduct. However, study drug will be 
discontinued should suspected or confirmed pregnancy or nursing during the study drug 
administration period occur. 
Patients who prematurely discontinue study drug due to any of the above reasons will 
complete the EOT assessments within 24 hours of withdrawal.  


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 41 
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6.14.2 
Withdrawal From the Study 
Patients may withdraw from the study for any reason or be withdrawn at the request of the 
Investigator or Sponsor. The reason for a patient’s withdrawal must be recorded on the 
appropriate page(s) of the eCRF. Reasons for withdrawal from the study may include, but are 
not limited to: 
• Withdrawal of consent  
• AEs or SAEs 
• Significant patient noncompliance, defined as refusal or inability to adhere to the protocol 
requirements 
• The Investigator determines that it is in the best interest of the patient to withdraw from 
study participation, due to a reason other than safety 
Each patient who withdraws from the study after receipt of any amount of study drug will be 
asked to undergo EOT assessments. However, patients may withdraw consent to participate 
in this study at any time without penalty. Withdrawn patients who receive any amount of 
study drug, will not be replaced. Withdrawn patients who do not receive any study drug will 
be replaced. 
6.14.3 
Study Stopping Criteria 
The study may be terminated if significant violations of Good Clinical Practice (GCP) that 
compromise the ability to achieve the study objectives or compromise patient safety are 
observed at any time during the study. With regard to safety, the study may be temporarily 
suspended or terminated should the Investigator, Sponsor, or IRB determine that the safety of 
patients is significantly jeopardized. The decision for a temporary or permanent study hold 
will depend on the nature, frequency, and severity of AEs that were observed in all enrolled 
patients to date. In a temporary study hold, no additional patients will be enrolled into the 
study or dosed with study drug until the study team members (including the Investigator and 
the Medical Monitor) decide it is safe to proceed with the study.  
6.15 
Appropriateness of Measurements 
Safety will be measured by AEs (including SAEs), vital signs, physical examinations, and 
clinical laboratory and HbA1c tests.  
Because treatment with BH4 is hypothesized to restore nNOS function in the control of 
gastric accommodation, the nutrient satiety test (Section 6.7) was chosen for the primary 
endpoint for this study. Gastric accommodation has been measured using ultrasonography 
(Undeland et al, 1998), single-photon emission computed tomography (Bredenoord et al, 
2003), and barostat testing (Coulie et al, 1998; Sarnelli et al, 2001). Barostat studies have 
been shown to be reproducible (Sarnelli et al, 2001) but are invasive and not widely 
available. Satiety testing using a nutrient liquid has been shown to be reproducible (Kindt et 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 42 
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al, 2008) and correlate with impairment in gastric accommodation but not gastric emptying 
or visceral sensitivity (Tack et al, 2003). 
The GEBT is nonradioactive, noninvasive test of gastric emptying rate that has been 
validated against the reference method of gastric scintigraphy. It has been accepted by the 
United States Food and Drug Administration (FDA) for use in the measurement of the rate of 
gastric emptying of solids and as an aid in the diagnosis of delayed gastric emptying 
(gastroparesis) in adult humans who are symptomatic for gastroparesis. The GEBT can 
determine how fast the stomach empties a standardized meal with a 13C-labeled egg 
component by measuring the ratio of 13CO2 to carbon-12 dioxide (12CO2) collected in breath 
samples at multiple time points after the meal is consumed compared to baseline. The breath 
samples are collected in capped glass tubes and sent to a specified local laboratory for 
analysis. By measuring the change in the ratio of 13CO2 to 12CO2 over time in comparison to 
the premeal value, the rate of 13CO2 excretion can be calculated and the gastric emptying rate 
determined. The GEBT does not require administration by specially trained health care 
professionals or special precautions related to radiation-emitting compounds (Section 6.10).  
The GCSI (Section 6.8, Appendix 2), consisting of a subset of items from the PAGI-SYM 
instrument (Section 6.9, Appendix 2) (described below), is based on reviews of the medical 
literature and results from clinician interviews and patient focus groups. Its reliability and 
validity were examined in 169 gastroparesis patients from 7 clinical centers in the US. 
Patients completed the GCSI, SF-36 Health Survey, and disability day questions at baseline 
and again at 8 weeks. Clinicians independently rated the severity of the patients' symptoms, 
and both clinicians and patients rated the changes in gastroparesis-related symptoms over the 
8weeks. For the GCSI total score, the internal consistency reliability was 0.84, and the test-
re-test reliability was 0.76. Significant relationships were observed between the clinician-
assessed symptom severity and the GCSI total score, and significant associations were found 
between the GCSI scores and SF-36 physical and mental component summary scores and 
restricted activity and bed disability days. Patients with greater symptom severity, as rated by 
clinicians, reported greater symptom severity on the GCSI. The GCSI total scores were 
responsive to changes in overall gastroparesis symptoms as assessed by clinicians 
(p = 0.0002) and patients (p = 0.002) (Revicki et al, 2003). 
The PAGI-SYM (Section 6.9, Appendix 2) is a 20-item upper GI symptom severity 
instrument with 6 subscales: heartburn/regurgitation, fullness/early satiety, nausea/vomiting, 
bloating, upper abdominal pain, and lower abdominal pain. To develop the instrument, 
patients with GERD (n = 810), dyspepsia (n = 767), or gastroparesis (n = 169) from the US, 
France, Germany, Italy, the Netherlands, and Poland completed the PAGI-SYM, the SF-36 
Health Survey, a disease-specific health-related quality of life measure (Patient Assessment 
of Upper Gastrointestinal Disorders-Quality of Life [PAGI-QOL]), and disability day 
questions. Two-week reproducibility was evaluated in 277 stable patients. Construct validity 
was evaluated by correlating subscale scores with SF-36, PAGI-QOL and global symptom 
severity scores and disability days. Internal consistency reliability ranged from 0.79 to 0.91, 
and test-retest reliability ranged from 0.60 to 0.82 for the PAGI-SYM subscales. The 
PAGI-SYM subscale scores correlated significantly with SF-36 scores (all p <0.0001), 
PAGI-QOL scores (all p <0.0001), disability days (p <0.0001), and global symptom severity 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 43 
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(p <0.0001). Mean PAGI-SYM scores varied significantly in groups defined by disability 
days (all p <0.0001), in which greater symptom severity was associated with more disability 
days (Rentz et al, 2004; Revicki et al, 2004). 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 44 
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7 
STUDY ACTIVITIES 
7.1 
Screening Procedures (Day –28 to Day -1) 
The following will be performed/collected during the Screening Period from Day -28 to 
Day -1 after obtaining informed consent with a properly signed ICF (Section 10.4): 
• Obtain demographic data (age, gender, self-reported race/ethnicity) 
• Obtain medical/surgical history, including specific information related to any prior or 
existing medical conditions or surgical procedures involving the dermatologic, HEENT, 
lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and neurological systems 
(Section 6.2) 
• Obtain vital signs (blood pressure, pulse, respiratory rate, and temperature) prior to 
collection of any laboratory samples and after patients have rested for 5 minutes in a 
supine position; obtain the patient’s weight (as necessary to determine the response to 
Exclusion Criterion #5 [Section 4.3] and on Day -1) and height (Section 6.3) 
• Conduct a complete physical examination, including assessments of general appearance, 
dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and 
neurological parameters (Section 6.4) 
• Collect blood samples for clinical chemistry, hematology, and HbA1c after the patient 
has fasted overnight (a minimum of 8 hours before blood sample collection) and a urine 
sample for urinalysis (Section 6.5) 
• Perform a serum pregnancy test for all women who are of childbearing potential  
• Obtain 12-lead ECGs in triplicate, with 1 minute separating the first and second 
recordings and 1 minute separating second and third recordings (Section 6.6) 
 Administer the GCSI (Section 6.8, Appendix 2) 
• Record all prescription and over-the-counter medications (including herbal medications) 
taken within 30 days before the Screening 
• Assess/record AEs from the time of informed consent 
• Administer the nutrient satiety test (Section 6.76.10) after the patient has fasted overnight 
and after any medications that can alter GI sensation or accommodation or gastric 
emptying have been held overnight 
• Confirm patient meets inclusion criteria and no exclusion criteria (Section 4.2 and 
Section 4.3, respectively) 
• Administer the GEBT (Section 6.10) on Day -1 after the patient has fasted overnight (a 
minimum of 8 hours before test administration with the exception of 4 ounces of water up 
to 1 hour before the test) 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 45 
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• Instruct the patient regarding fasting overnight before blood is drawn for the clinical 
laboratory evaluations (Section 6.5) and the nutrient satiety test (Section 6.7) is 
administered on Day 1 predose 
• Instruct the patient regarding not taking any medications that can alter GI sensation or 
accommodation or gastric emptying overnight before the days of the nutrient satiety test 
(Section 6.7)  
• Randomize patient on Day -1 
7.2 
Day 1 Predose 
The following will be performed/collected on Day 1 in the clinic before the patient receives 
study drug: 
 Obtain medical/surgical history since Screening, including specific information related to 
any prior or existing medical conditions or surgical procedures involving the 
dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and 
neurological systems (Section 6.2) 
 Obtain vital signs (blood pressure, pulse, respiratory rate, and temperature) prior to 
collection of any laboratory samples and after patients have rested 5 minutes in a supine 
position (Section 6.3) 
 Conduct a complete physical examination, including assessments of general appearance, 
dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and 
neurological parameters (Section 6.4) 
 Collect blood samples for clinical chemistry, and hematology after the patient has fasted 
overnight (a minimum of 8 hours before blood sample collection) and a urine sample for 
urinalysis (Section 6.5) 
 Perform a urine pregnancy test for all women who are of childbearing potential; confirm 
any positive urine pregnancy test by performing a serum pregnancy test 
 Record all prior prescription and over-the-counter medications (including herbal 
medications) taken since Screening 
 Assess/record AEs since Screening 
 Administer:  
o Nutrient satiety test (Section 6.76.10) 
o GCSI (Section 6.8, Appendix 2) 
o PAGI-SYM (Section 6.9, Appendix 2) 
7.3 
Day 1 After Baseline Evaluations Through Day 13 
7.3.1 
Day 1  
• Administer first dose of study drug in the clinic 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 46 
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• Obtain vital signs (blood pressure, pulse, respiratory rate, and temperature) 2 hours 
postdose after patients have rested 5 minutes in a supine position (Section 6.3) 
• Dispense study drug and instruct the patient on its preparation and administration BID 
starting with the second dose on Day 1 and continuing through Day 14 (Section 5.2 and 
Section 6.11) 
• Dispense dosing diary and instruct the patient on its completion (Section 5.8.1) 
• Instruct the patient not to take any Day 14 doses of study drug before the Day 14 clinic 
visit, and to bring the dosing diary and all study drug supplies to the Day 14 visit 
• Record all medications the patient received since the predose assessment 
• Assess/record AEs since the predose assessment 
• Instruct the patient regarding fasting overnight before blood is drawn for the clinical 
laboratory evaluations, the nutrient satiety test (Section 6.7), and the GEBT 
(Section 6.10) on Day 14 and/or on Day 15  
• Instruct the patient regarding not taking any medications that can alter GI sensation or 
accommodation or gastric emptying overnight before the Day 14 visit (for the nutrient 
satiety test)  
7.4 
Early Termination Procedures 
If a patient discontinues study drug early (Section 6.14.1), the patient should return to the 
study site within 24 hours of withdrawal and complete all of the procedures outlined for the 
EOT (Section 7.5). If a patient withdraws early from the study (Section 6.14.2), the patient 
will be asked to return to the study site within 24 hours of withdrawal and complete all of the 
procedures outlined for the EOT (Section 7.5). All study drug and supplies and the dosing 
diary will be collected.  
7.5 
End of Treatment Visits (Day 14 and Day 15) 
Patients will complete EOT visit(s) at early termination (Section 7.4) or on Day 14 and 
Day 15. During the EOT visits, the following will be completed: 
 Obtain vital signs (blood pressure, pulse, respiratory rate, and temperature), prior to 
collection of any laboratory samples and after patients have rested 5 minutes in a supine 
(Section 6.3) on Day 14 or Day 15 
 Conduct a complete physical examination, including assessments of general appearance, 
dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and 
neurological parameters (Section 6.4) on Day 14 or Day 15 
• Collect blood samples for clinical chemistry, hematology, and HbA1c after the patient 
has fasted overnight (a minimum of 8 hours before blood sample collection) and a urine 
sample for urinalysis (Section 6.5) on Day 14 or Day 15 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 47 
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 Perform a urine pregnancy test for all women who are of childbearing potential; confirm 
any positive urine pregnancy test by performing a serum pregnancy test on Day 14 or 
Day 15 
 Administer:  
o Nutrient satiety test (Section 6.76.10) on Day 14 
o GCSI (Section 6.8, Appendix 2) on Day 14 or Day 15 
o PAGI-SYM (Section 6.9, Appendix 2) on Day 14 or Day 15 
o GEBT (Section 6.10) on Day 15 
 Administer first Day 14 dose of study drug on Day 14; administer the second Day 14 
dose of study drug on Day 14 or instruct patient to take second Day 14 dose of study drug 
on Day 14 after the patient leaves the clinic 
 Record all prescription and over-the-counter medications (including herbal medications) 
taken since the Day 1 visit through Day 15 before the patient leaves the clinic 
 Assess/record AEs since last visit through Day 15 before the patient leaves the clinic 
 Collect study drug, dosing diary, and assess study drug compliance on Day 14 if the 
patient takes the last dose of study drug on Day 14 while in the clinic or, if the patient 
takes the last dose of study drug on Day 14 after leaving the clinic, on Day 15 
 Instruct the patient regarding fasting overnight before blood is drawn for the clinical 
laboratory evaluations on Day 28 (±1 day), the nutrient satiety test (Section 6.7) on 
Day 28, and the GEBT (Section 6.10) on Day 27 or Day 29 
 Instruct the patient regarding not taking any medications that can alter GI sensation or 
accommodation or gastric emptying overnight before the Day 28 visit (for the nutrient 
satiety test) 
7.6 
End of Study (Day 28 ±1 Day) 
Patients will complete the EOS assessments on Days 27 through Day 29. The following EOS 
assessments will be completed: 
• Obtain vital signs (blood pressure, pulse, respiratory rate, and temperature), prior to 
collection of any laboratory samples and after patients have rested 5 minutes in a supine 
position (Section 6.3) on Day 28 (±1 day) 
 Conduct a complete physical examination, including assessments of general appearance, 
dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and 
neurological parameters (Section 6.4) on Day 28 (±1 day) 
• Collect blood samples for clinical chemistry, hematology, and HbA1c after the patient 
has fasted overnight (a minimum of 8 hours before blood sample collection) and a urine 
sample for urinalysis (Section 6.5) on Day 28 (±1 day) 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 48 
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 Perform a urine pregnancy test for all women who are of childbearing potential; confirm 
any positive urine pregnancy test by performing a serum pregnancy test on Day 28 
(±1 day) 
 Administer:  
o Nutrient satiety test (Section 6.76.10) on Day 28 
o GCSI (Section 6.8, Appendix 2) on Day 28 (±1 day) 
o PAGI-SYM (Section 6.9, Appendix 2) on Day 28 (±1 day) 
o GEBT (Section 6.10) on Day 27 or Day 29 
 Collect study drug, dosing diary, and assess study drug compliance on Day 28 (±1 day) 
(if not done on Day 14 or Day 15)  
 Record all prescription and over-the-counter medications (including herbal medications) 
taken since the last visit through Day 28 (±1 day) before the patient leaves the clinic after 
completion of all EOS evaluations  
 Assess/record AEs since last visit through Day 28 (±1 day) before the patient leaves the 
clinic after completion of all EOS evaluations 
7.7 
Telephone Follow-up Day 44 (±3 Days) (30 ±3 Days After Last Dose) 
During telephone Follow-up on Day 44 (±3 days), the following will be completed: 
 Call the patient to see if any SAEs were experienced during the 30 ±3 days after the last 
dose of study drug  
 Record SAEs in the eCRF, if applicable 
 Report SAEs following SAE reporting timelines per Section 6.12.1 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 49 
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8 
QUALITY CONTROL AND ASSURANCE 
Regular monitoring and an independent audit, if conducted, must be performed according to 
International Council on Harmonisation (ICH)-GCP (Section 10.6). 
Quality control procedures will be implemented beginning with the data entry system and 
data quality control checks that will be run on the database will be generated. Any missing 
data or data anomalies will be communicated to the site(s) for clarification/resolution. 
Following written Standard Operating Procedures, the monitors will verify that the clinical 
trial is conducted and data are generated, documented (recorded), and reported in compliance 
with the protocol, GCP, and the applicable regulatory requirements (e.g., GLPs, Good 
Manufacturing Practices). 
The investigational site will provide direct access to all trial-related sites, source 
data/documents (including patient diaries), and reports for the purpose of monitoring and 
auditing by Censa Pharmaceuticals (or designee), and inspection by local and regulatory 
authorities. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 50 
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9 
PLANNED STATISTICAL METHODS 
9.1 
General Considerations 
Descriptive statistics, including numbers and percentages for categorical variables, and 
numbers, means, standard deviations, medians, minimums, and maximums for continuous 
variables will be provided. Exploratory analyses may also be performed. Listings of 
individual patient data will be produced. Additional details can be found in the statistical 
analysis plan. 
9.2 
Determination of Sample Size 
The primary objective of this study is to assess the impact of CNSA-001 on gastric 
accommodation, as measured by nutrient satiety testing (Section 6.7), in women with 
moderate to severe diabetic gastroparesis. A total of 10 patients will be enrolled in each 
treatment group. If it is assumed that the standard deviation for the change from baseline in 
nutrient meal volume ingested is approximately 235 mL (data on file), and using a one-sided 
t-test at the 0.025 significance level, this trial has 80% power to detect a treatment difference 
greater than 288 mL (i.e., an effect size of 1.23) in the CNSA-001group. The study also has 
90% power to detect a treatment difference greater than 330 mL (i.e., an effect size of 1.41) 
in the CNSA-001 group. 
9.3 
Analysis Populations 
Two study populations will be analyzed: 
 Safety population: all patients who were randomized and received any amount of study 
drug (CNSA-001 or placebo) 
 Efficacy population: all patients who were randomized, received any amount of study 
drug (CNSA-001 or placebo), and had available Day 1 predose and Day 14 nutrient 
satiety test (Section 6.7) maximum tolerated volume results 
9.4 
Demographics, Baseline Characteristics, Enrollment, Protocol Deviations, 
and Patient Disposition 
Enrollment, protocol deviations, demographics (age, sex, race/ethnicity), prior and 
concomitant medications, and medical history will be summarized by treatment group using 
descriptive statistics. Discontinuations from study drug and the study will be summarized by 
treatment group as well and the reasons for discontinuation will be listed. 
9.5 
Statistical Analysis of Efficacy Variables 
Efficacy will be assessed in the Efficacy population.  
The primary efficacy measure will be the changes in maximal tolerated volume consumed 
during the nutrient satiety test (Section 6.7) from Day 1 to Day 14 and Day 28. The changes 
from Day 1 to Day 14 and from Day 1 to Day 28 in maximal tolerated volume consumed 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 51 
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during the nutrient satiety test will be compared between treatment groups using a student’s 
t-test.  
Secondary efficacy measures will consist of changes in the following from baseline through 
Day 14 (±1 day) and through Day 28 (±1 day):  
 PAGI-SYM (Section 6.9, Appendix 2) subscale (heartburn/regurgitation, fullness/early 
satiety, nausea/vomiting, bloating, upper abdominal pain, and lower abdominal pain) 
scores 
 Gastric emptying as measured by the GEBT (Section 6.10) 
The primary and secondary measures will be summarized by treatment group at each visit as 
well as changes from baseline using summary statistics (number of patients, mean, standard 
deviation, median, and range) including 95% confidence intervals for changes from baseline. 
Additional analyses may be conducted, and details will be provided in the statistical analysis 
plan (SAP). 
9.6 
Safety Analysis 
Safety will be assessed in the Safety population. The AEs will be coded using the Medical 
Dictionary for Regulatory Activities (MedDRA®). The number and percentage of patients 
with TEAEs will be tabulated by system organ class, preferred term, and treatment group. 
Severity of AEs and SAEs will be summarized similarly. Those AEs leading to premature 
discontinuation from the study drug and the serious TEAEs will be presented in a table or a 
listing. Clinical laboratory and HbA1c test results and vital signs will be summarized at each 
visit as will changes from baseline for each treatment group. A frequency distribution of 
abnormal physical examination results will be provided. Additional details will be provided 
in the SAP. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 52 
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10 
ADMINISTRATIVE CONSIDERATIONS 
10.1 
Investigators and Study Administrative Structure 
Table 1 summarizes the administrative structure for this study. 
Table 1: 
Administrative Structure for GAS-001 Study 
Contract Research Organization 
InClin, Inc.  
2655 Campus Drive, Suite 100 
San Mateo, CA, 94403 
Phone: 
 
 
10.2 
Institutional Review Board Approval 
The Investigator will submit this protocol, any protocol modifications, and the patient 
consent form to be utilized in this study, to the appropriate IRB for review and approval. This 
committee must operate in accordance with the ICH GCP. Documentation of approval of the 
protocol and the informed consent document must be forwarded to Censa Pharmaceuticals 
(or designee) prior to initiation of this study. 
The Investigator is responsible for assuring continuing review and approval of the clinical 
study. The Investigator must also promptly report all changes in the research activity and all 
unanticipated problems involving risk to the patients or others to his/her IRB. The 
Investigator will not make any changes in the protocol without IRB approval except as 
necessary to eliminate apparent immediate hazards to the patients. The Investigator will 
provide progress reports to the IRB as required by the IRB. If the study remains in progress 
for >1 year, the Investigator must obtain annual renewal and re-approval from the IRB. 
Documentation of renewal must be submitted to Censa Pharmaceuticals (or designee). The 
Investigator will provide notice to the IRB of completion of participation in the study. 
10.3 
Ethical Conduct of the Study 
This study will be conducted in compliance with the protocol; GCPs, including ICH 
Technical Requirements for Registration of Pharmaceuticals for Human Use Guidelines; 
applicable regional regulatory requirements (i.e., ICH E6); and in accordance with the ethical 
principles of the Declaration of Helsinki. 
10.4 
Patient Information and Consent 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate 
in the study and continues throughout the individual’s study participation. Discussion in 
understandable terms of the purposes, procedures, risks and possible benefits of participation, 
and rights of study patients will be conducted with patients, and, as appropriate, their legally 
authorized representatives (LARs; henceforth in the discussion of informed consent, study 
patient means “patient and/or LAR”) and family members. The study patients should have 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 53 
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the opportunity to discuss the study with their surrogates or think about it prior to agreeing to 
participate. Study patients will be asked to carefully review the ICF approved by Censa 
Pharmaceuticals (or designee) and the IRB. After any needed discussion and consideration of 
study participation and before undergoing any procedures specifically for the study, the 
patient will sign the ICF. The ICF will be retained in the study patient’s study records, and a 
copy of the ICF will be given to the study patient. 
Patients may decline to participate in the study and withdraw consent at any time or for any 
reason throughout the course of the study without AEs on the quality of their medical care. 
10.5 
Confidentiality 
The Investigator must assure that patients’ anonymity is strictly maintained and that their 
identities are protected from unauthorized parties. This extends to testing of biological 
samples and genetic tests in addition to the clinical information relating to participants. Only 
an identification code (i.e., not names) should be recorded on any form or document 
submitted to Censa Pharmaceuticals, the Contract Research Organization (CRO), or the IRB. 
The Investigator must keep logs on screened and enrolled patients. In addition, the 
Investigator must have a list where the identity of all treated patients can be found. 
The Investigator agrees that all information received from Censa Pharmaceuticals, including, 
but not limited to, the Investigator’s Brochure, this protocol, CRFs, and any other 
information related to the protocol-specified treatment of the study, remain the sole and 
exclusive property of Censa Pharmaceuticals during the conduct of the study and thereafter. 
This information is not to be disclosed to any third party (except employees or agents directly 
involved in the conduct of the study or as required by law) without prior written consent from 
Censa Pharmaceuticals. The Investigator further agrees to take all reasonable precautions to 
prevent the disclosure by any employee or agent of the study center to any third party or 
otherwise into the public domain. 
The study monitor, other authorized representatives of Censa Pharmaceuticals, and 
representatives of the IRB may inspect all documents and records required to be maintained 
by the Investigator, including but not limited to, medical records (office, clinic, and hospital) 
and pharmacy records for the participants in this study. The clinical study site’s research staff 
will permit access to such records. 
The study patient’s contact information will be securely stored at each clinical site for 
internal use during the study. At the end of the study, all records will be kept in a secure 
location for as long a period as dictated by local IRB and Institutional regulations. 
10.6 
Study Monitoring 
A clinical monitor authorized to represent Censa Pharmaceuticals will conduct site visits to 
inspect study data, patient’s medical records, and eCRFs in accordance with ICH guidelines 
GCP, and applicable regulations and guidelines. The clinical monitor will also monitor 
ongoing drug accountability and adherence to protocol procedures. Details of clinical site 
monitoring are specified in a Clinical Monitoring Plan. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 54 
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Independent audits may be conducted to ensure that monitoring practices are performed 
consistently across all participating sites and that monitors are following the Clinical 
Monitoring Plan. 
The Investigator will allow representatives of the Censa Pharmaceuticals and regulatory 
authorities to inspect facilities and records relevant to this study. 
10.7 
Case Report Forms and Study Records 
The eCRFs will be supplied by Censa Pharmaceuticals or designee for the recording of all 
information and study data as specified by this protocol. Original eCRF data should be 
handled in accordance with instructions from Censa Pharmaceuticals or designee. All eCRFs 
must be completed by the clinical study site’s research staff authorized to do so by the 
Investigator. The Investigator is responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported. 
Data reported in the eCRF derived from source documents should be consistent with the 
source documents. Source documents are defined as records of documentation related to 
original observations and activities of a clinical investigation. Source documents may 
include, but are not limited to, study progress notes, study- or patient-specific email 
correspondence, computer printouts, laboratory data, and recorded data from automated 
instruments. All source documents produced in this study will be maintained by the 
Investigator and made available for inspections by Censa Pharmaceuticals or designee and by 
regulatory authorities. The original ICF for each participating patient shall be filed with 
records kept by the Investigator, and copies shall be given to the patient. 
Once all data queries and issues have been resolved for each patient the Investigator will 
electronically sign each patient’s eCRF. This signature will indicate that the data have been 
thoroughly inspected and will thereby certify the contents of the eCRF. 
Clinical data will be entered into a 21 Code of Federal Regulations (CFR) Part 11-compliant 
electronic data capture system. The data system includes password protection and internal 
quality checks, such as automatic range checks, to identify data that appear inconsistent, 
incomplete, or inaccurate. Clinical data will be entered by the clinical study site’s research 
staff directly from the source documents. 
10.8 
Protocol Violations/Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol requirements. The 
noncompliance may be either on the part of the patient, the Investigator, or the study site 
staff. Because of deviations, corrective actions are to be developed by the site and 
implemented promptly. This is consistent with the following sections in ICH E6: 
• 4.5 Compliance with Protocol, Sections 4.5.1, 4.5.2, and 4.5.3 
• 5.1 Quality Assurance and Quality Control, Section 5.1.1 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 55 
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• 5.20 Noncompliance, Sections 5.20.1, and 5.20.2. 
10.9 
Access to Source Documentation 
The Investigator agrees by his/her participation that the results of this study may be used for 
submission for national or international registration. If required, national or international 
authorities will be provided with the name of the Investigator and his or her address, full 
disclosure of his or her qualifications, any potential conflicts of interests, payments, and 
extent of involvement. 
During site visits, the clinical monitor will review original patient records, drug 
accountability records, and additional documents as needed. During the course of the study, 
Censa Pharmaceutical’s (or designee’s) Quality Assurance personnel may conduct an on-site 
audit visit. The Investigator will provide direct access to and allow verification and copying 
of all trial-related documents (e.g., source data) for trial-related monitoring, audits, IRB 
reviews, and regulatory inspections. 
10.10 
Data Generation and Analysis 
Some or all of the obligations of implementing or conducting this study may be transferred 
from Censa Pharmaceuticals to the CRO. 
A case report, comprised of individual eCRFs, will be completed for every patient who signs 
an ICF and is enrolled into the study. 
All original source documentation (laboratory results, treatment records, audit query 
responses, etc.) will be retained by the Investigator or institution unless specified otherwise 
by the protocol. The results as they become available will be entered on the appropriate 
eCRFs. Legible reproductions of the original laboratory reports for selected tests or variables 
will be submitted to Censa Pharmaceuticals or CRO as requested. 
The eCRFs will be reviewed by a clinical monitor who will evaluate the completeness and 
accuracy of the data. Queries will be generated for omissions, corrections, and clarifications. 
Data may also be reviewed in-house by a clinical auditor and data management or other 
personnel. 
Data analyses will be performed after database lock, when all queries have been resolved. 
10.11 
Retention of Data 
Study documents should be retained for a minimum of 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region or until at least 2 years have elapsed since the 
formal discontinuation of clinical development of the investigational product. These 
documents should be retained for a longer period, however, if required by local regulations. 
No records will be destroyed without the written consent of Censa Pharmaceuticals, if 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 56 
FINAL 06SEP2018 
 
CONFIDENTIAL 
applicable. It is the responsibility of Censa Pharmaceuticals to inform the Investigator when 
these documents no longer need to be retained. 
10.12 
Financial Disclosure 
Each Investigator must submit to Censa Pharmaceuticals (or designee) financial disclosure 
information according to national law and/or local regulations. 
10.13 
Publication and Disclosure Policy 
The data generated in this clinical study are the exclusive property of Censa Pharmaceuticals 
and are confidential. Authorship on any publication of the results from this study will be 
based on contributions to study design, patient enrollment, data analysis, interpretation of 
results, and drafting and editing of any publication in accordance with published authorship 
ethical guidelines for publication of research studies. Independent analysis and/or publication 
of these data by the Investigator(s) or any member of their staff is not permitted without the 
prior, written consent of Censa Pharmaceuticals. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 57 
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11 
REFERENCE LIST 
Anaparthy R, Pehlivanov N, Grady J, et al. Gastroparesis and gastroparesis-like syndrome: 
response to therapy and its predictors. Dig Dis Sci. 2009 May;54(5):1003-10. 
Arts J, Caenepeel P, Verbeke K, et al. Influence of erythromycin on gastric emptying and 
meal related symptoms in functional dyspepsia with delayed gastric emptying. Gut. 2005 
Apr;54(4):455-60. 
Bredenoord AJ, Chial HJ, Camilleri M et al. Gastric accommodation and emptying in 
evaluation of patients with upper gastrointestinal symptoms. Clin Gastroenterol Hepatol. 
2003 Jul;1(4):264-72 
Cairn Diagnostics™. Interpreting Cairn Gastric Emptying Breath Test results. Available 
from https://cairndiagnostics.com/wp-
content/uploads/2016/08/interpretation_of_cairn_gebt_test_results_101915.pdf. Accessed 
2018 Aug 15. 
Camilleri M, Parkman HP, Shafi MA, et al. Clinical Guideline: Management of 
Gastroparesis. Clinical Guideline: Management of Gastroparesis. The American journal of 
gastroenterology. 2013;108(1):18-38. 
Coulie B, Tack J, Peeters T, et al. Involvement of two different pathways in the motor effects 
of erythromycin on the gastric antrum in humans. Gut. 1998 Sep;43(3):395-400. 
Fass R. Treatment Options for Diabetic Gastroparesis. Gastroenterology and Hepatology 
Volume 6, Issue 6, Supplement 9 June 2010. 
Feldman M, Schiller LR. Disorders of gastrointestinal motility associated with diabetes 
mellitus. Ann Intern Med. 1983 Mar;98(3):378-84. 
Gangula PR, Maner WL, Micci MA, et al. Diabetes induces sex-dependent changes in 
neuronal nitric oxide synthase dimerization and function in the rat gastric antrum. Am J 
Physiol Gastrointest Liver Physiol. 2007 Mar;292(3):G725-33. 
Gastric Emptying Breath Test (GEBT) [package insert]. Brentwood TN: ADVANCED 
BREATH DIAGNOSTICS LLC; 2015 Apr. 
Hoogerwerf WA, Pasricha PJ, Kalloo AN, et al. Pain: the overlooked symptom in 
gastroparesis. Am J Gastroenterol. 1999 Apr;94(4):1029-33. 
Horowitz M, O'Donovan D, Jones KL, et al. Gastric emptying in diabetes: clinical 
significance and treatment. Diabet Med. 2002 Mar;19(3):177-94. 
Ishiguchi T, Nakajima M, Sone H, et al. Gastric distension-induced pyloric relaxation: 
central nervous system regulation and effects of acute hyperglycaemia in the rat. J Physiol. 
2001 Jun 15;533(Pt 3):801-13. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 58 
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Karamanolis G, Caenepeel P, Arts J, et al. Determinants of symptom pattern in idiopathic 
severely delayed gastric emptying: gastric emptying rate or proximal stomach dysfunction? 
Gut. 2007 Jan;56(1):29-36. 
Khoury V, Dubois, D. GCSI Gastroparesis Cardinal Symptom Index information booklet. 
2nd ed. Lyon, France: Mapi Research Trust; 2015. p 30. 
Kindt S, Coulie B, Wajs E, Janssens J, Tack J. Reproducibility and symptomatic predictors 
of a slow nutrient drinking test in health and in functional dyspepsia. Neurogastroenterol 
Motil. 2008 Apr;20(4):320-9. 
Kumar A, Attaluri A, Hashmi S, et al. Visceral hypersensitivity and impaired 
accommodation in refractory diabetic gastroparesis. Neurogastroenterol Motil. 2008 
Jun;20(6):635-42. 
Mayer B, Werner ER. In search of a function for tetrahydrobiopterin in the biosynthesis of 
nitric oxide. Naunyn Schmiedebergs Arch Pharmacol. 1995;351(5):453-463. 
Park MI. How to Interpret Nutrition Drink Test. Journal of Neurogastroenterology and 
Motility. 2011;17(1):88-90. 
Parkman HP, Hasler WL, Fisher RS, et al, American Gastroenterological Association 
technical review on the diagnosis and treatment of gastroparesis. Gastroenterology. 2004 
Nov;127(5):1592-622.   
Prakash A, Wagstaff AJ. Domperidone. A review of its use in diabetic gastropathy. Drugs. 
1998 Sep;56(3):429-45. 
Rentz AM, Kahrilas P, Stanghellini V, et al. Development and psychometric evaluation of 
the Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM) in 
patients with upper gastrointestinal disorders. Qual Life Res. 2004 Dec;13(10):1737-49. 
Revicki DA, Rentz AM, Dubois D, et al. Development and validation of a patient-assessed 
gastroparesis symptom severity measure: the Gastroparesis Cardinal Symptom Index. 
Aliment Pharmacol Ther. 2003 Jul 1;18(1):141-50.  
Revicki DA, Rentz AM, Tack J, et al. Responsiveness and interpretation of a symptom 
severity index specific to upper gastrointestinal disorders. Clin Gastroenterol Hepatol. 2004 
Sep;2(9):769-77. 
Sarnelli G, Vos R, Cuomo R, et al. Reproducibility of gastric barostat studies in healthy 
controls and in dyspeptic patients. Am J Gastroenterol. 2001 Apr;96(4):1047-53. 
Sawabe K, Yamamoto K, Kamata T, et al. (2002) Sepiapterin Administration Raises Tissue 
BH4 Levels More Efficiently Than BH4 Supplement in Normal Mice. In: Milstien S, et al. 
(eds) Chemistry and Biology of Pteridines and Folates. Springer Science+Business Media 
New York. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 59 
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Snape WJ, Jr., Battle WM, Schwartz SS, et al. Metoclopramide to treat gastroparesis due to 
diabetes mellitus: a double-blind, controlled trial. Ann Intern Med. 1982 Apr;96(4):444-6. 
Soykan I, Sivri B, Sarosiek I, et al. Demography, clinical characteristics, psychological and 
abuse profiles, treatment, and long-term follow-up of patients with gastroparesis. Dig Dis 
Sci. 1998 Nov;43(11):2398-404. 
Stacher G. Diabetes mellitus and the stomach. Diabetologia. 2001 Sep;44(9):1080-93. 
Sutton KL, Sims CD, Honeywell MS. et al. Gastric Emptying Breath Test. 2015 Dec 14. 
Available from https://www.uspharmacist.com/article/diagnostic-spotlight-gastric-emptying-
breath-test. Accessed 2018 Aug 15. 
Tack J, Caenepeel P, Piessevaux H, et al. Assessment of meal induced gastric 
accommodation by a satiety drinking test in health and in severe functional dyspepsia. Gut. 
2003 Sep;52(9):1271-7. 
Takahashi T. Pathophysiological significance of neuronal nitric oxide synthase in the 
gastrointestinal tract. J Gastroenterol. 2003;38(5):421-30. 
Takahashi T, Nakamura K, Itoh H, et al. Impaired expression of nitric oxide synthase in the 
gastric myenteric plexus of spontaneously diabetic rats. Gastroenterology. 1997 
Nov;113(5):1535-44. 
Talley NJ, Verlinden M, Jones M. Can symptoms discriminate among those with delayed or 
normal gastric emptying in dysmotility-like dyspepsia? The American journal of 
gastroenterology. 2001 May;96(5):1422-8. 
Undeland KA, Hausken T, Gilja OH, et al. Gastric meal accommodation studied by 
ultrasound in diabetes. Relation to vagal tone. Scand J Gastroenterol. 1998 Mar;33(3):236-
41. 
United States Food and Drug Administration. Gastroparesis: Clinical Evaluation of Drugs for 
Treatment Guidance for Industry. 2015 Jul. Available from 
https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/
ucm455645.pdf. Accessed 2018 Jun 4. 
Werner ER, Gorren AC, Heller R, et al. Tetrahydrobiopterin and nitric oxide: mechanistic 
and pharmacological aspects. Exp Biol Med (Maywood). 2003 Dec;228(11):1291-302. 
Wood JD, Alpers DH, Andrews PL. Fundamentals of neurogastroenterology. Gut. 1999 
Sep;45 Suppl 2:II6-II16. 
Xu J, Wu Y, Song P, et al. Proteasome-dependent degradation of guanosine 5'-triphosphate 
cyclohydrolase I causes tetrahydrobiopterin deficiency in diabetes mellitus. Circulation. 2007 
Aug 21;116(8):944-53 


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Clinical Trial Protocol: GAS-001 
 
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APPENDIX 1 
SCHEDULE OF EVENTS 
Evaluation 
Screening Period 
Treatment Period 
Follow-up Period 
EOT 
EOS 
Telephone 
Follow-up 
-28 to -1 
Day 1 
(Predose) 
Day 1 
Through 
Day 13 
Day 14a 
Day 14a Day 15 
Day 28 (±1 
Day)  
Day 44 (±3 
Days) 
Informed consent 
X 
 
 
 
 
 
 
 
Confirm inclusion/exclusion criteria eligibility 
X 
 
 
 
 
 
 
 
Randomization 
Xb 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical historyc 
X 
X 
 
 
 
 
 
 
Vital signs, weight, and heightd 
X 
X 
X 
 
X 
X 
 
Physical examinatione 
X 
X 
 
 
X 
X 
 
Clinical laboratory testsf 
X 
X 
 
 
X 
X 
 
HbA1cg 
X 
 
 
 
X 
X 
 
Serum/urine pregnancy testh 
X 
X 
 
 
X 
X 
 
ECGi 
X 
 
 
 
 
 
 
 
Prior/concomitant medicationsj 
X 
X 
X 
X 
X 
 
X 
 
AEsk 
X 
X 
X 
X 
X 
 
X 
Xl 
Nutrient satiety testm 
Xn 
X 
 
 
X 
 
X 
 
GCSIo 
Xp 
X 
 
 
X 
X 
 
PAGI-SYMq 
 
X 
 
 
X 
X 
 
GEBTr 
X 
 
 
 
 
X 
X 
 
Dispense study drug 
 
 
X 
 
 
 
 
 
Dispense dosing diary 
 
 
Xs 
 
 
 
 
 
Study drug dosingt 
 
 
Xu 
X 
 
 
 
 
Collect study drug, dosing diary, assess 
compliance 
 
 
 
 
Xv 
Xv 
Xv 
 
a Study Day 14 is included both in the Treatment Period and EOT. 
b Randomize patient on Day -1. 


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c Includes specific information related to any prior or existing medical conditions or surgical procedures involving the following systems: dermatologic, HEENT, lymphatic, 
cardiovascular, respiratory, GI, musculoskeletal, and neurological.  
d Includes blood pressure, pulse, respiratory rate, and temperature. Obtain vital signs before collection of any laboratory samples and after patients have rested for 5 minutes in a 
supine position. Obtain vital signs both predose and 2 hours postdose on Day 1; for all other timepoints, obtain at any time during the indicated visits. Obtain height only at 
Screening. Obtain weight at Screening to determine response to Exclusion Criterion #5 (Section 4.3) and on Day -1 (Section 6.3). 
e Conduct a complete physical examination of general appearance, dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and neurological 
parameters.  
f Includes clinical chemistry panel (ALB, AP, ALT, AST, BUN, Ca, CO2, Cl, creatinine, GGT, glucose, LDH, phosphorus, K, Na, total bilirubin, direct bilirubin, total cholesterol, 
total protein, uric acid); hematology panel (HCT, HGB, platelet count, RBC count, WBC count, and WBC differential); and urinalysis (bilirubin, glucose, ketones, occult blood, 
pH, protein, specific gravity, urobilinogen and microscopic examination of WBC, RBC, and epithelial cells). Patients will fast overnight before blood sample collections. 
g Patients will fast overnight before blood sample collections. 
h Serum and urine pregnancy tests required for all women of childbearing potential; serum testing is to occur during the Screening Period, and urine testing is to occur before 
dosing on Day 1 and at an EOT visit on Day 28 (±1 day). Any positive urine pregnancy test should be confirmed by a serum pregnancy test. 
i Obtain 12-lead ECG recordings in triplicate with 1 minute separating the first and second and second and third recordings. 
j Record all treatments and over-the-counter medications (including herbal medications) received from 30 days prior to Screening (to determine responses to Inclusion Criterion 
#9 [Section 4.2] and Exclusion Criteria #11 through #14 and #21 [Section 4.3] concerning medications) and through Day 28 ±1 day before the patient leaves the clinic after 
completion of all EOS evaluations. 
k Collect AEs from the time of informed consent through Day 28 ±1 day before the patient leaves the clinic after completion of all EOS evaluations and SAEs from the time of 
informed consent through telephone Follow-up. 
l Telephone Follow-up is to assess SAEs only. 
m Administer the nutrient satiety test (Section 6.7) at Screening, on Day 1 (predose), and on Day 14 and Day 28 after overnight fasts and after any medications that can alter GI 
sensation or accommodation or gastric emptying have been held overnight. 
n Administer the nutrient satiety test at Screening to determine the response to Inclusion Criterion #6 (Section 4.2) 
o Administer the GCSI (Section 6.8, Appendix 2) at Screening, on Day 1 (predose), on Day 14 (+1 day) and on Day 28 (±1 day). 
p Administer the GCSI (Section 6.8, Appendix 2) to determine response to Inclusion Criterion #5 (Section 4.2). 
q Administer the PAGI-SYM (Section 6.9, Appendix 2) in the clinic on Day 1 (predose), on Day 14 (+1 day), and on Day 28 (±1 day). 
r Administer the GEBT on Day -1, on Day 15, and on Day 27 or Day 29. For the GEBT (Section 6.10), patients will fast overnight before the GEBT (a minimum of 8 hours 
before test administration with the exception of 4 ounces of water up to 1 hour before the test). Collect a premeal breath sample and then provide a standardized 230 kCal meal, 
consisting of a proprietary standardized 13C-labeled egg component (which is rehydrated and then microwaved for 1.5 minutes) and 6 saltine crackers, accompanied by 6 ounces 
of water. Encourage the patient to consume the meal within 10 minutes. Collect single postmeal breath samples in capped glass tubes at 45, 90, 120, 150, 180, and 240 minutes 
after the meal is consumed and send the samples to the specified local laboratory for analysis. 
s Dispense a dosing diary with instructions to record times all doses of study drug are taken. 
t If a patient vomits after taking a dose of study drug, the patient should wait until the next scheduled timepoint to take another dose. A missed dose should be taken as soon as 
possible, but >2 doses should not be taken on the same day. 
u Patients will take their first doses of study drug (CNSA-001 or placebo) on Day 1 while in the clinic. 
v Collect study drug, dosing diary, assess compliance on Day 14 if the patient takes the last dose of study drug on Day 14 while in the clinic or, if the patient takes the last dose of 
study drug on Day 14 after leaving the clinic, on Day 15 or Day 28 (±1 day). 
 
Abbreviations: AE = adverse event; ALB = albumin; ALT = alanine aminotransferase (serum glutamic pyruvic transaminase [SGPT]); AP = alkaline phosphatase; AST = aspartate 
aminotransferase (serum glutamic oxaloacetic transaminase [SGOT]); BUN = blood urea nitrogen; 13C = carbon-13; Ca = calcium; CO2 = carbon dioxide; Cl = chloride; 
ECG = electrocardiogram; EOS = End of Study; EOT = End of Treatment; GCSI = Gastroparesis Cardinal Symptom Index; GEBT = Gastric Emptying Breath Test; 


CNSA-001 (sepiapterin) 
 
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Clinical Trial Protocol: GAS-001 
 
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CONFIDENTIAL 
GI = gastrointestinal; GGT = gamma glutamyl transferase; HCT = hematocrit; HGB = hemoglobin; HEENT = head, eyes, ears, nose, and throat; HbA1c = glycosylated 
hemoglobin A1c; K = potassium; LDH = lactate dehydrogenase; Na = sodium; PAGI-SYM = Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity; 
RBC = red blood cell; SAE = serious adverse event; WBC = white blood cell.


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 63 
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APPENDIX 2 
GCSI AND PAGI-SYM ASSESSMENT INSTRUMENTS  
Gastroparesis Cardinal Symptom Index Questionnaire (English Version):  
  
Khoury V, Dubois, D. GCSI Gastroparesis Cardinal Symptom Index information booklet. 
2nd ed. Lyon, France: Mapi Research Trust; 2015. p 30. 
 












CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 1 
AMENDMENT 1: 09 Oct 2018 
 
CONFIDENTIAL 
 
CLINICAL TRIAL PROTOCOL 
Study Title: 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Pilot Study of 
CNSA-001 in Women With Moderate to Severe Diabetic Gastroparesis 
Study Number: 
GAS-001 
Study Phase: 
2 Pilot 
Product Name: 
CNSA-001 (sepiapterin)  
Dosage Form:  
Oral powder for suspension 
 
 
Indication: 
Treatment of women with moderate to severe diabetic gastroparesis 
Investigators: 
Multicenter study  
 
 
Sponsor: 
Censa Pharmaceuticals 
65 William Street 
Wellesley, MA 02481 
Sponsor Contact: 
 
Medical Monitor: 
 
 
 
Date 
Original Protocol: 
06 September 2018 
Amendment 1: 
09 October 2018 
 
 
 
 
 
Confidentiality Statement 
The confidential information in this document is provided to you as an Investigator or consultant for 
review by you, your staff, and the applicable Institutional Review Board/Independent Ethics 
Committee. Your acceptance of this document constitutes agreement that you will not disclose the 
information contained herein to others without written authorization from the Sponsor.  




CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 3 
AMENDMENT 1: 09 Oct 2018 
 
CONFIDENTIAL 
INVESTIGATOR’S SIGNATURE 
Study Title: 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Pilot Study 
of CNSA-001 in Women With Moderate to Severe Diabetic 
Gastroparesis 
Study Number: 
GAS-001 
Final Date: 
06 September 2018 
Amendment 1: 
09 October 2018 
I have read the protocol described above. I agree to comply with all applicable regulations 
and to conduct the study as described in the protocol. 
 
 
 
Signature 
 
Date (DD Month YYYY) 
 
 
 
Printed Name, Credentials 
 
 
 
 
 
Affiliation 
 
 
 
 
 
Address 
 
 
 
 
 
Phone Number 
 
 
 
 
 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 4 
AMENDMENT 1: 09 Oct 2018 
 
CONFIDENTIAL 
PROTOCOL AMENDMENT 1 (OCTOBER 9, 2018) 
Protocol GAS-001 is amended primarily for the following reasons: 
1. Added Exclusion Criterion to exclude patients with baseline cardiovascular instability. 
2. Added Exclusion Criterion to exclude patients with PKU or hyperphenylalaninemia. 
3. Updated the discontinuation criteria related to AEs in Section 6.14.1. 
4. Updated the study stopping criteria to include specific examples of adverse event criteria 
for temporarily or permanently stopping the study. 
 
Major changes to the protocol are as follows: 
Synopsis and Section 4.3: Added two additional exclusion criteria for patients with baseline 
cardiovascular instability and for patients with PKU or hyperphenylalaninemia. 
Section 6.14.1: Added drug class adverse events to individual discontinuation criteria, 
specifically, hypersensitivity reactions, anaphylaxis, and gastritis. 
Section 6.14.3: Added examples of study stopping criteria associated with adverse event 
criteria of severity, frequency, and relatedness. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 5 
AMENDMENT 1: 09 Oct 2018 
 
CONFIDENTIAL 
SYNOPSIS 
Sponsor: 
Censa Pharmaceuticals 
Name of Finished Product: 
CNSA-001 
Name of Active Ingredient: 
Sepiapterin 
Name of Inactive Ingredients: 
Microcrystalline cellulose, colloidal silicon dioxide, croscarmellose, and ascorbic acid 
Study Title: 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Pilot Study of CNSA-001 in Women 
With Moderate to Severe Diabetic Gastroparesis 
Study Number: 
GAS-001 
Study Phase: Phase 2 pilot 
Primary Objective: 
• 
To assess the impact of CNSA-001 on gastric accommodation, as measured by nutrient 
satiety testing, in women with moderate to severe diabetic gastroparesis 
Secondary Objectives: 
In women with moderate to severe diabetic gastroparesis: 
• 
To evaluate improvement of gastroparesis symptoms measured by global assessment of 
symptoms and symptom severity (Gastroparesis Cardinal Symptom Index [GCSI]) 
(Section 6.8, Appendix 2) 
• 
To evaluate patient-reported outcomes (PROs) as measured by the quality of life 
questionnaire Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity 
(PAGI-SYM) (Section 6.9, Appendix 2)  
• 
To evaluate the emptying of the stomach as measured by the Gastric Emptying Breath Test 
(GEBT) 
• 
To assess the safety and tolerability of CNSA-001 20 mg/kg/day 
Study Design: 
This is a Phase 2, randomized, double-blind, placebo-controlled pilot study of multiple doses of 
CNSA-001 (sepiapterin) powder for suspension administered orally in women with moderate to 
severe diabetic gastroparesis. Patients will be randomized in a ratio of 1:1 to receive CNSA-001 
20 mg/kg/day or placebo, each dosed twice a day (BID); each group will consist of 10 patients. All 
patients will receive the standard of care for diabetic gastroparesis. Approximately 4 centers will 
participate in this study. The study design is summarized in the study schema below. A schedule of 
study events is provided in Appendix 1. 
All study clinic visits will be outpatient visits.  
Patients will continue their usual diet without modification throughout the study. Patients are 
required to have been fasting overnight for the following assessments:  
• 
Clinical laboratory, including glycosylated hemoglobin A1c (HbA1c), tests  
• 
The nutrient satiety test 
• 
The GEBT  


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 6 
AMENDMENT 1: 09 Oct 2018 
 
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Screening Period (Day -28 Through Day 1 Predose): 
An informed consent form (ICF) must be signed before any study-related procedures are 
performed. After providing consent, patients will undergo Screening procedures to determine study 
eligibility, as indicated in Appendix 1. Patients who are eligible based on Screening evaluations 
will undergo baseline evaluations before initiation of study drug (CNSA-001 or placebo), be 
randomized, and proceed to the Treatment Period.  
Treatment Period (Day 1 Through Day 14) 
Following the Screening Period and completion of baseline evaluations, all randomized patients 
will take their first dose of study drug (CNSA-001 or placebo) on Day 1 while in the clinic. 
Patients will undergo procedures during the Treatment Period as indicated in Appendix 1. 
End of Treatment Period (Day 14 Through Day 15 Evaluations) 
Patients will undergo End of Treatment (EOT) evaluations on Day 14 and Day 15 as indicated in 
Appendix 1. Preliminary efficacy will be assessed by the changes from Day 1 in the nutrient satiety 
test on Day 14. The GCSI (Section 6.8, Appendix 2) and PAGI-SYM (Section 6.9, Appendix 2) 
will also be administered on Day 14 (+1 day), and the GEBT will be conducted on Day 15. 
End of Study Period (Day 15 After Evaluations Through Day 28 [±1 Day] Evaluations) 
Patients will undergo End of Study evaluations on Day 28 (±1 day) as indicated in Appendix 1. 
Preliminary efficacy will be assessed by the changes from Day 1 in the nutrient satiety test on 
Day 28. The GCSI (Section 6.8, Appendix 2) and PAGI-SYM (Section 6.9, Appendix 2) will also 
be administered on Day 28 ±1, and the GEBT will be conducted on Day 27 or Day 29. 
Follow-up Period (Day 28 [±1 Day] After Evaluations Through Day 44 [±3 Days]) 
Patients will undergo telephone Follow-up on Day 44 ±3 days as indicated in Appendix 1.  


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 7 
AMENDMENT 1: 09 Oct 2018 
 
CONFIDENTIAL 
Number of Patients: 
Up to 20 women ≥18 and ≤65 years of age will be enrolled in this study and randomized in a ratio 
of 1:1 to receive CNSA-001 or placebo.  
Main Criteria for Inclusion and Exclusion: 
Patients are eligible to participate if they meet all the following inclusion criteria: 
1. Informed consent 
2. Females ≥18 and ≤65 years of age 
3. Diagnosis of diabetes mellitus  
4. Documentation of delayed gastric emptying on gastric emptying scintigraphy (within 1 year 
of enrollment) 
5. Symptoms of gastroparesis for at least 6 months with GCSI (Section 6.8, Appendix 2) score 
>21 indicating moderate to severe symptoms 
6. Gastric accommodation, as measured by nutrient satiety testing, of ≤600 mL 
7. Negative upper endoscopy or upper gastrointestinal (GI) series within 3 years of enrollment 
(no evidence of mechanical obstruction or peptic ulcer disease) 
8. Either postmenopausal for ≥1 year or surgically sterile (having undergone tubal ligation, 
hysterectomy, or bilateral oophorectomy) for at least 6 months or, if of childbearing 
potential and not abstinent, willing to use a highly effective method of contraception 
throughout the study such as 1 of the following: 
• 
Hormonal contraception (stable dose for 3 months) 
• 
Intrauterine device/Intrauterine Hormone-releasing System 
• 
Barrier contraceptive method (diaphragm, cervical cap, contraceptive sponge, condom) 
Patients who are abstinent will not be required to use a contraceptive method unless they 
become sexually active. 
9. If on analgesics, including narcotics; promotility agents, including metoclopramide, or 
neuromodulators, including tricyclic antidepressants, gabapentin, and pregabalin, doses are 
stable for >30 days before randomization and the patient is not expected to require dose 
changes during the study through the EOT 
10. Have not used tobacco (e.g., cigarettes, e-cigarettes, cigars, smokeless tobacco, nicotine 
replacement) for 2 weeks prior to Day 1 and willingness to abstain from these products 
during the study through the EOT 
Patients are not eligible to participate if they meet any of the following exclusion criteria:  
1. Male gender 
2. Normal gastric emptying  
3. Gastroparesis from postsurgical etiologies 
4. Another active disorder that could, in the opinion of the Investigator, explain symptoms  
5. Weight >100 kg 
6. Alanine aminotransferase > 2× upper limit of normal (ULN) 
7. Pregnant, breastfeeding, or considering pregnancy 
8. Clinically significant cardiac arrhythmia at Screening 
9. QT interval corrected for heart rate (QTc) ≥480 msec (based on triplicate measurements 
taken at Screening) 
10. Resting heart rate ≤40 or ≥110 bpm or resting blood pressure <90/40 mmHg or >150/90 
mmHg at Screening or prior to the first administration of study drug. 
11. Recent clinically GI significant bleeding 
12. Taking levodopa or domperidone within 30 days before randomization or expected to 
require domperidone during the study through the EOT 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 8 
AMENDMENT 1: 09 Oct 2018 
 
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13. Taking erythromycin within 30 days before randomization or expected to require 
erythromycin within 30 days before randomization or expected to require erythromycin 
during the study through the EOT; if a patient is taking erythromycin and is otherwise 
eligible to participate in the study, following signing the ICF, the patient may go through an 
erythromycin washout period of 30 days before randomization 
14. Taking any fundic-relaxing agents including, but not limited to, buspirone, clonidine, 
nitrates, phosphodiesterase inhibitors (i.e., sildenafil citrate [Viagra®]) and triptan-containing 
medications, within 30 days before randomization or expected to require any of these agents 
during the study through the EOT 
15. Taking any systemic antifolates, including, but not limited to, methotrexate, pemetrexed, and 
trimetrexate or expected to require any systemic antifolates during the study through the 
EOT (topical antifolates [e.g., cream, ointment, gel] or eye drops with antifolates are 
allowed) 
16. Pulmonary dysfunction (e.g., chronic obstructive pulmonary disease) 
17. Surgery for placement of a gastric stimulator within the past 6 months (patients 
postoperative >6 months with persistent symptoms and delayed gastric emptying are 
eligible) 
18. Gastrointestinal disease (such as irritable bowel syndrome, inflammatory bowel disease, 
chronic gastritis, peptic ulcer disease, small bowel malabsorption) that could affect the 
absorption of study drug or contraindicate undergoing the GEBT 
19. History of gastric surgery, including Roux-en-Y gastric bypass surgery or an antrectomy 
with vagotomy, or gastrectomy 
20. History of allergies or adverse reactions to tetrahydrobiopterin or related compounds, to any 
excipients in the study drug formulation, or to egg, wheat, or algae (Spirulina)  
21. Inability to tolerate oral medication 
22. Current participation in any other investigational drug study or use of any investigational 
agent, investigational device, or approved therapy for investigational use within 30 days or 
5 half-lives (whichever is longer) before Screening 
23. Any clinically significant laboratory abnormality; in general, each laboratory value from 
Screening and baseline chemistry and hematology panels should fall within the limits of the 
normal laboratory reference range unless deemed not clinically significant by the 
Investigator 
24. Major surgery within the previous 90 days  
25. The patient, in the opinion of the Investigator, is unwilling or unable to adhere to the 
requirements of the study 
26. History of alcohol or drug abuse within 6 months prior to Screening or current evidence of 
substance dependence as determined by the Investigator 
27. Episodes of ketoacidosis or hypoglycemia that are frequent as defined by the Investigator 
28. History of phenylketonuria (PKU) or hyperphenylalaninemia. 
29. Any other conditions, including diabetic comorbidities, that, in the opinion of the 
Investigator or Sponsor, would interfere with the patient’s ability to participate in the study 
or increase the risk of participation for that patient 
Test Product, Dose, and Mode of Administration: 
The test product is CNSA-001 (sepiapterin) oral powder for suspension. CNSA-001 will be 
suspended in Medisca® Oral Mix prior to dispensing to the patient. Patients randomized to receive 
CNSA-001 will receive CNSA-001 20 mg/kg/day (i.e., 10 mg/kg BID) for 14 days. 
Reference Therapy; Dose; and Mode of Administration: 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 9 
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The reference product is placebo. The placebo is a ready-made suspension containing 
microcrystalline cellulose, colloidal silicon dioxide, croscarmellose, ascorbic acid, and colorant 
(Yellow No. 6) that is suspended in Medisca® Oral Mix.  
Duration of Treatment: 
Patients will be treated for a total of 14 days.  
Criteria for Evaluation: 
Safety: 
Safety and tolerability of CNSA-001 as measured by severity and number of treatment-emergent 
adverse events (TEAEs), including assessment of severity of TEAEs, and changes in clinical 
laboratory and HbA1c tests, vital signs, and physical examinations 
Efficacy: 
The primary efficacy measure will be the change in maximal tolerated volume consumed during 
the nutrient satiety test from Day 1 to Day 14 and Day 1 to Day 28. 
Secondary efficacy measures will consist of changes in the following from baseline to Day 14 and 
baseline to Day 28 (±1 day):  
• 
GCSI (Section 6.8, Appendix 2) PAGI-SYM (Section 6.9, Appendix 2) subscale 
(heartburn/regurgitation, fullness/early satiety, nausea/vomiting, bloating, upper abdominal 
pain, and lower abdominal pain) scores 
• 
Gastric emptying as measured by the GEBT  
Statistical Methods: 
The following study populations will be analyzed: 
• 
Safety population: all patients who were randomized and received any amount of study 
drug (CNSA-001 or placebo) 
• 
Efficacy population: all patients who were randomized, received any amount of study drug 
(CNSA-001 or placebo), and had available Day 1 and Day 14 nutrient satiety test 
maximum tolerated volume results  
Safety will be assessed in the Safety population. Adverse events (AEs) will be coded using the 
Medical Dictionary for Regulatory Activities (MedDRA®). The number and percentage of patients 
with TEAEs will be tabulated by system organ class, preferred term, and treatment group. Severity 
of AEs and serious adverse events (SAEs) will be summarized similarly. Those AEs leading to 
premature discontinuation from the study drug and the serious TEAEs will be presented in a table 
or a listing. Clinical laboratory and HbA1c test results and vital signs will be summarized at each 
visit as will changes from baseline for each treatment group. A frequency distribution of abnormal 
physical examination results will be provided. 
Efficacy will be assessed in the Efficacy population. The changes from Day 1 to Day 14 and from 
Day 1 to Day 28 in maximal tolerated volume consumed during the nutrient satiety test will be 
compared between treatment groups using a student’s t-test. Results from the nutrient satiety test 
through Day 14 and Day 28, the GEBT through Day 15 and Day 27 or Day 29, and the GCSI 
(Section 6.8, Appendix 2) and PAGI-SYM (Section 6.9, Appendix 2) through Day 14 (+1) and 
through Day 28 (±1) will be summarized using summary statistics (number of patients, mean, 
standard deviation, median, and range) at each visit as well as changes from baseline within each 
treatment group. The 95% confidence intervals for the changes from baseline will be provided. 
Additional analyses may be conducted, and details will be provided in the statistical analysis plan. 
Date of Original Protocol: 06 September 2018 
Date of Amendment 1: 09 October 2018 
 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 10 
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TABLE OF CONTENTS 
CLINICAL TRIAL PROTOCOL ..............................................................................................1 
SPONSOR SIGNATURES ........................................................................................................2 
INVESTIGATOR’S SIGNATURE ...........................................................................................3 
PROTOCOL AMENDMENT 1 (OCTOBER 9, 2018) .............................................................4 
SYNOPSIS .................................................................................................................................5 
TABLE OF CONTENTS .........................................................................................................10 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ..........................................13 
1 
INTRODUCTION .................................................................................................16 
1.1 
Diabetic Gastroparesis .....................................................................................16 
1.2 
Impaired Gastric Accommodation in Gastroparesis ........................................17 
1.3 
Current Treatment of Diabetic Gastroparesis ..................................................17 
1.4 
CNSA-001 (Sepiapterin) ..................................................................................18 
1.5 
Rationale for Study ..........................................................................................18 
2 
STUDY OBJECTIVES ..........................................................................................20 
2.1 
Primary Objective ............................................................................................20 
2.2 
Secondary Objectives.......................................................................................20 
3 
INVESTIGATIONAL PLAN ................................................................................21 
3.1 
Overall Study Design and Plan ........................................................................21 
3.2 
Rationale for Study Design and Control Group ...............................................22 
3.3 
Study Duration and Dates ................................................................................23 
4 
STUDY POPULATION SELECTION .................................................................24 
4.1 
Study Population ..............................................................................................24 
4.2 
Inclusion Criteria .............................................................................................24 
4.3 
Exclusion Criteria ............................................................................................25 
5 
STUDY TREATMENTS .......................................................................................27 
5.1 
Description of Treatments................................................................................27 
5.1.1 
Test Product .........................................................................................27 
5.1.2 
Placebo Control ....................................................................................27 
5.2 
Treatments Administered .................................................................................27 
5.3 
Selection and Timing of Dose for Each Patient ...............................................27 
5.4 
Method of Assigning Patients to Treatment Groups........................................28 
5.5 
Blinding............................................................................................................28 
5.6 
Concomitant Therapy.......................................................................................28 
5.7 
Restrictions ......................................................................................................29 
5.7.1 
Prior Therapy and Concomitant Therapy ............................................29 
5.7.2 
Food Intake ..........................................................................................30 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 11 
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5.7.3 
Total Blood Volume ............................................................................30 
5.7.4 
Patient Activity and Tobacco Restrictions ...........................................30 
5.8 
Treatment Compliance .....................................................................................30 
5.8.1 
Dosing Diary ........................................................................................30 
5.9 
Packaging and Labeling ...................................................................................31 
5.10 
Storage and Accountability ..............................................................................31 
5.11 
Investigational Product Retention at Study Site ..............................................31 
6 
STUDY PROCEDURES .......................................................................................32 
6.1 
Informed Consent.............................................................................................32 
6.2 
Medical History and Demographic Data .........................................................32 
6.3 
Vital Signs, Weight, and Height ......................................................................32 
6.4 
Physical Examination.......................................................................................32 
6.5 
Clinical Laboratory Tests and Glycosylated Hemoglobin A1c .......................32 
6.6 
Electrocardiogram ............................................................................................33 
6.7 
Nutrient Satiety Test ........................................................................................34 
6.8 
Gastroparesis Cardinal Symptom Index ..........................................................34 
6.9 
Patient Assessment of Upper Gastrointestinal Disorders-Symptom 
Severity ............................................................................................................34 
6.10 
Gastric Emptying Breath Test ..........................................................................34 
6.11 
Dispensing Study Drug ....................................................................................35 
6.12 
Adverse Events Assessments ...........................................................................35 
6.12.1 
Reporting Timelines.............................................................................35 
6.12.2 
Severity ................................................................................................37 
6.12.3 
Relationship .........................................................................................37 
6.12.4 
Expectedness ........................................................................................38 
6.12.5 
Clinical Laboratory Adverse Events ....................................................39 
6.12.6 
Serious Adverse Events .......................................................................39 
6.12.7 
Treatment-Emergent Adverse Events ..................................................40 
6.13 
Prior and Concomitant Medication Assessments ............................................41 
6.14 
Removal of Patients From the Trial or Study Drug .........................................41 
6.14.1 
Early Discontinuation From Study Drug Administration ....................41 
6.14.2 
Withdrawal From the Study .................................................................42 
6.14.3 
Study Stopping Criteria........................................................................42 
6.15 
Appropriateness of Measurements ...................................................................43 
7 
STUDY ACTIVITIES ...........................................................................................45 
7.1 
Screening Procedures (Day –28 to Day -1) .....................................................45 
7.2 
Day 1 Predose ..................................................................................................46 
7.3 
Day 1 After Baseline Evaluations Through Day 13 ........................................46 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 12 
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7.3.1 
Day 1 ....................................................................................................46 
7.4 
Early Termination Procedures .........................................................................47 
7.5 
End of Treatment Visits (Day 14 and Day 15) ................................................47 
7.6 
End of Study (Day 28 ±1 Day) ........................................................................48 
7.7 
Telephone Follow-up Day 44 (±3 Days) (30 ±3 Days After Last Dose) .........49 
8 
QUALITY CONTROL AND ASSURANCE .......................................................50 
9 
PLANNED STATISTICAL METHODS ..............................................................51 
9.1 
General Considerations ....................................................................................51 
9.2 
Determination of Sample Size .........................................................................51 
9.3 
Analysis Populations ........................................................................................51 
9.4 
Demographics, Baseline Characteristics, Enrollment, Protocol Deviations, 
and Patient Disposition ....................................................................................51 
9.5 
Statistical Analysis of Efficacy Variables ........................................................51 
9.6 
Safety Analysis ................................................................................................52 
10 
ADMINISTRATIVE CONSIDERATIONS ..........................................................53 
10.1 
Investigators and Study Administrative Structure ...........................................53 
10.2 
Institutional Review Board Approval ..............................................................53 
10.3 
Ethical Conduct of the Study ...........................................................................53 
10.4 
Patient Information and Consent .....................................................................53 
10.5 
Confidentiality .................................................................................................54 
10.6 
Study Monitoring .............................................................................................54 
10.7 
Case Report Forms and Study Records ...........................................................55 
10.8 
Protocol Violations/Deviations ........................................................................55 
10.9 
Access to Source Documentation ....................................................................56 
10.10 
Data Generation and Analysis .........................................................................56 
10.11 
Retention of Data .............................................................................................56 
10.12 
Financial Disclosure.........................................................................................57 
10.13 
Publication and Disclosure Policy ...................................................................57 
11 
REFERENCE LIST ...............................................................................................58 
Appendix 1 
Schedule of Events ...............................................................................61 
Appendix 2 
GCSI and PAGI-SYM Assessment Instruments..................................64 
LIST OF TABLES 
Table 1: 
Administrative Structure for GAS-001 Study............................................53 
LIST OF FIGURES 
Figure 1: 
Study Schema.............................................................................................22 
 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 13 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
AE 
Adverse event 
ALB 
Albumin  
ALT 
Alanine aminotransferase (serum glutamic pyruvic transaminase [SGPT]) 
AP 
Alkaline phosphatase 
AST 
Aspartate aminotransferase (serum glutamic oxaloacetic transaminase [SGOT]) 
AUC0-last 
Area under the concentration time curve from 0 to the last measurement 
BH4 
Tetrahydrobiopterin 
BID 
Twice a day 
BUN 
Blood urea nitrogen 
13C 
Carbon-13 
Ca 
Calcium  
CFR 
Code of Federal Regulations 
Cl 
Chloride 
Cmax 
Maximum concentration 
CO2 
Carbon dioxide  
12CO2 
Carbon-12 dioxide 
13CO2 
Carbon-13 dioxide 
CRO 
Contract Research Organization 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EOS 
End of Study 
EOT 
End of Treatment 
FDA 
United States Food and Drug Administration 
GCP 
Good Clinical Practice 
GCSI 
Gastroparesis Cardinal Symptom Index 
GEBT 
Gastric Emptying Breath Test 
GGT 
Gamma glutamyl transferase 
GI 
Gastrointestinal 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 14 
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GLP 
Good Laboratory Practice 
HbA1c 
Glycosylated hemoglobin A1c  
HCG 
Human chorionic gonadotropin 
HCT 
Hematocrit 
HEENT 
Head, eyes, ears, nose, and throat 
HGB 
Hemoglobin 
ICF 
Informed consent form 
ICH 
International Council on Harmonisation  
IRB 
Institutional Review Board 
K 
Potassium 
kPCD 
the Gastric Emptying Breath Test metric; “k” is a multiplier of 1000, and 
“PCD” is an acronym for percent carbon-13 dose excreted (as carbon-13 
dioxide)  
LAR 
legally authorized representative 
LDH 
Lactate dehydrogenase 
MedDRA® 
Medical Dictionary for Regulatory Activities 
Na 
Sodium  
NADPH 
nicotinamide adenine dinucleotide phosphate hydrogen 
nNOS 
Neuronal nitric oxide synthase 
NO 
Nitric oxide 
NOS 
Nitric oxide synthase 
PAGI-QOL 
Upper Gastrointestinal Disorders-Quality of Life 
 
 
PAGI-SYM 
Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity 
PRO 
Patient-reported outcome 
QTc  
QT interval corrected for heart rate 
RBC 
Red blood cell 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SUSAR 
Suspected unexpected serious adverse reaction 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 15 
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TEAE 
Treatment-emergent adverse event 
ULN 
Upper limit of normal 
WBC 
White blood cell 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 16 
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1 
INTRODUCTION 
1.1 
Diabetic Gastroparesis  
Gastroparesis is characterized by delayed gastric emptying in the absence of mechanical 
obstruction; symptoms are chronic with episodic symptom exacerbation (Parkman et al, 
2004). Gastroparesis affects women 4 times more than men (Soykan, et al, 1998). Idiopathic 
gastroparesis accounts for most cases, but gastroparesis is frequently associated with diabetes 
(diabetic gastroparesis) (Soykan, et al, 1998; Karamanolis et al, 2007). Several 
cross-sectional studies have found delayed gastric emptying of solids and/or liquids in 30% 
to 50% of patients with Type 1 or Type 2 diabetes (Horowitz et al, 2002). Patients with 
diabetes mellitus commonly experience gastric and intestinal dysfunction (Feldman and 
Schiller, 1983).  
The actual mechanism of diabetic gastroparesis is not well known. Vagal nerve dysfunction 
and/or damage, interstitial cells of Cajal loss, and smooth muscle and enteric neuron 
dysfunction have all been implicated in the pathogenesis of diabetic gastroparesis (Stacher, 
2001; Parkman et al, 2004). In addition, acute hyperglycemia has the potential to slow gastric 
emptying (Camilleri et al, 2013).  
At a molecular level, attention has been devoted to the potential role of altered nitrergic 
signaling in the enteric nervous system. Gastric motility is regulated in large part by neurons 
of the enteric nervous system located in the muscle wall (Wood et al, 1999). These neurons 
are either excitatory (releasing acetylcholine) or inhibitory (releasing nitric oxide [NO] and 
vasoactive intestinal peptide). Nerves throughout the luminal gastrointestinal (GI) tract 
express neuronal nitric oxide synthase (nNOS), which generates NO, a key neurotransmitter 
in the regulation of GI motility (Takahashi, 2003); it is the principal nonadrenergic 
noncholinergic inhibitory neurotransmitter in the GI tract. In diabetic rats, which serve as a 
model for type 1 diabetes, nNOS expression was found to be impaired. This impairment in 
nNOS messenger RNA expression was associated with impaired smooth muscle relaxation in 
response to electrical stimulation of circular muscle fibers obtained from the proximal 
stomach of these rats (Takahashi et al, 1997). It has been demonstrated that female diabetic 
rats had slower gastric emptying than age matched diabetic male rats, female control rats had 
greater nitrergic relaxation of circular antral muscle strips compared to male controls, and 
nitrergic relaxation was impaired in diabetic female rats but not matched diabetic male rats 
(Gangula et al, 2007). 
The core signs and symptoms of gastroparesis by incidence are nausea (92% to 96%), 
vomiting (68% to 88%), postprandial fullness (54% to 77%), early satiety (42% to 60%), and 
upper abdominal pain (36% to 85%) (Soykan et al, 1998; Hoogerwerf et al, 1999; Anaparthy 
et al, 2009). Patients may experience any combination of signs and symptoms with varying 
degrees of severity. Pain is less prevalent in diabetic gastroparesis than idiopathic 
gastroparesis. Patients with diabetic gastroparesis may experience further derangement of 
glucose control because of unpredictable gastric emptying and altered absorption of orally 
administered hypoglycemic drugs, which may, in turn, affect measurement of core signs and 
symptoms. Severe signs and symptoms may cause complications such as malnutrition, 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 17 
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esophagitis, and Mallory-Weiss tears. Gastroparesis adversely affects the lives of patients 
with the disease, resulting in decreased social interaction, poor work functionality, and 
development of anxiety or depression (Soykan et al, 1998; Parkman et al, 2004). 
1.2 
Impaired Gastric Accommodation in Gastroparesis 
Patients with diabetic gastroparesis have also been shown to have gastric hypersensitivity, 
especially in the postprandial state, and impairment of the postprandial accommodation 
response. (Kumar et al, 2008). The stomach functions as 2 separate regions: the fundus acts 
as a reservoir accommodating a meal without a significant increase in intragastric pressure, 
and the distal stomach/antrum triturates gastric contents. Receptive relaxation or 
accommodation is vagally mediated resulting in the release of NO and activation of nitrergic 
myenteric neurons. Nitrergic signaling is responsible for gastric accommodation and pyloric 
relaxation in response to a meal (Ishiguchi et al, 2001). 
Impaired accommodation has been associated with symptoms of early satiety and weight loss 
in patients with idiopathic gastroparesis (Karamanolis et al, 2007). A study of patients with 
diabetic gastroparesis found that 90% of patients had impaired gastric accommodation to a 
nutrient meal (Kumar et al, 2008). In the distal stomach, NO is required for the propulsive 
contractions that triturate gastric contents and control of pyloric closure; lack of NO can lead 
to delayed gastric emptying and impaired gastric accommodation (Gangula et al, 2007). 
Several co-factors are known to be important for nNOS activity, including nicotinamide 
adenine dinucleotide phosphate hydrogen (NADPH), calcium, and tetrahydrobiopterin (BH4) 
(Werner et al, 2003). The homodimeric conformation of all 3 isoforms of nitric oxide 
synthase (NOS) is regulated by BH4 (Werner et al, 2003). In the absence of BH4, uncoupling 
of NO production occurs and leads to super oxide production, resulting in further impaired 
nNOS bioactivity. 
1.3 
Current Treatment of Diabetic Gastroparesis  
Therapies for gastroparesis have been targeted at accelerating gastric emptying or controlling 
symptoms. Available therapies for accelerating gastric emptying are limited in number and 
efficacy. These include metoclopramide (Snape et al, 1982), erythromycin (Arts et al, 2005), 
and domperidone (not available in the United States [US]) (Prakash and Wagstaff, 1998). 
There is also poor correlation between gastric emptying and baseline symptom severity 
(Karamanolis et al, 2007; Talley et al, 2001) and in response to therapeutic intervention. In 
part, as a result of lack of understanding of the underlying pathogenesis that leads to 
alterations in GI motility and sensation, medical therapies have not been targeted at the 
underlying pathophysiology of gastroparesis.  
The first-line medical therapy for patients with diabetic gastroparesis is generally a 
combination of an antiemetic agent in addition to the promotility drug. Unfortunately, many 
patients with diabetic gastroparesis will not experience adequate symptom relief despite 
first-line therapy. For patients with refractory disease, options include combination prokinetic 
therapy, psychotropic medications, pyloric botulinum toxin injection, and gastric electric 
stimulation (Fass, 2010; Camilleri et al, 2013). 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 18 
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1.4 
CNSA-001 (Sepiapterin) 
Sepiapterin is 2-amino-6-[(2S)-2-hydroxypropanoyl]-7,8-dihydro-1H-pteridin-4-one with a 
molecular weight of 237.2 and a molecular formula of C9H11 N5O3. 
The chemical structure of sepiapterin is: 
 
Sepiapterin serves as a substrate for BH4 synthesis via the pterin salvage pathway (Mayer 
and Werner, 1995). Oral administration of sepiapterin was shown to be more potent (>2 fold) 
than oral administration of BH4 in increasing intracellular BH4 in normal mice (Sawabe et 
al, 2002). Translation of this finding to humans has been confirmed in a Phase 1 study, 
PKU-001, conducted by Censa Pharmaceuticals.  
1.5 
Rationale for Study 
BH4 biosynthesis is impaired in chronic diabetes. The mechanism of impairment is not well 
understood but is thought to be a result of hyperglycemia-induced proteasome-mediated 
degradation of GTP-cyclohydrolase, the rate-limiting enzyme in the synthesis pathway for 
BH4 (Xu et al, 2007).  
CNSA-001 is the first viable formulation of sepiapterin, shown to increase intracellular BH4 
(Section 1.4), intended for the treatment of female patients with diabetic gastroparesis. 
CNSA-001 was studied in a single and multiple ascending-dose study in healthy volunteers, 
the Phase 1 study, Study PKU-001. Part A of this study assessed the safety and 
pharmacokinetics of CNSA-001 at 6 dose levels inclusive of an assessment of food effect 
(i.e., 2.5 mg/kg, 7.5 mg/kg, 20 mg/kg, 40 mg/kg, 80 mg/kg, and 10 mg/kg [to assess food 
effect]). Additionally, Kuvan® (sapropterin dihydrochloride), a synthetic BH4 commercially 
available product, was administered at equivalent doses for the first 3 dose levels (2.5 mg/kg, 
7.5 mg/kg, and 20 mg/kg). Dose-dependent correlations between CNSA-001 and plasma 
BH4 concentrations were observed with each successive dose level. Dose proportionality was 
observed between the top 2 dose levels (40 mg/kg and 80 mg/kg) and resultant BH4 
concentrations. Administration with a standard high-fat (approximately 50 percent of total 
caloric content of the meal) and high calorie (approximately 800 to 1000 calories) meal 
resulted in approximately 80% higher plasma BH4 concentrations (area under the 
concentration time curve from 0 to the last measurement [AUC0-last] and maximum 
concentration [Cmax]) than in subjects who had fasted before receipt of CNSA-001. 
Treatment-emergent adverse events (TEAEs) in Part A of Study PKU-001 were reported in 
26 subjects (44.1%, 26/59). The TEAEs for CNSA-001 were generally mild and consistent 
with reported adverse events (AEs) for Kuvan® and placebo. The frequency of TEAEs did 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 19 
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not appear to increase with increasing dose. The TEAEs that were judged to be related to 
study treatment were reported in 17 subjects: 11 subjects (26.2%, 11/42) who received 
CNSA-001, 4 subjects (44.4%, 4/9) who received Kuvan®, and 2 subjects (25.0%, 2/8) who 
received placebo. No TEAEs were severe or serious or led to discontinuation of study drug. 
Headache and dizziness were the most common TEAEs , but these TEAEs occurred at a 
similar frequency as with placebo. 
Part B of Study PKU-001 assessed multiple ascending doses CNSA-001 in healthy 
volunteers. Data indicate CNSA-001 was well tolerated following daily doses of 5, 20, and 
60 mg/kg/day for 7 days and that TEAEs were reported in 14 subjects (58.3%, 14/24). The 
TEAEs in subjects who received CNSA 001 were mild or moderate and consistent with the 
TEAEs in subjects who received placebo: TEAEs were experienced by 10 subjects (55.6%, 
10/18) who received CNSA-001 at doses from 5 mg/kg to 60 mg/kg daily for 7 days and by 
4 subjects (66.7%, 4/6) who received placebo. No TEAEs were severe, serious, or led to 
discontinuation. Of the 10 TEAEs reported in subjects who received CNSA-001, only 4 were 
judged to be related to study drug, and, of the 4 TEAEs reported in subjects who received 
placebo, only 1 was judged to be related to study drug. Somnolence, fatigue, headache, and 
procedural pain (secondary to performance of 2 sequential lumbar punctures 7 days apart) 
were the most common TEAEs reported, and they occurred at a similar frequency when 
compared with placebo with the exception of fatigue and headache, which were each 
reported in 2 subjects who received CNSA-001 (11.1%, 2/18). 
This Phase 2 pilot study will assess CNSA-001 doses of 20 mg/kg/day administered as 
10 mg/kg twice a day (BID) in comparison to placebo administered BID in female patients 
with diabetic gastroparesis. This study will help support the design of future Phase 2/3 
studies in patients with diabetic gastroparesis.  


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 20 
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2 
STUDY OBJECTIVES 
2.1 
Primary Objective 
The primary objective of this study is to assess the impact of CNSA-001 on gastric 
accommodation, as measured by nutrient satiety testing (Section 6.7), in women with 
moderate to severe diabetic gastroparesis. 
2.2 
Secondary Objectives 
The secondary objectives of this study are, in women with moderate to severe diabetic 
gastroparesis: 
• To evaluate improvement of gastroparesis symptoms measured by global assessment of 
symptoms and symptom severity (Gastroparesis Cardinal Symptom Index [GCSI]) 
(Section 6.8, Appendix 2) 
• To evaluate patient-reported outcomes (PROs) as measured by the quality of life 
questionnaire Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity 
(PAGI-SYM) (Section 6.9, Appendix 2)  
• To evaluate the emptying of the stomach, as measured by the Gastric Emptying Breath 
Test (GEBT) (Section 6.10) 
• To assess the safety and tolerability of CNSA-001 20 mg/kg/day 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 21 
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3 
INVESTIGATIONAL PLAN 
3.1 
Overall Study Design and Plan 
Study GAS-001 is a Phase 2, randomized, double-blind, placebo-controlled pilot study of 
multiple doses of CNSA-001 (sepiapterin) powder for suspension administered orally in 
women with moderate to severe diabetic gastroparesis. This is an outpatient study in which 
up to 20 patients will be enrolled at approximately 4 centers. 
The Schedule of Events is provided in Appendix 1. The study schema is displayed in Figure 
1.  
Screening Period (Day -28 Through Day 1 Predose) 
An informed consent form (ICF) must be signed before any study-related procedures are 
performed. After providing consent, patients will undergo Screening procedures to determine 
study eligibility, as indicated in Appendix 1. Patients who are eligible based on Screening 
evaluations will undergo baseline evaluations before initiation of study drug (CNSA-001 or 
placebo), be randomized, and proceed to the Treatment Period.  
Treatment Period (Day 1 Through Day 14) 
Following the Screening Period and completion of baseline evaluations, all randomized 
patients will take their first dose of study drug (CNSA-001 or placebo) on Day 1 while in the 
clinic. Patients will undergo procedures during the Treatment Period as indicated in 
Appendix 1. 
Study drug may be prematurely discontinued for safety reasons, as described in 
Section 6.14.1. Patients may also withdraw from the study for any reason, as described in 
Section 6.14.2. If a patient discontinues study drug early, the patient should return to the 
study site within 24 hours of withdrawal and complete all of the procedures outlined for the 
End of Treatment (EOT) (Section 7.5, Appendix 1). If a patient withdraws early from the 
study before undergoing EOT evaluations, the patient will be asked to return to the study site 
within 24 hours of withdrawal and complete all of the procedures outlined for the EOT 
(Section 7.5, Appendix 1). If a patient withdraws from the study before undergoing End of 
Study (EOS) evaluations, the patient will be asked to return to the study site within 24 hours 
of withdrawal and complete all of the procedures outlined for the EOS (Section 7.6, 
Appendix 1).  
End of Treatment Period (Day 14 Through Day 15 Evaluations) 
Patients will undergo EOT evaluations on Day 14 and Day 15 as indicated in Appendix 1. 
Preliminary efficacy will be assessed by the changes from Day 1 in the nutrient satiety test 
(Section 6.7) on Day 14. The GCSI (Section 6.8, Appendix 2) and PAGI-SYM (Section 6.9, 
Appendix 2) will also be administered on Day 14 (+1 day), and the GEBT (Section 6.10) will 
be conducted on Day 15. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 22 
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End of Study Period (Day 15 After Evaluations Through Day 28 [±1 Day] Evaluations) 
Patients will undergo EOS evaluations on Day 28 (±1 day) as indicated in Appendix 1. 
Preliminary efficacy will be assessed by the changes from Day 1 in the nutrient satiety test 
(Section 6.7) on Day 28. The GCSI (Section 6.8, Appendix 2) and PAGI-SYM (Section 6.9, 
Appendix 2) will also be administered on Day 28 ±1, and the GEBT (Section 6.10) will be 
conducted on Day 27 or Day 29. 
Follow-up Period (Day 28 [±1 Day] After Evaluations Through Day 44 [±3 Days]) 
Patients will undergo telephone Follow-up on Day 44 ±3 days as indicated in Appendix 1.  
Figure 1: 
Study Schema  
 
Abbreviations: BID = twice a day.  
 
3.2 
Rationale for Study Design and Control Group 
CNSA-001 (sepiapterin) is a new chemical entity that is an endogenous, naturally occurring 
precursor of BH4 via the pterin salvage pathway. Animal studies and data from a Phase 1 
single and multiple ascending-dose study in healthy volunteers conducted by Censa 
Pharmaceuticals indicate rapid intracellular conversion of sepiapterin to BH4. It is expected 
that oral administration of CNSA-001 to women with diabetic gastroparesis will result in 
increases in both intracellular and circulating BH4 concentrations. In chronic diabetes, BH4 
biosynthesis is impaired (Xu et al, 2007). 
CNSA-001 was studied in two 14-day Good Laboratory Practice (GLP) toxicity studies, as 
described in Section 5.3, and in a single and multiple ascending-dose study in healthy 
volunteers, Study PKU-001, as described in Section 1.5.  
Because all patients will receive the standard of care for diabetic gastroparesis in addition to 
their assigned study drug, the study design of a randomized study of CNSA-001 versus 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 23 
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placebo in female patients with diabetic gastroparesis will not expose patients to the risk of 
no treatment.  
This study has a double-blind design intended to reduce bias. 
3.3 
Study Duration and Dates 
The study duration for each patient will be up to 75 days, extending from Screening (Day -28 
through Day -1) through the final assessments on Day 44 (±3 days).  


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 24 
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4 
STUDY POPULATION SELECTION 
4.1 
Study Population 
Approximately 4 study centers will enroll up to 20 women with moderate to severe diabetic 
gastroparesis this study.  
4.2 
Inclusion Criteria 
Patients are eligible to participate in this study if they meet all the following inclusion 
criteria: 
1. Informed consent 
2. Females ≥18 and ≤65 years of age 
3. Diagnosis of diabetes mellitus  
4. Documentation of delayed gastric emptying on gastric emptying scintigraphy (within 
1 year of enrollment) 
5. Symptoms of gastroparesis for at least 6 months with GCSI (Section 6.8, Appendix 2) 
score >21 indicating moderate to severe symptoms 
6. Gastric accommodation, as measured by nutrient satiety testing, of ≤600 mL 
7. Negative upper endoscopy or upper GI series within 3 years of enrollment (no evidence 
of mechanical obstruction or peptic ulcer disease) 
8. Either postmenopausal for ≥1 year or surgically sterile (having undergone tubal ligation, 
hysterectomy, or bilateral oophorectomy) for at least 6 months or, if of childbearing 
potential and not abstinent, willing to use a highly effective method of contraception 
throughout the study such as 1 of the following: 
• Hormonal contraception (stable dose for 3 months) 
• Intrauterine device/Intrauterine Hormone-releasing System 
• Barrier contraceptive method (diaphragm, cervical cap, contraceptive sponge, 
condom) 
Patients who are abstinent will not be required to use a contraceptive method unless they 
become sexually active 
9. If on analgesics (including narcotics), promotility agents (including metoclopramide), or 
neuromodulators (including tricyclic antidepressants, gabapentin, and pregabalin), doses 
are stable for >30 days before randomization and the patient is not expected to require 
dose changes during the study through the EOT 
10. Have not used tobacco (e.g., cigarettes, e-cigarettes, cigars, smokeless tobacco, nicotine 
replacement) for 2 weeks prior to Day 1 and willingness to abstain from these products 
during the study through the EOT 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 25 
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4.3 
Exclusion Criteria 
Patients are not eligible to participate in this study if they meet any of the following 
exclusion criteria: 
1. Male gender 
2. Normal gastric emptying  
3. Gastroparesis from postsurgical etiologies 
4. Another active disorder that could, in the opinion of the Investigator, explain symptoms  
5. Weight >100 kg 
6. Alanine aminotransferase > 2× upper limit of normal (ULN) 
7. Pregnant, breastfeeding, or considering pregnancy 
8. Clinically significant cardiac arrhythmia at Screening 
9. QT interval corrected for heart rate (QTc) ≥480 msec (based on triplicate measurements 
taken at Screening)  
10. Resting heart rate ≤40 or ≥110 bpm or resting blood pressure <90/40 mmHg or >150/90 
mmHg at Screening or prior to the first administration of study drug. 
11. Recent clinically significant GI bleeding 
12. Taking levodopa or domperidone within 30 days before randomization or expected to 
require domperidone during the study through the EOT 
13. Taking erythromycin within 30 days before randomization or expected to require 
erythromycin within 30 days before randomization or expected to require erythromycin 
during the study through the EOT; if a patient is taking erythromycin and is otherwise 
eligible to participate in the study, following signing the ICF, the patient may go through 
an erythromycin washout period of 30 days before randomization 
14. Taking any fundic-relaxing agents including, but not limited to, buspirone, clonidine, 
nitrates, phosphodiesterase inhibitors (i.e., sildenafil citrate [Viagra®]) and 
triptan-containing medications, within 30 days before randomization or expected to 
require any of these agents during the study through the EOT 
15. Taking any systemic antifolates, including, but not limited to, methotrexate, pemetrexed, 
and trimetrexate or expected to require any systemic antifolates during the study through 
the EOT (topical antifolates [e.g., cream, ointment, gel] or eye drops with antifolates are 
allowed) 
16. Pulmonary dysfunction (e.g., chronic obstructive pulmonary disease) 
17. Surgery for placement of a gastric stimulator within the past 6 months (patients 
postoperative >6 months with persistent symptoms and delayed gastric emptying are 
eligible) 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 26 
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18. Gastrointestinal disease (such as irritable bowel syndrome, inflammatory bowel disease, 
chronic gastritis, peptic ulcer disease, small bowel malabsorption) that could affect the 
absorption of study drug or contraindicate undergoing the GEBT (Section 6.10)  
19. History of gastric surgery, including Roux-en-Y gastric bypass surgery or an antrectomy 
with vagotomy, or gastrectomy 
20. History of allergies or adverse reactions to BH4 or related compounds, to any excipients 
in the study drug formulation, or to egg, wheat, or algae (Spirulina)  
21. Inability to tolerate oral medication 
22. Current participation in any other investigational drug study or use of any investigational 
agent, investigational device, or approved therapy for investigational use within 30 days 
or 5 half-lives (whichever is longer) before Screening 
23. Any clinically significant laboratory abnormality; in general, each laboratory value from 
Screening and baseline chemistry and hematology panels should fall within the limits of 
the normal laboratory reference range unless deemed not clinically significant by the 
Investigator 
24. Major surgery within the previous 90 days  
25. The patient, in the opinion of the Investigator, is unwilling or unable to adhere to the 
requirements of the study 
26. History of alcohol or drug abuse within 6 months prior to Screening or current evidence 
of substance dependence as determined by the Investigator 
27. Episodes of ketoacidosis or hypoglycemia that are frequent as defined by the Investigator 
28. History of phenylketonuria (PKU) or hyperphenylalaninemia. 
29. Any other conditions, including diabetic comorbidities, that, in the opinion of the 
Investigator or Sponsor, would interfere with the patient’s ability to participate in the 
study or increase the risk of participation for that patient 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 27 
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5 
STUDY TREATMENTS 
5.1 
Description of Treatments 
5.1.1 
Test Product 
The test product is CNSA-001 (sepiapterin) oral powder for suspension. CNSA-001 contains 
the new chemical entity, sepiapterin. Sepiapterin is 2-amino-6-[(2S)-2-hydroxypropanoyl]-
7,8-dihydro-1H-pteridin-4-one with a molecular weight of 237.2 and a molecular formula of 
C9H11 N5O3. Inactive ingredients in CNSA-001 include microcrystalline cellulose, colloidal 
silicon dioxide, croscarmellose, and ascorbic acid. CNSA-001 will be suspended in Medisca® 
Oral Mix prior to dispensing it to the patient.  
5.1.2 
Placebo Control 
The placebo is a ready-made suspension containing microcrystalline cellulose, colloidal 
silicon dioxide, croscarmellose, ascorbic acid, and colorant (Yellow No. 6) that is suspended 
in Medisca® Oral Mix.  
5.2 
Treatments Administered 
Patients will be randomized in a ratio of 1:1 to the following treatment groups:  
• CNSA-001 20 mg/kg/day (10 mg/kg BID) for 14 days 
• Placebo BID for 14 days 
Dosing of CNSA-001 is based on the patient’s weight. The weight obtained on Day -1 will 
be used to calculate the exact amount (mg) of CNSA-001 active ingredient (sepiapterin) 
required for each patient’s daily dose.  
The placebo is formulated as ready-made suspension. The placebo will be administered in the 
same manner (volume) as CNSA-001. 
Details on preparation of study drug and dosing guidelines will be provided in a pharmacy 
manual for the site and an instruction guide for patients.  
5.3 
Selection and Timing of Dose for Each Patient 
All patients will be randomly assigned in a ratio of 1:1 to receive CNSA-001 20 mg/kg/day 
(10 mg/kg BID) or placebo BID.  
The CNSA-001 dose was selected following completion of two 14-day GLP toxicity studies 
in the rat and marmoset. The no observed adverse effect level from both studies was set at 
1000 mg/kg/day, which represents a human equivalent dose of 161.3 mg/kg/day based on 
allometric scaling. Consequently, the proposed dose of 20 mg/kg/day represents an 8.1-fold 
safety margin. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 28 
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Study drug will be dispensed on Day 1 (Section 6.11) with a dosing diary in which patients 
will record all doses taken and times they were taken (Section 5.8.1). The first dose on Day 1 
will be taken in the clinic after patients undergo the nutrient satiety test (Section 6.7). 
If a patient vomits after taking a dose of study drug, the patient should wait until the next 
scheduled timepoint to take another dose. A missed dose should be taken as soon as possible, 
but >2 doses should not be taken on the same day. 
5.4 
Method of Assigning Patients to Treatment Groups 
Patients who fulfill the eligibility criteria and provide informed consent will be randomized 
in a ratio of 1:1 to the CNSA-001 or placebo group via the randomization scheme generated 
for the study. Patients who are randomized will be considered to be enrolled.  
5.5 
Blinding 
This study has a double-blind design. The Investigator, study personnel, and patients will not 
make any effort to determine which study drug is being received. Unblinded pharmacy (or 
other qualified site) personnel will be utilized in this study to prepare the study drug. 
Patients will be blinded to study drug assignment. Only in an emergency, when knowledge of 
the study drug is essential for the clinical management or welfare of a specific patient, may 
the Investigator unblind a patient’s study drug assignment. Copies of the randomization 
sequence and treatment codes will be kept in the pharmacy at the sites. If emergency 
unblinding is required, the Investigator will have immediate access to individual sealed codes 
containing treatment allocations. However, before any unblinding occurs, the Investigator is 
strongly advised to discuss options with the Sponsor’s Medical Monitor or appropriate 
Sponsor study personnel. As soon as possible and without revealing the patient’s study drug 
assignment (unless important to the safety of patients remaining in the study), the 
Investigator must notify the Sponsor if the blind is broken for any reason and the Investigator 
was unable to contact the Sponsor prior to the unblinding. The Investigator will record in 
source documentation the date and reason for revealing the blinded study drug assignment 
for any patient and the names and roles of personnel unblinded. 
5.6 
Concomitant Therapy 
Patients will be permitted to take:  
• Analgesics, including narcotics, if the patient has been on a stable dose of the 
medication for >30 days before randomization; dose escalation is NOT permitted 
during the study through the EOT 
• Promotility agents, including metoclopramide if the patient has been on a stable dose 
of the medication >30 days before randomization; dose changes are NOT permitted 
during the study through the EOT 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 29 
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• Neuromodulators, including any tricyclic antidepressant, gabapentin, and pregabalin, 
if the patient has been on a stable dose >30 days before randomization; dose changes 
are NOT permitted during the study through the EOT 
• Rescue medications that patients would usually take, including ondansetron 
(Zofran®), promethazine (Phenergan®) or prochlorperazine (Compazine®) for nausea 
and tramadol (Ultram®), if symptoms related to gastroparesis require further 
treatment during the study through the EOT 
All prescription and over-the-counter medications (including herbal medications) that the 
patient took within 30 days before Screening though the EOT should be recorded.  
5.7 
Restrictions 
5.7.1 
Prior Therapy and Concomitant Therapy 
The following are prohibited: 
• Any investigational agent, investigational device, or approved therapy for 
investigational use within 30 days or 5 half-lives (whichever is longer) before 
Screening  
• Domperidone within 30 days before randomization or expected to require 
domperidone during the study through the EOT 
• Dose escalation of analgesic or promotility agents or neuromodulators within 30 days 
before randomization or during the study through the EOT 
• Erythromycin within 30 days before randomization or during the study through the 
EOT; if a patient is taking erythromycin and is otherwise eligible to participate in the 
study, following signing the ICF, the patient may go through an erythromycin 
washout period of 30 days before randomization 
• Systemic antifolates, including, but not limited to, methotrexate, pemetrexed, and 
trimetrexate or expected to require any systemic antifolates during the study through 
the EOT (topical antifolates [e.g., cream, ointment, gel] or eye drops with antifolates 
are allowed) 
• Fundic-relaxing agents, including, but not limited to, buspirone, clonidine, nitrates, 
phosphodiesterase inhibitors (i.e., sildenafil citrate [Viagra®]) and triptan-containing 
medications, within 30 days before randomization or expected to require any of these 
agents during the study through the EOT 
• Medications that can alter GI sensation or accommodation or gastric emptying 
overnight before the nutrient satiety test (Section 6.7) 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 30 
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5.7.2 
Food Intake 
Patients will continue their usual diet without modification throughout the study. Patients are 
required to have been fasting overnight for the following assessments: 
• Clinical laboratory, including glycosylated hemoglobin A1c (HbA1c), tests 
• The nutrient satiety test (Section 6.7), which requires the consumption of Ensure™ 
(Abbott Laboratories, Abbott Park, IL, USA)  
• The GEBT (Section 6.10), which requires consumption of a standardized 230 kCal 
meal, consisting of a standardized carbon-13 (13C)-labeled egg component and 
6 saltine crackers, with 6 ounces of water 
5.7.3 
Total Blood Volume 
The total volume of blood obtained from an individual study patient is expected to be 
approximately 40 mL, for clinical laboratory tests inclusive of the HbA1c test. 
5.7.4 
Patient Activity and Tobacco Restrictions 
Patients will not be confined during the study and will not require any activity restrictions. 
Patients must abstain from tobacco use (e.g., cigarettes, e-cigarettes, cigars, smokeless 
tobacco, nicotine replacement) for 2 weeks before Day 1 and during the study through the 
EOT. 
5.8 
Treatment Compliance 
Patients will be instructed to return all used (empty containers) and unused study drug on 
Day 14 if the patient takes the last dose of study drug on Day 14 while in the clinic or, if the 
patient takes the last dose of study drug on Day 14 after leaving the clinic, on Day 15 or Day 
28 (±1 day). Compliance with the dosing regimen will be assessed by reconciliation of used 
and unused study drug. The quantities dispensed, returned, used, and lost will be recorded on 
the dispensing log provided for the study.  
5.8.1 
Dosing Diary 
Patients will be provided with a dosing diary on Day 1 along with instructions for recording 
all doses of study drug and times they were taken. The dosing diary will be collected on 
Day 14 if the patient takes the last dose of study drug on Day 14 while in the clinic or, if the 
patient takes the last dose of study drug on Day 14 after leaving the clinic, on Day 15 or 
Day 28 (±1 day), and the Investigator (or designee) will transcribe all entries into the 
electronic case report form (eCRF).  


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 31 
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5.9 
Packaging and Labeling 
CNSA-001 Oral Powder for Suspension is packaged in 10 mL amber glass vials with black 
child proof caps. Each glass vial contains 175 mg of sepiapterin.  
Each vial of CNSA-001 Oral Powder for Suspension will contain the product name, strength, 
content, expiry/retest date, and company name. Each vial label will contain the words, 
“Caution: Investigational medicine for clinical trial use only.” 
CNSA-001 PLACEBO suspension is packaged in 500 mL bottles. Each bottle of CNSA-001 
PLACEBO suspension will contain the content and company name as well as “CNSA-001 
PLACEBO” on its label. 
The suspending vehicle, Medisca® Oral Mix, is commercially available and will be provided 
separately. 
5.10 
Storage and Accountability 
All drug product required for completion of this study will be provided by Censa 
Pharmaceuticals. It is the responsibility of the pharmacy staff or study staff to ensure that a 
current record of drug inventory and drug accountability is maintained. Inventory and 
accountability records must be readily available for inspection by the study monitor and are 
open to inspection at any time by applicable regulatory authorities. 
CNSA-001 Oral Powder for Suspension (non-reconstituted) may be stored frozen at -20°C or 
at refrigerated conditions (2 to 8°C). If not administered on the same day of suspending, 
CNSA-001 suspension should be stored at refrigerated conditions (2 to 8°C) until time of 
dosing. Once suspended, CNSA-001 is stable for 14 days.  
CNSA-001 PLACEBO suspension may be stored refrigerated at 2 to 8°C.  
5.11 
Investigational Product Retention at Study Site 
Upon completion of the study and once inventoried by the study site, all used (empty) 
containers of study drug will be destroyed. Any unused containers of study drug may be 
either destroyed or returned to the Sponsor following discussion with the Sponsor. If study 
drug is destroyed, a certificate of destruction will be provided to the Sponsor by the 
appropriate facility performing the destruction. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 32 
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6 
STUDY PROCEDURES 
6.1 
Informed Consent 
Consent forms describing in detail the study drug, study procedures, and risks are given to 
the patient, and written documentation of informed consent is required prior to conducting 
study-related procedures. See Section 10.4 for more information on the informed consent 
process. 
6.2 
Medical History and Demographic Data 
A detailed medical/surgical history will be obtained at Screening. The history will include 
specific information related to any prior or existing medical conditions or surgical procedures 
involving the following systems: dermatologic; head, eyes, ears, nose, and throat (HEENT); 
lymphatic; cardiovascular; respiratory; GI; musculoskeletal; and neurological. The medical 
history will be updated on Day 1 before the start of study drug. 
Demographic data obtained at Screening will include age, gender, and self-reported 
race/ethnicity. 
6.3 
Vital Signs, Weight, and Height 
Vital signs, including blood pressure, pulse, respiratory rate, and temperature, will be 
measured at Screening, Day 1 (predose and 2 hours postdose), and at the EOT and EOS 
visits. Vital signs will be measured prior to collection of laboratory samples and after patients 
have rested for 5 minutes  in the supine position. For timepoints other than Day 1, vital signs 
will be taken at any time during the visit after resting and laboratory sample collection.  
Weight will only be collected at Screening as necessary to determine the response to 
Exclusion Criterion #5 (Section 4.3) and on Day -1. Height will only be collected at 
Screening. 
6.4 
Physical Examination 
A complete physical examination will be performed at Screening, on Day 1 before start of 
study drug and at the EOT and EOS visits. The examination will assess general appearance, 
as well as dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, 
musculoskeletal, and neurological parameters.  
6.5 
Clinical Laboratory Tests and Glycosylated Hemoglobin A1c 
Clinical laboratory tests will be performed by qualified local laboratories. Blood and urine 
samples for clinical chemistry, hematology, and urinalysis will be collected at Screening, 
Day 1 (predose), and at the EOT and EOS visits. Patients should fast overnight prior to 
collection of blood samples (minimum of 8 hours before blood sample collection). Blood 
samples for HbA1c will be collected at Screening and at the EOT and EOS visits. Clinically 
significant laboratory abnormalities should be followed to a satisfactory resolution, as 
determined by the Investigator. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 33 
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The following clinical laboratory and other laboratory parameters will be assessed: 
Hematology: 
Hematocrit (HCT) 
Hemoglobin (HGB) 
Platelet count 
Red blood cell (RBC) count 
White blood cell (WBC) count with differential 
(neutrophils, eosinophils, basophils, 
lymphocytes, and monocytes) 
Urinalysis: 
Bilirubin 
Glucose 
Ketones 
Occult blood 
pH 
Protein 
Specific gravity 
Urobilinogen  
Microscopy: 
WBCs 
RBCs 
Epithelial cells 
Pregnancy Testing: a 
Serum human chorionic gonadotropin (HCG) 
at Screening 
Urine HCG Day 1 (predose) and Day 14 (±1 
day) 
Serum Chemistry: 
Albumin (ALB) 
Alkaline phosphatase (AP) 
Alanine aminotransferase (ALT; serum 
glutamic pyruvic transaminase [SGPT]) 
Aspartate aminotransferase (AST; serum 
glutamic oxaloacetic transaminase [SGOT]) 
Blood urea nitrogen (BUN) 
Calcium (Ca) 
Carbon dioxide (CO2) 
Chloride (Cl) 
Creatinine 
Gamma glutamyl transferase (GGT) 
Glucose 
Lactate dehydrogenase (LDH) 
Phosphorus 
Potassium (K) 
Sodium (Na) 
Total bilirubin 
Direct bilirubin 
Total cholesterol 
Total protein 
Uric acid 
Other: 
Glycosylated hemoglobin A1(HbA1c) 
a 
Required for all women who are of childbearing potential. Any positive urine pregnancy test should be 
confirmed by a serum pregnancy test. 
 
6.6 
Electrocardiogram 
At Screening, 12-lead electrocardiograms (ECGs) will be obtained in triplicate, with 
1 minute separating the first and second recordings and 1 minute separating second and third 
recordings. The following ECG parameters will be collected and recorded in the eCRF: RR, 
PR, QRS, QT, and QTc intervals. In addition, the ECG tracing should be reported as normal, 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 34 
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abnormal clinically significant, or abnormal not clinically significant. If abnormalities are 
noted on the ECG, these should be recorded in the eCRF. 
6.7 
Nutrient Satiety Test  
For the nutrient satiety test, patients consume 120 mL of Ensure™ every 4 minutes. At 
5-minute intervals, patients score their fullness using a rating scale that combines verbal 
descriptors on a scale graded 0 to 5 (0: no symptoms, 1: first sensation of fullness [threshold], 
2: mild, 3: moderate, 4: severe and 5: maximum or unbearable fullness). Patients are told to 
stop when a score of 5 is obtained. The actual volume of Ensure™ consumed at this point is 
the maximum tolerated volume. Symptoms are measured 30 minutes after completing the test 
with patients scoring each symptom of bloating, fullness, nausea and pain on a visual 
analogue scale with 100-mm lines and the words “unnoticeable” and “unbearable” as 
anchors. The sum of the four 100-mm visual analogue scales provides an aggregate symptom 
score (Park, 2011). 
The nutrient satiety test will be administered in the clinic at Screening, on Day 1 (predose), 
and on Day 14 and Day 28 after overnight fasts and after any medications that can alter GI 
sensation or accommodation or gastric emptying have been held overnight. A nutrient satiety 
test volume of ≤600 mL at Screening is required for patients to participate in this study. 
6.8 
Gastroparesis Cardinal Symptom Index 
The GCSI (Appendix 2) consisting of a subset of items from the PAGI-SYM instrument 
(Section 6.9, Appendix 2), will be administered in the clinic at Screening and on Day 1 
(predose), Day 14 (+1 day), and Day 28 (±1 day). A GCSI score >21 at Screening, indicating 
moderate to severe symptoms, is required for patients to participate in this study. 
6.9 
Patient Assessment of Upper Gastrointestinal Disorders-Symptom 
Severity 
The PAGI-SYM (Appendix 2) is a 20-item upper GI symptom severity instrument with 
6 subscales: heartburn/regurgitation, fullness/early satiety, nausea/vomiting, bloating, upper 
abdominal pain, and lower abdominal pain. It will be administered in the clinic on Day 1 
(predose) and on Day 14 (+1 day), and Day 28 (±1 day).  
6.10 
Gastric Emptying Breath Test 
The GEBT, which is a nonradioactive noninvasive test, will be administered in the clinic on 
Day -1, Day 15, and Day 27 or Day 29 after the patient has fasted overnight (a minimum of 
8 hours before test administration with the exception of 4 ounces of water up to 1 hour before 
the test). At the clinic, the patient provides baseline (premeal) breath samples and then 
consumes a standardized 230 kCal meal, consisting of a proprietary standardized 13C-labeled 
egg component (which is rehydrated and then microwaved for 1.5 minutes) and 6 saltine 
crackers, accompanied by 6 ounces of water. The meal is to be consumed within 10 minutes. 
Single postmeal breath samples are collected in capped glass tubes at 45, 90, 120, 150, 180, 
and 240 minutes after the meal is consumed and sent to the specified local laboratory for 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 35 
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analysis by Gas Isotope Ratio Mass Spectrometry. By adding 13C to the test meal, the GEBT 
can determine how fast the stomach empties the meal by measuring the rate of carbon-13 
dioxide (13CO2) excretion arising from the digested test meal. The rate of 13CO2 excretion 
found in the patient’s breath is proportional to the patient’s rate of gastric emptying. The 
patient’s 13CO2 excretion rate at each breath collection time is reported using the GEBT 
metric “kPCD.” The “k” is a multiplier of 1000, and “PCD” is an acronym for percent 13C 
dose excreted (as 13CO2). The test should not be administered to patients with a known 
allergy to egg, wheat, or algae (Spirulina) (Cairn Diagnostics™; Sutton et al, 2015; GEBT 
package insert, 2015; United States Food and Drug Administration, 2015).  
6.11 
Dispensing Study Drug  
Study drug will be dispensed on Day 1 along with a dosing diary to record all doses taken 
and times they were taken. A sufficient supply of study drug will be dispensed for dosing 
through Day 14. Details on the preparation of study drug, dosing guidelines, and storage will 
be provided in a pharmacy manual for the site and an instruction guide for patients. 
6.12 
Adverse Events Assessments 
An AE is defined as any untoward medical occurrence associated with the use of an 
intervention in humans, whether or not considered intervention-related. 
The occurrence of an AE or serious adverse event (SAE) (Section 6.12.6) may come to the 
attention of study personnel during study visits and interviews of a study patient presenting 
for medical care, or upon review by a study monitor. All AEs including local and systemic 
reactions not meeting the criteria for SAEs will be captured on the appropriate eCRF. 
Information to be collected includes, but is not limited to, the event description, time of 
onset, clinician’s assessment of severity, relationship to study drug (assessed only by those 
with the training and authority to make a diagnosis), and date of resolution/stabilization of 
the event. Action taken regarding study medication (e.g., drug withdrawn, interrupted) will 
also be collected in the eCRF. All AEs that start during the study must be documented 
appropriately regardless of relationship. All treatment-related AEs or AEs leading to 
discontinuation will be followed to an adequate resolution, as determined by the Investigator. 
Any medical condition that is present at the time that the patient is screened will be 
considered as medical history and not reported as an AE. However, if the patient’s condition 
deteriorates at any time during the study, it will be recorded as an AE. 
Changes in the severity of an AE will be documented to allow an assessment of the duration 
of the event at each level of severity to be performed. The AEs characterized as intermittent 
require documentation of onset and duration of each episode. 
6.12.1 
Reporting Timelines 
The Investigator will record all reportable events with start dates occurring any time after 
informed consent and continue through clinical study completion or, in the case of 
withdrawal, until the outcome is determined. The AEs will be assessed at each visit and/or 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 36 
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through telephone contact with the patient. A neutral question, such as “How have you been 
feeling since your last visit?” may be asked.  
All SAEs should be reported after the patient signs the informed consent and followed until 
resolution, stabilization, or until the Investigator provides sufficient evidence that no further 
information can be obtained. 
All SAEs and pregnancies (in a patient or partner of a male patient) occurring while the 
patient is on the study or within 30 (±3) days after the patient received the last dose of study 
drug must be reported within 24 hours of the knowledge of the event by study personnel 
whether or not considered to be related to study drug. 
Deaths that occur ≥30 (±3) days after the patient’s last study dose must be reported within 
24 hours of knowledge of the event, if deemed related to study drug by the Investigator. 
Although pregnancy is not considered an AE or SAE by regulatory definition, for this study 
pregnancies must be processed following SAE timelines (e.g., within 24 hours of knowledge 
of the pregnancy) for data transmission purposes. In the event that a pregnancy complication 
occurs, or elective termination of a pregnancy is required for medical reasons, then the 
complication will be recorded as an AE or SAE, as appropriate. 
While elective and uncomplicated induced abortion not required for medical reasons does not 
constitute an AE or SAE (even if the patient or patient’s partner is hospitalized to undergo 
abortion), spontaneous abortion is considered a fatal event and must be reported as an AE 
and SAE, as appropriate. 
Any pregnancy and/or suspected pregnancy that occurs during the study in a female patient 
should be reported using Pregnancy Reporting Form within 24 hours of knowledge of the 
event by study personnel. Any pregnancy and/or suspected pregnancy will be followed for 
outcome. 
If the patient has received the investigational drug prior to becoming pregnant, the patient 
will continue the efficacy assessment and Follow-up periods and measures of safety and 
efficacy will be obtained. 
The patient will be followed until the outcome of the pregnancy is determined. It is the 
responsibility of the Investigator to obtain and document pregnancy information on the most 
recent Pregnancy Report Form. Furthermore, any SAE occurring as an outcome of the 
pregnancy must be reported according to the procedures outlined for SAE reporting. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 37 
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6.12.2 
Severity 
The intensity of each AE will be graded as follows: 
Mild: 
Events require minimal or no treatment and do not interfere with the 
patient’s daily activities.  
Moderate: 
Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning.  
Severe: 
Events interrupt a patient’s usual daily activity and may require systemic 
drug therapy or other treatment. Severe events are usually potentially 
life-threatening or incapacitating.  
 
It is important to distinguish between serious and severe AEs. Severity is a measure of 
intensity; however, an AE of severe intensity need not necessarily be considered serious. For 
example, nausea that persists for several hours may be considered severe nausea but may not 
be considered an SAE. Alternatively, a stroke that results in only a limited degree of 
disability may be considered only a mild stroke but would be considered an SAE. 
6.12.3 
Relationship 
The Investigator’s assessment of causality must be provided for all AEs (serious and 
nonserious). An Investigator’s causality assessment is the determination of whether there 
exists a reasonable possibility that the study drug caused or contributed to an AE. For 
purposes of consistency, guidelines for assessing causality are provided below: 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 38 
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Not Related 
The AE is completely independent of study drug administration, and/or 
evidence exists that the event is definitely related to another etiology. There 
must be an alternative, definitive etiology documented by the clinician. 
No relationship between the experience and the administration of study 
drug; related to other etiologies such as concomitant medications or 
patient’s clinical state. 
Unlikely to be 
Related 
A clinical event, including an abnormal laboratory test result, whose 
temporal relationship to drug administration makes a causal relationship 
improbable (e.g., the event did not occur within a reasonable time after 
administration of the trial medication) and in which other drugs or chemicals 
or underlying disease provides plausible explanations (e.g., the patient’s 
clinical condition, other concomitant treatments). 
Possibly 
Related 
There is some evidence to suggest a causal relationship (e.g., the event 
occurred within a reasonable time after administration of the trial 
medication). However, other factors may have contributed to the event 
(e.g., the patient’s clinical condition, other concomitant events). Although 
an AE may rate only as “possibly related” soon after discovery, it can be 
flagged as requiring more information and later be upgraded to “probably 
related” or “definitely related,” as appropriate. 
Probably 
Related 
There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely. The clinical event, including an abnormal laboratory test 
result, occurs within a reasonable time after administration of the drug, is 
unlikely to be attributed to concurrent disease or other drugs or chemicals, 
and follows a clinically reasonable response on withdrawal (dechallenge). 
Rechallenge information is not required to fulfill this definition.  
Definitely 
Related 
There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an 
abnormal laboratory test result, occurs in a plausible time relationship to 
drug administration and cannot be explained by concurrent disease or other 
drugs or chemicals. The response to withdrawal of the drug (dechallenge) 
should be clinically plausible. The event must be pharmacologically or 
phenomenologically definitive, with use of a satisfactory rechallenge 
procedure if necessary.  
 
These criteria, in addition to good clinical judgment, should be used as a guide for 
determining the causal assessment. If the event is believed to be unrelated to study drug 
administration, then an alternative explanation should be provided, if available. 
6.12.4 
Expectedness 
An AE or suspected adverse reaction is considered “unexpected” if it is not listed in the 
Investigators’ Brochure or is not listed at the specificity or severity that has been observed; 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 39 
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or, if an Investigators’ Brochure is not required or available, is not consistent with the risk 
information described in the general investigational plan or elsewhere in the protocol. 
The drug safety medical reviewer will be responsible for determining whether an AE is 
expected or unexpected. An AE will be considered unexpected if the nature, severity, or 
frequency of the event is not consistent with the risk information previously described for the 
study agent (e.g., Investigators’ Brochure). 
6.12.5 
Clinical Laboratory Adverse Events 
Laboratory abnormalities should not be recorded as AEs or SAEs unless they are associated 
with clinical signs or symptoms or require medical intervention, as determined by the 
Investigator. However, each laboratory abnormality (e.g., clinically significant changes 
detected in hematology, serum chemistry panel, urinalysis, urine microscopic, and HbA1c 
evaluations) independent from any underlying medical condition that requires medical or 
surgical intervention, or that leads to study drug interruption or discontinuation, must be 
recorded as an AE, or SAE if applicable. If the laboratory abnormality is part of a clinical 
condition or syndrome, it should be recorded as the syndrome or diagnosis rather than as the 
individual laboratory abnormality. In addition, laboratory abnormalities or other abnormal 
test assessments (e.g., vital signs) performed that are associated with signs or symptoms must 
be recorded as AEs or SAEs if they meet the definition of an AE (or SAE) as described 
below. 
6.12.6 
Serious Adverse Events 
6.12.6.1 
Definition 
An SAE is defined as an AE or suspected adverse reaction occurring at any dose that results 
in any of the following outcomes: death, life-threatening AE, inpatient hospitalization or 
prolongation of existing hospitalization, a persistent or significant disability/incapacity or a 
substantial disruption of the ability to conduct normal life functions, or a congenital 
anomaly/birth defect. 
An AE or suspected adverse reaction is considered ‘‘life-threatening’’ if, in the view of either 
the Investigator or Sponsor, its occurrence places the patient at immediate risk of death. It 
does not include an AE or suspected adverse reaction that, had it occurred in a more severe 
form, might have caused death. 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical judgment, 
they may jeopardize the patient and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. Examples of such medical events include 
allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of 
drug dependency or drug abuse. Medical and scientific judgment should be exercised in 
deciding whether expedited reporting is appropriate in these other situations. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 40 
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6.12.6.2 
Suspected Unexpected Serious Adverse Reaction (SUSAR) 
The Sponsor must submit a safety report for any suspected adverse reaction to study 
treatment that is both serious and unexpected. Before submitting a safety report, the Sponsor 
needs to ensure that the event meets all 3 of the definitions: 
• Suspected adverse reaction 
• Serious 
• Unexpected 
If the AE does not meet all 3 of the definitions, it should not be submitted as a safety report. 
6.12.6.3 
Reporting Serious Adverse Events 
The Investigator will report all SAEs to the designated drug safety team within 24 hours of 
knowledge of the event whether or not considered to be related to study drug using the SAE 
Report Form provided. 
Although not all information required for a complete SAE Report Form may be readily 
available at the time of the event, the Investigator must include sufficient information on the 
SAE Report Form to allow for a complete medical assessment. This should include at a 
minimum the patient number, site number, detailed description of the event, seriousness 
criteria, causality/relationship to study drug, and Investigator signature. 
The designated drug safety team will acknowledge the receipt of the SAE via email to the 
clinical site. After submission of the initial report, the Investigator will provide follow-up 
information to the drug safety team as requested (e.g., concomitant medications, hospital 
discharge summary) to further evaluate the event and assure that all appropriate information 
is received. Once all information is received and the SAE has been deemed appropriate for 
closure, the SAE Report Form must be signed and dated by the Investigator. 
The Investigator is responsible for informing the Institutional Review Board (IRB) of the 
SAE in accordance with institutional policies and procedures including relevant initial and 
follow-up information about the SAE. 
Treatment-related SAEs or events leading to discontinuation of study drug will be followed 
for outcome information until resolution or stabilization. Other supporting documentation of 
the event may be requested by Censa Pharmaceuticals (or designee) and should be provided 
as soon as possible. The Medical Monitor should be contacted when the Investigator 
considers an SAE to be treatment-related. 
6.12.7 
Treatment-Emergent Adverse Events 
Those AEs that start at the time of or after the first dose of study drug are TEAEs. Those AEs 
that worsen at or after the time of first dose of study drug are also considered 
treatment-emergent. All AEs that occur on or after the ICF has been signed, including all 
TEAEs, through Day 29 will be recorded in the eCRF. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 41 
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All SAEs through Day 44 ±3 days [30 ±3 days after the patient received last dose of study 
drug] will be recorded in the eCRF and reported as described in Section 6.12.6.3. 
6.13 
Prior and Concomitant Medication Assessments 
All prescription and over-the-counter medications (including herbal medications) taken by a 
patient starting from the 30-day period before Screening through Day 28 (±1 day) before the 
patient leaves the clinic after completion of all EOS evaluations will be recorded. Any 
concomitant medications added or discontinued during the study will be recorded at each 
visit. 
6.14 
Removal of Patients From the Trial or Study Drug 
6.14.1 
Early Discontinuation From Study Drug Administration 
Premature discontinuation of study drug administration is defined as the discontinuation of 
study drug for an individual patient before the required full course of study drug is 
completed. Reasons for premature discontinuation from study drug administration should be 
recorded on the appropriate page(s) of the eCRF and may include, but are not limited to the 
following: 
• Occurrence of an AE, SAE, or clinically significant laboratory abnormality that, in the 
opinion of the Investigator, warrants the patient’s permanent discontinuation from study 
drug administration 
• In the judgment of the Investigator, the patient experiences a general or specific 
change(s) that renders the patient unsuitable for continued study drug administration 
• There is a need for concomitant medication that makes the patient ineligible for further 
study drug administration 
• Pregnancy 
• Specific reasons related to adverse events that have been observed in pre- and post-
marketing treatment with the same drug class of CNSA-001 (i.e., sapropterin): 
o Hypersensitivity reactions including anaphylaxis  
o Gastritis  
o Abnormal liver function tests in patients with liver impairment  
o Unexplained hyperactivity 
Given the requirement for pregnancy testing in women of childbearing potential at Screening 
and the requirement for highly effective methods of contraception during the study, it is 
unlikely that pregnancies will occur during study conduct. However, study drug will be 
discontinued should suspected or confirmed pregnancy or nursing during the study drug 
administration period occur. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 42 
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Patients who prematurely discontinue study drug due to any of the above reasons will 
complete the EOT assessments within 24 hours of withdrawal.  
6.14.2 
Withdrawal From the Study 
Patients may withdraw from the study for any reason or be withdrawn at the request of the 
Investigator or Sponsor. The reason for a patient’s withdrawal must be recorded on the 
appropriate page(s) of the eCRF. Reasons for withdrawal from the study may include, but are 
not limited to: 
• Withdrawal of consent  
• AEs or SAEs 
• Significant patient noncompliance, defined as refusal or inability to adhere to the protocol 
requirements 
• The Investigator determines that it is in the best interest of the patient to withdraw from 
study participation, due to a reason other than safety 
Each patient who withdraws from the study after receipt of any amount of study drug will be 
asked to undergo EOT assessments. However, patients may withdraw consent to participate 
in this study at any time without penalty. Withdrawn patients who receive any amount of 
study drug, will not be replaced. Withdrawn patients who do not receive any study drug will 
be replaced. 
6.14.3 
Study Stopping Criteria 
The study may be terminated if significant violations of Good Clinical Practice (GCP) that 
compromise the ability to achieve the study objectives or compromise patient safety are 
observed at any time during the study. With regard to safety, the study may be temporarily 
suspended or terminated should the Investigator, Sponsor, or IRB determine that the safety of 
patients is significantly jeopardized. The decision for a temporary or permanent study hold 
will depend on the nature, frequency, and severity of AEs that were observed in all enrolled 
patients to date. For example, the study will be temporarily or permanently halted should 
either of the following occur: 
• The presence of the same system organ class (e,g., gastrointestinal, cardiac, etc.) 
severe AE for which no other alternative etiology can be identified, considered 
related to study drug, in 2 or more patients (Severity defined in Section 6.12.2). 
• The presence of life-threatening AE or AE requiring urgent intervention in 1 or more 
patients. 
• Death related to Adverse Event. 
 
 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 43 
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In a temporary study hold, no additional patients will be enrolled into the study or dosed with 
study drug until the study team members (including the Investigator and the Medical 
Monitor) decide it is safe to proceed with the study. 
  
6.15 
Appropriateness of Measurements 
Safety will be measured by AEs (including SAEs), vital signs, physical examinations, and 
clinical laboratory and HbA1c tests.  
Because treatment with BH4 is hypothesized to restore nNOS function in the control of 
gastric accommodation, the nutrient satiety test (Section 6.7) was chosen for the primary 
endpoint for this study. Gastric accommodation has been measured using ultrasonography 
(Undeland et al, 1998), single-photon emission computed tomography (Bredenoord et al, 
2003), and barostat testing (Coulie et al, 1998; Sarnelli et al, 2001). Barostat studies have 
been shown to be reproducible (Sarnelli et al, 2001) but are invasive and not widely 
available. Satiety testing using a nutrient liquid has been shown to be reproducible (Kindt et 
al, 2008) and correlate with impairment in gastric accommodation but not gastric emptying 
or visceral sensitivity (Tack et al, 2003). 
The GEBT is nonradioactive, noninvasive test of gastric emptying rate that has been 
validated against the reference method of gastric scintigraphy. It has been accepted by the 
United States Food and Drug Administration (FDA) for use in the measurement of the rate of 
gastric emptying of solids and as an aid in the diagnosis of delayed gastric emptying 
(gastroparesis) in adult humans who are symptomatic for gastroparesis. The GEBT can 
determine how fast the stomach empties a standardized meal with a 13C-labeled egg 
component by measuring the ratio of 13CO2 to carbon-12 dioxide (12CO2) collected in breath 
samples at multiple time points after the meal is consumed compared to baseline. The breath 
samples are collected in capped glass tubes and sent to a specified local laboratory for 
analysis. By measuring the change in the ratio of 13CO2 to 12CO2 over time in comparison to 
the premeal value, the rate of 13CO2 excretion can be calculated and the gastric emptying rate 
determined. The GEBT does not require administration by specially trained health care 
professionals or special precautions related to radiation-emitting compounds (Section 6.10).  
The GCSI (Section 6.8, Appendix 2), consisting of a subset of items from the PAGI-SYM 
instrument (Section 6.9, Appendix 2) (described below), is based on reviews of the medical 
literature and results from clinician interviews and patient focus groups. Its reliability and 
validity were examined in 169 gastroparesis patients from 7 clinical centers in the US. 
Patients completed the GCSI, SF-36 Health Survey, and disability day questions at baseline 
and again at 8 weeks. Clinicians independently rated the severity of the patients' symptoms, 
and both clinicians and patients rated the changes in gastroparesis-related symptoms over the 
8weeks. For the GCSI total score, the internal consistency reliability was 0.84, and the test-
re-test reliability was 0.76. Significant relationships were observed between the clinician-
assessed symptom severity and the GCSI total score, and significant associations were found 
between the GCSI scores and SF-36 physical and mental component summary scores and 
restricted activity and bed disability days. Patients with greater symptom severity, as rated by 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 44 
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clinicians, reported greater symptom severity on the GCSI. The GCSI total scores were 
responsive to changes in overall gastroparesis symptoms as assessed by clinicians 
(p = 0.0002) and patients (p = 0.002) (Revicki et al, 2003). 
The PAGI-SYM (Section 6.9, Appendix 2) is a 20-item upper GI symptom severity 
instrument with 6 subscales: heartburn/regurgitation, fullness/early satiety, nausea/vomiting, 
bloating, upper abdominal pain, and lower abdominal pain. To develop the instrument, 
patients with GERD (n = 810), dyspepsia (n = 767), or gastroparesis (n = 169) from the US, 
France, Germany, Italy, the Netherlands, and Poland completed the PAGI-SYM, the SF-36 
Health Survey, a disease-specific health-related quality of life measure (Patient Assessment 
of Upper Gastrointestinal Disorders-Quality of Life [PAGI-QOL]), and disability day 
questions. Two-week reproducibility was evaluated in 277 stable patients. Construct validity 
was evaluated by correlating subscale scores with SF-36, PAGI-QOL and global symptom 
severity scores and disability days. Internal consistency reliability ranged from 0.79 to 0.91, 
and test-retest reliability ranged from 0.60 to 0.82 for the PAGI-SYM subscales. The 
PAGI-SYM subscale scores correlated significantly with SF-36 scores (all p <0.0001), 
PAGI-QOL scores (all p <0.0001), disability days (p <0.0001), and global symptom severity 
(p <0.0001). Mean PAGI-SYM scores varied significantly in groups defined by disability 
days (all p <0.0001), in which greater symptom severity was associated with more disability 
days (Rentz et al, 2004; Revicki et al, 2004). 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 45 
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7 
STUDY ACTIVITIES 
7.1 
Screening Procedures (Day –28 to Day -1) 
The following will be performed/collected during the Screening Period from Day -28 to 
Day -1 after obtaining informed consent with a properly signed ICF (Section 10.4): 
• Obtain demographic data (age, gender, self-reported race/ethnicity) 
• Obtain medical/surgical history, including specific information related to any prior or 
existing medical conditions or surgical procedures involving the dermatologic, HEENT, 
lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and neurological systems 
(Section 6.2) 
• Obtain vital signs (blood pressure, pulse, respiratory rate, and temperature) prior to 
collection of any laboratory samples and after patients have rested for 5 minutes in a 
supine position; obtain the patient’s weight (as necessary to determine the response to 
Exclusion Criterion #5 [Section 4.3] and on Day -1) and height (Section 6.3) 
• Conduct a complete physical examination, including assessments of general appearance, 
dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and 
neurological parameters (Section 6.4) 
• Collect blood samples for clinical chemistry, hematology, and HbA1c after the patient 
has fasted overnight (a minimum of 8 hours before blood sample collection) and a urine 
sample for urinalysis (Section 6.5) 
• Perform a serum pregnancy test for all women who are of childbearing potential  
• Obtain 12-lead ECGs in triplicate, with 1 minute separating the first and second 
recordings and 1 minute separating second and third recordings (Section 6.6) 
• Administer the GCSI (Section 6.8, Appendix 2) 
• Record all prescription and over-the-counter medications (including herbal medications) 
taken within 30 days before the Screening 
• Assess/record AEs from the time of informed consent 
• Administer the nutrient satiety test (Section 6.76.10) after the patient has fasted overnight 
and after any medications that can alter GI sensation or accommodation or gastric 
emptying have been held overnight 
• Confirm patient meets inclusion criteria and no exclusion criteria (Section 4.2 and 
Section 4.3, respectively) 
• Administer the GEBT (Section 6.10) on Day -1 after the patient has fasted overnight (a 
minimum of 8 hours before test administration with the exception of 4 ounces of water up 
to 1 hour before the test) 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 46 
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• Instruct the patient regarding fasting overnight before blood is drawn for the clinical 
laboratory evaluations (Section 6.5) and the nutrient satiety test (Section 6.7) is 
administered on Day 1 predose 
• Instruct the patient regarding not taking any medications that can alter GI sensation or 
accommodation or gastric emptying overnight before the days of the nutrient satiety test 
(Section 6.7)  
• Randomize patient on Day -1 
7.2 
Day 1 Predose 
The following will be performed/collected on Day 1 in the clinic before the patient receives 
study drug: 
• Obtain medical/surgical history since Screening, including specific information related to 
any prior or existing medical conditions or surgical procedures involving the 
dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and 
neurological systems (Section 6.2) 
• Obtain vital signs (blood pressure, pulse, respiratory rate, and temperature) prior to 
collection of any laboratory samples and after patients have rested 5 minutes in a supine 
position (Section 6.3) 
• Conduct a complete physical examination, including assessments of general appearance, 
dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and 
neurological parameters (Section 6.4) 
• Collect blood samples for clinical chemistry, and hematology after the patient has fasted 
overnight (a minimum of 8 hours before blood sample collection) and a urine sample for 
urinalysis (Section 6.5) 
• Perform a urine pregnancy test for all women who are of childbearing potential; confirm 
any positive urine pregnancy test by performing a serum pregnancy test 
• Record all prior prescription and over-the-counter medications (including herbal 
medications) taken since Screening 
• Assess/record AEs since Screening 
• Administer:  
o Nutrient satiety test (Section 6.76.10) 
o GCSI (Section 6.8, Appendix 2) 
o PAGI-SYM (Section 6.9, Appendix 2) 
7.3 
Day 1 After Baseline Evaluations Through Day 13 
7.3.1 
Day 1  
• Administer first dose of study drug in the clinic 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 47 
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• Obtain vital signs (blood pressure, pulse, respiratory rate, and temperature) 2 hours 
postdose after patients have rested 5 minutes in a supine position (Section 6.3) 
• Dispense study drug and instruct the patient on its preparation and administration BID 
starting with the second dose on Day 1 and continuing through Day 14 (Section 5.2 and 
Section 6.11) 
• Dispense dosing diary and instruct the patient on its completion (Section 5.8.1) 
• Instruct the patient not to take any Day 14 doses of study drug before the Day 14 clinic 
visit, and to bring the dosing diary and all study drug supplies to the Day 14 visit 
• Record all medications the patient received since the predose assessment 
• Assess/record AEs since the predose assessment 
• Instruct the patient regarding fasting overnight before blood is drawn for the clinical 
laboratory evaluations, the nutrient satiety test (Section 6.7), and the GEBT 
(Section 6.10) on Day 14 and/or on Day 15  
• Instruct the patient regarding not taking any medications that can alter GI sensation or 
accommodation or gastric emptying overnight before the Day 14 visit (for the nutrient 
satiety test)  
7.4 
Early Termination Procedures 
If a patient discontinues study drug early (Section 6.14.1), the patient should return to the 
study site within 24 hours of withdrawal and complete all of the procedures outlined for the 
EOT (Section 7.5). If a patient withdraws early from the study (Section 6.14.2), the patient 
will be asked to return to the study site within 24 hours of withdrawal and complete all of the 
procedures outlined for the EOT (Section 7.5). All study drug and supplies and the dosing 
diary will be collected.  
7.5 
End of Treatment Visits (Day 14 and Day 15) 
Patients will complete EOT visit(s) at early termination (Section 7.4) or on Day 14 and 
Day 15. During the EOT visits, the following will be completed: 
• Obtain vital signs (blood pressure, pulse, respiratory rate, and temperature), prior to 
collection of any laboratory samples and after patients have rested 5 minutes in a supine 
(Section 6.3) on Day 14 or Day 15 
• Conduct a complete physical examination, including assessments of general appearance, 
dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and 
neurological parameters (Section 6.4) on Day 14 or Day 15 
• Collect blood samples for clinical chemistry, hematology, and HbA1c after the patient 
has fasted overnight (a minimum of 8 hours before blood sample collection) and a urine 
sample for urinalysis (Section 6.5) on Day 14 or Day 15 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 48 
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• Perform a urine pregnancy test for all women who are of childbearing potential; confirm 
any positive urine pregnancy test by performing a serum pregnancy test on Day 14 or 
Day 15 
• Administer:  
o Nutrient satiety test (Section 6.76.10) on Day 14 
o GCSI (Section 6.8, Appendix 2) on Day 14 or Day 15 
o PAGI-SYM (Section 6.9, Appendix 2) on Day 14 or Day 15 
o GEBT (Section 6.10) on Day 15 
• Administer first Day 14 dose of study drug on Day 14; administer the second Day 14 
dose of study drug on Day 14 or instruct patient to take second Day 14 dose of study drug 
on Day 14 after the patient leaves the clinic 
• Record all prescription and over-the-counter medications (including herbal medications) 
taken since the Day 1 visit through Day 15 before the patient leaves the clinic 
• Assess/record AEs since last visit through Day 15 before the patient leaves the clinic 
• Collect study drug, dosing diary, and assess study drug compliance on Day 14 if the 
patient takes the last dose of study drug on Day 14 while in the clinic or, if the patient 
takes the last dose of study drug on Day 14 after leaving the clinic, on Day 15 
• Instruct the patient regarding fasting overnight before blood is drawn for the clinical 
laboratory evaluations on Day 28 (±1 day), the nutrient satiety test (Section 6.7) on 
Day 28, and the GEBT (Section 6.10) on Day 27 or Day 29 
• Instruct the patient regarding not taking any medications that can alter GI sensation or 
accommodation or gastric emptying overnight before the Day 28 visit (for the nutrient 
satiety test) 
7.6 
End of Study (Day 28 ±1 Day) 
Patients will complete the EOS assessments on Days 27 through Day 29. The following EOS 
assessments will be completed: 
• Obtain vital signs (blood pressure, pulse, respiratory rate, and temperature), prior to 
collection of any laboratory samples and after patients have rested 5 minutes in a supine 
position (Section 6.3) on Day 28 (±1 day) 
• Conduct a complete physical examination, including assessments of general appearance, 
dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and 
neurological parameters (Section 6.4) on Day 28 (±1 day) 
• Collect blood samples for clinical chemistry, hematology, and HbA1c after the patient 
has fasted overnight (a minimum of 8 hours before blood sample collection) and a urine 
sample for urinalysis (Section 6.5) on Day 28 (±1 day) 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 49 
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• Perform a urine pregnancy test for all women who are of childbearing potential; confirm 
any positive urine pregnancy test by performing a serum pregnancy test on Day 28 
(±1 day) 
• Administer:  
o Nutrient satiety test (Section 6.76.10) on Day 28 
o GCSI (Section 6.8, Appendix 2) on Day 28 (±1 day) 
o PAGI-SYM (Section 6.9, Appendix 2) on Day 28 (±1 day) 
o GEBT (Section 6.10) on Day 27 or Day 29 
• Collect study drug, dosing diary, and assess study drug compliance on Day 28 (±1 day) 
(if not done on Day 14 or Day 15)  
• Record all prescription and over-the-counter medications (including herbal medications) 
taken since the last visit through Day 28 (±1 day) before the patient leaves the clinic after 
completion of all EOS evaluations  
• Assess/record AEs since last visit through Day 28 (±1 day) before the patient leaves the 
clinic after completion of all EOS evaluations 
7.7 
Telephone Follow-up Day 44 (±3 Days) (30 ±3 Days After Last Dose) 
During telephone Follow-up on Day 44 (±3 days), the following will be completed: 
• Call the patient to see if any SAEs were experienced during the 30 ±3 days after the last 
dose of study drug  
• Record SAEs in the eCRF, if applicable 
• Report SAEs following SAE reporting timelines per Section 6.12.1 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 50 
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8 
QUALITY CONTROL AND ASSURANCE 
Regular monitoring and an independent audit, if conducted, must be performed according to 
International Council on Harmonisation (ICH)-GCP (Section 10.6). 
Quality control procedures will be implemented beginning with the data entry system and 
data quality control checks that will be run on the database will be generated. Any missing 
data or data anomalies will be communicated to the site(s) for clarification/resolution. 
Following written Standard Operating Procedures, the monitors will verify that the clinical 
trial is conducted and data are generated, documented (recorded), and reported in compliance 
with the protocol, GCP, and the applicable regulatory requirements (e.g., GLPs, Good 
Manufacturing Practices). 
The investigational site will provide direct access to all trial-related sites, source 
data/documents (including patient diaries), and reports for the purpose of monitoring and 
auditing by Censa Pharmaceuticals (or designee), and inspection by local and regulatory 
authorities. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 51 
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9 
PLANNED STATISTICAL METHODS 
9.1 
General Considerations 
Descriptive statistics, including numbers and percentages for categorical variables, and 
numbers, means, standard deviations, medians, minimums, and maximums for continuous 
variables will be provided. Exploratory analyses may also be performed. Listings of 
individual patient data will be produced. Additional details can be found in the statistical 
analysis plan. 
9.2 
Determination of Sample Size 
The primary objective of this study is to assess the impact of CNSA-001 on gastric 
accommodation, as measured by nutrient satiety testing (Section 6.7), in women with 
moderate to severe diabetic gastroparesis. A total of 10 patients will be enrolled in each 
treatment group. If it is assumed that the standard deviation for the change from baseline in 
nutrient meal volume ingested is approximately 235 mL (data on file), and using a one-sided 
t-test at the 0.025 significance level, this trial has 80% power to detect a treatment difference 
greater than 288 mL (i.e., an effect size of 1.23) in the CNSA-001group. The study also has 
90% power to detect a treatment difference greater than 330 mL (i.e., an effect size of 1.41) 
in the CNSA-001 group. 
9.3 
Analysis Populations 
Two study populations will be analyzed: 
• Safety population: all patients who were randomized and received any amount of study 
drug (CNSA-001 or placebo) 
• Efficacy population: all patients who were randomized, received any amount of study 
drug (CNSA-001 or placebo), and had available Day 1 predose and Day 14 nutrient 
satiety test (Section 6.7) maximum tolerated volume results 
9.4 
Demographics, Baseline Characteristics, Enrollment, Protocol Deviations, 
and Patient Disposition 
Enrollment, protocol deviations, demographics (age, sex, race/ethnicity), prior and 
concomitant medications, and medical history will be summarized by treatment group using 
descriptive statistics. Discontinuations from study drug and the study will be summarized by 
treatment group as well and the reasons for discontinuation will be listed. 
9.5 
Statistical Analysis of Efficacy Variables 
Efficacy will be assessed in the Efficacy population.  
The primary efficacy measure will be the changes in maximal tolerated volume consumed 
during the nutrient satiety test (Section 6.7) from Day 1 to Day 14 and Day 28. The changes 
from Day 1 to Day 14 and from Day 1 to Day 28 in maximal tolerated volume consumed 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 52 
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during the nutrient satiety test will be compared between treatment groups using a student’s 
t-test.  
Secondary efficacy measures will consist of changes in the following from baseline through 
Day 14 (±1 day) and through Day 28 (±1 day):  
• PAGI-SYM (Section 6.9, Appendix 2) subscale (heartburn/regurgitation, fullness/early 
satiety, nausea/vomiting, bloating, upper abdominal pain, and lower abdominal pain) 
scores 
• Gastric emptying as measured by the GEBT (Section 6.10) 
The primary and secondary measures will be summarized by treatment group at each visit as 
well as changes from baseline using summary statistics (number of patients, mean, standard 
deviation, median, and range) including 95% confidence intervals for changes from baseline. 
Additional analyses may be conducted, and details will be provided in the statistical analysis 
plan (SAP). 
9.6 
Safety Analysis 
Safety will be assessed in the Safety population. The AEs will be coded using the Medical 
Dictionary for Regulatory Activities (MedDRA®). The number and percentage of patients 
with TEAEs will be tabulated by system organ class, preferred term, and treatment group. 
Severity of AEs and SAEs will be summarized similarly. Those AEs leading to premature 
discontinuation from the study drug and the serious TEAEs will be presented in a table or a 
listing. Clinical laboratory and HbA1c test results and vital signs will be summarized at each 
visit as will changes from baseline for each treatment group. A frequency distribution of 
abnormal physical examination results will be provided. Additional details will be provided 
in the SAP. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 53 
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10 
ADMINISTRATIVE CONSIDERATIONS 
10.1 
Investigators and Study Administrative Structure 
Table 1 summarizes the administrative structure for this study. 
Table 1: 
Administrative Structure for GAS-001 Study 
Contract Research Organization 
InClin, Inc.  
2655 Campus Drive, Suite 100 
San Mateo, CA, 94403 
Phone: 
 
 
10.2 
Institutional Review Board Approval 
The Investigator will submit this protocol, any protocol modifications, and the patient 
consent form to be utilized in this study, to the appropriate IRB for review and approval. This 
committee must operate in accordance with the ICH GCP. Documentation of approval of the 
protocol and the informed consent document must be forwarded to Censa Pharmaceuticals 
(or designee) prior to initiation of this study. 
The Investigator is responsible for assuring continuing review and approval of the clinical 
study. The Investigator must also promptly report all changes in the research activity and all 
unanticipated problems involving risk to the patients or others to his/her IRB. The 
Investigator will not make any changes in the protocol without IRB approval except as 
necessary to eliminate apparent immediate hazards to the patients. The Investigator will 
provide progress reports to the IRB as required by the IRB. If the study remains in progress 
for >1 year, the Investigator must obtain annual renewal and re-approval from the IRB. 
Documentation of renewal must be submitted to Censa Pharmaceuticals (or designee). The 
Investigator will provide notice to the IRB of completion of participation in the study. 
10.3 
Ethical Conduct of the Study 
This study will be conducted in compliance with the protocol; GCPs, including ICH 
Technical Requirements for Registration of Pharmaceuticals for Human Use Guidelines; 
applicable regional regulatory requirements (i.e., ICH E6); and in accordance with the ethical 
principles of the Declaration of Helsinki. 
10.4 
Patient Information and Consent 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate 
in the study and continues throughout the individual’s study participation. Discussion in 
understandable terms of the purposes, procedures, risks and possible benefits of participation, 
and rights of study patients will be conducted with patients, and, as appropriate, their legally 
authorized representatives (LARs; henceforth in the discussion of informed consent, study 
patient means “patient and/or LAR”) and family members. The study patients should have 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 54 
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the opportunity to discuss the study with their surrogates or think about it prior to agreeing to 
participate. Study patients will be asked to carefully review the ICF approved by Censa 
Pharmaceuticals (or designee) and the IRB. After any needed discussion and consideration of 
study participation and before undergoing any procedures specifically for the study, the 
patient will sign the ICF. The ICF will be retained in the study patient’s study records, and a 
copy of the ICF will be given to the study patient. 
Patients may decline to participate in the study and withdraw consent at any time or for any 
reason throughout the course of the study without AEs on the quality of their medical care. 
10.5 
Confidentiality 
The Investigator must assure that patients’ anonymity is strictly maintained and that their 
identities are protected from unauthorized parties. This extends to testing of biological 
samples and genetic tests in addition to the clinical information relating to participants. Only 
an identification code (i.e., not names) should be recorded on any form or document 
submitted to Censa Pharmaceuticals, the Contract Research Organization (CRO), or the IRB. 
The Investigator must keep logs on screened and enrolled patients. In addition, the 
Investigator must have a list where the identity of all treated patients can be found. 
The Investigator agrees that all information received from Censa Pharmaceuticals, including, 
but not limited to, the Investigator’s Brochure, this protocol, CRFs, and any other 
information related to the protocol-specified treatment of the study, remain the sole and 
exclusive property of Censa Pharmaceuticals during the conduct of the study and thereafter. 
This information is not to be disclosed to any third party (except employees or agents directly 
involved in the conduct of the study or as required by law) without prior written consent from 
Censa Pharmaceuticals. The Investigator further agrees to take all reasonable precautions to 
prevent the disclosure by any employee or agent of the study center to any third party or 
otherwise into the public domain. 
The study monitor, other authorized representatives of Censa Pharmaceuticals, and 
representatives of the IRB may inspect all documents and records required to be maintained 
by the Investigator, including but not limited to, medical records (office, clinic, and hospital) 
and pharmacy records for the participants in this study. The clinical study site’s research staff 
will permit access to such records. 
The study patient’s contact information will be securely stored at each clinical site for 
internal use during the study. At the end of the study, all records will be kept in a secure 
location for as long a period as dictated by local IRB and Institutional regulations. 
10.6 
Study Monitoring 
A clinical monitor authorized to represent Censa Pharmaceuticals will conduct site visits to 
inspect study data, patient’s medical records, and eCRFs in accordance with ICH guidelines 
GCP, and applicable regulations and guidelines. The clinical monitor will also monitor 
ongoing drug accountability and adherence to protocol procedures. Details of clinical site 
monitoring are specified in a Clinical Monitoring Plan. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 55 
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Independent audits may be conducted to ensure that monitoring practices are performed 
consistently across all participating sites and that monitors are following the Clinical 
Monitoring Plan. 
The Investigator will allow representatives of the Censa Pharmaceuticals and regulatory 
authorities to inspect facilities and records relevant to this study. 
10.7 
Case Report Forms and Study Records 
The eCRFs will be supplied by Censa Pharmaceuticals or designee for the recording of all 
information and study data as specified by this protocol. Original eCRF data should be 
handled in accordance with instructions from Censa Pharmaceuticals or designee. All eCRFs 
must be completed by the clinical study site’s research staff authorized to do so by the 
Investigator. The Investigator is responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported. 
Data reported in the eCRF derived from source documents should be consistent with the 
source documents. Source documents are defined as records of documentation related to 
original observations and activities of a clinical investigation. Source documents may 
include, but are not limited to, study progress notes, study- or patient-specific email 
correspondence, computer printouts, laboratory data, and recorded data from automated 
instruments. All source documents produced in this study will be maintained by the 
Investigator and made available for inspections by Censa Pharmaceuticals or designee and by 
regulatory authorities. The original ICF for each participating patient shall be filed with 
records kept by the Investigator, and copies shall be given to the patient. 
Once all data queries and issues have been resolved for each patient the Investigator will 
electronically sign each patient’s eCRF. This signature will indicate that the data have been 
thoroughly inspected and will thereby certify the contents of the eCRF. 
Clinical data will be entered into a 21 Code of Federal Regulations (CFR) Part 11-compliant 
electronic data capture system. The data system includes password protection and internal 
quality checks, such as automatic range checks, to identify data that appear inconsistent, 
incomplete, or inaccurate. Clinical data will be entered by the clinical study site’s research 
staff directly from the source documents. 
10.8 
Protocol Violations/Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol requirements. The 
noncompliance may be either on the part of the patient, the Investigator, or the study site 
staff. Because of deviations, corrective actions are to be developed by the site and 
implemented promptly. This is consistent with the following sections in ICH E6: 
• 4.5 Compliance with Protocol, Sections 4.5.1, 4.5.2, and 4.5.3 
• 5.1 Quality Assurance and Quality Control, Section 5.1.1 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 56 
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• 5.20 Noncompliance, Sections 5.20.1, and 5.20.2. 
10.9 
Access to Source Documentation 
The Investigator agrees by his/her participation that the results of this study may be used for 
submission for national or international registration. If required, national or international 
authorities will be provided with the name of the Investigator and his or her address, full 
disclosure of his or her qualifications, any potential conflicts of interests, payments, and 
extent of involvement. 
During site visits, the clinical monitor will review original patient records, drug 
accountability records, and additional documents as needed. During the course of the study, 
Censa Pharmaceutical’s (or designee’s) Quality Assurance personnel may conduct an on-site 
audit visit. The Investigator will provide direct access to and allow verification and copying 
of all trial-related documents (e.g., source data) for trial-related monitoring, audits, IRB 
reviews, and regulatory inspections. 
10.10 
Data Generation and Analysis 
Some or all of the obligations of implementing or conducting this study may be transferred 
from Censa Pharmaceuticals to the CRO. 
A case report, comprised of individual eCRFs, will be completed for every patient who signs 
an ICF and is enrolled into the study. 
All original source documentation (laboratory results, treatment records, audit query 
responses, etc.) will be retained by the Investigator or institution unless specified otherwise 
by the protocol. The results as they become available will be entered on the appropriate 
eCRFs. Legible reproductions of the original laboratory reports for selected tests or variables 
will be submitted to Censa Pharmaceuticals or CRO as requested. 
The eCRFs will be reviewed by a clinical monitor who will evaluate the completeness and 
accuracy of the data. Queries will be generated for omissions, corrections, and clarifications. 
Data may also be reviewed in-house by a clinical auditor and data management or other 
personnel. 
Data analyses will be performed after database lock, when all queries have been resolved. 
10.11 
Retention of Data 
Study documents should be retained for a minimum of 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region or until at least 2 years have elapsed since the 
formal discontinuation of clinical development of the investigational product. These 
documents should be retained for a longer period, however, if required by local regulations. 
No records will be destroyed without the written consent of Censa Pharmaceuticals, if 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 57 
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applicable. It is the responsibility of Censa Pharmaceuticals to inform the Investigator when 
these documents no longer need to be retained. 
10.12 
Financial Disclosure 
Each Investigator must submit to Censa Pharmaceuticals (or designee) financial disclosure 
information according to national law and/or local regulations. 
10.13 
Publication and Disclosure Policy 
The data generated in this clinical study are the exclusive property of Censa Pharmaceuticals 
and are confidential. Authorship on any publication of the results from this study will be 
based on contributions to study design, patient enrollment, data analysis, interpretation of 
results, and drafting and editing of any publication in accordance with published authorship 
ethical guidelines for publication of research studies. Independent analysis and/or publication 
of these data by the Investigator(s) or any member of their staff is not permitted without the 
prior, written consent of Censa Pharmaceuticals. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 58 
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11 
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CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 59 
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CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 60 
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United States Food and Drug Administration. Gastroparesis: Clinical Evaluation of Drugs for 
Treatment Guidance for Industry. 2015 Jul. Available from 
https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/
ucm455645.pdf. Accessed 2018 Jun 4. 
Werner ER, Gorren AC, Heller R, et al. Tetrahydrobiopterin and nitric oxide: mechanistic 
and pharmacological aspects. Exp Biol Med (Maywood). 2003 Dec;228(11):1291-302. 
Wood JD, Alpers DH, Andrews PL. Fundamentals of neurogastroenterology. Gut. 1999 
Sep;45 Suppl 2:II6-II16. 
Xu J, Wu Y, Song P, et al. Proteasome-dependent degradation of guanosine 5'-triphosphate 
cyclohydrolase I causes tetrahydrobiopterin deficiency in diabetes mellitus. Circulation. 2007 
Aug 21;116(8):944-53 


CNSA-001 (sepiapterin) 
 
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Clinical Trial Protocol: GAS-001 
 
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CONFIDENTIAL 
APPENDIX 1 
SCHEDULE OF EVENTS 
Evaluation 
Screening Period 
Treatment Period 
Follow-up Period 
EOT 
EOS 
Telephone 
Follow-up 
-28 to -1 
Day 1 
(Predose) 
Day 1 
Through 
Day 13 
Day 14a 
Day 14a Day 15 
Day 28 (±1 
Day)  
Day 44 (±3 
Days) 
Informed consent 
X 
 
 
 
 
 
 
 
Confirm inclusion/exclusion criteria eligibility 
X 
 
 
 
 
 
 
 
Randomization 
Xb 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical historyc 
X 
X 
 
 
 
 
 
 
Vital signs, weight, and heightd 
X 
X 
X 
 
X 
X 
 
Physical examinatione 
X 
X 
 
 
X 
X 
 
Clinical laboratory testsf 
X 
X 
 
 
X 
X 
 
HbA1cg 
X 
 
 
 
X 
X 
 
Serum/urine pregnancy testh 
X 
X 
 
 
X 
X 
 
ECGi 
X 
 
 
 
 
 
 
 
Prior/concomitant medicationsj 
X 
X 
X 
X 
X 
 
X 
 
AEsk 
X 
X 
X 
X 
X 
 
X 
Xl 
Nutrient satiety testm 
Xn 
X 
 
 
X 
 
X 
 
GCSIo 
Xp 
X 
 
 
X 
X 
 
PAGI-SYMq 
 
X 
 
 
X 
X 
 
GEBTr 
X 
 
 
 
 
X 
X 
 
Dispense study drug 
 
 
X 
 
 
 
 
 
Dispense dosing diary 
 
 
Xs 
 
 
 
 
 
Study drug dosingt 
 
 
Xu 
X 
 
 
 
 
Collect study drug, dosing diary, assess 
compliance 
 
 
 
 
Xv 
Xv 
Xv 
 
a Study Day 14 is included both in the Treatment Period and EOT. 
b Randomize patient on Day -1. 


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Clinical Trial Protocol: GAS-001 
 
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c Includes specific information related to any prior or existing medical conditions or surgical procedures involving the following systems: dermatologic, HEENT, lymphatic, 
cardiovascular, respiratory, GI, musculoskeletal, and neurological.  
d Includes blood pressure, pulse, respiratory rate, and temperature. Obtain vital signs before collection of any laboratory samples and after patients have rested for 5 minutes in a 
supine position. Obtain vital signs both predose and 2 hours postdose on Day 1; for all other timepoints, obtain at any time during the indicated visits. Obtain height only at 
Screening. Obtain weight at Screening to determine response to Exclusion Criterion #5 (Section 4.3) and on Day -1 (Section 6.3). 
e Conduct a complete physical examination of general appearance, dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and neurological 
parameters.  
f Includes clinical chemistry panel (ALB, AP, ALT, AST, BUN, Ca, CO2, Cl, creatinine, GGT, glucose, LDH, phosphorus, K, Na, total bilirubin, direct bilirubin, total cholesterol, 
total protein, uric acid); hematology panel (HCT, HGB, platelet count, RBC count, WBC count, and WBC differential); and urinalysis (bilirubin, glucose, ketones, occult blood, 
pH, protein, specific gravity, urobilinogen and microscopic examination of WBC, RBC, and epithelial cells). Patients will fast overnight before blood sample collections. 
g Patients will fast overnight before blood sample collections. 
h Serum and urine pregnancy tests required for all women of childbearing potential; serum testing is to occur during the Screening Period, and urine testing is to occur before 
dosing on Day 1 and at an EOT visit on Day 28 (±1 day). Any positive urine pregnancy test should be confirmed by a serum pregnancy test. 
i Obtain 12-lead ECG recordings in triplicate with 1 minute separating the first and second and second and third recordings. 
j Record all treatments and over-the-counter medications (including herbal medications) received from 30 days prior to Screening (to determine responses to Inclusion Criterion 
#9 [Section 4.2] and Exclusion Criteria #11 through #14 and #21 [Section 4.3] concerning medications) and through Day 28 ±1 day before the patient leaves the clinic after 
completion of all EOS evaluations. 
k Collect AEs from the time of informed consent through Day 28 ±1 day before the patient leaves the clinic after completion of all EOS evaluations and SAEs from the time of 
informed consent through telephone Follow-up. 
l Telephone Follow-up is to assess SAEs only. 
m Administer the nutrient satiety test (Section 6.7) at Screening, on Day 1 (predose), and on Day 14 and Day 28 after overnight fasts and after any medications that can alter GI 
sensation or accommodation or gastric emptying have been held overnight. 
n Administer the nutrient satiety test at Screening to determine the response to Inclusion Criterion #6 (Section 4.2) 
o Administer the GCSI (Section 6.8, Appendix 2) at Screening, on Day 1 (predose), on Day 14 (+1 day) and on Day 28 (±1 day). 
p Administer the GCSI (Section 6.8, Appendix 2) to determine response to Inclusion Criterion #5 (Section 4.2). 
q Administer the PAGI-SYM (Section 6.9, Appendix 2) in the clinic on Day 1 (predose), on Day 14 (+1 day), and on Day 28 (±1 day). 
r Administer the GEBT on Day -1, on Day 15, and on Day 27 or Day 29. For the GEBT (Section 6.10), patients will fast overnight before the GEBT (a minimum of 8 hours 
before test administration with the exception of 4 ounces of water up to 1 hour before the test). Collect a premeal breath sample and then provide a standardized 230 kCal meal, 
consisting of a proprietary standardized 13C-labeled egg component (which is rehydrated and then microwaved for 1.5 minutes) and 6 saltine crackers, accompanied by 6 ounces 
of water. Encourage the patient to consume the meal within 10 minutes. Collect single postmeal breath samples in capped glass tubes at 45, 90, 120, 150, 180, and 240 minutes 
after the meal is consumed and send the samples to the specified local laboratory for analysis. 
s Dispense a dosing diary with instructions to record times all doses of study drug are taken. 
t If a patient vomits after taking a dose of study drug, the patient should wait until the next scheduled timepoint to take another dose. A missed dose should be taken as soon as 
possible, but >2 doses should not be taken on the same day. 
u Patients will take their first doses of study drug (CNSA-001 or placebo) on Day 1 while in the clinic. 
v Collect study drug, dosing diary, assess compliance on Day 14 if the patient takes the last dose of study drug on Day 14 while in the clinic or, if the patient takes the last dose of 
study drug on Day 14 after leaving the clinic, on Day 15 or Day 28 (±1 day). 
 
Abbreviations: AE = adverse event; ALB = albumin; ALT = alanine aminotransferase (serum glutamic pyruvic transaminase [SGPT]); AP = alkaline phosphatase; AST = aspartate 
aminotransferase (serum glutamic oxaloacetic transaminase [SGOT]); BUN = blood urea nitrogen; 13C = carbon-13; Ca = calcium; CO2 = carbon dioxide; Cl = chloride; 
ECG = electrocardiogram; EOS = End of Study; EOT = End of Treatment; GCSI = Gastroparesis Cardinal Symptom Index; GEBT = Gastric Emptying Breath Test; 


CNSA-001 (sepiapterin) 
 
Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001 
 
Page 63  
FINAL 06SEP2018 
 
CONFIDENTIAL 
GI = gastrointestinal; GGT = gamma glutamyl transferase; HCT = hematocrit; HGB = hemoglobin; HEENT = head, eyes, ears, nose, and throat; HbA1c = glycosylated 
hemoglobin A1c; K = potassium; LDH = lactate dehydrogenase; Na = sodium; PAGI-SYM = Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity; 
RBC = red blood cell; SAE = serious adverse event; WBC = white blood cell.


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 64 
FINAL 06SEP2018 
 
CONFIDENTIAL 
APPENDIX 2 
GCSI AND PAGI-SYM ASSESSMENT INSTRUMENTS  
Gastroparesis Cardinal Symptom Index Questionnaire (English Version):  
  
Khoury V, Dubois, D. GCSI Gastroparesis Cardinal Symptom Index information booklet. 
2nd ed. Lyon, France: Mapi Research Trust; 2015. p 30. 
 












CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 1 
AMENDMENT 2: 12 Nov 2018 
 
CONFIDENTIAL 
 
CLINICAL TRIAL PROTOCOL 
Study Title: 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Pilot Study of 
CNSA-001 in Women With Moderate to Severe Diabetic Gastroparesis 
Study Number: 
GAS-001 
Study Phase: 
2 Pilot 
Product Name: 
CNSA-001 (sepiapterin)  
Dosage Form:  
Oral powder for suspension 
 
 
Indication: 
Treatment of women with moderate to severe diabetic gastroparesis 
Investigators: 
Multicenter study  
 
 
Sponsor: 
Censa Pharmaceuticals 
65 William Street 
Wellesley, MA 02481 
Sponsor Contact: 
 
Medical Monitor: 
 
 
 
Date 
Original Protocol: 
06 September 2018 
Amendment 1: 
09 October 2018 
Amendment 2: 
12 November 2018 
 
 
 
 
 
Confidentiality Statement 
The confidential information in this document is provided to you as an Investigator or consultant for 
review by you, your staff, and the applicable Institutional Review Board/Independent Ethics 
Committee. Your acceptance of this document constitutes agreement that you will not disclose the 
information contained herein to others without written authorization from the Sponsor.  




CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 3 
AMENDMENT 2: 12 Nov 2018 
 
CONFIDENTIAL 
INVESTIGATOR’S SIGNATURE 
Study Title: 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Pilot Study 
of CNSA-001 in Women With Moderate to Severe Diabetic 
Gastroparesis 
Study Number: 
GAS-001 
Final Date: 
06 September 2018 
Amendment 1: 
09 October 2018 
Amendment 2: 
12 November 2018 
I have read the protocol described above. I agree to comply with all applicable regulations 
and to conduct the study as described in the protocol. 
 
 
 
Signature 
 
Date (DD Month YYYY) 
 
 
 
Printed Name, Credentials 
 
 
 
 
 
Affiliation 
 
 
 
 
 
Address 
 
 
 
 
 
Phone Number 
 
 
 
 
 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 4 
AMENDMENT 2: 12 Nov 2018 
 
CONFIDENTIAL 
PROTOCOL AMENDMENT 2 (NOVEMBER 12, 2018) 
Protocol GAS-001 is amended primarily for the following reasons: 
1. Modified Exclusion Criterion #9 to exclude patients with a marked baseline prolongation 
of QT/QTc interval of ≥470 msec (based on triplicate measurements taken at screening). 
2. Removed reference to Quality of Life measurements using the PAGI-SYM. 
3. Corrected wording of secondary endpoints to more accurately reference change resulting 
from CNSA-001 treatment. 
4. Corrected the methods of administration of the nutrient satiety test to 150mL of Ensure 
every 5 minutes. 
 
Major changes to the protocol are as follows: 
Synopsis and Section 4.3: Modified exclusion criterion #9 to QTc ≥470 msec. 
Synopsis and Section 2.2: Corrected wording of secondary endpoints to reflect an effect of 
CNSA-001 treatment.  Corrected the usage of PAGI-SYM as a symptom scale versus a 
quality of life scale. 
Section 6.7: Corrected the methods for administering the nutrient satiety test. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 5 
AMENDMENT 2: 12 Nov 2018 
 
CONFIDENTIAL 
PROTOCOL AMENDMENT 1 (OCTOBER 9, 2018) 
Protocol GAS-001 is amended primarily for the following reasons: 
1. Added Exclusion Criterion to exclude patients with baseline cardiovascular instability. 
2. Added Exclusion Criterion to exclude patients with PKU or hyperphenylalaninemia. 
3. Updated the discontinuation criteria related to AEs in Section 6.14.1. 
4. Updated the study stopping criteria to include specific examples of adverse event criteria 
for temporarily or permanently stopping the study. 
 
Major changes to the protocol are as follows: 
Synopsis and Section 4.3: Added two additional exclusion criteria for patients with baseline 
cardiovascular instability and for patients with PKU or hyperphenylalaninemia. 
Section 6.14.1: Added drug class adverse events to individual discontinuation criteria, 
specifically, hypersensitivity reactions, anaphylaxis, and gastritis. 
Section 6.14.3: Added examples of study stopping criteria associated with adverse event 
criteria of severity, frequency, and relatedness. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 6 
AMENDMENT 2: 12 Nov 2018 
 
CONFIDENTIAL 
SYNOPSIS 
Sponsor: 
Censa Pharmaceuticals 
Name of Finished Product: 
CNSA-001 
Name of Active Ingredient: 
Sepiapterin 
Name of Inactive Ingredients: 
Microcrystalline cellulose, colloidal silicon dioxide, croscarmellose, and ascorbic acid 
Study Title: 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Pilot Study of CNSA-001 in Women 
With Moderate to Severe Diabetic Gastroparesis 
Study Number: 
GAS-001 
Study Phase: Phase 2 pilot 
Primary Objective: 
• 
To assess the impact of CNSA-001 on gastric accommodation, as measured by nutrient 
satiety testing, in women with moderate to severe diabetic gastroparesis 
Secondary Objectives: 
In women with moderate to severe diabetic gastroparesis: 
• 
To evaluate the effect of CNSA-001 on improvement of gastroparesis symptoms as 
measured by the change from baseline in the global assessment of symptoms and symptom 
severity (Gastroparesis Cardinal Symptom Index [GCSI]) (Section 6.8, Appendix 2) 
• 
To evaluate the effect of CNSA-001 on patient-reported symptoms as measured by the 
change from baseline in the Patient Assessment of Upper Gastrointestinal Disorders-
Symptom Severity (PAGI-SYM) (Section 6.9, Appendix 2)  
• 
To evaluate the effect of CNSA-001 on emptying of the stomach as measured by the 
change from baseline in the Gastric Emptying Breath Test (GEBT) 
• 
To assess the safety and tolerability of CNSA-001 20 mg/kg/day 
Study Design: 
This is a Phase 2, randomized, double-blind, placebo-controlled pilot study of multiple doses of 
CNSA-001 (sepiapterin) powder for suspension administered orally in women with moderate to 
severe diabetic gastroparesis. Patients will be randomized in a ratio of 1:1 to receive CNSA-001 
20 mg/kg/day or placebo, each dosed twice a day (BID); each group will consist of 10 patients. All 
patients will receive the standard of care for diabetic gastroparesis. Approximately 4 centers will 
participate in this study. The study design is summarized in the study schema below. A schedule of 
study events is provided in Appendix 1. 
All study clinic visits will be outpatient visits.  
Patients will continue their usual diet without modification throughout the study. Patients are 
required to have been fasting overnight for the following assessments:  
• 
Clinical laboratory, including glycosylated hemoglobin A1c (HbA1c), tests  
• 
The nutrient satiety test 
• 
The GEBT  


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 7 
AMENDMENT 2: 12 Nov 2018 
 
CONFIDENTIAL 
 
 
 
Screening Period (Day -28 Through Day 1 Predose): 
An informed consent form (ICF) must be signed before any study-related procedures are 
performed. After providing consent, patients will undergo Screening procedures to determine study 
eligibility, as indicated in Appendix 1. Patients who are eligible based on Screening evaluations 
will undergo baseline evaluations before initiation of study drug (CNSA-001 or placebo), be 
randomized, and proceed to the Treatment Period.  
Treatment Period (Day 1 Through Day 14) 
Following the Screening Period and completion of baseline evaluations, all randomized patients 
will take their first dose of study drug (CNSA-001 or placebo) on Day 1 while in the clinic. 
Patients will undergo procedures during the Treatment Period as indicated in Appendix 1. 
End of Treatment Period (Day 14 Through Day 15 Evaluations) 
Patients will undergo End of Treatment (EOT) evaluations on Day 14 and Day 15 as indicated in 
Appendix 1. Preliminary efficacy will be assessed by the changes from Day 1 in the nutrient satiety 
test on Day 14. The GCSI (Section 6.8, Appendix 2) and PAGI-SYM (Section 6.9, Appendix 2) 
will also be administered on Day 14 (+1 day), and the GEBT will be conducted on Day 15. 
End of Study Period (Day 15 After Evaluations Through Day 28 [±1 Day] Evaluations) 
Patients will undergo End of Study evaluations on Day 28 (±1 day) as indicated in Appendix 1. 
Preliminary efficacy will be assessed by the changes from Day 1 in the nutrient satiety test on 
Day 28. The GCSI (Section 6.8, Appendix 2) and PAGI-SYM (Section 6.9, Appendix 2) will also 
be administered on Day 28 ±1, and the GEBT will be conducted on Day 27 or Day 29. 
Follow-up Period (Day 28 [±1 Day] After Evaluations Through Day 44 [±3 Days]) 
Patients will undergo telephone Follow-up on Day 44 ±3 days as indicated in Appendix 1.  


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 8 
AMENDMENT 2: 12 Nov 2018 
 
CONFIDENTIAL 
Number of Patients: 
Up to 20 women ≥18 and ≤65 years of age will be enrolled in this study and randomized in a ratio 
of 1:1 to receive CNSA-001 or placebo.  
Main Criteria for Inclusion and Exclusion: 
Patients are eligible to participate if they meet all the following inclusion criteria: 
1. Informed consent 
2. Females ≥18 and ≤65 years of age 
3. Diagnosis of diabetes mellitus  
4. Documentation of delayed gastric emptying on gastric emptying scintigraphy (within 1 year 
of enrollment) 
5. Symptoms of gastroparesis for at least 6 months with GCSI (Section 6.8, Appendix 2) score 
>21 indicating moderate to severe symptoms 
6. Gastric accommodation, as measured by nutrient satiety testing, of ≤600 mL 
7. Negative upper endoscopy or upper gastrointestinal (GI) series within 3 years of enrollment 
(no evidence of mechanical obstruction or peptic ulcer disease) 
8. Either postmenopausal for ≥1 year or surgically sterile (having undergone tubal ligation, 
hysterectomy, or bilateral oophorectomy) for at least 6 months or, if of childbearing 
potential and not abstinent, willing to use a highly effective method of contraception 
throughout the study such as 1 of the following: 
• 
Hormonal contraception (stable dose for 3 months) 
• 
Intrauterine device/Intrauterine Hormone-releasing System 
• 
Barrier contraceptive method (diaphragm, cervical cap, contraceptive sponge, condom) 
Patients who are abstinent will not be required to use a contraceptive method unless they 
become sexually active. 
9. If on analgesics, including narcotics; promotility agents, including metoclopramide, or 
neuromodulators, including tricyclic antidepressants, gabapentin, and pregabalin, doses are 
stable for >30 days before randomization and the patient is not expected to require dose 
changes during the study through the EOT 
10. Have not used tobacco (e.g., cigarettes, e-cigarettes, cigars, smokeless tobacco, nicotine 
replacement) for 2 weeks prior to Day 1 and willingness to abstain from these products 
during the study through the EOT 
Patients are not eligible to participate if they meet any of the following exclusion criteria:  
1. Male gender 
2. Normal gastric emptying  
3. Gastroparesis from postsurgical etiologies 
4. Another active disorder that could, in the opinion of the Investigator, explain symptoms  
5. Weight >100 kg 
6. Alanine aminotransferase > 2× upper limit of normal (ULN) 
7. Pregnant, breastfeeding, or considering pregnancy 
8. Clinically significant cardiac arrhythmia at Screening 
9. QT interval corrected for heart rate (QTc) ≥470 msec (based on triplicate measurements 
taken at Screening) 
10. Resting heart rate ≤40 or ≥110 bpm or resting blood pressure <90/40 mmHg or >150/90 
mmHg at Screening or prior to the first administration of study drug. 
11. Recent clinically GI significant bleeding 
12. Taking levodopa or domperidone within 30 days before randomization or expected to 
require domperidone during the study through the EOT 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 9 
AMENDMENT 2: 12 Nov 2018 
 
CONFIDENTIAL 
13. Taking erythromycin within 30 days before randomization or expected to require 
erythromycin within 30 days before randomization or expected to require erythromycin 
during the study through the EOT; if a patient is taking erythromycin and is otherwise 
eligible to participate in the study, following signing the ICF, the patient may go through an 
erythromycin washout period of 30 days before randomization 
14. Taking any fundic-relaxing agents including, but not limited to, buspirone, clonidine, 
nitrates, phosphodiesterase inhibitors (i.e., sildenafil citrate [Viagra®]) and triptan-containing 
medications, within 30 days before randomization or expected to require any of these agents 
during the study through the EOT 
15. Taking any systemic antifolates, including, but not limited to, methotrexate, pemetrexed, and 
trimetrexate or expected to require any systemic antifolates during the study through the 
EOT (topical antifolates [e.g., cream, ointment, gel] or eye drops with antifolates are 
allowed) 
16. Pulmonary dysfunction (e.g., chronic obstructive pulmonary disease) 
17. Surgery for placement of a gastric stimulator within the past 6 months (patients 
postoperative >6 months with persistent symptoms and delayed gastric emptying are 
eligible) 
18. Gastrointestinal disease (such as irritable bowel syndrome, inflammatory bowel disease, 
chronic gastritis, peptic ulcer disease, small bowel malabsorption) that could affect the 
absorption of study drug or contraindicate undergoing the GEBT 
19. History of gastric surgery, including Roux-en-Y gastric bypass surgery or an antrectomy 
with vagotomy, or gastrectomy 
20. History of allergies or adverse reactions to tetrahydrobiopterin or related compounds, to any 
excipients in the study drug formulation, or to egg, wheat, or algae (Spirulina)  
21. Inability to tolerate oral medication 
22. Current participation in any other investigational drug study or use of any investigational 
agent, investigational device, or approved therapy for investigational use within 30 days or 
5 half-lives (whichever is longer) before Screening 
23. Any clinically significant laboratory abnormality; in general, each laboratory value from 
Screening and baseline chemistry and hematology panels should fall within the limits of the 
normal laboratory reference range unless deemed not clinically significant by the 
Investigator 
24. Major surgery within the previous 90 days  
25. The patient, in the opinion of the Investigator, is unwilling or unable to adhere to the 
requirements of the study 
26. History of alcohol or drug abuse within 6 months prior to Screening or current evidence of 
substance dependence as determined by the Investigator 
27. Episodes of ketoacidosis or hypoglycemia that are frequent as defined by the Investigator 
28. History of phenylketonuria (PKU) or hyperphenylalaninemia. 
29. Any other conditions, including diabetic comorbidities, that, in the opinion of the 
Investigator or Sponsor, would interfere with the patient’s ability to participate in the study 
or increase the risk of participation for that patient 
Test Product, Dose, and Mode of Administration: 
The test product is CNSA-001 (sepiapterin) oral powder for suspension. CNSA-001 will be 
suspended in Medisca® Oral Mix prior to dispensing to the patient. Patients randomized to receive 
CNSA-001 will receive CNSA-001 20 mg/kg/day (i.e., 10 mg/kg BID) for 14 days. 
Reference Therapy; Dose; and Mode of Administration: 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 10 
AMENDMENT 2: 12 Nov 2018 
 
CONFIDENTIAL 
The reference product is placebo. The placebo is a ready-made suspension containing 
microcrystalline cellulose, colloidal silicon dioxide, croscarmellose, ascorbic acid, and colorant 
(Yellow No. 6) that is suspended in Medisca® Oral Mix.  
Duration of Treatment: 
Patients will be treated for a total of 14 days.  
Criteria for Evaluation: 
Safety: 
Safety and tolerability of CNSA-001 as measured by severity and number of treatment-emergent 
adverse events (TEAEs), including assessment of severity of TEAEs, and changes in clinical 
laboratory and HbA1c tests, vital signs, and physical examinations 
Efficacy: 
The primary efficacy measure will be the change in maximal tolerated volume consumed during 
the nutrient satiety test from Day 1 to Day 14 and Day 1 to Day 28. 
Secondary efficacy measures will consist of changes in the following from baseline to Day 14 and 
baseline to Day 28 (±1 day):  
• 
GCSI (Section 6.8, Appendix 2) PAGI-SYM (Section 6.9, Appendix 2) subscale 
(heartburn/regurgitation, fullness/early satiety, nausea/vomiting, bloating, upper abdominal 
pain, and lower abdominal pain) scores 
• 
Gastric emptying as measured by the GEBT  
Statistical Methods: 
The following study populations will be analyzed: 
• 
Safety population: all patients who were randomized and received any amount of study 
drug (CNSA-001 or placebo) 
• 
Efficacy population: all patients who were randomized, received any amount of study drug 
(CNSA-001 or placebo), and had available Day 1 and Day 14 nutrient satiety test 
maximum tolerated volume results  
Safety will be assessed in the Safety population. Adverse events (AEs) will be coded using the 
Medical Dictionary for Regulatory Activities (MedDRA®). The number and percentage of patients 
with TEAEs will be tabulated by system organ class, preferred term, and treatment group. Severity 
of AEs and serious adverse events (SAEs) will be summarized similarly. Those AEs leading to 
premature discontinuation from the study drug and the serious TEAEs will be presented in a table 
or a listing. Clinical laboratory and HbA1c test results and vital signs will be summarized at each 
visit as will changes from baseline for each treatment group. A frequency distribution of abnormal 
physical examination results will be provided. 
Efficacy will be assessed in the Efficacy population. The changes from Day 1 to Day 14 and from 
Day 1 to Day 28 in maximal tolerated volume consumed during the nutrient satiety test will be 
compared between treatment groups using a student’s t-test. Results from the nutrient satiety test 
through Day 14 and Day 28, the GEBT through Day 15 and Day 27 or Day 29, and the GCSI 
(Section 6.8, Appendix 2) and PAGI-SYM (Section 6.9, Appendix 2) through Day 14 (+1) and 
through Day 28 (±1) will be summarized using summary statistics (number of patients, mean, 
standard deviation, median, and range) at each visit as well as changes from baseline within each 
treatment group. The 95% confidence intervals for the changes from baseline will be provided. 
Additional analyses may be conducted, and details will be provided in the statistical analysis plan. 
Date of Original Protocol: 06 September 2018 
Date of Amendment 1: 09 October 2018 
Date of Amendment 2: 12 November 2018 
 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 11 
AMENDMENT 2: 12 Nov 2018 
 
CONFIDENTIAL 
TABLE OF CONTENTS 
CLINICAL TRIAL PROTOCOL ..............................................................................................1 
SPONSOR SIGNATURES ........................................................................................................2 
INVESTIGATOR’S SIGNATURE ...........................................................................................3 
PROTOCOL AMENDMENT 2 (NOVEMBER 12, 2018) .......................................................4 
PROTOCOL AMENDMENT 1 (OCTOBER 9, 2018) .............................................................5 
SYNOPSIS .................................................................................................................................6 
TABLE OF CONTENTS .........................................................................................................11 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ..........................................14 
1 
INTRODUCTION .................................................................................................17 
1.1 
Diabetic Gastroparesis .....................................................................................17 
1.2 
Impaired Gastric Accommodation in Gastroparesis ........................................18 
1.3 
Current Treatment of Diabetic Gastroparesis ..................................................18 
1.4 
CNSA-001 (Sepiapterin) ..................................................................................19 
1.5 
Rationale for Study ..........................................................................................19 
2 
STUDY OBJECTIVES ..........................................................................................21 
2.1 
Primary Objective ............................................................................................21 
2.2 
Secondary Objectives.......................................................................................21 
3 
INVESTIGATIONAL PLAN ................................................................................22 
3.1 
Overall Study Design and Plan ........................................................................22 
3.2 
Rationale for Study Design and Control Group ...............................................23 
3.3 
Study Duration and Dates ................................................................................24 
4 
STUDY POPULATION SELECTION .................................................................25 
4.1 
Study Population ..............................................................................................25 
4.2 
Inclusion Criteria .............................................................................................25 
4.3 
Exclusion Criteria ............................................................................................26 
5 
STUDY TREATMENTS .......................................................................................28 
5.1 
Description of Treatments................................................................................28 
5.1.1 
Test Product .........................................................................................28 
5.1.2 
Placebo Control ....................................................................................28 
5.2 
Treatments Administered .................................................................................28 
5.3 
Selection and Timing of Dose for Each Patient ...............................................28 
5.4 
Method of Assigning Patients to Treatment Groups........................................29 
5.5 
Blinding............................................................................................................29 
5.6 
Concomitant Therapy.......................................................................................29 
5.7 
Restrictions ......................................................................................................30 
5.7.1 
Prior Therapy and Concomitant Therapy ............................................30 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 12 
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5.7.2 
Food Intake ..........................................................................................31 
5.7.3 
Total Blood Volume ............................................................................31 
5.7.4 
Patient Activity and Tobacco Restrictions ...........................................31 
5.8 
Treatment Compliance .....................................................................................31 
5.8.1 
Dosing Diary ........................................................................................31 
5.9 
Packaging and Labeling ...................................................................................32 
5.10 
Storage and Accountability ..............................................................................32 
5.11 
Investigational Product Retention at Study Site ..............................................32 
6 
STUDY PROCEDURES .......................................................................................33 
6.1 
Informed Consent.............................................................................................33 
6.2 
Medical History and Demographic Data .........................................................33 
6.3 
Vital Signs, Weight, and Height ......................................................................33 
6.4 
Physical Examination.......................................................................................33 
6.5 
Clinical Laboratory Tests and Glycosylated Hemoglobin A1c .......................33 
6.6 
Electrocardiogram ............................................................................................34 
6.7 
Nutrient Satiety Test ........................................................................................35 
6.8 
Gastroparesis Cardinal Symptom Index ..........................................................35 
6.9 
Patient Assessment of Upper Gastrointestinal Disorders-Symptom 
Severity ............................................................................................................35 
6.10 
Gastric Emptying Breath Test ..........................................................................35 
6.11 
Dispensing Study Drug ....................................................................................36 
6.12 
Adverse Events Assessments ...........................................................................36 
6.12.1 
Reporting Timelines.............................................................................36 
6.12.2 
Severity ................................................................................................38 
6.12.3 
Relationship .........................................................................................38 
6.12.4 
Expectedness ........................................................................................39 
6.12.5 
Clinical Laboratory Adverse Events ....................................................40 
6.12.6 
Serious Adverse Events .......................................................................40 
6.12.7 
Treatment-Emergent Adverse Events ..................................................41 
6.13 
Prior and Concomitant Medication Assessments ............................................42 
6.14 
Removal of Patients From the Trial or Study Drug .........................................42 
6.14.1 
Early Discontinuation From Study Drug Administration ....................42 
6.14.2 
Withdrawal From the Study .................................................................43 
6.14.3 
Study Stopping Criteria........................................................................43 
6.15 
Appropriateness of Measurements ...................................................................44 
7 
STUDY ACTIVITIES ...........................................................................................46 
7.1 
Screening Procedures (Day –28 to Day -1) .....................................................46 
7.2 
Day 1 Predose ..................................................................................................47 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 13 
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7.3 
Day 1 After Baseline Evaluations Through Day 13 ........................................47 
7.3.1 
Day 1 ....................................................................................................47 
7.4 
Early Termination Procedures .........................................................................48 
7.5 
End of Treatment Visits (Day 14 and Day 15) ................................................48 
7.6 
End of Study (Day 28 ±1 Day) ........................................................................49 
7.7 
Telephone Follow-up Day 44 (±3 Days) (30 ±3 Days After Last Dose) .........50 
8 
QUALITY CONTROL AND ASSURANCE .......................................................51 
9 
PLANNED STATISTICAL METHODS ..............................................................52 
9.1 
General Considerations ....................................................................................52 
9.2 
Determination of Sample Size .........................................................................52 
9.3 
Analysis Populations ........................................................................................52 
9.4 
Demographics, Baseline Characteristics, Enrollment, Protocol Deviations, 
and Patient Disposition ....................................................................................52 
9.5 
Statistical Analysis of Efficacy Variables ........................................................52 
9.6 
Safety Analysis ................................................................................................53 
10 
ADMINISTRATIVE CONSIDERATIONS ..........................................................54 
10.1 
Investigators and Study Administrative Structure ...........................................54 
10.2 
Institutional Review Board Approval ..............................................................54 
10.3 
Ethical Conduct of the Study ...........................................................................54 
10.4 
Patient Information and Consent .....................................................................54 
10.5 
Confidentiality .................................................................................................55 
10.6 
Study Monitoring .............................................................................................55 
10.7 
Case Report Forms and Study Records ...........................................................56 
10.8 
Protocol Violations/Deviations ........................................................................56 
10.9 
Access to Source Documentation ....................................................................57 
10.10 
Data Generation and Analysis .........................................................................57 
10.11 
Retention of Data .............................................................................................57 
10.12 
Financial Disclosure.........................................................................................58 
10.13 
Publication and Disclosure Policy ...................................................................58 
11 
REFERENCE LIST ...............................................................................................59 
Appendix 1 
Schedule of Events ...............................................................................62 
Appendix 2 
GCSI and PAGI-SYM Assessment Instruments..................................65 
LIST OF TABLES 
Table 1: 
Administrative Structure for GAS-001 Study............................................54 
LIST OF FIGURES 
Figure 1: 
Study Schema.............................................................................................23 
 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 14 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
AE 
Adverse event 
ALB 
Albumin  
ALT 
Alanine aminotransferase (serum glutamic pyruvic transaminase [SGPT]) 
AP 
Alkaline phosphatase 
AST 
Aspartate aminotransferase (serum glutamic oxaloacetic transaminase [SGOT]) 
AUC0-last 
Area under the concentration time curve from 0 to the last measurement 
BH4 
Tetrahydrobiopterin 
BID 
Twice a day 
BUN 
Blood urea nitrogen 
13C 
Carbon-13 
Ca 
Calcium  
CFR 
Code of Federal Regulations 
Cl 
Chloride 
Cmax 
Maximum concentration 
CO2 
Carbon dioxide  
12CO2 
Carbon-12 dioxide 
13CO2 
Carbon-13 dioxide 
CRO 
Contract Research Organization 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EOS 
End of Study 
EOT 
End of Treatment 
FDA 
United States Food and Drug Administration 
GCP 
Good Clinical Practice 
GCSI 
Gastroparesis Cardinal Symptom Index 
GEBT 
Gastric Emptying Breath Test 
GGT 
Gamma glutamyl transferase 
GI 
Gastrointestinal 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 15 
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GLP 
Good Laboratory Practice 
HbA1c 
Glycosylated hemoglobin A1c  
HCG 
Human chorionic gonadotropin 
HCT 
Hematocrit 
HEENT 
Head, eyes, ears, nose, and throat 
HGB 
Hemoglobin 
ICF 
Informed consent form 
ICH 
International Council on Harmonisation  
IRB 
Institutional Review Board 
K 
Potassium 
kPCD 
the Gastric Emptying Breath Test metric; “k” is a multiplier of 1000, and 
“PCD” is an acronym for percent carbon-13 dose excreted (as carbon-13 
dioxide)  
LAR 
legally authorized representative 
LDH 
Lactate dehydrogenase 
MedDRA® 
Medical Dictionary for Regulatory Activities 
Na 
Sodium  
NADPH 
nicotinamide adenine dinucleotide phosphate hydrogen 
nNOS 
Neuronal nitric oxide synthase 
NO 
Nitric oxide 
NOS 
Nitric oxide synthase 
PAGI-QOL 
Upper Gastrointestinal Disorders-Quality of Life 
 
 
PAGI-SYM 
Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity 
PRO 
Patient-reported outcome 
QTc  
QT interval corrected for heart rate 
RBC 
Red blood cell 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SUSAR 
Suspected unexpected serious adverse reaction 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 16 
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TEAE 
Treatment-emergent adverse event 
ULN 
Upper limit of normal 
WBC 
White blood cell 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 17 
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1 
INTRODUCTION 
1.1 
Diabetic Gastroparesis  
Gastroparesis is characterized by delayed gastric emptying in the absence of mechanical 
obstruction; symptoms are chronic with episodic symptom exacerbation (Parkman et al, 
2004). Gastroparesis affects women 4 times more than men (Soykan, et al, 1998). Idiopathic 
gastroparesis accounts for most cases, but gastroparesis is frequently associated with diabetes 
(diabetic gastroparesis) (Soykan, et al, 1998; Karamanolis et al, 2007). Several 
cross-sectional studies have found delayed gastric emptying of solids and/or liquids in 30% 
to 50% of patients with Type 1 or Type 2 diabetes (Horowitz et al, 2002). Patients with 
diabetes mellitus commonly experience gastric and intestinal dysfunction (Feldman and 
Schiller, 1983).  
The actual mechanism of diabetic gastroparesis is not well known. Vagal nerve dysfunction 
and/or damage, interstitial cells of Cajal loss, and smooth muscle and enteric neuron 
dysfunction have all been implicated in the pathogenesis of diabetic gastroparesis (Stacher, 
2001; Parkman et al, 2004). In addition, acute hyperglycemia has the potential to slow gastric 
emptying (Camilleri et al, 2013).  
At a molecular level, attention has been devoted to the potential role of altered nitrergic 
signaling in the enteric nervous system. Gastric motility is regulated in large part by neurons 
of the enteric nervous system located in the muscle wall (Wood et al, 1999). These neurons 
are either excitatory (releasing acetylcholine) or inhibitory (releasing nitric oxide [NO] and 
vasoactive intestinal peptide). Nerves throughout the luminal gastrointestinal (GI) tract 
express neuronal nitric oxide synthase (nNOS), which generates NO, a key neurotransmitter 
in the regulation of GI motility (Takahashi, 2003); it is the principal nonadrenergic 
noncholinergic inhibitory neurotransmitter in the GI tract. In diabetic rats, which serve as a 
model for type 1 diabetes, nNOS expression was found to be impaired. This impairment in 
nNOS messenger RNA expression was associated with impaired smooth muscle relaxation in 
response to electrical stimulation of circular muscle fibers obtained from the proximal 
stomach of these rats (Takahashi et al, 1997). It has been demonstrated that female diabetic 
rats had slower gastric emptying than age matched diabetic male rats, female control rats had 
greater nitrergic relaxation of circular antral muscle strips compared to male controls, and 
nitrergic relaxation was impaired in diabetic female rats but not matched diabetic male rats 
(Gangula et al, 2007). 
The core signs and symptoms of gastroparesis by incidence are nausea (92% to 96%), 
vomiting (68% to 88%), postprandial fullness (54% to 77%), early satiety (42% to 60%), and 
upper abdominal pain (36% to 85%) (Soykan et al, 1998; Hoogerwerf et al, 1999; Anaparthy 
et al, 2009). Patients may experience any combination of signs and symptoms with varying 
degrees of severity. Pain is less prevalent in diabetic gastroparesis than idiopathic 
gastroparesis. Patients with diabetic gastroparesis may experience further derangement of 
glucose control because of unpredictable gastric emptying and altered absorption of orally 
administered hypoglycemic drugs, which may, in turn, affect measurement of core signs and 
symptoms. Severe signs and symptoms may cause complications such as malnutrition, 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 18 
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esophagitis, and Mallory-Weiss tears. Gastroparesis adversely affects the lives of patients 
with the disease, resulting in decreased social interaction, poor work functionality, and 
development of anxiety or depression (Soykan et al, 1998; Parkman et al, 2004). 
1.2 
Impaired Gastric Accommodation in Gastroparesis 
Patients with diabetic gastroparesis have also been shown to have gastric hypersensitivity, 
especially in the postprandial state, and impairment of the postprandial accommodation 
response. (Kumar et al, 2008). The stomach functions as 2 separate regions: the fundus acts 
as a reservoir accommodating a meal without a significant increase in intragastric pressure, 
and the distal stomach/antrum triturates gastric contents. Receptive relaxation or 
accommodation is vagally mediated resulting in the release of NO and activation of nitrergic 
myenteric neurons. Nitrergic signaling is responsible for gastric accommodation and pyloric 
relaxation in response to a meal (Ishiguchi et al, 2001). 
Impaired accommodation has been associated with symptoms of early satiety and weight loss 
in patients with idiopathic gastroparesis (Karamanolis et al, 2007). A study of patients with 
diabetic gastroparesis found that 90% of patients had impaired gastric accommodation to a 
nutrient meal (Kumar et al, 2008). In the distal stomach, NO is required for the propulsive 
contractions that triturate gastric contents and control of pyloric closure; lack of NO can lead 
to delayed gastric emptying and impaired gastric accommodation (Gangula et al, 2007). 
Several co-factors are known to be important for nNOS activity, including nicotinamide 
adenine dinucleotide phosphate hydrogen (NADPH), calcium, and tetrahydrobiopterin (BH4) 
(Werner et al, 2003). The homodimeric conformation of all 3 isoforms of nitric oxide 
synthase (NOS) is regulated by BH4 (Werner et al, 2003). In the absence of BH4, uncoupling 
of NO production occurs and leads to super oxide production, resulting in further impaired 
nNOS bioactivity. 
1.3 
Current Treatment of Diabetic Gastroparesis  
Therapies for gastroparesis have been targeted at accelerating gastric emptying or controlling 
symptoms. Available therapies for accelerating gastric emptying are limited in number and 
efficacy. These include metoclopramide (Snape et al, 1982), erythromycin (Arts et al, 2005), 
and domperidone (not available in the United States [US]) (Prakash and Wagstaff, 1998). 
There is also poor correlation between gastric emptying and baseline symptom severity 
(Karamanolis et al, 2007; Talley et al, 2001) and in response to therapeutic intervention. In 
part, as a result of lack of understanding of the underlying pathogenesis that leads to 
alterations in GI motility and sensation, medical therapies have not been targeted at the 
underlying pathophysiology of gastroparesis.  
The first-line medical therapy for patients with diabetic gastroparesis is generally a 
combination of an antiemetic agent in addition to the promotility drug. Unfortunately, many 
patients with diabetic gastroparesis will not experience adequate symptom relief despite 
first-line therapy. For patients with refractory disease, options include combination prokinetic 
therapy, psychotropic medications, pyloric botulinum toxin injection, and gastric electric 
stimulation (Fass, 2010; Camilleri et al, 2013). 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 19 
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1.4 
CNSA-001 (Sepiapterin) 
Sepiapterin is 2-amino-6-[(2S)-2-hydroxypropanoyl]-7,8-dihydro-1H-pteridin-4-one with a 
molecular weight of 237.2 and a molecular formula of C9H11 N5O3. 
The chemical structure of sepiapterin is: 
 
Sepiapterin serves as a substrate for BH4 synthesis via the pterin salvage pathway (Mayer 
and Werner, 1995). Oral administration of sepiapterin was shown to be more potent (>2 fold) 
than oral administration of BH4 in increasing intracellular BH4 in normal mice (Sawabe et 
al, 2002). Translation of this finding to humans has been confirmed in a Phase 1 study, 
PKU-001, conducted by Censa Pharmaceuticals.  
1.5 
Rationale for Study 
BH4 biosynthesis is impaired in chronic diabetes. The mechanism of impairment is not well 
understood but is thought to be a result of hyperglycemia-induced proteasome-mediated 
degradation of GTP-cyclohydrolase, the rate-limiting enzyme in the synthesis pathway for 
BH4 (Xu et al, 2007).  
CNSA-001 is the first viable formulation of sepiapterin, shown to increase intracellular BH4 
(Section 1.4), intended for the treatment of female patients with diabetic gastroparesis. 
CNSA-001 was studied in a single and multiple ascending-dose study in healthy volunteers, 
the Phase 1 study, Study PKU-001. Part A of this study assessed the safety and 
pharmacokinetics of CNSA-001 at 6 dose levels inclusive of an assessment of food effect 
(i.e., 2.5 mg/kg, 7.5 mg/kg, 20 mg/kg, 40 mg/kg, 80 mg/kg, and 10 mg/kg [to assess food 
effect]). Additionally, Kuvan® (sapropterin dihydrochloride), a synthetic BH4 commercially 
available product, was administered at equivalent doses for the first 3 dose levels (2.5 mg/kg, 
7.5 mg/kg, and 20 mg/kg). Dose-dependent correlations between CNSA-001 and plasma 
BH4 concentrations were observed with each successive dose level. Dose proportionality was 
observed between the top 2 dose levels (40 mg/kg and 80 mg/kg) and resultant BH4 
concentrations. Administration with a standard high-fat (approximately 50 percent of total 
caloric content of the meal) and high calorie (approximately 800 to 1000 calories) meal 
resulted in approximately 80% higher plasma BH4 concentrations (area under the 
concentration time curve from 0 to the last measurement [AUC0-last] and maximum 
concentration [Cmax]) than in subjects who had fasted before receipt of CNSA-001. 
Treatment-emergent adverse events (TEAEs) in Part A of Study PKU-001 were reported in 
26 subjects (44.1%, 26/59). The TEAEs for CNSA-001 were generally mild and consistent 
with reported adverse events (AEs) for Kuvan® and placebo. The frequency of TEAEs did 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 20 
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not appear to increase with increasing dose. The TEAEs that were judged to be related to 
study treatment were reported in 17 subjects: 11 subjects (26.2%, 11/42) who received 
CNSA-001, 4 subjects (44.4%, 4/9) who received Kuvan®, and 2 subjects (25.0%, 2/8) who 
received placebo. No TEAEs were severe or serious or led to discontinuation of study drug. 
Headache and dizziness were the most common TEAEs , but these TEAEs occurred at a 
similar frequency as with placebo. 
Part B of Study PKU-001 assessed multiple ascending doses CNSA-001 in healthy 
volunteers. Data indicate CNSA-001 was well tolerated following daily doses of 5, 20, and 
60 mg/kg/day for 7 days and that TEAEs were reported in 14 subjects (58.3%, 14/24). The 
TEAEs in subjects who received CNSA 001 were mild or moderate and consistent with the 
TEAEs in subjects who received placebo: TEAEs were experienced by 10 subjects (55.6%, 
10/18) who received CNSA-001 at doses from 5 mg/kg to 60 mg/kg daily for 7 days and by 
4 subjects (66.7%, 4/6) who received placebo. No TEAEs were severe, serious, or led to 
discontinuation. Of the 10 TEAEs reported in subjects who received CNSA-001, only 4 were 
judged to be related to study drug, and, of the 4 TEAEs reported in subjects who received 
placebo, only 1 was judged to be related to study drug. Somnolence, fatigue, headache, and 
procedural pain (secondary to performance of 2 sequential lumbar punctures 7 days apart) 
were the most common TEAEs reported, and they occurred at a similar frequency when 
compared with placebo with the exception of fatigue and headache, which were each 
reported in 2 subjects who received CNSA-001 (11.1%, 2/18). 
This Phase 2 pilot study will assess CNSA-001 doses of 20 mg/kg/day administered as 
10 mg/kg twice a day (BID) in comparison to placebo administered BID in female patients 
with diabetic gastroparesis. This study will help support the design of future Phase 2/3 
studies in patients with diabetic gastroparesis.  


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 21 
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2 
STUDY OBJECTIVES 
2.1 
Primary Objective 
The primary objective of this study is to assess the impact of CNSA-001 on gastric 
accommodation, as measured by nutrient satiety testing (Section 6.7), in women with 
moderate to severe diabetic gastroparesis. 
2.2 
Secondary Objectives 
The secondary objectives of this study are, in women with moderate to severe diabetic 
gastroparesis: 
• To evaluate the effect of CNSA-001 on improvement of gastroparesis symptoms as 
measured by the change from baseline in the global assessment of symptoms and 
symptom severity (Gastroparesis Cardinal Symptom Index [GCSI]) (Section 6.8, 
Appendix 2) 
• To evaluate the effect of CNSA-001 on patient-reported symptoms as measured by the 
change from baseline in the Patient Assessment of Upper Gastrointestinal Disorders-
Symptom Severity (PAGI-SYM) (Section 6.9, Appendix 2)  
• To evaluate the effect of CNSA-001 on emptying of the stomach as measured by the 
change from baseline in the Gastric Emptying Breath Test (GEBT) (Section 6.10) 
• To assess the safety and tolerability of CNSA-001 20 mg/kg/day 
 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 22 
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3 
INVESTIGATIONAL PLAN 
3.1 
Overall Study Design and Plan 
Study GAS-001 is a Phase 2, randomized, double-blind, placebo-controlled pilot study of 
multiple doses of CNSA-001 (sepiapterin) powder for suspension administered orally in 
women with moderate to severe diabetic gastroparesis. This is an outpatient study in which 
up to 20 patients will be enrolled at approximately 4 centers. 
The Schedule of Events is provided in Appendix 1. The study schema is displayed in Figure 
1.  
Screening Period (Day -28 Through Day 1 Predose) 
An informed consent form (ICF) must be signed before any study-related procedures are 
performed. After providing consent, patients will undergo Screening procedures to determine 
study eligibility, as indicated in Appendix 1. Patients who are eligible based on Screening 
evaluations will undergo baseline evaluations before initiation of study drug (CNSA-001 or 
placebo), be randomized, and proceed to the Treatment Period.  
Treatment Period (Day 1 Through Day 14) 
Following the Screening Period and completion of baseline evaluations, all randomized 
patients will take their first dose of study drug (CNSA-001 or placebo) on Day 1 while in the 
clinic. Patients will undergo procedures during the Treatment Period as indicated in 
Appendix 1. 
Study drug may be prematurely discontinued for safety reasons, as described in 
Section 6.14.1. Patients may also withdraw from the study for any reason, as described in 
Section 6.14.2. If a patient discontinues study drug early, the patient should return to the 
study site within 24 hours of withdrawal and complete all of the procedures outlined for the 
End of Treatment (EOT) (Section 7.5, Appendix 1). If a patient withdraws early from the 
study before undergoing EOT evaluations, the patient will be asked to return to the study site 
within 24 hours of withdrawal and complete all of the procedures outlined for the EOT 
(Section 7.5, Appendix 1). If a patient withdraws from the study before undergoing End of 
Study (EOS) evaluations, the patient will be asked to return to the study site within 24 hours 
of withdrawal and complete all of the procedures outlined for the EOS (Section 7.6, 
Appendix 1).  
End of Treatment Period (Day 14 Through Day 15 Evaluations) 
Patients will undergo EOT evaluations on Day 14 and Day 15 as indicated in Appendix 1. 
Preliminary efficacy will be assessed by the changes from Day 1 in the nutrient satiety test 
(Section 6.7) on Day 14. The GCSI (Section 6.8, Appendix 2) and PAGI-SYM (Section 6.9, 
Appendix 2) will also be administered on Day 14 (+1 day), and the GEBT (Section 6.10) will 
be conducted on Day 15. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 23 
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End of Study Period (Day 15 After Evaluations Through Day 28 [±1 Day] Evaluations) 
Patients will undergo EOS evaluations on Day 28 (±1 day) as indicated in Appendix 1. 
Preliminary efficacy will be assessed by the changes from Day 1 in the nutrient satiety test 
(Section 6.7) on Day 28. The GCSI (Section 6.8, Appendix 2) and PAGI-SYM (Section 6.9, 
Appendix 2) will also be administered on Day 28 ±1, and the GEBT (Section 6.10) will be 
conducted on Day 27 or Day 29. 
Follow-up Period (Day 28 [±1 Day] After Evaluations Through Day 44 [±3 Days]) 
Patients will undergo telephone Follow-up on Day 44 ±3 days as indicated in Appendix 1.  
Figure 1: 
Study Schema  
 
Abbreviations: BID = twice a day.  
 
3.2 
Rationale for Study Design and Control Group 
CNSA-001 (sepiapterin) is a new chemical entity that is an endogenous, naturally occurring 
precursor of BH4 via the pterin salvage pathway. Animal studies and data from a Phase 1 
single and multiple ascending-dose study in healthy volunteers conducted by Censa 
Pharmaceuticals indicate rapid intracellular conversion of sepiapterin to BH4. It is expected 
that oral administration of CNSA-001 to women with diabetic gastroparesis will result in 
increases in both intracellular and circulating BH4 concentrations. In chronic diabetes, BH4 
biosynthesis is impaired (Xu et al, 2007). 
CNSA-001 was studied in two 14-day Good Laboratory Practice (GLP) toxicity studies, as 
described in Section 5.3, and in a single and multiple ascending-dose study in healthy 
volunteers, Study PKU-001, as described in Section 1.5.  
Because all patients will receive the standard of care for diabetic gastroparesis in addition to 
their assigned study drug, the study design of a randomized study of CNSA-001 versus 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 24 
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placebo in female patients with diabetic gastroparesis will not expose patients to the risk of 
no treatment.  
This study has a double-blind design intended to reduce bias. 
3.3 
Study Duration and Dates 
The study duration for each patient will be up to 75 days, extending from Screening (Day -28 
through Day -1) through the final assessments on Day 44 (±3 days).  


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 25 
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4 
STUDY POPULATION SELECTION 
4.1 
Study Population 
Approximately 4 study centers will enroll up to 20 women with moderate to severe diabetic 
gastroparesis this study.  
4.2 
Inclusion Criteria 
Patients are eligible to participate in this study if they meet all the following inclusion 
criteria: 
1. Informed consent 
2. Females ≥18 and ≤65 years of age 
3. Diagnosis of diabetes mellitus  
4. Documentation of delayed gastric emptying on gastric emptying scintigraphy (within 
1 year of enrollment) 
5. Symptoms of gastroparesis for at least 6 months with GCSI (Section 6.8, Appendix 2) 
score >21 indicating moderate to severe symptoms 
6. Gastric accommodation, as measured by nutrient satiety testing, of ≤600 mL 
7. Negative upper endoscopy or upper GI series within 3 years of enrollment (no evidence 
of mechanical obstruction or peptic ulcer disease) 
8. Either postmenopausal for ≥1 year or surgically sterile (having undergone tubal ligation, 
hysterectomy, or bilateral oophorectomy) for at least 6 months or, if of childbearing 
potential and not abstinent, willing to use a highly effective method of contraception 
throughout the study such as 1 of the following: 
• Hormonal contraception (stable dose for 3 months) 
• Intrauterine device/Intrauterine Hormone-releasing System 
• Barrier contraceptive method (diaphragm, cervical cap, contraceptive sponge, 
condom) 
Patients who are abstinent will not be required to use a contraceptive method unless they 
become sexually active 
9. If on analgesics (including narcotics), promotility agents (including metoclopramide), or 
neuromodulators (including tricyclic antidepressants, gabapentin, and pregabalin), doses 
are stable for >30 days before randomization and the patient is not expected to require 
dose changes during the study through the EOT 
10. Have not used tobacco (e.g., cigarettes, e-cigarettes, cigars, smokeless tobacco, nicotine 
replacement) for 2 weeks prior to Day 1 and willingness to abstain from these products 
during the study through the EOT 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 26 
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4.3 
Exclusion Criteria 
Patients are not eligible to participate in this study if they meet any of the following 
exclusion criteria: 
1. Male gender 
2. Normal gastric emptying  
3. Gastroparesis from postsurgical etiologies 
4. Another active disorder that could, in the opinion of the Investigator, explain symptoms  
5. Weight >100 kg 
6. Alanine aminotransferase > 2× upper limit of normal (ULN) 
7. Pregnant, breastfeeding, or considering pregnancy 
8. Clinically significant cardiac arrhythmia at Screening 
9. QT interval corrected for heart rate (QTc) ≥470 msec (based on triplicate measurements 
taken at Screening)  
10. Resting heart rate ≤40 or ≥110 bpm or resting blood pressure <90/40 mmHg or >150/90 
mmHg at Screening or prior to the first administration of study drug. 
11. Recent clinically significant GI bleeding 
12. Taking levodopa or domperidone within 30 days before randomization or expected to 
require domperidone during the study through the EOT 
13. Taking erythromycin within 30 days before randomization or expected to require 
erythromycin within 30 days before randomization or expected to require erythromycin 
during the study through the EOT; if a patient is taking erythromycin and is otherwise 
eligible to participate in the study, following signing the ICF, the patient may go through 
an erythromycin washout period of 30 days before randomization 
14. Taking any fundic-relaxing agents including, but not limited to, buspirone, clonidine, 
nitrates, phosphodiesterase inhibitors (i.e., sildenafil citrate [Viagra®]) and 
triptan-containing medications, within 30 days before randomization or expected to 
require any of these agents during the study through the EOT 
15. Taking any systemic antifolates, including, but not limited to, methotrexate, pemetrexed, 
and trimetrexate or expected to require any systemic antifolates during the study through 
the EOT (topical antifolates [e.g., cream, ointment, gel] or eye drops with antifolates are 
allowed) 
16. Pulmonary dysfunction (e.g., chronic obstructive pulmonary disease) 
17. Surgery for placement of a gastric stimulator within the past 6 months (patients 
postoperative >6 months with persistent symptoms and delayed gastric emptying are 
eligible) 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 27 
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18. Gastrointestinal disease (such as irritable bowel syndrome, inflammatory bowel disease, 
chronic gastritis, peptic ulcer disease, small bowel malabsorption) that could affect the 
absorption of study drug or contraindicate undergoing the GEBT (Section 6.10)  
19. History of gastric surgery, including Roux-en-Y gastric bypass surgery or an antrectomy 
with vagotomy, or gastrectomy 
20. History of allergies or adverse reactions to BH4 or related compounds, to any excipients 
in the study drug formulation, or to egg, wheat, or algae (Spirulina)  
21. Inability to tolerate oral medication 
22. Current participation in any other investigational drug study or use of any investigational 
agent, investigational device, or approved therapy for investigational use within 30 days 
or 5 half-lives (whichever is longer) before Screening 
23. Any clinically significant laboratory abnormality; in general, each laboratory value from 
Screening and baseline chemistry and hematology panels should fall within the limits of 
the normal laboratory reference range unless deemed not clinically significant by the 
Investigator 
24. Major surgery within the previous 90 days  
25. The patient, in the opinion of the Investigator, is unwilling or unable to adhere to the 
requirements of the study 
26. History of alcohol or drug abuse within 6 months prior to Screening or current evidence 
of substance dependence as determined by the Investigator 
27. Episodes of ketoacidosis or hypoglycemia that are frequent as defined by the Investigator 
28. History of phenylketonuria (PKU) or hyperphenylalaninemia. 
29. Any other conditions, including diabetic comorbidities, that, in the opinion of the 
Investigator or Sponsor, would interfere with the patient’s ability to participate in the 
study or increase the risk of participation for that patient 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 28 
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5 
STUDY TREATMENTS 
5.1 
Description of Treatments 
5.1.1 
Test Product 
The test product is CNSA-001 (sepiapterin) oral powder for suspension. CNSA-001 contains 
the new chemical entity, sepiapterin. Sepiapterin is 2-amino-6-[(2S)-2-hydroxypropanoyl]-
7,8-dihydro-1H-pteridin-4-one with a molecular weight of 237.2 and a molecular formula of 
C9H11 N5O3. Inactive ingredients in CNSA-001 include microcrystalline cellulose, colloidal 
silicon dioxide, croscarmellose, and ascorbic acid. CNSA-001 will be suspended in Medisca® 
Oral Mix prior to dispensing it to the patient.  
5.1.2 
Placebo Control 
The placebo is a ready-made suspension containing microcrystalline cellulose, colloidal 
silicon dioxide, croscarmellose, ascorbic acid, and colorant (Yellow No. 6) that is suspended 
in Medisca® Oral Mix.  
5.2 
Treatments Administered 
Patients will be randomized in a ratio of 1:1 to the following treatment groups:  
• CNSA-001 20 mg/kg/day (10 mg/kg BID) for 14 days 
• Placebo BID for 14 days 
Dosing of CNSA-001 is based on the patient’s weight. The weight obtained on Day -1 will 
be used to calculate the exact amount (mg) of CNSA-001 active ingredient (sepiapterin) 
required for each patient’s daily dose.  
The placebo is formulated as ready-made suspension. The placebo will be administered in the 
same manner (volume) as CNSA-001. 
Details on preparation of study drug and dosing guidelines will be provided in a pharmacy 
manual for the site and an instruction guide for patients.  
5.3 
Selection and Timing of Dose for Each Patient 
All patients will be randomly assigned in a ratio of 1:1 to receive CNSA-001 20 mg/kg/day 
(10 mg/kg BID) or placebo BID.  
The CNSA-001 dose was selected following completion of two 14-day GLP toxicity studies 
in the rat and marmoset. The no observed adverse effect level from both studies was set at 
1000 mg/kg/day, which represents a human equivalent dose of 161.3 mg/kg/day based on 
allometric scaling. Consequently, the proposed dose of 20 mg/kg/day represents an 8.1-fold 
safety margin. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 29 
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Study drug will be dispensed on Day 1 (Section 6.11) with a dosing diary in which patients 
will record all doses taken and times they were taken (Section 5.8.1). The first dose on Day 1 
will be taken in the clinic after patients undergo the nutrient satiety test (Section 6.7). 
If a patient vomits after taking a dose of study drug, the patient should wait until the next 
scheduled timepoint to take another dose. A missed dose should be taken as soon as possible, 
but >2 doses should not be taken on the same day. 
5.4 
Method of Assigning Patients to Treatment Groups 
Patients who fulfill the eligibility criteria and provide informed consent will be randomized 
in a ratio of 1:1 to the CNSA-001 or placebo group via the randomization scheme generated 
for the study. Patients who are randomized will be considered to be enrolled.  
5.5 
Blinding 
This study has a double-blind design. The Investigator, study personnel, and patients will not 
make any effort to determine which study drug is being received. Unblinded pharmacy (or 
other qualified site) personnel will be utilized in this study to prepare the study drug. 
Patients will be blinded to study drug assignment. Only in an emergency, when knowledge of 
the study drug is essential for the clinical management or welfare of a specific patient, may 
the Investigator unblind a patient’s study drug assignment. Copies of the randomization 
sequence and treatment codes will be kept in the pharmacy at the sites. If emergency 
unblinding is required, the Investigator will have immediate access to individual sealed codes 
containing treatment allocations. However, before any unblinding occurs, the Investigator is 
strongly advised to discuss options with the Sponsor’s Medical Monitor or appropriate 
Sponsor study personnel. As soon as possible and without revealing the patient’s study drug 
assignment (unless important to the safety of patients remaining in the study), the 
Investigator must notify the Sponsor if the blind is broken for any reason and the Investigator 
was unable to contact the Sponsor prior to the unblinding. The Investigator will record in 
source documentation the date and reason for revealing the blinded study drug assignment 
for any patient and the names and roles of personnel unblinded. 
5.6 
Concomitant Therapy 
Patients will be permitted to take:  
• Analgesics, including narcotics, if the patient has been on a stable dose of the 
medication for >30 days before randomization; dose escalation is NOT permitted 
during the study through the EOT 
• Promotility agents, including metoclopramide if the patient has been on a stable dose 
of the medication >30 days before randomization; dose changes are NOT permitted 
during the study through the EOT 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 30 
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• Neuromodulators, including any tricyclic antidepressant, gabapentin, and pregabalin, 
if the patient has been on a stable dose >30 days before randomization; dose changes 
are NOT permitted during the study through the EOT 
• Rescue medications that patients would usually take, including ondansetron 
(Zofran®), promethazine (Phenergan®) or prochlorperazine (Compazine®) for nausea 
and tramadol (Ultram®), if symptoms related to gastroparesis require further 
treatment during the study through the EOT 
All prescription and over-the-counter medications (including herbal medications) that the 
patient took within 30 days before Screening though the EOT should be recorded.  
5.7 
Restrictions 
5.7.1 
Prior Therapy and Concomitant Therapy 
The following are prohibited: 
• Any investigational agent, investigational device, or approved therapy for 
investigational use within 30 days or 5 half-lives (whichever is longer) before 
Screening  
• Domperidone within 30 days before randomization or expected to require 
domperidone during the study through the EOT 
• Dose escalation of analgesic or promotility agents or neuromodulators within 30 days 
before randomization or during the study through the EOT 
• Erythromycin within 30 days before randomization or during the study through the 
EOT; if a patient is taking erythromycin and is otherwise eligible to participate in the 
study, following signing the ICF, the patient may go through an erythromycin 
washout period of 30 days before randomization 
• Systemic antifolates, including, but not limited to, methotrexate, pemetrexed, and 
trimetrexate or expected to require any systemic antifolates during the study through 
the EOT (topical antifolates [e.g., cream, ointment, gel] or eye drops with antifolates 
are allowed) 
• Fundic-relaxing agents, including, but not limited to, buspirone, clonidine, nitrates, 
phosphodiesterase inhibitors (i.e., sildenafil citrate [Viagra®]) and triptan-containing 
medications, within 30 days before randomization or expected to require any of these 
agents during the study through the EOT 
• Medications that can alter GI sensation or accommodation or gastric emptying 
overnight before the nutrient satiety test (Section 6.7) 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 31 
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5.7.2 
Food Intake 
Patients will continue their usual diet without modification throughout the study. Patients are 
required to have been fasting overnight for the following assessments: 
• Clinical laboratory, including glycosylated hemoglobin A1c (HbA1c), tests 
• The nutrient satiety test (Section 6.7), which requires the consumption of Ensure™ 
(Abbott Laboratories, Abbott Park, IL, USA)  
• The GEBT (Section 6.10), which requires consumption of a standardized 230 kCal 
meal, consisting of a standardized carbon-13 (13C)-labeled egg component and 
6 saltine crackers, with 6 ounces of water 
5.7.3 
Total Blood Volume 
The total volume of blood obtained from an individual study patient is expected to be 
approximately 40 mL, for clinical laboratory tests inclusive of the HbA1c test. 
5.7.4 
Patient Activity and Tobacco Restrictions 
Patients will not be confined during the study and will not require any activity restrictions. 
Patients must abstain from tobacco use (e.g., cigarettes, e-cigarettes, cigars, smokeless 
tobacco, nicotine replacement) for 2 weeks before Day 1 and during the study through the 
EOT. 
5.8 
Treatment Compliance 
Patients will be instructed to return all used (empty containers) and unused study drug on 
Day 14 if the patient takes the last dose of study drug on Day 14 while in the clinic or, if the 
patient takes the last dose of study drug on Day 14 after leaving the clinic, on Day 15 or Day 
28 (±1 day). Compliance with the dosing regimen will be assessed by reconciliation of used 
and unused study drug. The quantities dispensed, returned, used, and lost will be recorded on 
the dispensing log provided for the study.  
5.8.1 
Dosing Diary 
Patients will be provided with a dosing diary on Day 1 along with instructions for recording 
all doses of study drug and times they were taken. The dosing diary will be collected on 
Day 14 if the patient takes the last dose of study drug on Day 14 while in the clinic or, if the 
patient takes the last dose of study drug on Day 14 after leaving the clinic, on Day 15 or 
Day 28 (±1 day), and the Investigator (or designee) will transcribe all entries into the 
electronic case report form (eCRF).  


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 32 
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5.9 
Packaging and Labeling 
CNSA-001 Oral Powder for Suspension is packaged in 10 mL amber glass vials with black 
child proof caps. Each glass vial contains 175 mg of sepiapterin.  
Each vial of CNSA-001 Oral Powder for Suspension will contain the product name, strength, 
content, expiry/retest date, and company name. Each vial label will contain the words, 
“Caution: Investigational medicine for clinical trial use only.” 
CNSA-001 PLACEBO suspension is packaged in 500 mL bottles. Each bottle of CNSA-001 
PLACEBO suspension will contain the content and company name as well as “CNSA-001 
PLACEBO” on its label. 
The suspending vehicle, Medisca® Oral Mix, is commercially available and will be provided 
separately. 
5.10 
Storage and Accountability 
All drug product required for completion of this study will be provided by Censa 
Pharmaceuticals. It is the responsibility of the pharmacy staff or study staff to ensure that a 
current record of drug inventory and drug accountability is maintained. Inventory and 
accountability records must be readily available for inspection by the study monitor and are 
open to inspection at any time by applicable regulatory authorities. 
CNSA-001 Oral Powder for Suspension (non-reconstituted) may be stored frozen at -20°C or 
at refrigerated conditions (2 to 8°C). If not administered on the same day of suspending, 
CNSA-001 suspension should be stored at refrigerated conditions (2 to 8°C) until time of 
dosing. Once suspended, CNSA-001 is stable for 14 days.  
CNSA-001 PLACEBO suspension may be stored refrigerated at 2 to 8°C.  
5.11 
Investigational Product Retention at Study Site 
Upon completion of the study and once inventoried by the study site, all used (empty) 
containers of study drug will be destroyed. Any unused containers of study drug may be 
either destroyed or returned to the Sponsor following discussion with the Sponsor. If study 
drug is destroyed, a certificate of destruction will be provided to the Sponsor by the 
appropriate facility performing the destruction. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 33 
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6 
STUDY PROCEDURES 
6.1 
Informed Consent 
Consent forms describing in detail the study drug, study procedures, and risks are given to 
the patient, and written documentation of informed consent is required prior to conducting 
study-related procedures. See Section 10.4 for more information on the informed consent 
process. 
6.2 
Medical History and Demographic Data 
A detailed medical/surgical history will be obtained at Screening. The history will include 
specific information related to any prior or existing medical conditions or surgical procedures 
involving the following systems: dermatologic; head, eyes, ears, nose, and throat (HEENT); 
lymphatic; cardiovascular; respiratory; GI; musculoskeletal; and neurological. The medical 
history will be updated on Day 1 before the start of study drug. 
Demographic data obtained at Screening will include age, gender, and self-reported 
race/ethnicity. 
6.3 
Vital Signs, Weight, and Height 
Vital signs, including blood pressure, pulse, respiratory rate, and temperature, will be 
measured at Screening, Day 1 (predose and 2 hours postdose), and at the EOT and EOS 
visits. Vital signs will be measured prior to collection of laboratory samples and after patients 
have rested for 5 minutes in the supine position. For timepoints other than Day 1, vital signs 
will be taken at any time during the visit after resting and laboratory sample collection.  
Weight will only be collected at Screening as necessary to determine the response to 
Exclusion Criterion #5 (Section 4.3) and on Day -1. Height will only be collected at 
Screening. 
6.4 
Physical Examination 
A complete physical examination will be performed at Screening, on Day 1 before start of 
study drug and at the EOT and EOS visits. The examination will assess general appearance, 
as well as dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, 
musculoskeletal, and neurological parameters.  
6.5 
Clinical Laboratory Tests and Glycosylated Hemoglobin A1c 
Clinical laboratory tests will be performed by qualified local laboratories. Blood and urine 
samples for clinical chemistry, hematology, and urinalysis will be collected at Screening, 
Day 1 (predose), and at the EOT and EOS visits. Patients should fast overnight prior to 
collection of blood samples (minimum of 8 hours before blood sample collection). Blood 
samples for HbA1c will be collected at Screening and at the EOT and EOS visits. Clinically 
significant laboratory abnormalities should be followed to a satisfactory resolution, as 
determined by the Investigator. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 34 
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The following clinical laboratory and other laboratory parameters will be assessed: 
Hematology: 
Hematocrit (HCT) 
Hemoglobin (HGB) 
Platelet count 
Red blood cell (RBC) count 
White blood cell (WBC) count with differential 
(neutrophils, eosinophils, basophils, 
lymphocytes, and monocytes) 
Urinalysis: 
Bilirubin 
Glucose 
Ketones 
Occult blood 
pH 
Protein 
Specific gravity 
Urobilinogen  
Microscopy: 
WBCs 
RBCs 
Epithelial cells 
Pregnancy Testing: a 
Serum human chorionic gonadotropin (HCG) 
at Screening 
Urine HCG Day 1 (predose) and Day 14 (±1 
day) 
Serum Chemistry: 
Albumin (ALB) 
Alkaline phosphatase (AP) 
Alanine aminotransferase (ALT; serum 
glutamic pyruvic transaminase [SGPT]) 
Aspartate aminotransferase (AST; serum 
glutamic oxaloacetic transaminase [SGOT]) 
Blood urea nitrogen (BUN) 
Calcium (Ca) 
Carbon dioxide (CO2) 
Chloride (Cl) 
Creatinine 
Gamma glutamyl transferase (GGT) 
Glucose 
Lactate dehydrogenase (LDH) 
Phosphorus 
Potassium (K) 
Sodium (Na) 
Total bilirubin 
Direct bilirubin 
Total cholesterol 
Total protein 
Uric acid 
Other: 
Glycosylated hemoglobin A1(HbA1c) 
a 
Required for all women who are of childbearing potential. Any positive urine pregnancy test should be 
confirmed by a serum pregnancy test. 
 
6.6 
Electrocardiogram 
At Screening, 12-lead electrocardiograms (ECGs) will be obtained in triplicate, with 
1 minute separating the first and second recordings and 1 minute separating second and third 
recordings. The following ECG parameters will be collected and recorded in the eCRF: RR, 
PR, QRS, QT, and QTc intervals. In addition, the ECG tracing should be reported as normal, 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 35 
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abnormal clinically significant, or abnormal not clinically significant. If abnormalities are 
noted on the ECG, these should be recorded in the eCRF. 
6.7 
Nutrient Satiety Test  
For the nutrient satiety test, patients consume 150 mL of Ensure™ every 5 minutes. At 
5-minute intervals, patients score their fullness using a rating scale that combines verbal 
descriptors on a scale graded 0 to 5 (0: no symptoms, 1: first sensation of fullness [threshold], 
2: mild, 3: moderate, 4: severe and 5: maximum or unbearable fullness). Patients are told to 
stop when a score of 5 is obtained. The actual volume of Ensure™ consumed at this point is 
the maximum tolerated volume. Symptoms are measured 30 minutes after completing the test 
with patients scoring each symptom of bloating, fullness, nausea and pain on a visual 
analogue scale with 100-mm lines and the words “unnoticeable” and “unbearable” as 
anchors. The sum of the four 100-mm visual analogue scales provides an aggregate symptom 
score (Park, 2011). 
The nutrient satiety test will be administered in the clinic at Screening, on Day 1 (predose), 
and on Day 14 and Day 28 after overnight fasts and after any medications that can alter GI 
sensation or accommodation or gastric emptying have been held overnight. A nutrient satiety 
test volume of ≤600 mL at Screening is required for patients to participate in this study. 
6.8 
Gastroparesis Cardinal Symptom Index 
The GCSI (Appendix 2) consisting of a subset of items from the PAGI-SYM instrument 
(Section 6.9, Appendix 2), will be administered in the clinic at Screening and on Day 1 
(predose), Day 14 (+1 day), and Day 28 (±1 day). A GCSI score >21 at Screening, indicating 
moderate to severe symptoms, is required for patients to participate in this study. 
6.9 
Patient Assessment of Upper Gastrointestinal Disorders-Symptom 
Severity 
The PAGI-SYM (Appendix 2) is a 20-item upper GI symptom severity instrument with 
6 subscales: heartburn/regurgitation, fullness/early satiety, nausea/vomiting, bloating, upper 
abdominal pain, and lower abdominal pain. It will be administered in the clinic on Day 1 
(predose) and on Day 14 (+1 day), and Day 28 (±1 day).  
6.10 
Gastric Emptying Breath Test 
The GEBT, which is a nonradioactive noninvasive test, will be administered in the clinic on 
Day -1, Day 15, and Day 27 or Day 29 after the patient has fasted overnight (a minimum of 
8 hours before test administration with the exception of 4 ounces of water up to 1 hour before 
the test). At the clinic, the patient provides baseline (premeal) breath samples and then 
consumes a standardized 230 kCal meal, consisting of a proprietary standardized 13C-labeled 
egg component (which is rehydrated and then microwaved for 1.5 minutes) and 6 saltine 
crackers, accompanied by 6 ounces of water. The meal is to be consumed within 10 minutes. 
Single postmeal breath samples are collected in capped glass tubes at 45, 90, 120, 150, 180, 
and 240 minutes after the meal is consumed and sent to the specified local laboratory for 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 36 
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analysis by Gas Isotope Ratio Mass Spectrometry. By adding 13C to the test meal, the GEBT 
can determine how fast the stomach empties the meal by measuring the rate of carbon-13 
dioxide (13CO2) excretion arising from the digested test meal. The rate of 13CO2 excretion 
found in the patient’s breath is proportional to the patient’s rate of gastric emptying. The 
patient’s 13CO2 excretion rate at each breath collection time is reported using the GEBT 
metric “kPCD.” The “k” is a multiplier of 1000, and “PCD” is an acronym for percent 13C 
dose excreted (as 13CO2). The test should not be administered to patients with a known 
allergy to egg, wheat, or algae (Spirulina) (Cairn Diagnostics™; Sutton et al, 2015; GEBT 
package insert, 2015; United States Food and Drug Administration, 2015).  
6.11 
Dispensing Study Drug  
Study drug will be dispensed on Day 1 along with a dosing diary to record all doses taken 
and times they were taken. A sufficient supply of study drug will be dispensed for dosing 
through Day 14. Details on the preparation of study drug, dosing guidelines, and storage will 
be provided in a pharmacy manual for the site and an instruction guide for patients. 
6.12 
Adverse Events Assessments 
An AE is defined as any untoward medical occurrence associated with the use of an 
intervention in humans, whether or not considered intervention-related. 
The occurrence of an AE or serious adverse event (SAE) (Section 6.12.6) may come to the 
attention of study personnel during study visits and interviews of a study patient presenting 
for medical care, or upon review by a study monitor. All AEs including local and systemic 
reactions not meeting the criteria for SAEs will be captured on the appropriate eCRF. 
Information to be collected includes, but is not limited to, the event description, time of 
onset, clinician’s assessment of severity, relationship to study drug (assessed only by those 
with the training and authority to make a diagnosis), and date of resolution/stabilization of 
the event. Action taken regarding study medication (e.g., drug withdrawn, interrupted) will 
also be collected in the eCRF. All AEs that start during the study must be documented 
appropriately regardless of relationship. All treatment-related AEs or AEs leading to 
discontinuation will be followed to an adequate resolution, as determined by the Investigator. 
Any medical condition that is present at the time that the patient is screened will be 
considered as medical history and not reported as an AE. However, if the patient’s condition 
deteriorates at any time during the study, it will be recorded as an AE. 
Changes in the severity of an AE will be documented to allow an assessment of the duration 
of the event at each level of severity to be performed. The AEs characterized as intermittent 
require documentation of onset and duration of each episode. 
6.12.1 
Reporting Timelines 
The Investigator will record all reportable events with start dates occurring any time after 
informed consent and continue through clinical study completion or, in the case of 
withdrawal, until the outcome is determined. The AEs will be assessed at each visit and/or 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 37 
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through telephone contact with the patient. A neutral question, such as “How have you been 
feeling since your last visit?” may be asked.  
All SAEs should be reported after the patient signs the informed consent and followed until 
resolution, stabilization, or until the Investigator provides sufficient evidence that no further 
information can be obtained. 
All SAEs and pregnancies (in a patient or partner of a male patient) occurring while the 
patient is on the study or within 30 (±3) days after the patient received the last dose of study 
drug must be reported within 24 hours of the knowledge of the event by study personnel 
whether or not considered to be related to study drug. 
Deaths that occur ≥30 (±3) days after the patient’s last study dose must be reported within 
24 hours of knowledge of the event, if deemed related to study drug by the Investigator. 
Although pregnancy is not considered an AE or SAE by regulatory definition, for this study 
pregnancies must be processed following SAE timelines (e.g., within 24 hours of knowledge 
of the pregnancy) for data transmission purposes. In the event that a pregnancy complication 
occurs, or elective termination of a pregnancy is required for medical reasons, then the 
complication will be recorded as an AE or SAE, as appropriate. 
While elective and uncomplicated induced abortion not required for medical reasons does not 
constitute an AE or SAE (even if the patient or patient’s partner is hospitalized to undergo 
abortion), spontaneous abortion is considered a fatal event and must be reported as an AE 
and SAE, as appropriate. 
Any pregnancy and/or suspected pregnancy that occurs during the study in a female patient 
should be reported using Pregnancy Reporting Form within 24 hours of knowledge of the 
event by study personnel. Any pregnancy and/or suspected pregnancy will be followed for 
outcome. 
If the patient has received the investigational drug prior to becoming pregnant, the patient 
will continue the efficacy assessment and Follow-up periods and measures of safety and 
efficacy will be obtained. 
The patient will be followed until the outcome of the pregnancy is determined. It is the 
responsibility of the Investigator to obtain and document pregnancy information on the most 
recent Pregnancy Report Form. Furthermore, any SAE occurring as an outcome of the 
pregnancy must be reported according to the procedures outlined for SAE reporting. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 38 
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6.12.2 
Severity 
The intensity of each AE will be graded as follows: 
Mild: 
Events require minimal or no treatment and do not interfere with the 
patient’s daily activities.  
Moderate: 
Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning.  
Severe: 
Events interrupt a patient’s usual daily activity and may require systemic 
drug therapy or other treatment. Severe events are usually potentially 
life-threatening or incapacitating.  
 
It is important to distinguish between serious and severe AEs. Severity is a measure of 
intensity; however, an AE of severe intensity need not necessarily be considered serious. For 
example, nausea that persists for several hours may be considered severe nausea but may not 
be considered an SAE. Alternatively, a stroke that results in only a limited degree of 
disability may be considered only a mild stroke but would be considered an SAE. 
6.12.3 
Relationship 
The Investigator’s assessment of causality must be provided for all AEs (serious and 
nonserious). An Investigator’s causality assessment is the determination of whether there 
exists a reasonable possibility that the study drug caused or contributed to an AE. For 
purposes of consistency, guidelines for assessing causality are provided below: 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 39 
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Not Related 
The AE is completely independent of study drug administration, and/or 
evidence exists that the event is definitely related to another etiology. There 
must be an alternative, definitive etiology documented by the clinician. 
No relationship between the experience and the administration of study 
drug; related to other etiologies such as concomitant medications or 
patient’s clinical state. 
Unlikely to be 
Related 
A clinical event, including an abnormal laboratory test result, whose 
temporal relationship to drug administration makes a causal relationship 
improbable (e.g., the event did not occur within a reasonable time after 
administration of the trial medication) and in which other drugs or chemicals 
or underlying disease provides plausible explanations (e.g., the patient’s 
clinical condition, other concomitant treatments). 
Possibly 
Related 
There is some evidence to suggest a causal relationship (e.g., the event 
occurred within a reasonable time after administration of the trial 
medication). However, other factors may have contributed to the event 
(e.g., the patient’s clinical condition, other concomitant events). Although 
an AE may rate only as “possibly related” soon after discovery, it can be 
flagged as requiring more information and later be upgraded to “probably 
related” or “definitely related,” as appropriate. 
Probably 
Related 
There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely. The clinical event, including an abnormal laboratory test 
result, occurs within a reasonable time after administration of the drug, is 
unlikely to be attributed to concurrent disease or other drugs or chemicals, 
and follows a clinically reasonable response on withdrawal (dechallenge). 
Rechallenge information is not required to fulfill this definition.  
Definitely 
Related 
There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an 
abnormal laboratory test result, occurs in a plausible time relationship to 
drug administration and cannot be explained by concurrent disease or other 
drugs or chemicals. The response to withdrawal of the drug (dechallenge) 
should be clinically plausible. The event must be pharmacologically or 
phenomenologically definitive, with use of a satisfactory rechallenge 
procedure if necessary.  
 
These criteria, in addition to good clinical judgment, should be used as a guide for 
determining the causal assessment. If the event is believed to be unrelated to study drug 
administration, then an alternative explanation should be provided, if available. 
6.12.4 
Expectedness 
An AE or suspected adverse reaction is considered “unexpected” if it is not listed in the 
Investigators’ Brochure or is not listed at the specificity or severity that has been observed; 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 40 
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or, if an Investigators’ Brochure is not required or available, is not consistent with the risk 
information described in the general investigational plan or elsewhere in the protocol. 
The drug safety medical reviewer will be responsible for determining whether an AE is 
expected or unexpected. An AE will be considered unexpected if the nature, severity, or 
frequency of the event is not consistent with the risk information previously described for the 
study agent (e.g., Investigators’ Brochure). 
6.12.5 
Clinical Laboratory Adverse Events 
Laboratory abnormalities should not be recorded as AEs or SAEs unless they are associated 
with clinical signs or symptoms or require medical intervention, as determined by the 
Investigator. However, each laboratory abnormality (e.g., clinically significant changes 
detected in hematology, serum chemistry panel, urinalysis, urine microscopic, and HbA1c 
evaluations) independent from any underlying medical condition that requires medical or 
surgical intervention, or that leads to study drug interruption or discontinuation, must be 
recorded as an AE, or SAE if applicable. If the laboratory abnormality is part of a clinical 
condition or syndrome, it should be recorded as the syndrome or diagnosis rather than as the 
individual laboratory abnormality. In addition, laboratory abnormalities or other abnormal 
test assessments (e.g., vital signs) performed that are associated with signs or symptoms must 
be recorded as AEs or SAEs if they meet the definition of an AE (or SAE) as described 
below. 
6.12.6 
Serious Adverse Events 
6.12.6.1 
Definition 
An SAE is defined as an AE or suspected adverse reaction occurring at any dose that results 
in any of the following outcomes: death, life-threatening AE, inpatient hospitalization or 
prolongation of existing hospitalization, a persistent or significant disability/incapacity or a 
substantial disruption of the ability to conduct normal life functions, or a congenital 
anomaly/birth defect. 
An AE or suspected adverse reaction is considered ‘‘life-threatening’’ if, in the view of either 
the Investigator or Sponsor, its occurrence places the patient at immediate risk of death. It 
does not include an AE or suspected adverse reaction that, had it occurred in a more severe 
form, might have caused death. 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical judgment, 
they may jeopardize the patient and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. Examples of such medical events include 
allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of 
drug dependency or drug abuse. Medical and scientific judgment should be exercised in 
deciding whether expedited reporting is appropriate in these other situations. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 41 
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6.12.6.2 
Suspected Unexpected Serious Adverse Reaction (SUSAR) 
The Sponsor must submit a safety report for any suspected adverse reaction to study 
treatment that is both serious and unexpected. Before submitting a safety report, the Sponsor 
needs to ensure that the event meets all 3 of the definitions: 
• Suspected adverse reaction 
• Serious 
• Unexpected 
If the AE does not meet all 3 of the definitions, it should not be submitted as a safety report. 
6.12.6.3 
Reporting Serious Adverse Events 
The Investigator will report all SAEs to the designated drug safety team within 24 hours of 
knowledge of the event whether or not considered to be related to study drug using the SAE 
Report Form provided. 
Although not all information required for a complete SAE Report Form may be readily 
available at the time of the event, the Investigator must include sufficient information on the 
SAE Report Form to allow for a complete medical assessment. This should include at a 
minimum the patient number, site number, detailed description of the event, seriousness 
criteria, causality/relationship to study drug, and Investigator signature. 
The designated drug safety team will acknowledge the receipt of the SAE via email to the 
clinical site. After submission of the initial report, the Investigator will provide follow-up 
information to the drug safety team as requested (e.g., concomitant medications, hospital 
discharge summary) to further evaluate the event and assure that all appropriate information 
is received. Once all information is received and the SAE has been deemed appropriate for 
closure, the SAE Report Form must be signed and dated by the Investigator. 
The Investigator is responsible for informing the Institutional Review Board (IRB) of the 
SAE in accordance with institutional policies and procedures including relevant initial and 
follow-up information about the SAE. 
Treatment-related SAEs or events leading to discontinuation of study drug will be followed 
for outcome information until resolution or stabilization. Other supporting documentation of 
the event may be requested by Censa Pharmaceuticals (or designee) and should be provided 
as soon as possible. The Medical Monitor should be contacted when the Investigator 
considers an SAE to be treatment-related. 
6.12.7 
Treatment-Emergent Adverse Events 
Those AEs that start at the time of or after the first dose of study drug are TEAEs. Those AEs 
that worsen at or after the time of first dose of study drug are also considered 
treatment-emergent. All AEs that occur on or after the ICF has been signed, including all 
TEAEs, through Day 29 will be recorded in the eCRF. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 42 
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All SAEs through Day 44 ±3 days [30 ±3 days after the patient received last dose of study 
drug] will be recorded in the eCRF and reported as described in Section 6.12.6.3. 
6.13 
Prior and Concomitant Medication Assessments 
All prescription and over-the-counter medications (including herbal medications) taken by a 
patient starting from the 30-day period before Screening through Day 28 (±1 day) before the 
patient leaves the clinic after completion of all EOS evaluations will be recorded. Any 
concomitant medications added or discontinued during the study will be recorded at each 
visit. 
6.14 
Removal of Patients From the Trial or Study Drug 
6.14.1 
Early Discontinuation From Study Drug Administration 
Premature discontinuation of study drug administration is defined as the discontinuation of 
study drug for an individual patient before the required full course of study drug is 
completed. Reasons for premature discontinuation from study drug administration should be 
recorded on the appropriate page(s) of the eCRF and may include, but are not limited to the 
following: 
• Occurrence of an AE, SAE, or clinically significant laboratory abnormality that, in the 
opinion of the Investigator, warrants the patient’s permanent discontinuation from study 
drug administration 
• In the judgment of the Investigator, the patient experiences a general or specific 
change(s) that renders the patient unsuitable for continued study drug administration 
• There is a need for concomitant medication that makes the patient ineligible for further 
study drug administration 
• Pregnancy 
• Specific reasons related to adverse events that have been observed in pre- and post-
marketing treatment with the same drug class of CNSA-001 (i.e., sapropterin): 
o Hypersensitivity reactions including anaphylaxis  
o Gastritis  
o Abnormal liver function tests in patients with liver impairment  
o Unexplained hyperactivity 
Given the requirement for pregnancy testing in women of childbearing potential at Screening 
and the requirement for highly effective methods of contraception during the study, it is 
unlikely that pregnancies will occur during study conduct. However, study drug will be 
discontinued should suspected or confirmed pregnancy or nursing during the study drug 
administration period occur. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 43 
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Patients who prematurely discontinue study drug due to any of the above reasons will 
complete the EOT assessments within 24 hours of withdrawal.  
6.14.2 
Withdrawal From the Study 
Patients may withdraw from the study for any reason or be withdrawn at the request of the 
Investigator or Sponsor. The reason for a patient’s withdrawal must be recorded on the 
appropriate page(s) of the eCRF. Reasons for withdrawal from the study may include, but are 
not limited to: 
• Withdrawal of consent  
• AEs or SAEs 
• Significant patient noncompliance, defined as refusal or inability to adhere to the protocol 
requirements 
• The Investigator determines that it is in the best interest of the patient to withdraw from 
study participation, due to a reason other than safety 
Each patient who withdraws from the study after receipt of any amount of study drug will be 
asked to undergo EOT assessments. However, patients may withdraw consent to participate 
in this study at any time without penalty. Withdrawn patients who receive any amount of 
study drug, will not be replaced. Withdrawn patients who do not receive any study drug will 
be replaced. 
6.14.3 
Study Stopping Criteria 
The study may be terminated if significant violations of Good Clinical Practice (GCP) that 
compromise the ability to achieve the study objectives or compromise patient safety are 
observed at any time during the study. With regard to safety, the study may be temporarily 
suspended or terminated should the Investigator, Sponsor, or IRB determine that the safety of 
patients is significantly jeopardized. The decision for a temporary or permanent study hold 
will depend on the nature, frequency, and severity of AEs that were observed in all enrolled 
patients to date. For example, the study will be temporarily or permanently halted should 
either of the following occur: 
• The presence of the same system organ class (e,g., gastrointestinal, cardiac, etc.) 
severe AE for which no other alternative etiology can be identified, considered 
related to study drug, in 2 or more patients (Severity defined in Section 6.12.2). 
• The presence of life-threatening AE or AE requiring urgent intervention in 1 or more 
patients. 
• Death related to Adverse Event. 
 
 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 44 
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In a temporary study hold, no additional patients will be enrolled into the study or dosed with 
study drug until the study team members (including the Investigator and the Medical 
Monitor) decide it is safe to proceed with the study. 
  
6.15 
Appropriateness of Measurements 
Safety will be measured by AEs (including SAEs), vital signs, physical examinations, and 
clinical laboratory and HbA1c tests.  
Because treatment with BH4 is hypothesized to restore nNOS function in the control of 
gastric accommodation, the nutrient satiety test (Section 6.7) was chosen for the primary 
endpoint for this study. Gastric accommodation has been measured using ultrasonography 
(Undeland et al, 1998), single-photon emission computed tomography (Bredenoord et al, 
2003), and barostat testing (Coulie et al, 1998; Sarnelli et al, 2001). Barostat studies have 
been shown to be reproducible (Sarnelli et al, 2001) but are invasive and not widely 
available. Satiety testing using a nutrient liquid has been shown to be reproducible (Kindt et 
al, 2008) and correlate with impairment in gastric accommodation but not gastric emptying 
or visceral sensitivity (Tack et al, 2003). 
The GEBT is nonradioactive, noninvasive test of gastric emptying rate that has been 
validated against the reference method of gastric scintigraphy. It has been accepted by the 
United States Food and Drug Administration (FDA) for use in the measurement of the rate of 
gastric emptying of solids and as an aid in the diagnosis of delayed gastric emptying 
(gastroparesis) in adult humans who are symptomatic for gastroparesis. The GEBT can 
determine how fast the stomach empties a standardized meal with a 13C-labeled egg 
component by measuring the ratio of 13CO2 to carbon-12 dioxide (12CO2) collected in breath 
samples at multiple time points after the meal is consumed compared to baseline. The breath 
samples are collected in capped glass tubes and sent to a specified local laboratory for 
analysis. By measuring the change in the ratio of 13CO2 to 12CO2 over time in comparison to 
the premeal value, the rate of 13CO2 excretion can be calculated and the gastric emptying rate 
determined. The GEBT does not require administration by specially trained health care 
professionals or special precautions related to radiation-emitting compounds (Section 6.10).  
The GCSI (Section 6.8, Appendix 2), consisting of a subset of items from the PAGI-SYM 
instrument (Section 6.9, Appendix 2) (described below), is based on reviews of the medical 
literature and results from clinician interviews and patient focus groups. Its reliability and 
validity were examined in 169 gastroparesis patients from 7 clinical centers in the US. 
Patients completed the GCSI, SF-36 Health Survey, and disability day questions at baseline 
and again at 8 weeks. Clinicians independently rated the severity of the patients' symptoms, 
and both clinicians and patients rated the changes in gastroparesis-related symptoms over the 
8weeks. For the GCSI total score, the internal consistency reliability was 0.84, and the test-
re-test reliability was 0.76. Significant relationships were observed between the clinician-
assessed symptom severity and the GCSI total score, and significant associations were found 
between the GCSI scores and SF-36 physical and mental component summary scores and 
restricted activity and bed disability days. Patients with greater symptom severity, as rated by 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 45 
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clinicians, reported greater symptom severity on the GCSI. The GCSI total scores were 
responsive to changes in overall gastroparesis symptoms as assessed by clinicians 
(p = 0.0002) and patients (p = 0.002) (Revicki et al, 2003). 
The PAGI-SYM (Section 6.9, Appendix 2) is a 20-item upper GI symptom severity 
instrument with 6 subscales: heartburn/regurgitation, fullness/early satiety, nausea/vomiting, 
bloating, upper abdominal pain, and lower abdominal pain. To develop the instrument, 
patients with GERD (n = 810), dyspepsia (n = 767), or gastroparesis (n = 169) from the US, 
France, Germany, Italy, the Netherlands, and Poland completed the PAGI-SYM, the SF-36 
Health Survey, a disease-specific health-related quality of life measure (Patient Assessment 
of Upper Gastrointestinal Disorders-Quality of Life [PAGI-QOL]), and disability day 
questions. Two-week reproducibility was evaluated in 277 stable patients. Construct validity 
was evaluated by correlating subscale scores with SF-36, PAGI-QOL and global symptom 
severity scores and disability days. Internal consistency reliability ranged from 0.79 to 0.91, 
and test-retest reliability ranged from 0.60 to 0.82 for the PAGI-SYM subscales. The 
PAGI-SYM subscale scores correlated significantly with SF-36 scores (all p <0.0001), 
PAGI-QOL scores (all p <0.0001), disability days (p <0.0001), and global symptom severity 
(p <0.0001). Mean PAGI-SYM scores varied significantly in groups defined by disability 
days (all p <0.0001), in which greater symptom severity was associated with more disability 
days (Rentz et al, 2004; Revicki et al, 2004). 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 46 
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7 
STUDY ACTIVITIES 
7.1 
Screening Procedures (Day –28 to Day -1) 
The following will be performed/collected during the Screening Period from Day -28 to 
Day -1 after obtaining informed consent with a properly signed ICF (Section 10.4): 
• Obtain demographic data (age, gender, self-reported race/ethnicity) 
• Obtain medical/surgical history, including specific information related to any prior or 
existing medical conditions or surgical procedures involving the dermatologic, HEENT, 
lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and neurological systems 
(Section 6.2) 
• Obtain vital signs (blood pressure, pulse, respiratory rate, and temperature) prior to 
collection of any laboratory samples and after patients have rested for 5 minutes in a 
supine position; obtain the patient’s weight (as necessary to determine the response to 
Exclusion Criterion #5 [Section 4.3] and on Day -1) and height (Section 6.3) 
• Conduct a complete physical examination, including assessments of general appearance, 
dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and 
neurological parameters (Section 6.4) 
• Collect blood samples for clinical chemistry, hematology, and HbA1c after the patient 
has fasted overnight (a minimum of 8 hours before blood sample collection) and a urine 
sample for urinalysis (Section 6.5) 
• Perform a serum pregnancy test for all women who are of childbearing potential  
• Obtain 12-lead ECGs in triplicate, with 1 minute separating the first and second 
recordings and 1 minute separating second and third recordings (Section 6.6) 
• Administer the GCSI (Section 6.8, Appendix 2) 
• Record all prescription and over-the-counter medications (including herbal medications) 
taken within 30 days before the Screening 
• Assess/record AEs from the time of informed consent 
• Administer the nutrient satiety test (Section 6.76.10) after the patient has fasted overnight 
and after any medications that can alter GI sensation or accommodation or gastric 
emptying have been held overnight 
• Confirm patient meets inclusion criteria and no exclusion criteria (Section 4.2 and 
Section 4.3, respectively) 
• Administer the GEBT (Section 6.10) on Day -1 after the patient has fasted overnight (a 
minimum of 8 hours before test administration with the exception of 4 ounces of water up 
to 1 hour before the test) 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 47 
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• Instruct the patient regarding fasting overnight before blood is drawn for the clinical 
laboratory evaluations (Section 6.5) and the nutrient satiety test (Section 6.7) is 
administered on Day 1 predose 
• Instruct the patient regarding not taking any medications that can alter GI sensation or 
accommodation or gastric emptying overnight before the days of the nutrient satiety test 
(Section 6.7)  
• Randomize patient on Day -1 
7.2 
Day 1 Predose 
The following will be performed/collected on Day 1 in the clinic before the patient receives 
study drug: 
• Obtain medical/surgical history since Screening, including specific information related to 
any prior or existing medical conditions or surgical procedures involving the 
dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and 
neurological systems (Section 6.2) 
• Obtain vital signs (blood pressure, pulse, respiratory rate, and temperature) prior to 
collection of any laboratory samples and after patients have rested 5 minutes in a supine 
position (Section 6.3) 
• Conduct a complete physical examination, including assessments of general appearance, 
dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and 
neurological parameters (Section 6.4) 
• Collect blood samples for clinical chemistry, and hematology after the patient has fasted 
overnight (a minimum of 8 hours before blood sample collection) and a urine sample for 
urinalysis (Section 6.5) 
• Perform a urine pregnancy test for all women who are of childbearing potential; confirm 
any positive urine pregnancy test by performing a serum pregnancy test 
• Record all prior prescription and over-the-counter medications (including herbal 
medications) taken since Screening 
• Assess/record AEs since Screening 
• Administer:  
o Nutrient satiety test (Section 6.76.10) 
o GCSI (Section 6.8, Appendix 2) 
o PAGI-SYM (Section 6.9, Appendix 2) 
7.3 
Day 1 After Baseline Evaluations Through Day 13 
7.3.1 
Day 1  
• Administer first dose of study drug in the clinic 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 48 
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• Obtain vital signs (blood pressure, pulse, respiratory rate, and temperature) 2 hours 
postdose after patients have rested 5 minutes in a supine position (Section 6.3) 
• Dispense study drug and instruct the patient on its preparation and administration BID 
starting with the second dose on Day 1 and continuing through Day 14 (Section 5.2 and 
Section 6.11) 
• Dispense dosing diary and instruct the patient on its completion (Section 5.8.1) 
• Instruct the patient not to take any Day 14 doses of study drug before the Day 14 clinic 
visit, and to bring the dosing diary and all study drug supplies to the Day 14 visit 
• Record all medications the patient received since the predose assessment 
• Assess/record AEs since the predose assessment 
• Instruct the patient regarding fasting overnight before blood is drawn for the clinical 
laboratory evaluations, the nutrient satiety test (Section 6.7), and the GEBT 
(Section 6.10) on Day 14 and/or on Day 15  
• Instruct the patient regarding not taking any medications that can alter GI sensation or 
accommodation or gastric emptying overnight before the Day 14 visit (for the nutrient 
satiety test)  
7.4 
Early Termination Procedures 
If a patient discontinues study drug early (Section 6.14.1), the patient should return to the 
study site within 24 hours of withdrawal and complete all of the procedures outlined for the 
EOT (Section 7.5). If a patient withdraws early from the study (Section 6.14.2), the patient 
will be asked to return to the study site within 24 hours of withdrawal and complete all of the 
procedures outlined for the EOT (Section 7.5). All study drug and supplies and the dosing 
diary will be collected.  
7.5 
End of Treatment Visits (Day 14 and Day 15) 
Patients will complete EOT visit(s) at early termination (Section 7.4) or on Day 14 and 
Day 15. During the EOT visits, the following will be completed: 
• Obtain vital signs (blood pressure, pulse, respiratory rate, and temperature), prior to 
collection of any laboratory samples and after patients have rested 5 minutes in a supine 
(Section 6.3) on Day 14 or Day 15 
• Conduct a complete physical examination, including assessments of general appearance, 
dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and 
neurological parameters (Section 6.4) on Day 14 or Day 15 
• Collect blood samples for clinical chemistry, hematology, and HbA1c after the patient 
has fasted overnight (a minimum of 8 hours before blood sample collection) and a urine 
sample for urinalysis (Section 6.5) on Day 14 or Day 15 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 49 
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• Perform a urine pregnancy test for all women who are of childbearing potential; confirm 
any positive urine pregnancy test by performing a serum pregnancy test on Day 14 or 
Day 15 
• Administer:  
o Nutrient satiety test (Section 6.76.10) on Day 14 
o GCSI (Section 6.8, Appendix 2) on Day 14 or Day 15 
o PAGI-SYM (Section 6.9, Appendix 2) on Day 14 or Day 15 
o GEBT (Section 6.10) on Day 15 
• Administer first Day 14 dose of study drug on Day 14; administer the second Day 14 
dose of study drug on Day 14 or instruct patient to take second Day 14 dose of study drug 
on Day 14 after the patient leaves the clinic 
• Record all prescription and over-the-counter medications (including herbal medications) 
taken since the Day 1 visit through Day 15 before the patient leaves the clinic 
• Assess/record AEs since last visit through Day 15 before the patient leaves the clinic 
• Collect study drug, dosing diary, and assess study drug compliance on Day 14 if the 
patient takes the last dose of study drug on Day 14 while in the clinic or, if the patient 
takes the last dose of study drug on Day 14 after leaving the clinic, on Day 15 
• Instruct the patient regarding fasting overnight before blood is drawn for the clinical 
laboratory evaluations on Day 28 (±1 day), the nutrient satiety test (Section 6.7) on 
Day 28, and the GEBT (Section 6.10) on Day 27 or Day 29 
• Instruct the patient regarding not taking any medications that can alter GI sensation or 
accommodation or gastric emptying overnight before the Day 28 visit (for the nutrient 
satiety test) 
7.6 
End of Study (Day 28 ±1 Day) 
Patients will complete the EOS assessments on Days 27 through Day 29. The following EOS 
assessments will be completed: 
• Obtain vital signs (blood pressure, pulse, respiratory rate, and temperature), prior to 
collection of any laboratory samples and after patients have rested 5 minutes in a supine 
position (Section 6.3) on Day 28 (±1 day) 
• Conduct a complete physical examination, including assessments of general appearance, 
dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and 
neurological parameters (Section 6.4) on Day 28 (±1 day) 
• Collect blood samples for clinical chemistry, hematology, and HbA1c after the patient 
has fasted overnight (a minimum of 8 hours before blood sample collection) and a urine 
sample for urinalysis (Section 6.5) on Day 28 (±1 day) 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 50 
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• Perform a urine pregnancy test for all women who are of childbearing potential; confirm 
any positive urine pregnancy test by performing a serum pregnancy test on Day 28 
(±1 day) 
• Administer:  
o Nutrient satiety test (Section 6.76.10) on Day 28 
o GCSI (Section 6.8, Appendix 2) on Day 28 (±1 day) 
o PAGI-SYM (Section 6.9, Appendix 2) on Day 28 (±1 day) 
o GEBT (Section 6.10) on Day 27 or Day 29 
• Collect study drug, dosing diary, and assess study drug compliance on Day 28 (±1 day) 
(if not done on Day 14 or Day 15)  
• Record all prescription and over-the-counter medications (including herbal medications) 
taken since the last visit through Day 28 (±1 day) before the patient leaves the clinic after 
completion of all EOS evaluations  
• Assess/record AEs since last visit through Day 28 (±1 day) before the patient leaves the 
clinic after completion of all EOS evaluations 
7.7 
Telephone Follow-up Day 44 (±3 Days) (30 ±3 Days After Last Dose) 
During telephone Follow-up on Day 44 (±3 days), the following will be completed: 
• Call the patient to see if any SAEs were experienced during the 30 ±3 days after the last 
dose of study drug  
• Record SAEs in the eCRF, if applicable 
• Report SAEs following SAE reporting timelines per Section 6.12.1 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 51 
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8 
QUALITY CONTROL AND ASSURANCE 
Regular monitoring and an independent audit, if conducted, must be performed according to 
International Council on Harmonisation (ICH)-GCP (Section 10.6). 
Quality control procedures will be implemented beginning with the data entry system and 
data quality control checks that will be run on the database will be generated. Any missing 
data or data anomalies will be communicated to the site(s) for clarification/resolution. 
Following written Standard Operating Procedures, the monitors will verify that the clinical 
trial is conducted and data are generated, documented (recorded), and reported in compliance 
with the protocol, GCP, and the applicable regulatory requirements (e.g., GLPs, Good 
Manufacturing Practices). 
The investigational site will provide direct access to all trial-related sites, source 
data/documents (including patient diaries), and reports for the purpose of monitoring and 
auditing by Censa Pharmaceuticals (or designee), and inspection by local and regulatory 
authorities. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 52 
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9 
PLANNED STATISTICAL METHODS 
9.1 
General Considerations 
Descriptive statistics, including numbers and percentages for categorical variables, and 
numbers, means, standard deviations, medians, minimums, and maximums for continuous 
variables will be provided. Exploratory analyses may also be performed. Listings of 
individual patient data will be produced. Additional details can be found in the statistical 
analysis plan. 
9.2 
Determination of Sample Size 
The primary objective of this study is to assess the impact of CNSA-001 on gastric 
accommodation, as measured by nutrient satiety testing (Section 6.7), in women with 
moderate to severe diabetic gastroparesis. A total of 10 patients will be enrolled in each 
treatment group. If it is assumed that the standard deviation for the change from baseline in 
nutrient meal volume ingested is approximately 235 mL (data on file), and using a one-sided 
t-test at the 0.025 significance level, this trial has 80% power to detect a treatment difference 
greater than 288 mL (i.e., an effect size of 1.23) in the CNSA-001group. The study also has 
90% power to detect a treatment difference greater than 330 mL (i.e., an effect size of 1.41) 
in the CNSA-001 group. 
9.3 
Analysis Populations 
Two study populations will be analyzed: 
• Safety population: all patients who were randomized and received any amount of study 
drug (CNSA-001 or placebo) 
• Efficacy population: all patients who were randomized, received any amount of study 
drug (CNSA-001 or placebo), and had available Day 1 predose and Day 14 nutrient 
satiety test (Section 6.7) maximum tolerated volume results 
9.4 
Demographics, Baseline Characteristics, Enrollment, Protocol Deviations, 
and Patient Disposition 
Enrollment, protocol deviations, demographics (age, sex, race/ethnicity), prior and 
concomitant medications, and medical history will be summarized by treatment group using 
descriptive statistics. Discontinuations from study drug and the study will be summarized by 
treatment group as well and the reasons for discontinuation will be listed. 
9.5 
Statistical Analysis of Efficacy Variables 
Efficacy will be assessed in the Efficacy population.  
The primary efficacy measure will be the changes in maximal tolerated volume consumed 
during the nutrient satiety test (Section 6.7) from Day 1 to Day 14 and Day 28. The changes 
from Day 1 to Day 14 and from Day 1 to Day 28 in maximal tolerated volume consumed 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 53 
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during the nutrient satiety test will be compared between treatment groups using a student’s 
t-test.  
Secondary efficacy measures will consist of changes in the following from baseline through 
Day 14 (±1 day) and through Day 28 (±1 day):  
• PAGI-SYM (Section 6.9, Appendix 2) subscale (heartburn/regurgitation, fullness/early 
satiety, nausea/vomiting, bloating, upper abdominal pain, and lower abdominal pain) 
scores 
• Gastric emptying as measured by the GEBT (Section 6.10) 
The primary and secondary measures will be summarized by treatment group at each visit as 
well as changes from baseline using summary statistics (number of patients, mean, standard 
deviation, median, and range) including 95% confidence intervals for changes from baseline. 
Additional analyses may be conducted, and details will be provided in the statistical analysis 
plan (SAP). 
9.6 
Safety Analysis 
Safety will be assessed in the Safety population. The AEs will be coded using the Medical 
Dictionary for Regulatory Activities (MedDRA®). The number and percentage of patients 
with TEAEs will be tabulated by system organ class, preferred term, and treatment group. 
Severity of AEs and SAEs will be summarized similarly. Those AEs leading to premature 
discontinuation from the study drug and the serious TEAEs will be presented in a table or a 
listing. Clinical laboratory and HbA1c test results and vital signs will be summarized at each 
visit as will changes from baseline for each treatment group. A frequency distribution of 
abnormal physical examination results will be provided. Additional details will be provided 
in the SAP. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 54 
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10 
ADMINISTRATIVE CONSIDERATIONS 
10.1 
Investigators and Study Administrative Structure 
Table 1 summarizes the administrative structure for this study. 
Table 1: 
Administrative Structure for GAS-001 Study 
Contract Research Organization 
InClin, Inc.  
2655 Campus Drive, Suite 100 
San Mateo, CA, 94403 
Phone: 
 
 
10.2 
Institutional Review Board Approval 
The Investigator will submit this protocol, any protocol modifications, and the patient 
consent form to be utilized in this study, to the appropriate IRB for review and approval. This 
committee must operate in accordance with the ICH GCP. Documentation of approval of the 
protocol and the informed consent document must be forwarded to Censa Pharmaceuticals 
(or designee) prior to initiation of this study. 
The Investigator is responsible for assuring continuing review and approval of the clinical 
study. The Investigator must also promptly report all changes in the research activity and all 
unanticipated problems involving risk to the patients or others to his/her IRB. The 
Investigator will not make any changes in the protocol without IRB approval except as 
necessary to eliminate apparent immediate hazards to the patients. The Investigator will 
provide progress reports to the IRB as required by the IRB. If the study remains in progress 
for >1 year, the Investigator must obtain annual renewal and re-approval from the IRB. 
Documentation of renewal must be submitted to Censa Pharmaceuticals (or designee). The 
Investigator will provide notice to the IRB of completion of participation in the study. 
10.3 
Ethical Conduct of the Study 
This study will be conducted in compliance with the protocol; GCPs, including ICH 
Technical Requirements for Registration of Pharmaceuticals for Human Use Guidelines; 
applicable regional regulatory requirements (i.e., ICH E6); and in accordance with the ethical 
principles of the Declaration of Helsinki. 
10.4 
Patient Information and Consent 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate 
in the study and continues throughout the individual’s study participation. Discussion in 
understandable terms of the purposes, procedures, risks and possible benefits of participation, 
and rights of study patients will be conducted with patients, and, as appropriate, their legally 
authorized representatives (LARs; henceforth in the discussion of informed consent, study 
patient means “patient and/or LAR”) and family members. The study patients should have 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 55 
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the opportunity to discuss the study with their surrogates or think about it prior to agreeing to 
participate. Study patients will be asked to carefully review the ICF approved by Censa 
Pharmaceuticals (or designee) and the IRB. After any needed discussion and consideration of 
study participation and before undergoing any procedures specifically for the study, the 
patient will sign the ICF. The ICF will be retained in the study patient’s study records, and a 
copy of the ICF will be given to the study patient. 
Patients may decline to participate in the study and withdraw consent at any time or for any 
reason throughout the course of the study without AEs on the quality of their medical care. 
10.5 
Confidentiality 
The Investigator must assure that patients’ anonymity is strictly maintained and that their 
identities are protected from unauthorized parties. This extends to testing of biological 
samples and genetic tests in addition to the clinical information relating to participants. Only 
an identification code (i.e., not names) should be recorded on any form or document 
submitted to Censa Pharmaceuticals, the Contract Research Organization (CRO), or the IRB. 
The Investigator must keep logs on screened and enrolled patients. In addition, the 
Investigator must have a list where the identity of all treated patients can be found. 
The Investigator agrees that all information received from Censa Pharmaceuticals, including, 
but not limited to, the Investigator’s Brochure, this protocol, CRFs, and any other 
information related to the protocol-specified treatment of the study, remain the sole and 
exclusive property of Censa Pharmaceuticals during the conduct of the study and thereafter. 
This information is not to be disclosed to any third party (except employees or agents directly 
involved in the conduct of the study or as required by law) without prior written consent from 
Censa Pharmaceuticals. The Investigator further agrees to take all reasonable precautions to 
prevent the disclosure by any employee or agent of the study center to any third party or 
otherwise into the public domain. 
The study monitor, other authorized representatives of Censa Pharmaceuticals, and 
representatives of the IRB may inspect all documents and records required to be maintained 
by the Investigator, including but not limited to, medical records (office, clinic, and hospital) 
and pharmacy records for the participants in this study. The clinical study site’s research staff 
will permit access to such records. 
The study patient’s contact information will be securely stored at each clinical site for 
internal use during the study. At the end of the study, all records will be kept in a secure 
location for as long a period as dictated by local IRB and Institutional regulations. 
10.6 
Study Monitoring 
A clinical monitor authorized to represent Censa Pharmaceuticals will conduct site visits to 
inspect study data, patient’s medical records, and eCRFs in accordance with ICH guidelines 
GCP, and applicable regulations and guidelines. The clinical monitor will also monitor 
ongoing drug accountability and adherence to protocol procedures. Details of clinical site 
monitoring are specified in a Clinical Monitoring Plan. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 56 
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Independent audits may be conducted to ensure that monitoring practices are performed 
consistently across all participating sites and that monitors are following the Clinical 
Monitoring Plan. 
The Investigator will allow representatives of the Censa Pharmaceuticals and regulatory 
authorities to inspect facilities and records relevant to this study. 
10.7 
Case Report Forms and Study Records 
The eCRFs will be supplied by Censa Pharmaceuticals or designee for the recording of all 
information and study data as specified by this protocol. Original eCRF data should be 
handled in accordance with instructions from Censa Pharmaceuticals or designee. All eCRFs 
must be completed by the clinical study site’s research staff authorized to do so by the 
Investigator. The Investigator is responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported. 
Data reported in the eCRF derived from source documents should be consistent with the 
source documents. Source documents are defined as records of documentation related to 
original observations and activities of a clinical investigation. Source documents may 
include, but are not limited to, study progress notes, study- or patient-specific email 
correspondence, computer printouts, laboratory data, and recorded data from automated 
instruments. All source documents produced in this study will be maintained by the 
Investigator and made available for inspections by Censa Pharmaceuticals or designee and by 
regulatory authorities. The original ICF for each participating patient shall be filed with 
records kept by the Investigator, and copies shall be given to the patient. 
Once all data queries and issues have been resolved for each patient the Investigator will 
electronically sign each patient’s eCRF. This signature will indicate that the data have been 
thoroughly inspected and will thereby certify the contents of the eCRF. 
Clinical data will be entered into a 21 Code of Federal Regulations (CFR) Part 11-compliant 
electronic data capture system. The data system includes password protection and internal 
quality checks, such as automatic range checks, to identify data that appear inconsistent, 
incomplete, or inaccurate. Clinical data will be entered by the clinical study site’s research 
staff directly from the source documents. 
10.8 
Protocol Violations/Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol requirements. The 
noncompliance may be either on the part of the patient, the Investigator, or the study site 
staff. Because of deviations, corrective actions are to be developed by the site and 
implemented promptly. This is consistent with the following sections in ICH E6: 
• 4.5 Compliance with Protocol, Sections 4.5.1, 4.5.2, and 4.5.3 
• 5.1 Quality Assurance and Quality Control, Section 5.1.1 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 57 
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• 5.20 Noncompliance, Sections 5.20.1, and 5.20.2. 
10.9 
Access to Source Documentation 
The Investigator agrees by his/her participation that the results of this study may be used for 
submission for national or international registration. If required, national or international 
authorities will be provided with the name of the Investigator and his or her address, full 
disclosure of his or her qualifications, any potential conflicts of interests, payments, and 
extent of involvement. 
During site visits, the clinical monitor will review original patient records, drug 
accountability records, and additional documents as needed. During the course of the study, 
Censa Pharmaceutical’s (or designee’s) Quality Assurance personnel may conduct an on-site 
audit visit. The Investigator will provide direct access to and allow verification and copying 
of all trial-related documents (e.g., source data) for trial-related monitoring, audits, IRB 
reviews, and regulatory inspections. 
10.10 
Data Generation and Analysis 
Some or all of the obligations of implementing or conducting this study may be transferred 
from Censa Pharmaceuticals to the CRO. 
A case report, comprised of individual eCRFs, will be completed for every patient who signs 
an ICF and is enrolled into the study. 
All original source documentation (laboratory results, treatment records, audit query 
responses, etc.) will be retained by the Investigator or institution unless specified otherwise 
by the protocol. The results as they become available will be entered on the appropriate 
eCRFs. Legible reproductions of the original laboratory reports for selected tests or variables 
will be submitted to Censa Pharmaceuticals or CRO as requested. 
The eCRFs will be reviewed by a clinical monitor who will evaluate the completeness and 
accuracy of the data. Queries will be generated for omissions, corrections, and clarifications. 
Data may also be reviewed in-house by a clinical auditor and data management or other 
personnel. 
Data analyses will be performed after database lock, when all queries have been resolved. 
10.11 
Retention of Data 
Study documents should be retained for a minimum of 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region or until at least 2 years have elapsed since the 
formal discontinuation of clinical development of the investigational product. These 
documents should be retained for a longer period, however, if required by local regulations. 
No records will be destroyed without the written consent of Censa Pharmaceuticals, if 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 58 
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applicable. It is the responsibility of Censa Pharmaceuticals to inform the Investigator when 
these documents no longer need to be retained. 
10.12 
Financial Disclosure 
Each Investigator must submit to Censa Pharmaceuticals (or designee) financial disclosure 
information according to national law and/or local regulations. 
10.13 
Publication and Disclosure Policy 
The data generated in this clinical study are the exclusive property of Censa Pharmaceuticals 
and are confidential. Authorship on any publication of the results from this study will be 
based on contributions to study design, patient enrollment, data analysis, interpretation of 
results, and drafting and editing of any publication in accordance with published authorship 
ethical guidelines for publication of research studies. Independent analysis and/or publication 
of these data by the Investigator(s) or any member of their staff is not permitted without the 
prior, written consent of Censa Pharmaceuticals. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 59 
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11 
REFERENCE LIST 
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response to therapy and its predictors. Dig Dis Sci. 2009 May;54(5):1003-10. 
Arts J, Caenepeel P, Verbeke K, et al. Influence of erythromycin on gastric emptying and 
meal related symptoms in functional dyspepsia with delayed gastric emptying. Gut. 2005 
Apr;54(4):455-60. 
Bredenoord AJ, Chial HJ, Camilleri M et al. Gastric accommodation and emptying in 
evaluation of patients with upper gastrointestinal symptoms. Clin Gastroenterol Hepatol. 
2003 Jul;1(4):264-72 
Cairn Diagnostics™. Interpreting Cairn Gastric Emptying Breath Test results. Available 
from https://cairndiagnostics.com/wp-
content/uploads/2016/08/interpretation_of_cairn_gebt_test_results_101915.pdf. Accessed 
2018 Aug 15. 
Camilleri M, Parkman HP, Shafi MA, et al. Clinical Guideline: Management of 
Gastroparesis. Clinical Guideline: Management of Gastroparesis. The American journal of 
gastroenterology. 2013;108(1):18-38. 
Coulie B, Tack J, Peeters T, et al. Involvement of two different pathways in the motor effects 
of erythromycin on the gastric antrum in humans. Gut. 1998 Sep;43(3):395-400. 
Fass R. Treatment Options for Diabetic Gastroparesis. Gastroenterology and Hepatology 
Volume 6, Issue 6, Supplement 9 June 2010. 
Feldman M, Schiller LR. Disorders of gastrointestinal motility associated with diabetes 
mellitus. Ann Intern Med. 1983 Mar;98(3):378-84. 
Gangula PR, Maner WL, Micci MA, et al. Diabetes induces sex-dependent changes in 
neuronal nitric oxide synthase dimerization and function in the rat gastric antrum. Am J 
Physiol Gastrointest Liver Physiol. 2007 Mar;292(3):G725-33. 
Gastric Emptying Breath Test (GEBT) [package insert]. Brentwood TN: ADVANCED 
BREATH DIAGNOSTICS LLC; 2015 Apr. 
Hoogerwerf WA, Pasricha PJ, Kalloo AN, et al. Pain: the overlooked symptom in 
gastroparesis. Am J Gastroenterol. 1999 Apr;94(4):1029-33. 
Horowitz M, O'Donovan D, Jones KL, et al. Gastric emptying in diabetes: clinical 
significance and treatment. Diabet Med. 2002 Mar;19(3):177-94. 
Ishiguchi T, Nakajima M, Sone H, et al. Gastric distension-induced pyloric relaxation: 
central nervous system regulation and effects of acute hyperglycaemia in the rat. J Physiol. 
2001 Jun 15;533(Pt 3):801-13. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 60 
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Karamanolis G, Caenepeel P, Arts J, et al. Determinants of symptom pattern in idiopathic 
severely delayed gastric emptying: gastric emptying rate or proximal stomach dysfunction? 
Gut. 2007 Jan;56(1):29-36. 
Khoury V, Dubois, D. GCSI Gastroparesis Cardinal Symptom Index information booklet. 
2nd ed. Lyon, France: Mapi Research Trust; 2015. p 30. 
Kindt S, Coulie B, Wajs E, Janssens J, Tack J. Reproducibility and symptomatic predictors 
of a slow nutrient drinking test in health and in functional dyspepsia. Neurogastroenterol 
Motil. 2008 Apr;20(4):320-9. 
Kumar A, Attaluri A, Hashmi S, et al. Visceral hypersensitivity and impaired 
accommodation in refractory diabetic gastroparesis. Neurogastroenterol Motil. 2008 
Jun;20(6):635-42. 
Mayer B, Werner ER. In search of a function for tetrahydrobiopterin in the biosynthesis of 
nitric oxide. Naunyn Schmiedebergs Arch Pharmacol. 1995;351(5):453-463. 
Park MI. How to Interpret Nutrition Drink Test. Journal of Neurogastroenterology and 
Motility. 2011;17(1):88-90. 
Parkman HP, Hasler WL, Fisher RS, et al, American Gastroenterological Association 
technical review on the diagnosis and treatment of gastroparesis. Gastroenterology. 2004 
Nov;127(5):1592-622.   
Prakash A, Wagstaff AJ. Domperidone. A review of its use in diabetic gastropathy. Drugs. 
1998 Sep;56(3):429-45. 
Rentz AM, Kahrilas P, Stanghellini V, et al. Development and psychometric evaluation of 
the Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM) in 
patients with upper gastrointestinal disorders. Qual Life Res. 2004 Dec;13(10):1737-49. 
Revicki DA, Rentz AM, Dubois D, et al. Development and validation of a patient-assessed 
gastroparesis symptom severity measure: the Gastroparesis Cardinal Symptom Index. 
Aliment Pharmacol Ther. 2003 Jul 1;18(1):141-50.  
Revicki DA, Rentz AM, Tack J, et al. Responsiveness and interpretation of a symptom 
severity index specific to upper gastrointestinal disorders. Clin Gastroenterol Hepatol. 2004 
Sep;2(9):769-77. 
Sarnelli G, Vos R, Cuomo R, et al. Reproducibility of gastric barostat studies in healthy 
controls and in dyspeptic patients. Am J Gastroenterol. 2001 Apr;96(4):1047-53. 
Sawabe K, Yamamoto K, Kamata T, et al. (2002) Sepiapterin Administration Raises Tissue 
BH4 Levels More Efficiently Than BH4 Supplement in Normal Mice. In: Milstien S, et al. 
(eds) Chemistry and Biology of Pteridines and Folates. Springer Science+Business Media 
New York. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 61 
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Snape WJ, Jr., Battle WM, Schwartz SS, et al. Metoclopramide to treat gastroparesis due to 
diabetes mellitus: a double-blind, controlled trial. Ann Intern Med. 1982 Apr;96(4):444-6. 
Soykan I, Sivri B, Sarosiek I, et al. Demography, clinical characteristics, psychological and 
abuse profiles, treatment, and long-term follow-up of patients with gastroparesis. Dig Dis 
Sci. 1998 Nov;43(11):2398-404. 
Stacher G. Diabetes mellitus and the stomach. Diabetologia. 2001 Sep;44(9):1080-93. 
Sutton KL, Sims CD, Honeywell MS. et al. Gastric Emptying Breath Test. 2015 Dec 14. 
Available from https://www.uspharmacist.com/article/diagnostic-spotlight-gastric-emptying-
breath-test. Accessed 2018 Aug 15. 
Tack J, Caenepeel P, Piessevaux H, et al. Assessment of meal induced gastric 
accommodation by a satiety drinking test in health and in severe functional dyspepsia. Gut. 
2003 Sep;52(9):1271-7. 
Takahashi T. Pathophysiological significance of neuronal nitric oxide synthase in the 
gastrointestinal tract. J Gastroenterol. 2003;38(5):421-30. 
Takahashi T, Nakamura K, Itoh H, et al. Impaired expression of nitric oxide synthase in the 
gastric myenteric plexus of spontaneously diabetic rats. Gastroenterology. 1997 
Nov;113(5):1535-44. 
Talley NJ, Verlinden M, Jones M. Can symptoms discriminate among those with delayed or 
normal gastric emptying in dysmotility-like dyspepsia? The American journal of 
gastroenterology. 2001 May;96(5):1422-8. 
Undeland KA, Hausken T, Gilja OH, et al. Gastric meal accommodation studied by 
ultrasound in diabetes. Relation to vagal tone. Scand J Gastroenterol. 1998 Mar;33(3):236-
41. 
United States Food and Drug Administration. Gastroparesis: Clinical Evaluation of Drugs for 
Treatment Guidance for Industry. 2015 Jul. Available from 
https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/
ucm455645.pdf. Accessed 2018 Jun 4. 
Werner ER, Gorren AC, Heller R, et al. Tetrahydrobiopterin and nitric oxide: mechanistic 
and pharmacological aspects. Exp Biol Med (Maywood). 2003 Dec;228(11):1291-302. 
Wood JD, Alpers DH, Andrews PL. Fundamentals of neurogastroenterology. Gut. 1999 
Sep;45 Suppl 2:II6-II16. 
Xu J, Wu Y, Song P, et al. Proteasome-dependent degradation of guanosine 5'-triphosphate 
cyclohydrolase I causes tetrahydrobiopterin deficiency in diabetes mellitus. Circulation. 2007 
Aug 21;116(8):944-53 


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APPENDIX 1 
SCHEDULE OF EVENTS 
Evaluation 
Screening Period 
Treatment Period 
Follow-up Period 
EOT 
EOS 
Telephone 
Follow-up 
-28 to -1 
Day 1 
(Predose) 
Day 1 
Through 
Day 13 
Day 14a 
Day 14a Day 15 
Day 28 (±1 
Day)  
Day 44 (±3 
Days) 
Informed consent 
X 
 
 
 
 
 
 
 
Confirm inclusion/exclusion criteria eligibility 
X 
 
 
 
 
 
 
 
Randomization 
Xb 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical historyc 
X 
X 
 
 
 
 
 
 
Vital signs, weight, and heightd 
X 
X 
X 
 
X 
X 
 
Physical examinatione 
X 
X 
 
 
X 
X 
 
Clinical laboratory testsf 
X 
X 
 
 
X 
X 
 
HbA1cg 
X 
 
 
 
X 
X 
 
Serum/urine pregnancy testh 
X 
X 
 
 
X 
X 
 
ECGi 
X 
 
 
 
 
 
 
 
Prior/concomitant medicationsj 
X 
X 
X 
X 
X 
 
X 
 
AEsk 
X 
X 
X 
X 
X 
 
X 
Xl 
Nutrient satiety testm 
Xn 
X 
 
 
X 
 
X 
 
GCSIo 
Xp 
X 
 
 
X 
X 
 
PAGI-SYMq 
 
X 
 
 
X 
X 
 
GEBTr 
X 
 
 
 
 
X 
X 
 
Dispense study drug 
 
 
X 
 
 
 
 
 
Dispense dosing diary 
 
 
Xs 
 
 
 
 
 
Study drug dosingt 
 
 
Xu 
X 
 
 
 
 
Collect study drug, dosing diary, assess 
compliance 
 
 
 
 
Xv 
Xv 
Xv 
 
a Study Day 14 is included both in the Treatment Period and EOT. 
b Randomize patient on Day -1. 


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c Includes specific information related to any prior or existing medical conditions or surgical procedures involving the following systems: dermatologic, HEENT, lymphatic, 
cardiovascular, respiratory, GI, musculoskeletal, and neurological.  
d Includes blood pressure, pulse, respiratory rate, and temperature. Obtain vital signs before collection of any laboratory samples and after patients have rested for 5 minutes in a 
supine position. Obtain vital signs both predose and 2 hours postdose on Day 1; for all other timepoints, obtain at any time during the indicated visits. Obtain height only at 
Screening. Obtain weight at Screening to determine response to Exclusion Criterion #5 (Section 4.3) and on Day -1 (Section 6.3). 
e Conduct a complete physical examination of general appearance, dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and neurological 
parameters.  
f Includes clinical chemistry panel (ALB, AP, ALT, AST, BUN, Ca, CO2, Cl, creatinine, GGT, glucose, LDH, phosphorus, K, Na, total bilirubin, direct bilirubin, total cholesterol, 
total protein, uric acid); hematology panel (HCT, HGB, platelet count, RBC count, WBC count, and WBC differential); and urinalysis (bilirubin, glucose, ketones, occult blood, 
pH, protein, specific gravity, urobilinogen and microscopic examination of WBC, RBC, and epithelial cells). Patients will fast overnight before blood sample collections. 
g Patients will fast overnight before blood sample collections. 
h Serum and urine pregnancy tests required for all women of childbearing potential; serum testing is to occur during the Screening Period, and urine testing is to occur before 
dosing on Day 1 and at an EOT visit on Day 28 (±1 day). Any positive urine pregnancy test should be confirmed by a serum pregnancy test. 
i Obtain 12-lead ECG recordings in triplicate with 1 minute separating the first and second and second and third recordings. 
j Record all treatments and over-the-counter medications (including herbal medications) received from 30 days prior to Screening (to determine responses to Inclusion Criterion 
#9 [Section 4.2] and Exclusion Criteria #11 through #14 and #21 [Section 4.3] concerning medications) and through Day 28 ±1 day before the patient leaves the clinic after 
completion of all EOS evaluations. 
k Collect AEs from the time of informed consent through Day 28 ±1 day before the patient leaves the clinic after completion of all EOS evaluations and SAEs from the time of 
informed consent through telephone Follow-up. 
l Telephone Follow-up is to assess SAEs only. 
m Administer the nutrient satiety test (Section 6.7) at Screening, on Day 1 (predose), and on Day 14 and Day 28 after overnight fasts and after any medications that can alter GI 
sensation or accommodation or gastric emptying have been held overnight. 
n Administer the nutrient satiety test at Screening to determine the response to Inclusion Criterion #6 (Section 4.2) 
o Administer the GCSI (Section 6.8, Appendix 2) at Screening, on Day 1 (predose), on Day 14 (+1 day) and on Day 28 (±1 day). 
p Administer the GCSI (Section 6.8, Appendix 2) to determine response to Inclusion Criterion #5 (Section 4.2). 
q Administer the PAGI-SYM (Section 6.9, Appendix 2) in the clinic on Day 1 (predose), on Day 14 (+1 day), and on Day 28 (±1 day). 
r Administer the GEBT on Day -1, on Day 15, and on Day 27 or Day 29. For the GEBT (Section 6.10), patients will fast overnight before the GEBT (a minimum of 8 hours 
before test administration with the exception of 4 ounces of water up to 1 hour before the test). Collect a premeal breath sample and then provide a standardized 230 kCal meal, 
consisting of a proprietary standardized 13C-labeled egg component (which is rehydrated and then microwaved for 1.5 minutes) and 6 saltine crackers, accompanied by 6 ounces 
of water. Encourage the patient to consume the meal within 10 minutes. Collect single postmeal breath samples in capped glass tubes at 45, 90, 120, 150, 180, and 240 minutes 
after the meal is consumed and send the samples to the specified local laboratory for analysis. 
s Dispense a dosing diary with instructions to record times all doses of study drug are taken. 
t If a patient vomits after taking a dose of study drug, the patient should wait until the next scheduled timepoint to take another dose. A missed dose should be taken as soon as 
possible, but >2 doses should not be taken on the same day. 
u Patients will take their first doses of study drug (CNSA-001 or placebo) on Day 1 while in the clinic. 
v Collect study drug, dosing diary, assess compliance on Day 14 if the patient takes the last dose of study drug on Day 14 while in the clinic or, if the patient takes the last dose of 
study drug on Day 14 after leaving the clinic, on Day 15 or Day 28 (±1 day). 
 
Abbreviations: AE = adverse event; ALB = albumin; ALT = alanine aminotransferase (serum glutamic pyruvic transaminase [SGPT]); AP = alkaline phosphatase; AST = aspartate 
aminotransferase (serum glutamic oxaloacetic transaminase [SGOT]); BUN = blood urea nitrogen; 13C = carbon-13; Ca = calcium; CO2 = carbon dioxide; Cl = chloride; 
ECG = electrocardiogram; EOS = End of Study; EOT = End of Treatment; GCSI = Gastroparesis Cardinal Symptom Index; GEBT = Gastric Emptying Breath Test; 


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GI = gastrointestinal; GGT = gamma glutamyl transferase; HCT = hematocrit; HGB = hemoglobin; HEENT = head, eyes, ears, nose, and throat; HbA1c = glycosylated 
hemoglobin A1c; K = potassium; LDH = lactate dehydrogenase; Na = sodium; PAGI-SYM = Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity; 
RBC = red blood cell; SAE = serious adverse event; WBC = white blood cell.


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 65 
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APPENDIX 2 
GCSI AND PAGI-SYM ASSESSMENT INSTRUMENTS  
Gastroparesis Cardinal Symptom Index Questionnaire (English Version):  
  
Khoury V, Dubois, D. GCSI Gastroparesis Cardinal Symptom Index information booklet. 
2nd ed. Lyon, France: Mapi Research Trust; 2015. p 30. 
 












CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 1 
AMENDMENT 3: 21 Feb 2019 
 
CONFIDENTIAL 
 
CLINICAL TRIAL PROTOCOL 
Study Title: 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Pilot Study of 
CNSA-001 in Women With Moderate to Severe Diabetic Gastroparesis 
Study Number: 
GAS-001 
Study Phase: 
2 Pilot 
Product Name: 
CNSA-001 (sepiapterin)  
Dosage Form:  
Oral powder for suspension 
 
 
Indication: 
Treatment of women with moderate to severe diabetic gastroparesis 
Investigators: 
Multicenter study  
 
 
Sponsor: 
Censa Pharmaceuticals 
65 William Street 
Wellesley, MA 02481 
Sponsor Contact: 
 
Medical Monitor: 
 
 
 
Date 
Original Protocol: 
06 September 2018 
Amendment 1: 
09 October 2018 
Amendment 2: 
12 November 2018 
Amendment 3: 
21 February 2019 
 
 
 
 
 
Confidentiality Statement 
The confidential information in this document is provided to you as an Investigator or consultant for 
review by you, your staff, and the applicable Institutional Review Board/Independent Ethics 
Committee. Your acceptance of this document constitutes agreement that you will not disclose the 
information contained herein to others without written authorization from the Sponsor.  




CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 3 
AMENDMENT 3: 21 Feb 2019 
 
CONFIDENTIAL 
INVESTIGATOR’S SIGNATURE 
Study Title: 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Pilot Study 
of CNSA-001 in Women With Moderate to Severe Diabetic 
Gastroparesis 
Study Number: 
GAS-001 
Final Date: 
06 September 2018 
Amendment 1: 
09 October 2018 
Amendment 2: 
12 November 2018 
Amendment 3: 
21 February 2019 
I have read the protocol described above. I agree to comply with all applicable regulations 
and to conduct the study as described in the protocol. 
 
 
 
Signature 
 
Date (DD Month YYYY) 
 
 
 
Printed Name, Credentials 
 
 
 
 
 
Affiliation 
 
 
 
 
 
Address 
 
 
 
 
 
Phone Number 
 
 
 
 
 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 4 
AMENDMENT 3: 21 Feb 2019 
 
CONFIDENTIAL 
PROTOCOL AMENDMENT 3 (FEBRUARY 21, 2019) 
Protocol GAS-001 is amended primarily for the following reasons: 
1. Modified Inclusion Criterion #2 to increase the upper age limit from 65 to 75 years. 
2. Modified Inclusion Criterion #4 to extend the evidence of gastric emptying to 2 years 
prior to enrollment and to offer the possibility of retesting during screening with either 
the GES or the GEBT for patients that have historical GES or GEBT greater than 2 years 
prior to enrollment.  Consistent with FDA draft guidance, either GES or GEBT may be 
used to confirm delayed gastric emptying. 
3. Modified Exclusion Criterion #9 to state the method of QT correction required.  
Fridericia’s correction is being applied to ensure consistency across Censa sponsored 
clinical studies. 
Major changes to the protocol are as follows: 
Synopsis, Section 4.2 and Appendix 1: Modified exclusion criteria #2 and #4 to increase the 
upper age limit from 65 to 75 and to permit testing for gastric emptying with either the GES 
or the GEBT during screening, respectively. 
Synopsis and Section 4.3: Modified exclusion criterion #9 to clarify that QTc will be 
reported using Fridericia’s correction. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 5 
AMENDMENT 3: 21 Feb 2019 
 
CONFIDENTIAL 
PROTOCOL AMENDMENT 2 (NOVEMBER 12, 2018) 
Protocol GAS-001 is amended primarily for the following reasons: 
1. Modified Exclusion Criterion #9 to exclude patients with a marked baseline prolongation 
of QT/QTc interval of ≥470 msec (based on triplicate measurements taken at screening). 
2. Removed reference to Quality of Life measurements using the PAGI-SYM. 
3. Corrected wording of secondary endpoints to more accurately reference change resulting 
from CNSA-001 treatment. 
4. Corrected the methods of administration of the nutrient satiety test to 150mL of Ensure 
every 5 minutes. 
 
Major changes to the protocol are as follows: 
Synopsis and Section 4.3: Modified exclusion criterion #9 to QTc ≥470 msec. 
Synopsis and Section 2.2: Corrected wording of secondary endpoints to reflect an effect of 
CNSA-001 treatment.  Corrected the usage of PAGI-SYM as a symptom scale versus a 
quality of life scale. 
Section 6.7: Corrected the methods for administering the nutrient satiety test. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 6 
AMENDMENT 3: 21 Feb 2019 
 
CONFIDENTIAL 
PROTOCOL AMENDMENT 1 (OCTOBER 9, 2018) 
Protocol GAS-001 is amended primarily for the following reasons: 
1. Added Exclusion Criterion to exclude patients with baseline cardiovascular instability. 
2. Added Exclusion Criterion to exclude patients with PKU or hyperphenylalaninemia. 
3. Updated the discontinuation criteria related to AEs in Section 6.14.1. 
4. Updated the study stopping criteria to include specific examples of adverse event criteria 
for temporarily or permanently stopping the study. 
 
Major changes to the protocol are as follows: 
Synopsis and Section 4.3: Added two additional exclusion criteria for patients with baseline 
cardiovascular instability and for patients with PKU or hyperphenylalaninemia. 
Section 6.14.1: Added drug class adverse events to individual discontinuation criteria, 
specifically, hypersensitivity reactions, anaphylaxis, and gastritis. 
Section 6.14.3: Added examples of study stopping criteria associated with adverse event 
criteria of severity, frequency, and relatedness. 


CNSA-001 (sepiapterin)         
     Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001         
      Page 7 
AMENDMENT 3: 21 Feb 2019 
CONFIDENTIAL 
SYNOPSIS 
Sponsor: 
Censa Pharmaceuticals 
Name of Finished Product: 
CNSA-001 
Name of Active Ingredient: 
Sepiapterin 
Name of Inactive Ingredients: 
Microcrystalline cellulose, colloidal silicon dioxide, croscarmellose, and ascorbic acid 
Study Title: 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Pilot Study of CNSA-001 in Women 
With Moderate to Severe Diabetic Gastroparesis 
Study Number: 
GAS-001 
Study Phase: Phase 2 pilot 
Primary Objective: 
•
To assess the impact of CNSA-001 on gastric accommodation, as measured by nutrient
satiety testing, in women with moderate to severe diabetic gastroparesis
Secondary Objectives: 
In women with moderate to severe diabetic gastroparesis: 
•
To evaluate the effect of CNSA-001 on improvement of gastroparesis symptoms as
measured by the change from baseline in the global assessment of symptoms and symptom
severity (Gastroparesis Cardinal Symptom Index [GCSI]) (Section 6.8, Appendix 2)
•
To evaluate the effect of CNSA-001 on patient-reported symptoms as measured by the
change from baseline in the Patient Assessment of Upper Gastrointestinal Disorders-
Symptom Severity (PAGI-SYM) (Section 6.9, Appendix 2)
•
To evaluate the effect of CNSA-001 on emptying of the stomach as measured by the
change from baseline in the Gastric Emptying Breath Test (GEBT)
•
To assess the safety and tolerability of CNSA-001 20 mg/kg/day
Study Design: 
This is a Phase 2, randomized, double-blind, placebo-controlled pilot study of multiple doses of 
CNSA-001 (sepiapterin) powder for suspension administered orally in women with moderate to 
severe diabetic gastroparesis. Patients will be randomized in a ratio of 1:1 to receive CNSA-001 
20 mg/kg/day or placebo, each dosed twice a day (BID); each group will consist of 10 patients. All 
patients will receive the standard of care for diabetic gastroparesis. Approximately 6 centers will 
participate in this study. The study design is summarized in the study schema below. A schedule of 
study events is provided in Appendix 1. 
All study clinic visits will be outpatient visits.  
Patients will continue their usual diet without modification throughout the study. Patients are 
required to have been fasting overnight for the following assessments:  
•
Clinical laboratory, including glycosylated hemoglobin A1c (HbA1c), tests
•
The nutrient satiety test
•
The GEBT


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 8 
AMENDMENT 3: 21 Feb 2019 
 
CONFIDENTIAL 
 
 
 
Screening Period (Day -28 Through Day 1 Predose): 
An informed consent form (ICF) must be signed before any study-related procedures are 
performed. After providing consent, patients will undergo Screening procedures to determine study 
eligibility, as indicated in Appendix 1. Patients who are eligible based on Screening evaluations 
will undergo baseline evaluations before initiation of study drug (CNSA-001 or placebo), be 
randomized, and proceed to the Treatment Period.  
Treatment Period (Day 1 Through Day 14) 
Following the Screening Period and completion of baseline evaluations, all randomized patients 
will take their first dose of study drug (CNSA-001 or placebo) on Day 1 while in the clinic. 
Patients will undergo procedures during the Treatment Period as indicated in Appendix 1. 
End of Treatment Period (Day 14 Through Day 15 Evaluations) 
Patients will undergo End of Treatment (EOT) evaluations on Day 14 and Day 15 as indicated in 
Appendix 1. Preliminary efficacy will be assessed by the changes from Day 1 in the nutrient satiety 
test on Day 14. The GCSI (Section 6.8, Appendix 2) and PAGI-SYM (Section 6.9, Appendix 2) 
will also be administered on Day 14 (+1 day), and the GEBT will be conducted on Day 15. 
End of Study Period (Day 15 After Evaluations Through Day 28 [±1 Day] Evaluations) 
Patients will undergo End of Study evaluations on Day 28 (±1 day) as indicated in Appendix 1. 
Preliminary efficacy will be assessed by the changes from Day 1 in the nutrient satiety test on 
Day 28. The GCSI (Section 6.8, Appendix 2) and PAGI-SYM (Section 6.9, Appendix 2) will also 
be administered on Day 28 ±1, and the GEBT will be conducted on Day 27 or Day 29. 
Follow-up Period (Day 28 [±1 Day] After Evaluations Through Day 44 [±3 Days]) 
Patients will undergo telephone Follow-up on Day 44 ±3 days as indicated in Appendix 1.  


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 9 
AMENDMENT 3: 21 Feb 2019 
 
CONFIDENTIAL 
Number of Patients: 
Up to 20 women ≥18 and ≤75 years of age will be enrolled in this study and randomized in a ratio 
of 1:1 to receive CNSA-001 or placebo.  
Main Criteria for Inclusion and Exclusion: 
Patients are eligible to participate if they meet all the following inclusion criteria: 
1. Informed consent 
2. Females ≥18 and ≤75 years of age 
3. Diagnosis of diabetes mellitus  
4. Documentation of delayed gastric emptying by either  
o gastric emptying scintigraphy (GES) (within 2 years of enrollment), or 
o gastric emptying breath test (GEBT) (within 2 years of enrollment) 
If historical documentation is >2 years, either the GES or the GEBT may be conducted 
at screening to confirm diagnosis. 
5. Symptoms of gastroparesis for at least 6 months with GCSI (Section 6.8, Appendix 2) score 
>21 indicating moderate to severe symptoms 
6. Gastric accommodation, as measured by nutrient satiety testing, of ≤600 mL 
7. Negative upper endoscopy or upper gastrointestinal (GI) series within 3 years of enrollment 
(no evidence of mechanical obstruction or peptic ulcer disease) 
8. Either postmenopausal for ≥1 year or surgically sterile (having undergone tubal ligation, 
hysterectomy, or bilateral oophorectomy) for at least 6 months or, if of childbearing potential 
and not abstinent, willing to use a highly effective method of contraception throughout the 
study such as 1 of the following: 
• 
Hormonal contraception (stable dose for 3 months) 
• 
Intrauterine device/Intrauterine Hormone-releasing System 
• 
Barrier contraceptive method (diaphragm, cervical cap, contraceptive sponge, condom) 
Patients who are abstinent will not be required to use a contraceptive method unless they 
become sexually active. 
9. If on analgesics, including narcotics; promotility agents, including metoclopramide, or 
neuromodulators, including tricyclic antidepressants, gabapentin, and pregabalin, doses are 
stable for >30 days before randomization and the patient is not expected to require dose 
changes during the study through the EOT 
10. Have not used tobacco (e.g., cigarettes, e-cigarettes, cigars, smokeless tobacco, nicotine 
replacement) for 2 weeks prior to Day 1 and willingness to abstain from these products 
during the study through the EOT 
Patients are not eligible to participate if they meet any of the following exclusion criteria:  
1. Male gender 
2. Normal gastric emptying  
3. Gastroparesis from postsurgical etiologies 
4. Another active disorder that could, in the opinion of the Investigator, explain symptoms  
5. Weight >100 kg 
6. Alanine aminotransferase > 2× upper limit of normal (ULN) 
7. Pregnant, breastfeeding, or considering pregnancy 
8. Clinically significant cardiac arrhythmia at Screening 
9. QT interval corrected for heart rate (QTc) ≥470 msec using Fridericia’s correction (based on 
triplicate measurements taken at Screening) 
10. Resting heart rate ≤40 or ≥110 bpm or resting blood pressure <90/40 mmHg or >150/90 
mmHg at Screening or prior to the first administration of study drug. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 10 
AMENDMENT 3: 21 Feb 2019 
 
CONFIDENTIAL 
11. Recent clinically GI significant bleeding 
12. Taking levodopa or domperidone within 30 days before randomization or expected to 
require domperidone during the study through the EOT 
13. Taking erythromycin within 30 days before randomization or expected to require 
erythromycin within 30 days before randomization or expected to require erythromycin 
during the study through the EOT; if a patient is taking erythromycin and is otherwise 
eligible to participate in the study, following signing the ICF, the patient may go through an 
erythromycin washout period of 30 days before randomization 
14. Taking any fundic-relaxing agents including, but not limited to, buspirone, clonidine, 
nitrates, phosphodiesterase inhibitors (i.e., sildenafil citrate [Viagra®]) and triptan-containing 
medications, within 30 days before randomization or expected to require any of these agents 
during the study through the EOT 
15. Taking any systemic antifolates, including, but not limited to, methotrexate, pemetrexed, and 
trimetrexate or expected to require any systemic antifolates during the study through the 
EOT (topical antifolates [e.g., cream, ointment, gel] or eye drops with antifolates are 
allowed) 
16. Pulmonary dysfunction (e.g., chronic obstructive pulmonary disease) 
17. Surgery for placement of a gastric stimulator within the past 6 months (patients 
postoperative >6 months with persistent symptoms and delayed gastric emptying are 
eligible) 
18. Gastrointestinal disease (such as irritable bowel syndrome, inflammatory bowel disease, 
chronic gastritis, peptic ulcer disease, small bowel malabsorption) that could affect the 
absorption of study drug or contraindicate undergoing the GEBT 
19. History of gastric surgery, including Roux-en-Y gastric bypass surgery or an antrectomy 
with vagotomy, or gastrectomy 
20. History of allergies or adverse reactions to tetrahydrobiopterin or related compounds, to any 
excipients in the study drug formulation, or to egg, wheat, or algae (Spirulina)  
21. Inability to tolerate oral medication 
22. Current participation in any other investigational drug study or use of any investigational 
agent, investigational device, or approved therapy for investigational use within 30 days or 
5 half-lives (whichever is longer) before Screening 
23. Any clinically significant laboratory abnormality; in general, each laboratory value from 
Screening and baseline chemistry and hematology panels should fall within the limits of the 
normal laboratory reference range unless deemed not clinically significant by the 
Investigator 
24. Major surgery within the previous 90 days  
25. The patient, in the opinion of the Investigator, is unwilling or unable to adhere to the 
requirements of the study 
26. History of alcohol or drug abuse within 6 months prior to Screening or current evidence of 
substance dependence as determined by the Investigator 
27. Episodes of ketoacidosis or hypoglycemia that are frequent as defined by the Investigator 
28. History of phenylketonuria (PKU) or hyperphenylalaninemia. 
29. Any other conditions, including diabetic comorbidities, that, in the opinion of the 
Investigator or Sponsor, would interfere with the patient’s ability to participate in the study 
or increase the risk of participation for that patient 
Test Product, Dose, and Mode of Administration: 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 11 
AMENDMENT 3: 21 Feb 2019 
 
CONFIDENTIAL 
The test product is CNSA-001 (sepiapterin) oral powder for suspension. CNSA-001 will be 
suspended in Medisca® Oral Mix prior to dispensing to the patient. Patients randomized to receive 
CNSA-001 will receive CNSA-001 20 mg/kg/day (i.e., 10 mg/kg BID) for 14 days. 
Reference Therapy; Dose; and Mode of Administration: 
The reference product is placebo. The placebo is a ready-made suspension containing 
microcrystalline cellulose, colloidal silicon dioxide, croscarmellose, ascorbic acid, and colorant 
(Yellow No. 6) that is suspended in Medisca® Oral Mix.  
Duration of Treatment: 
Patients will be treated for a total of 14 days.  
Criteria for Evaluation: 
Safety: 
Safety and tolerability of CNSA-001 as measured by severity and number of treatment-emergent 
adverse events (TEAEs), including assessment of severity of TEAEs, and changes in clinical 
laboratory and HbA1c tests, vital signs, and physical examinations 
Efficacy: 
The primary efficacy measure will be the change in maximal tolerated volume consumed during 
the nutrient satiety test from Day 1 to Day 14 and Day 1 to Day 28. 
Secondary efficacy measures will consist of changes in the following from baseline to Day 14 and 
baseline to Day 28 (±1 day):  
• 
GCSI (Section 6.8, Appendix 2) PAGI-SYM (Section 6.9, Appendix 2) subscale 
(heartburn/regurgitation, fullness/early satiety, nausea/vomiting, bloating, upper abdominal 
pain, and lower abdominal pain) scores 
• 
Gastric emptying as measured by the GEBT  
Statistical Methods: 
The following study populations will be analyzed: 
• 
Safety population: all patients who were randomized and received any amount of study 
drug (CNSA-001 or placebo) 
• 
Efficacy population: all patients who were randomized, received any amount of study drug 
(CNSA-001 or placebo), and had available Day 1 and Day 14 nutrient satiety test 
maximum tolerated volume results  
Safety will be assessed in the Safety population. Adverse events (AEs) will be coded using the 
Medical Dictionary for Regulatory Activities (MedDRA®). The number and percentage of patients 
with TEAEs will be tabulated by system organ class, preferred term, and treatment group. Severity 
of AEs and serious adverse events (SAEs) will be summarized similarly. Those AEs leading to 
premature discontinuation from the study drug and the serious TEAEs will be presented in a table 
or a listing. Clinical laboratory and HbA1c test results and vital signs will be summarized at each 
visit as will changes from baseline for each treatment group. A frequency distribution of abnormal 
physical examination results will be provided. 
Efficacy will be assessed in the Efficacy population. The changes from Day 1 to Day 14 and from 
Day 1 to Day 28 in maximal tolerated volume consumed during the nutrient satiety test will be 
compared between treatment groups using a student’s t-test. Results from the nutrient satiety test 
through Day 14 and Day 28, the GEBT through Day 15 and Day 27 or Day 29, and the GCSI 
(Section 6.8, Appendix 2) and PAGI-SYM (Section 6.9, Appendix 2) through Day 14 (+1) and 
through Day 28 (±1) will be summarized using summary statistics (number of patients, mean, 
standard deviation, median, and range) at each visit as well as changes from baseline within each 
treatment group. The 95% confidence intervals for the changes from baseline will be provided. 
Additional analyses may be conducted, and details will be provided in the statistical analysis plan. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 12 
AMENDMENT 3: 21 Feb 2019 
 
CONFIDENTIAL 
Date of Original Protocol: 06 September 2018 
Date of Amendment 1: 09 October 2018 
Date of Amendment 2: 12 November 2018 
Date of Amendment 3: 21 February 2019 
 


CNSA-001 (sepiapterin)         
     Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001         
      Page 13 
AMENDMENT 3: 21 Feb 2019 
CONFIDENTIAL 
TABLE OF CONTENTS 
CLINICAL TRIAL PROTOCOL ..............................................................................................1 
SPONSOR SIGNATURES ........................................................................................................2 
INVESTIGATOR’S SIGNATURE ...........................................................................................3 
PROTOCOL AMENDMENT 3 (FEBRUARY 21, 2019) ........................................................4 
PROTOCOL AMENDMENT 2 (NOVEMBER 12, 2018) .......................................................5 
PROTOCOL AMENDMENT 1 (OCTOBER 9, 2018) .............................................................6 
SYNOPSIS .................................................................................................................................7 
TABLE OF CONTENTS .........................................................................................................13 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ..........................................16 
1 
INTRODUCTION .................................................................................................19 
1.1 
Diabetic Gastroparesis .....................................................................................19 
1.2 
Impaired Gastric Accommodation in Gastroparesis ........................................20 
1.3 
Current Treatment of Diabetic Gastroparesis ..................................................20 
1.4 
CNSA-001 (Sepiapterin) ..................................................................................21 
1.5 
Rationale for Study ..........................................................................................21 
2 
STUDY OBJECTIVES ..........................................................................................23 
2.1 
Primary Objective ............................................................................................23 
2.2 
Secondary Objectives.......................................................................................23 
3 
INVESTIGATIONAL PLAN ................................................................................24 
3.1 
Overall Study Design and Plan ........................................................................24 
3.2 
Rationale for Study Design and Control Group ...............................................25 
3.3 
Study Duration and Dates ................................................................................26 
4 
STUDY POPULATION SELECTION .................................................................27 
4.1 
Study Population ..............................................................................................27 
4.2 
Inclusion Criteria .............................................................................................27 
4.3 
Exclusion Criteria ............................................................................................28 
5 
STUDY TREATMENTS .......................................................................................30 
5.1 
Description of Treatments................................................................................30 
5.1.1 
Test Product .........................................................................................30 
5.1.2 
Placebo Control ....................................................................................30 
5.2 
Treatments Administered .................................................................................30 
5.3 
Selection and Timing of Dose for Each Patient ...............................................30 
5.4 
Method of Assigning Patients to Treatment Groups........................................31 
5.5 
Blinding............................................................................................................31 
5.6 
Concomitant Therapy.......................................................................................31 
5.7 
Restrictions ......................................................................................................32 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 14 
AMENDMENT 3: 21 Feb 2019 
 
CONFIDENTIAL 
5.7.1 
Prior Therapy and Concomitant Therapy ............................................32 
5.7.2 
Food Intake ..........................................................................................33 
5.7.3 
Total Blood Volume ............................................................................33 
5.7.4 
Patient Activity and Tobacco Restrictions ...........................................33 
5.8 
Treatment Compliance .....................................................................................33 
5.8.1 
Dosing Diary ........................................................................................33 
5.9 
Packaging and Labeling ...................................................................................34 
5.10 
Storage and Accountability ..............................................................................34 
5.11 
Investigational Product Retention at Study Site ..............................................34 
6 
STUDY PROCEDURES .......................................................................................35 
6.1 
Informed Consent.............................................................................................35 
6.2 
Medical History and Demographic Data .........................................................35 
6.3 
Vital Signs, Weight, and Height ......................................................................35 
6.4 
Physical Examination.......................................................................................35 
6.5 
Clinical Laboratory Tests and Glycosylated Hemoglobin A1c .......................35 
6.6 
Electrocardiogram ............................................................................................36 
6.7 
Nutrient Satiety Test ........................................................................................37 
6.8 
Gastroparesis Cardinal Symptom Index ..........................................................37 
6.9 
Patient Assessment of Upper Gastrointestinal Disorders-Symptom 
Severity ............................................................................................................37 
6.10 
Gastric Emptying Breath Test ..........................................................................37 
6.11 
Dispensing Study Drug ....................................................................................38 
6.12 
Adverse Events Assessments ...........................................................................38 
6.12.1 
Reporting Timelines.............................................................................38 
6.12.2 
Severity ................................................................................................40 
6.12.3 
Relationship .........................................................................................40 
6.12.4 
Expectedness ........................................................................................41 
6.12.5 
Clinical Laboratory Adverse Events ....................................................42 
6.12.6 
Serious Adverse Events .......................................................................42 
6.12.7 
Treatment-Emergent Adverse Events ..................................................43 
6.13 
Prior and Concomitant Medication Assessments ............................................44 
6.14 
Removal of Patients From the Trial or Study Drug .........................................44 
6.14.1 
Early Discontinuation From Study Drug Administration ....................44 
6.14.2 
Withdrawal From the Study .................................................................45 
6.14.3 
Study Stopping Criteria........................................................................45 
6.15 
Appropriateness of Measurements ...................................................................46 
7 
STUDY ACTIVITIES ...........................................................................................48 
7.1 
Screening Procedures (Day –28 to Day -1) .....................................................48 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 15 
AMENDMENT 3: 21 Feb 2019 
 
CONFIDENTIAL 
7.2 
Day 1 Predose ..................................................................................................49 
7.3 
Day 1 After Baseline Evaluations Through Day 13 ........................................49 
7.3.1 
Day 1 ....................................................................................................49 
7.4 
Early Termination Procedures .........................................................................50 
7.5 
End of Treatment Visits (Day 14 and Day 15) ................................................50 
7.6 
End of Study (Day 28 ±1 Day) ........................................................................51 
7.7 
Telephone Follow-up Day 44 (±3 Days) (30 ±3 Days After Last Dose) .........52 
8 
QUALITY CONTROL AND ASSURANCE .......................................................53 
9 
PLANNED STATISTICAL METHODS ..............................................................54 
9.1 
General Considerations ....................................................................................54 
9.2 
Determination of Sample Size .........................................................................54 
9.3 
Analysis Populations ........................................................................................54 
9.4 
Demographics, Baseline Characteristics, Enrollment, Protocol Deviations, 
and Patient Disposition ....................................................................................54 
9.5 
Statistical Analysis of Efficacy Variables ........................................................54 
9.6 
Safety Analysis ................................................................................................55 
10 
ADMINISTRATIVE CONSIDERATIONS ..........................................................56 
10.1 
Investigators and Study Administrative Structure ...........................................56 
10.2 
Institutional Review Board Approval ..............................................................56 
10.3 
Ethical Conduct of the Study ...........................................................................56 
10.4 
Patient Information and Consent .....................................................................56 
10.5 
Confidentiality .................................................................................................57 
10.6 
Study Monitoring .............................................................................................57 
10.7 
Case Report Forms and Study Records ...........................................................58 
10.8 
Protocol Violations/Deviations ........................................................................58 
10.9 
Access to Source Documentation ....................................................................59 
10.10 
Data Generation and Analysis .........................................................................59 
10.11 
Retention of Data .............................................................................................59 
10.12 
Financial Disclosure.........................................................................................60 
10.13 
Publication and Disclosure Policy ...................................................................60 
11 
REFERENCE LIST ...............................................................................................61 
Appendix 1 
Schedule of Events ...............................................................................64 
Appendix 2 
GCSI and PAGI-SYM Assessment Instruments..................................67 
LIST OF TABLES 
Table 1: 
Administrative Structure for GAS-001 Study............................................56 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 16 
AMENDMENT 3: 21 Feb 2019 
 
CONFIDENTIAL 
LIST OF FIGURES 
Figure 1: 
Study Schema.............................................................................................25 
 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
AE 
Adverse event 
ALB 
Albumin  
ALT 
Alanine aminotransferase (serum glutamic pyruvic transaminase [SGPT]) 
AP 
Alkaline phosphatase 
AST 
Aspartate aminotransferase (serum glutamic oxaloacetic transaminase [SGOT]) 
AUC0-last 
Area under the concentration time curve from 0 to the last measurement 
BH4 
Tetrahydrobiopterin 
BID 
Twice a day 
BUN 
Blood urea nitrogen 
13C 
Carbon-13 
Ca 
Calcium  
CFR 
Code of Federal Regulations 
Cl 
Chloride 
Cmax 
Maximum concentration 
CO2 
Carbon dioxide  
12CO2 
Carbon-12 dioxide 
13CO2 
Carbon-13 dioxide 
CRO 
Contract Research Organization 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EOS 
End of Study 
EOT 
End of Treatment 
FDA 
United States Food and Drug Administration 
GCP 
Good Clinical Practice 
GCSI 
Gastroparesis Cardinal Symptom Index 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 17 
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GEBT 
Gastric Emptying Breath Test 
GES 
Gastric Emptying Scintigraphy 
GGT 
Gamma glutamyl transferase 
GI 
Gastrointestinal 
GLP 
Good Laboratory Practice 
HbA1c 
Glycosylated hemoglobin A1c  
HCG 
Human chorionic gonadotropin 
HCT 
Hematocrit 
HEENT 
Head, eyes, ears, nose, and throat 
HGB 
Hemoglobin 
ICF 
Informed consent form 
ICH 
International Council on Harmonisation  
IRB 
Institutional Review Board 
K 
Potassium 
kPCD 
the Gastric Emptying Breath Test metric; “k” is a multiplier of 1000, and 
“PCD” is an acronym for percent carbon-13 dose excreted (as carbon-13 
dioxide)  
LAR 
legally authorized representative 
LDH 
Lactate dehydrogenase 
MedDRA® 
Medical Dictionary for Regulatory Activities 
Na 
Sodium  
NADPH 
nicotinamide adenine dinucleotide phosphate hydrogen 
nNOS 
Neuronal nitric oxide synthase 
NO 
Nitric oxide 
NOS 
Nitric oxide synthase 
PAGI-QOL 
Upper Gastrointestinal Disorders-Quality of Life 
PAGI-SYM 
Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity 
PRO 
Patient-reported outcome 
QTc  
QT interval corrected for heart rate 
RBC 
Red blood cell 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 18 
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SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SUSAR 
Suspected unexpected serious adverse reaction 
TEAE 
Treatment-emergent adverse event 
ULN 
Upper limit of normal 
WBC 
White blood cell 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 19 
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1 
INTRODUCTION 
1.1 
Diabetic Gastroparesis  
Gastroparesis is characterized by delayed gastric emptying in the absence of mechanical 
obstruction; symptoms are chronic with episodic symptom exacerbation (Parkman et al, 
2004). Gastroparesis affects women 4 times more than men (Soykan, et al, 1998). Idiopathic 
gastroparesis accounts for most cases, but gastroparesis is frequently associated with diabetes 
(diabetic gastroparesis) (Soykan, et al, 1998; Karamanolis et al, 2007). Several 
cross-sectional studies have found delayed gastric emptying of solids and/or liquids in 30% 
to 50% of patients with Type 1 or Type 2 diabetes (Horowitz et al, 2002). Patients with 
diabetes mellitus commonly experience gastric and intestinal dysfunction (Feldman and 
Schiller, 1983).  
The actual mechanism of diabetic gastroparesis is not well known. Vagal nerve dysfunction 
and/or damage, interstitial cells of Cajal loss, and smooth muscle and enteric neuron 
dysfunction have all been implicated in the pathogenesis of diabetic gastroparesis (Stacher, 
2001; Parkman et al, 2004). In addition, acute hyperglycemia has the potential to slow gastric 
emptying (Camilleri et al, 2013).  
At a molecular level, attention has been devoted to the potential role of altered nitrergic 
signaling in the enteric nervous system. Gastric motility is regulated in large part by neurons 
of the enteric nervous system located in the muscle wall (Wood et al, 1999). These neurons 
are either excitatory (releasing acetylcholine) or inhibitory (releasing nitric oxide [NO] and 
vasoactive intestinal peptide). Nerves throughout the luminal gastrointestinal (GI) tract 
express neuronal nitric oxide synthase (nNOS), which generates NO, a key neurotransmitter 
in the regulation of GI motility (Takahashi, 2003); it is the principal nonadrenergic 
noncholinergic inhibitory neurotransmitter in the GI tract. In diabetic rats, which serve as a 
model for type 1 diabetes, nNOS expression was found to be impaired. This impairment in 
nNOS messenger RNA expression was associated with impaired smooth muscle relaxation in 
response to electrical stimulation of circular muscle fibers obtained from the proximal 
stomach of these rats (Takahashi et al, 1997). It has been demonstrated that female diabetic 
rats had slower gastric emptying than age matched diabetic male rats, female control rats had 
greater nitrergic relaxation of circular antral muscle strips compared to male controls, and 
nitrergic relaxation was impaired in diabetic female rats but not matched diabetic male rats 
(Gangula et al, 2007). 
The core signs and symptoms of gastroparesis by incidence are nausea (92% to 96%), 
vomiting (68% to 88%), postprandial fullness (54% to 77%), early satiety (42% to 60%), and 
upper abdominal pain (36% to 85%) (Soykan et al, 1998; Hoogerwerf et al, 1999; Anaparthy 
et al, 2009). Patients may experience any combination of signs and symptoms with varying 
degrees of severity. Pain is less prevalent in diabetic gastroparesis than idiopathic 
gastroparesis. Patients with diabetic gastroparesis may experience further derangement of 
glucose control because of unpredictable gastric emptying and altered absorption of orally 
administered hypoglycemic drugs, which may, in turn, affect measurement of core signs and 
symptoms. Severe signs and symptoms may cause complications such as malnutrition, 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 20 
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esophagitis, and Mallory-Weiss tears. Gastroparesis adversely affects the lives of patients 
with the disease, resulting in decreased social interaction, poor work functionality, and 
development of anxiety or depression (Soykan et al, 1998; Parkman et al, 2004). 
1.2 
Impaired Gastric Accommodation in Gastroparesis 
Patients with diabetic gastroparesis have also been shown to have gastric hypersensitivity, 
especially in the postprandial state, and impairment of the postprandial accommodation 
response. (Kumar et al, 2008). The stomach functions as 2 separate regions: the fundus acts 
as a reservoir accommodating a meal without a significant increase in intragastric pressure, 
and the distal stomach/antrum triturates gastric contents. Receptive relaxation or 
accommodation is vagally mediated resulting in the release of NO and activation of nitrergic 
myenteric neurons. Nitrergic signaling is responsible for gastric accommodation and pyloric 
relaxation in response to a meal (Ishiguchi et al, 2001). 
Impaired accommodation has been associated with symptoms of early satiety and weight loss 
in patients with idiopathic gastroparesis (Karamanolis et al, 2007). A study of patients with 
diabetic gastroparesis found that 90% of patients had impaired gastric accommodation to a 
nutrient meal (Kumar et al, 2008). In the distal stomach, NO is required for the propulsive 
contractions that triturate gastric contents and control of pyloric closure; lack of NO can lead 
to delayed gastric emptying and impaired gastric accommodation (Gangula et al, 2007). 
Several co-factors are known to be important for nNOS activity, including nicotinamide 
adenine dinucleotide phosphate hydrogen (NADPH), calcium, and tetrahydrobiopterin (BH4) 
(Werner et al, 2003). The homodimeric conformation of all 3 isoforms of nitric oxide 
synthase (NOS) is regulated by BH4 (Werner et al, 2003). In the absence of BH4, uncoupling 
of NO production occurs and leads to super oxide production, resulting in further impaired 
nNOS bioactivity. 
1.3 
Current Treatment of Diabetic Gastroparesis  
Therapies for gastroparesis have been targeted at accelerating gastric emptying or controlling 
symptoms. Available therapies for accelerating gastric emptying are limited in number and 
efficacy. These include metoclopramide (Snape et al, 1982), erythromycin (Arts et al, 2005), 
and domperidone (not available in the United States [US]) (Prakash and Wagstaff, 1998). 
There is also poor correlation between gastric emptying and baseline symptom severity 
(Karamanolis et al, 2007; Talley et al, 2001) and in response to therapeutic intervention. In 
part, as a result of lack of understanding of the underlying pathogenesis that leads to 
alterations in GI motility and sensation, medical therapies have not been targeted at the 
underlying pathophysiology of gastroparesis.  
The first-line medical therapy for patients with diabetic gastroparesis is generally a 
combination of an antiemetic agent in addition to the promotility drug. Unfortunately, many 
patients with diabetic gastroparesis will not experience adequate symptom relief despite 
first-line therapy. For patients with refractory disease, options include combination prokinetic 
therapy, psychotropic medications, pyloric botulinum toxin injection, and gastric electric 
stimulation (Fass, 2010; Camilleri et al, 2013). 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 21 
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1.4 
CNSA-001 (Sepiapterin) 
Sepiapterin is 2-amino-6-[(2S)-2-hydroxypropanoyl]-7,8-dihydro-1H-pteridin-4-one with a 
molecular weight of 237.2 and a molecular formula of C9H11 N5O3. 
The chemical structure of sepiapterin is: 
 
Sepiapterin serves as a substrate for BH4 synthesis via the pterin salvage pathway (Mayer 
and Werner, 1995). Oral administration of sepiapterin was shown to be more potent (>2 fold) 
than oral administration of BH4 in increasing intracellular BH4 in normal mice (Sawabe et 
al, 2002). Translation of this finding to humans has been confirmed in a Phase 1 study, 
PKU-001, conducted by Censa Pharmaceuticals.  
1.5 
Rationale for Study 
BH4 biosynthesis is impaired in chronic diabetes. The mechanism of impairment is not well 
understood but is thought to be a result of hyperglycemia-induced proteasome-mediated 
degradation of GTP-cyclohydrolase, the rate-limiting enzyme in the synthesis pathway for 
BH4 (Xu et al, 2007).  
CNSA-001 is the first viable formulation of sepiapterin, shown to increase intracellular BH4 
(Section 1.4), intended for the treatment of female patients with diabetic gastroparesis. 
CNSA-001 was studied in a single and multiple ascending-dose study in healthy volunteers, 
the Phase 1 study, Study PKU-001. Part A of this study assessed the safety and 
pharmacokinetics of CNSA-001 at 6 dose levels inclusive of an assessment of food effect 
(i.e., 2.5 mg/kg, 7.5 mg/kg, 20 mg/kg, 40 mg/kg, 80 mg/kg, and 10 mg/kg [to assess food 
effect]). Additionally, Kuvan® (sapropterin dihydrochloride), a synthetic BH4 commercially 
available product, was administered at equivalent doses for the first 3 dose levels (2.5 mg/kg, 
7.5 mg/kg, and 20 mg/kg). Dose-dependent correlations between CNSA-001 and plasma 
BH4 concentrations were observed with each successive dose level. Dose proportionality was 
observed between the top 2 dose levels (40 mg/kg and 80 mg/kg) and resultant BH4 
concentrations. Administration with a standard high-fat (approximately 50 percent of total 
caloric content of the meal) and high calorie (approximately 800 to 1000 calories) meal 
resulted in approximately 80% higher plasma BH4 concentrations (area under the 
concentration time curve from 0 to the last measurement [AUC0-last] and maximum 
concentration [Cmax]) than in subjects who had fasted before receipt of CNSA-001. 
Treatment-emergent adverse events (TEAEs) in Part A of Study PKU-001 were reported in 
26 subjects (44.1%, 26/59). The TEAEs for CNSA-001 were generally mild and consistent 
with reported adverse events (AEs) for Kuvan® and placebo. The frequency of TEAEs did 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 22 
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not appear to increase with increasing dose. The TEAEs that were judged to be related to 
study treatment were reported in 17 subjects: 11 subjects (26.2%, 11/42) who received 
CNSA-001, 4 subjects (44.4%, 4/9) who received Kuvan®, and 2 subjects (25.0%, 2/8) who 
received placebo. No TEAEs were severe or serious or led to discontinuation of study drug. 
Headache and dizziness were the most common TEAEs , but these TEAEs occurred at a 
similar frequency as with placebo. 
Part B of Study PKU-001 assessed multiple ascending doses CNSA-001 in healthy 
volunteers. Data indicate CNSA-001 was well tolerated following daily doses of 5, 20, and 
60 mg/kg/day for 7 days and that TEAEs were reported in 14 subjects (58.3%, 14/24). The 
TEAEs in subjects who received CNSA 001 were mild or moderate and consistent with the 
TEAEs in subjects who received placebo: TEAEs were experienced by 10 subjects (55.6%, 
10/18) who received CNSA-001 at doses from 5 mg/kg to 60 mg/kg daily for 7 days and by 
4 subjects (66.7%, 4/6) who received placebo. No TEAEs were severe, serious, or led to 
discontinuation. Of the 10 TEAEs reported in subjects who received CNSA-001, only 4 were 
judged to be related to study drug, and, of the 4 TEAEs reported in subjects who received 
placebo, only 1 was judged to be related to study drug. Somnolence, fatigue, headache, and 
procedural pain (secondary to performance of 2 sequential lumbar punctures 7 days apart) 
were the most common TEAEs reported, and they occurred at a similar frequency when 
compared with placebo with the exception of fatigue and headache, which were each 
reported in 2 subjects who received CNSA-001 (11.1%, 2/18). 
This Phase 2 pilot study will assess CNSA-001 doses of 20 mg/kg/day administered as 
10 mg/kg twice a day (BID) in comparison to placebo administered BID in female patients 
with diabetic gastroparesis. This study will help support the design of future Phase 2/3 
studies in patients with diabetic gastroparesis.  


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 23 
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2 
STUDY OBJECTIVES 
2.1 
Primary Objective 
The primary objective of this study is to assess the impact of CNSA-001 on gastric 
accommodation, as measured by nutrient satiety testing (Section 6.7), in women with 
moderate to severe diabetic gastroparesis. 
2.2 
Secondary Objectives 
The secondary objectives of this study are, in women with moderate to severe diabetic 
gastroparesis: 
• To evaluate the effect of CNSA-001 on improvement of gastroparesis symptoms as 
measured by the change from baseline in the global assessment of symptoms and 
symptom severity (Gastroparesis Cardinal Symptom Index [GCSI]) (Section 6.8, 
Appendix 2) 
• To evaluate the effect of CNSA-001 on patient-reported symptoms as measured by the 
change from baseline in the Patient Assessment of Upper Gastrointestinal Disorders-
Symptom Severity (PAGI-SYM) (Section 6.9, Appendix 2)  
• To evaluate the effect of CNSA-001 on emptying of the stomach as measured by the 
change from baseline in the Gastric Emptying Breath Test (GEBT) (Section 6.10) 
• To assess the safety and tolerability of CNSA-001 20 mg/kg/day 
 


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3 
INVESTIGATIONAL PLAN 
3.1 
Overall Study Design and Plan 
Study GAS-001 is a Phase 2, randomized, double-blind, placebo-controlled pilot study of 
multiple doses of CNSA-001 (sepiapterin) powder for suspension administered orally in 
women with moderate to severe diabetic gastroparesis. This is an outpatient study in which 
up to 20 patients will be enrolled at approximately 6 centers. 
The Schedule of Events is provided in Appendix 1. The study schema is displayed in Figure 
1.  
Screening Period (Day -28 Through Day 1 Predose) 
An informed consent form (ICF) must be signed before any study-related procedures are 
performed. After providing consent, patients will undergo Screening procedures to determine 
study eligibility, as indicated in Appendix 1. Patients who are eligible based on Screening 
evaluations will undergo baseline evaluations before initiation of study drug (CNSA-001 or 
placebo), be randomized, and proceed to the Treatment Period.  
Treatment Period (Day 1 Through Day 14) 
Following the Screening Period and completion of baseline evaluations, all randomized 
patients will take their first dose of study drug (CNSA-001 or placebo) on Day 1 while in the 
clinic. Patients will undergo procedures during the Treatment Period as indicated in 
Appendix 1. 
Study drug may be prematurely discontinued for safety reasons, as described in 
Section 6.14.1. Patients may also withdraw from the study for any reason, as described in 
Section 6.14.2. If a patient discontinues study drug early, the patient should return to the 
study site within 24 hours of withdrawal and complete all of the procedures outlined for the 
End of Treatment (EOT) (Section 7.5, Appendix 1). If a patient withdraws early from the 
study before undergoing EOT evaluations, the patient will be asked to return to the study site 
within 24 hours of withdrawal and complete all of the procedures outlined for the EOT 
(Section 7.5, Appendix 1). If a patient withdraws from the study before undergoing End of 
Study (EOS) evaluations, the patient will be asked to return to the study site within 24 hours 
of withdrawal and complete all of the procedures outlined for the EOS (Section 7.6, 
Appendix 1).  
End of Treatment Period (Day 14 Through Day 15 Evaluations) 
Patients will undergo EOT evaluations on Day 14 and Day 15 as indicated in Appendix 1. 
Preliminary efficacy will be assessed by the changes from Day 1 in the nutrient satiety test 
(Section 6.7) on Day 14. The GCSI (Section 6.8, Appendix 2) and PAGI-SYM (Section 6.9, 
Appendix 2) will also be administered on Day 14 (+1 day), and the GEBT (Section 6.10) will 
be conducted on Day 15. 
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CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 25 
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End of Study Period (Day 15 After Evaluations Through Day 28 [±1 Day] Evaluations) 
Patients will undergo EOS evaluations on Day 28 (±1 day) as indicated in Appendix 1. 
Preliminary efficacy will be assessed by the changes from Day 1 in the nutrient satiety test 
(Section 6.7) on Day 28. The GCSI (Section 6.8, Appendix 2) and PAGI-SYM (Section 6.9, 
Appendix 2) will also be administered on Day 28 ±1, and the GEBT (Section 6.10) will be 
conducted on Day 27 or Day 29. 
Follow-up Period (Day 28 [±1 Day] After Evaluations Through Day 44 [±3 Days]) 
Patients will undergo telephone Follow-up on Day 44 ±3 days as indicated in Appendix 1.  
Figure 1: 
Study Schema  
 
Abbreviations: BID = twice a day.  
 
3.2 
Rationale for Study Design and Control Group 
CNSA-001 (sepiapterin) is a new chemical entity that is an endogenous, naturally occurring 
precursor of BH4 via the pterin salvage pathway. Animal studies and data from a Phase 1 
single and multiple ascending-dose study in healthy volunteers conducted by Censa 
Pharmaceuticals indicate rapid intracellular conversion of sepiapterin to BH4. It is expected 
that oral administration of CNSA-001 to women with diabetic gastroparesis will result in 
increases in both intracellular and circulating BH4 concentrations. In chronic diabetes, BH4 
biosynthesis is impaired (Xu et al, 2007). 
CNSA-001 was studied in two 14-day Good Laboratory Practice (GLP) toxicity studies, as 
described in Section 5.3, and in a single and multiple ascending-dose study in healthy 
volunteers, Study PKU-001, as described in Section 1.5.  
Because all patients will receive the standard of care for diabetic gastroparesis in addition to 
their assigned study drug, the study design of a randomized study of CNSA-001 versus 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 26 
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placebo in female patients with diabetic gastroparesis will not expose patients to the risk of 
no treatment.  
This study has a double-blind design intended to reduce bias. 
3.3 
Study Duration and Dates 
The study duration for each patient will be up to 75 days, extending from Screening (Day -28 
through Day -1) through the final assessments on Day 44 (±3 days).  


CNSA-001 (sepiapterin)         
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4 
STUDY POPULATION SELECTION 
4.1 
Study Population 
Approximately 6 study centers will enroll up to 20 women with moderate to severe diabetic 
gastroparesis this study.  
4.2 
Inclusion Criteria 
Patients are eligible to participate in this study if they meet all the following inclusion 
criteria: 
1. Informed consent
2. Females ≥18 and ≤75 years of age
3. Diagnosis of diabetes mellitus
4.
Documentation of delayed gastric emptying by either
o
gastric emptying scintigraphy (GES) (within 2 years of enrollment), or
o
gastric emptying breath test (GEBT) (within 2 years of enrollment)
If historical documentation is >2 years, either the GES or the GEBT may be conducted at
screening to confirm diagnosis.
5. Symptoms of gastroparesis for at least 6 months with GCSI (Section 6.8, Appendix 2)
score >21 indicating moderate to severe symptoms
6. Gastric accommodation, as measured by nutrient satiety testing, of ≤600 mL
7. Negative upper endoscopy or upper GI series within 3 years of enrollment (no evidence
of mechanical obstruction or peptic ulcer disease)
8. Either postmenopausal for ≥1 year or surgically sterile (having undergone tubal ligation,
hysterectomy, or bilateral oophorectomy) for at least 6 months or, if of childbearing
potential and not abstinent, willing to use a highly effective method of contraception
throughout the study such as 1 of the following:
•
Hormonal contraception (stable dose for 3 months)
•
Intrauterine device/Intrauterine Hormone-releasing System
•
Barrier contraceptive method (diaphragm, cervical cap, contraceptive sponge,
condom)
Patients who are abstinent will not be required to use a contraceptive method unless they 
become sexually active 
9. If on analgesics (including narcotics), promotility agents (including metoclopramide), or
neuromodulators (including tricyclic antidepressants, gabapentin, and pregabalin), doses
are stable for >30 days before randomization and the patient is not expected to require
dose changes during the study through the EOT


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 28 
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10. Have not used tobacco (e.g., cigarettes, e-cigarettes, cigars, smokeless tobacco, nicotine 
replacement) for 2 weeks prior to Day 1 and willingness to abstain from these products 
during the study through the EOT 
4.3 
Exclusion Criteria 
Patients are not eligible to participate in this study if they meet any of the following 
exclusion criteria: 
1. Male gender 
2. Normal gastric emptying  
3. Gastroparesis from postsurgical etiologies 
4. Another active disorder that could, in the opinion of the Investigator, explain symptoms  
5. Weight >100 kg 
6. Alanine aminotransferase > 2× upper limit of normal (ULN) 
7. Pregnant, breastfeeding, or considering pregnancy 
8. Clinically significant cardiac arrhythmia at Screening 
9. QT interval corrected for heart rate (QTc) ≥470 msec using Fridericia’s correction (based 
on triplicate measurements taken at Screening)  
10. Resting heart rate ≤40 or ≥110 bpm or resting blood pressure <90/40 mmHg or >150/90 
mmHg at Screening or prior to the first administration of study drug. 
11. Recent clinically significant GI bleeding 
12. Taking levodopa or domperidone within 30 days before randomization or expected to 
require domperidone during the study through the EOT 
13. Taking erythromycin within 30 days before randomization or expected to require 
erythromycin within 30 days before randomization or expected to require erythromycin 
during the study through the EOT; if a patient is taking erythromycin and is otherwise 
eligible to participate in the study, following signing the ICF, the patient may go through 
an erythromycin washout period of 30 days before randomization 
14. Taking any fundic-relaxing agents including, but not limited to, buspirone, clonidine, 
nitrates, phosphodiesterase inhibitors (i.e., sildenafil citrate [Viagra®]) and 
triptan-containing medications, within 30 days before randomization or expected to 
require any of these agents during the study through the EOT 
15. Taking any systemic antifolates, including, but not limited to, methotrexate, pemetrexed, 
and trimetrexate or expected to require any systemic antifolates during the study through 
the EOT (topical antifolates [e.g., cream, ointment, gel] or eye drops with antifolates are 
allowed) 
16. Pulmonary dysfunction (e.g., chronic obstructive pulmonary disease) 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 29 
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17. Surgery for placement of a gastric stimulator within the past 6 months (patients 
postoperative >6 months with persistent symptoms and delayed gastric emptying are 
eligible) 
18. Gastrointestinal disease (such as irritable bowel syndrome, inflammatory bowel disease, 
chronic gastritis, peptic ulcer disease, small bowel malabsorption) that could affect the 
absorption of study drug or contraindicate undergoing the GEBT (Section 6.10)  
19. History of gastric surgery, including Roux-en-Y gastric bypass surgery or an antrectomy 
with vagotomy, or gastrectomy 
20. History of allergies or adverse reactions to BH4 or related compounds, to any excipients 
in the study drug formulation, or to egg, wheat, or algae (Spirulina)  
21. Inability to tolerate oral medication 
22. Current participation in any other investigational drug study or use of any investigational 
agent, investigational device, or approved therapy for investigational use within 30 days 
or 5 half-lives (whichever is longer) before Screening 
23. Any clinically significant laboratory abnormality; in general, each laboratory value from 
Screening and baseline chemistry and hematology panels should fall within the limits of 
the normal laboratory reference range unless deemed not clinically significant by the 
Investigator 
24. Major surgery within the previous 90 days  
25. The patient, in the opinion of the Investigator, is unwilling or unable to adhere to the 
requirements of the study 
26. History of alcohol or drug abuse within 6 months prior to Screening or current evidence 
of substance dependence as determined by the Investigator 
27. Episodes of ketoacidosis or hypoglycemia that are frequent as defined by the Investigator 
28. History of phenylketonuria (PKU) or hyperphenylalaninemia. 
29. Any other conditions, including diabetic comorbidities, that, in the opinion of the 
Investigator or Sponsor, would interfere with the patient’s ability to participate in the 
study or increase the risk of participation for that patient 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 30 
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5 
STUDY TREATMENTS 
5.1 
Description of Treatments 
5.1.1 
Test Product 
The test product is CNSA-001 (sepiapterin) oral powder for suspension. CNSA-001 contains 
the new chemical entity, sepiapterin. Sepiapterin is 2-amino-6-[(2S)-2-hydroxypropanoyl]-
7,8-dihydro-1H-pteridin-4-one with a molecular weight of 237.2 and a molecular formula of 
C9H11 N5O3. Inactive ingredients in CNSA-001 include microcrystalline cellulose, colloidal 
silicon dioxide, croscarmellose, and ascorbic acid. CNSA-001 will be suspended in Medisca® 
Oral Mix prior to dispensing it to the patient.  
5.1.2 
Placebo Control 
The placebo is a ready-made suspension containing microcrystalline cellulose, colloidal 
silicon dioxide, croscarmellose, ascorbic acid, and colorant (Yellow No. 6) that is suspended 
in Medisca® Oral Mix.  
5.2 
Treatments Administered 
Patients will be randomized in a ratio of 1:1 to the following treatment groups:  
• CNSA-001 20 mg/kg/day (10 mg/kg BID) for 14 days 
• Placebo BID for 14 days 
Dosing of CNSA-001 is based on the patient’s weight. The weight obtained on Day -1 will 
be used to calculate the exact amount (mg) of CNSA-001 active ingredient (sepiapterin) 
required for each patient’s daily dose.  
The placebo is formulated as ready-made suspension. The placebo will be administered in the 
same manner (volume) as CNSA-001. 
Details on preparation of study drug and dosing guidelines will be provided in a pharmacy 
manual for the site and an instruction guide for patients.  
5.3 
Selection and Timing of Dose for Each Patient 
All patients will be randomly assigned in a ratio of 1:1 to receive CNSA-001 20 mg/kg/day 
(10 mg/kg BID) or placebo BID.  
The CNSA-001 dose was selected following completion of two 14-day GLP toxicity studies 
in the rat and marmoset. The no observed adverse effect level from both studies was set at 
1000 mg/kg/day, which represents a human equivalent dose of 161.3 mg/kg/day based on 
allometric scaling. Consequently, the proposed dose of 20 mg/kg/day represents an 8.1-fold 
safety margin. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 31 
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Study drug will be dispensed on Day 1 (Section 6.11) with a dosing diary in which patients 
will record all doses taken and times they were taken (Section 5.8.1). The first dose on Day 1 
will be taken in the clinic after patients undergo the nutrient satiety test (Section 6.7). 
If a patient vomits after taking a dose of study drug, the patient should wait until the next 
scheduled timepoint to take another dose. A missed dose should be taken as soon as possible, 
but >2 doses should not be taken on the same day. 
5.4 
Method of Assigning Patients to Treatment Groups 
Patients who fulfill the eligibility criteria and provide informed consent will be randomized 
in a ratio of 1:1 to the CNSA-001 or placebo group via the randomization scheme generated 
for the study. Patients who are randomized will be considered to be enrolled.  
5.5 
Blinding 
This study has a double-blind design. The Investigator, study personnel, and patients will not 
make any effort to determine which study drug is being received. Unblinded pharmacy (or 
other qualified site) personnel will be utilized in this study to prepare the study drug. 
Patients will be blinded to study drug assignment. Only in an emergency, when knowledge of 
the study drug is essential for the clinical management or welfare of a specific patient, may 
the Investigator unblind a patient’s study drug assignment. Copies of the randomization 
sequence and treatment codes will be kept in the pharmacy at the sites. If emergency 
unblinding is required, the Investigator will have immediate access to individual sealed codes 
containing treatment allocations. However, before any unblinding occurs, the Investigator is 
strongly advised to discuss options with the Sponsor’s Medical Monitor or appropriate 
Sponsor study personnel. As soon as possible and without revealing the patient’s study drug 
assignment (unless important to the safety of patients remaining in the study), the 
Investigator must notify the Sponsor if the blind is broken for any reason and the Investigator 
was unable to contact the Sponsor prior to the unblinding. The Investigator will record in 
source documentation the date and reason for revealing the blinded study drug assignment 
for any patient and the names and roles of personnel unblinded. 
5.6 
Concomitant Therapy 
Patients will be permitted to take:  
• Analgesics, including narcotics, if the patient has been on a stable dose of the 
medication for >30 days before randomization; dose escalation is NOT permitted 
during the study through the EOT 
• Promotility agents, including metoclopramide if the patient has been on a stable dose 
of the medication >30 days before randomization; dose changes are NOT permitted 
during the study through the EOT 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 32 
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• Neuromodulators, including any tricyclic antidepressant, gabapentin, and pregabalin, 
if the patient has been on a stable dose >30 days before randomization; dose changes 
are NOT permitted during the study through the EOT 
• Rescue medications that patients would usually take, including ondansetron 
(Zofran®), promethazine (Phenergan®) or prochlorperazine (Compazine®) for nausea 
and tramadol (Ultram®), if symptoms related to gastroparesis require further 
treatment during the study through the EOT 
All prescription and over-the-counter medications (including herbal medications) that the 
patient took within 30 days before Screening though the EOT should be recorded.  
5.7 
Restrictions 
5.7.1 
Prior Therapy and Concomitant Therapy 
The following are prohibited: 
• Any investigational agent, investigational device, or approved therapy for 
investigational use within 30 days or 5 half-lives (whichever is longer) before 
Screening  
• Domperidone within 30 days before randomization or expected to require 
domperidone during the study through the EOT 
• Dose escalation of analgesic or promotility agents or neuromodulators within 30 days 
before randomization or during the study through the EOT 
• Erythromycin within 30 days before randomization or during the study through the 
EOT; if a patient is taking erythromycin and is otherwise eligible to participate in the 
study, following signing the ICF, the patient may go through an erythromycin 
washout period of 30 days before randomization 
• Systemic antifolates, including, but not limited to, methotrexate, pemetrexed, and 
trimetrexate or expected to require any systemic antifolates during the study through 
the EOT (topical antifolates [e.g., cream, ointment, gel] or eye drops with antifolates 
are allowed) 
• Fundic-relaxing agents, including, but not limited to, buspirone, clonidine, nitrates, 
phosphodiesterase inhibitors (i.e., sildenafil citrate [Viagra®]) and triptan-containing 
medications, within 30 days before randomization or expected to require any of these 
agents during the study through the EOT 
• Medications that can alter GI sensation or accommodation or gastric emptying 
overnight before the nutrient satiety test (Section 6.7) 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 33 
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5.7.2 
Food Intake 
Patients will continue their usual diet without modification throughout the study. Patients are 
required to have been fasting overnight for the following assessments: 
• Clinical laboratory, including glycosylated hemoglobin A1c (HbA1c), tests 
• The nutrient satiety test (Section 6.7), which requires the consumption of Ensure™ 
(Abbott Laboratories, Abbott Park, IL, USA)  
• The GEBT (Section 6.10), which requires consumption of a standardized 230 kCal 
meal, consisting of a standardized carbon-13 (13C)-labeled egg component and 
6 saltine crackers, with 6 ounces of water 
5.7.3 
Total Blood Volume 
The total volume of blood obtained from an individual study patient is expected to be 
approximately 40 mL, for clinical laboratory tests inclusive of the HbA1c test. 
5.7.4 
Patient Activity and Tobacco Restrictions 
Patients will not be confined during the study and will not require any activity restrictions. 
Patients must abstain from tobacco use (e.g., cigarettes, e-cigarettes, cigars, smokeless 
tobacco, nicotine replacement) for 2 weeks before Day 1 and during the study through the 
EOT. 
5.8 
Treatment Compliance 
Patients will be instructed to return all used (empty containers) and unused study drug on 
Day 14 if the patient takes the last dose of study drug on Day 14 while in the clinic or, if the 
patient takes the last dose of study drug on Day 14 after leaving the clinic, on Day 15 or Day 
28 (±1 day). Compliance with the dosing regimen will be assessed by reconciliation of used 
and unused study drug. The quantities dispensed, returned, used, and lost will be recorded on 
the dispensing log provided for the study.  
5.8.1 
Dosing Diary 
Patients will be provided with a dosing diary on Day 1 along with instructions for recording 
all doses of study drug and times they were taken. The dosing diary will be collected on 
Day 14 if the patient takes the last dose of study drug on Day 14 while in the clinic or, if the 
patient takes the last dose of study drug on Day 14 after leaving the clinic, on Day 15 or 
Day 28 (±1 day), and the Investigator (or designee) will transcribe all entries into the 
electronic case report form (eCRF).  


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 34 
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5.9 
Packaging and Labeling 
CNSA-001 Oral Powder for Suspension is packaged in 10 mL amber glass vials with black 
child proof caps. Each glass vial contains 175 mg of sepiapterin.  
Each vial of CNSA-001 Oral Powder for Suspension will contain the product name, strength, 
content, expiry/retest date, and company name. Each vial label will contain the words, 
“Caution: Investigational medicine for clinical trial use only.” 
CNSA-001 PLACEBO suspension is packaged in 500 mL bottles. Each bottle of CNSA-001 
PLACEBO suspension will contain the content and company name as well as “CNSA-001 
PLACEBO” on its label. 
The suspending vehicle, Medisca® Oral Mix, is commercially available and will be provided 
separately. 
5.10 
Storage and Accountability 
All drug product required for completion of this study will be provided by Censa 
Pharmaceuticals. It is the responsibility of the pharmacy staff or study staff to ensure that a 
current record of drug inventory and drug accountability is maintained. Inventory and 
accountability records must be readily available for inspection by the study monitor and are 
open to inspection at any time by applicable regulatory authorities. 
CNSA-001 Oral Powder for Suspension (non-reconstituted) may be stored frozen at -20°C or 
at refrigerated conditions (2 to 8°C). If not administered on the same day of suspending, 
CNSA-001 suspension should be stored at refrigerated conditions (2 to 8°C) until time of 
dosing. Once suspended, CNSA-001 is stable for 14 days.  
CNSA-001 PLACEBO suspension may be stored refrigerated at 2 to 8°C.  
5.11 
Investigational Product Retention at Study Site 
Upon completion of the study and once inventoried by the study site, all used (empty) 
containers of study drug will be destroyed. Any unused containers of study drug may be 
either destroyed or returned to the Sponsor following discussion with the Sponsor. If study 
drug is destroyed, a certificate of destruction will be provided to the Sponsor by the 
appropriate facility performing the destruction. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 35 
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6 
STUDY PROCEDURES 
6.1 
Informed Consent 
Consent forms describing in detail the study drug, study procedures, and risks are given to 
the patient, and written documentation of informed consent is required prior to conducting 
study-related procedures. See Section 10.4 for more information on the informed consent 
process. 
6.2 
Medical History and Demographic Data 
A detailed medical/surgical history will be obtained at Screening. The history will include 
specific information related to any prior or existing medical conditions or surgical procedures 
involving the following systems: dermatologic; head, eyes, ears, nose, and throat (HEENT); 
lymphatic; cardiovascular; respiratory; GI; musculoskeletal; and neurological. The medical 
history will be updated on Day 1 before the start of study drug. 
Demographic data obtained at Screening will include age, gender, and self-reported 
race/ethnicity. 
6.3 
Vital Signs, Weight, and Height 
Vital signs, including blood pressure, pulse, respiratory rate, and temperature, will be 
measured at Screening, Day 1 (predose and 2 hours postdose), and at the EOT and EOS 
visits. Vital signs will be measured prior to collection of laboratory samples and after patients 
have rested for 5 minutes in the supine position. For timepoints other than Day 1, vital signs 
will be taken at any time during the visit after resting and laboratory sample collection.  
Weight will only be collected at Screening as necessary to determine the response to 
Exclusion Criterion #5 (Section 4.3) and on Day -1. Height will only be collected at 
Screening. 
6.4 
Physical Examination 
A complete physical examination will be performed at Screening, on Day 1 before start of 
study drug and at the EOT and EOS visits. The examination will assess general appearance, 
as well as dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, 
musculoskeletal, and neurological parameters.  
6.5 
Clinical Laboratory Tests and Glycosylated Hemoglobin A1c 
Clinical laboratory tests will be performed by qualified local laboratories. Blood and urine 
samples for clinical chemistry, hematology, and urinalysis will be collected at Screening, 
Day 1 (predose), and at the EOT and EOS visits. Patients should fast overnight prior to 
collection of blood samples (minimum of 8 hours before blood sample collection). Blood 
samples for HbA1c will be collected at Screening and at the EOT and EOS visits. Clinically 
significant laboratory abnormalities should be followed to a satisfactory resolution, as 
determined by the Investigator. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 36 
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The following clinical laboratory and other laboratory parameters will be assessed: 
Hematology: 
Hematocrit (HCT) 
Hemoglobin (HGB) 
Platelet count 
Red blood cell (RBC) count 
White blood cell (WBC) count with differential 
(neutrophils, eosinophils, basophils, 
lymphocytes, and monocytes) 
Urinalysis: 
Bilirubin 
Glucose 
Ketones 
Occult blood 
pH 
Protein 
Specific gravity 
Urobilinogen  
Microscopy: 
WBCs 
RBCs 
Epithelial cells 
Pregnancy Testing: a 
Serum human chorionic gonadotropin (HCG) 
at Screening 
Urine HCG Day 1 (predose) and Day 14 (±1 
day) 
Serum Chemistry: 
Albumin (ALB) 
Alkaline phosphatase (AP) 
Alanine aminotransferase (ALT; serum 
glutamic pyruvic transaminase [SGPT]) 
Aspartate aminotransferase (AST; serum 
glutamic oxaloacetic transaminase [SGOT]) 
Blood urea nitrogen (BUN) 
Calcium (Ca) 
Carbon dioxide (CO2) 
Chloride (Cl) 
Creatinine 
Gamma glutamyl transferase (GGT) 
Glucose 
Lactate dehydrogenase (LDH) 
Phosphorus 
Potassium (K) 
Sodium (Na) 
Total bilirubin 
Direct bilirubin 
Total cholesterol 
Total protein 
Uric acid 
Other: 
Glycosylated hemoglobin A1(HbA1c) 
a 
Required for all women who are of childbearing potential. Any positive urine pregnancy test should be 
confirmed by a serum pregnancy test. 
 
6.6 
Electrocardiogram 
At Screening, 12-lead electrocardiograms (ECGs) will be obtained in triplicate, with 
1 minute separating the first and second recordings and 1 minute separating second and third 
recordings. The following ECG parameters will be collected and recorded in the eCRF: RR, 
PR, QRS, QT, and QTc intervals. In addition, the ECG tracing should be reported as normal, 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 37 
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abnormal clinically significant, or abnormal not clinically significant. If abnormalities are 
noted on the ECG, these should be recorded in the eCRF. 
6.7 
Nutrient Satiety Test  
For the nutrient satiety test, patients consume 150 mL of Ensure™ every 5 minutes. At 
5-minute intervals, patients score their fullness using a rating scale that combines verbal 
descriptors on a scale graded 0 to 5 (0: no symptoms, 1: first sensation of fullness [threshold], 
2: mild, 3: moderate, 4: severe and 5: maximum or unbearable fullness). Patients are told to 
stop when a score of 5 is obtained. The actual volume of Ensure™ consumed at this point is 
the maximum tolerated volume. Symptoms are measured 30 minutes after completing the test 
with patients scoring each symptom of bloating, fullness, nausea and pain on a visual 
analogue scale with 100-mm lines and the words “unnoticeable” and “unbearable” as 
anchors. The sum of the four 100-mm visual analogue scales provides an aggregate symptom 
score (Park, 2011). 
The nutrient satiety test will be administered in the clinic at Screening, on Day 1 (predose), 
and on Day 14 and Day 28 after overnight fasts and after any medications that can alter GI 
sensation or accommodation or gastric emptying have been held overnight. A nutrient satiety 
test volume of ≤600 mL at Screening is required for patients to participate in this study. 
6.8 
Gastroparesis Cardinal Symptom Index 
The GCSI (Appendix 2) consisting of a subset of items from the PAGI-SYM instrument 
(Section 6.9, Appendix 2), will be administered in the clinic at Screening and on Day 1 
(predose), Day 14 (+1 day), and Day 28 (±1 day). A GCSI score >21 at Screening, indicating 
moderate to severe symptoms, is required for patients to participate in this study. 
6.9 
Patient Assessment of Upper Gastrointestinal Disorders-Symptom 
Severity 
The PAGI-SYM (Appendix 2) is a 20-item upper GI symptom severity instrument with 
6 subscales: heartburn/regurgitation, fullness/early satiety, nausea/vomiting, bloating, upper 
abdominal pain, and lower abdominal pain. It will be administered in the clinic on Day 1 
(predose) and on Day 14 (+1 day), and Day 28 (±1 day).  
6.10 
Gastric Emptying Breath Test 
The GEBT, which is a nonradioactive noninvasive test, will be administered in the clinic on 
Day -1, Day 15, and Day 27 or Day 29 after the patient has fasted overnight (a minimum of 
8 hours before test administration with the exception of 4 ounces of water up to 1 hour before 
the test). At the clinic, the patient provides baseline (premeal) breath samples and then 
consumes a standardized 230 kCal meal, consisting of a proprietary standardized 13C-labeled 
egg component (which is rehydrated and then microwaved for 1.5 minutes) and 6 saltine 
crackers, accompanied by 6 ounces of water. The meal is to be consumed within 10 minutes. 
Single postmeal breath samples are collected in capped glass tubes at 45, 90, 120, 150, 180, 
and 240 minutes after the meal is consumed and sent to the specified local laboratory for 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 38 
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analysis by Gas Isotope Ratio Mass Spectrometry. By adding 13C to the test meal, the GEBT 
can determine how fast the stomach empties the meal by measuring the rate of carbon-13 
dioxide (13CO2) excretion arising from the digested test meal. The rate of 13CO2 excretion 
found in the patient’s breath is proportional to the patient’s rate of gastric emptying. The 
patient’s 13CO2 excretion rate at each breath collection time is reported using the GEBT 
metric “kPCD.” The “k” is a multiplier of 1000, and “PCD” is an acronym for percent 13C 
dose excreted (as 13CO2). The test should not be administered to patients with a known 
allergy to egg, wheat, or algae (Spirulina) (Cairn Diagnostics™; Sutton et al, 2015; GEBT 
package insert, 2015; United States Food and Drug Administration, 2015).  
6.11 
Dispensing Study Drug  
Study drug will be dispensed on Day 1 along with a dosing diary to record all doses taken 
and times they were taken. A sufficient supply of study drug will be dispensed for dosing 
through Day 14. Details on the preparation of study drug, dosing guidelines, and storage will 
be provided in a pharmacy manual for the site and an instruction guide for patients. 
6.12 
Adverse Events Assessments 
An AE is defined as any untoward medical occurrence associated with the use of an 
intervention in humans, whether or not considered intervention-related. 
The occurrence of an AE or serious adverse event (SAE) (Section 6.12.6) may come to the 
attention of study personnel during study visits and interviews of a study patient presenting 
for medical care, or upon review by a study monitor. All AEs including local and systemic 
reactions not meeting the criteria for SAEs will be captured on the appropriate eCRF. 
Information to be collected includes, but is not limited to, the event description, time of 
onset, clinician’s assessment of severity, relationship to study drug (assessed only by those 
with the training and authority to make a diagnosis), and date of resolution/stabilization of 
the event. Action taken regarding study medication (e.g., drug withdrawn, interrupted) will 
also be collected in the eCRF. All AEs that start during the study must be documented 
appropriately regardless of relationship. All treatment-related AEs or AEs leading to 
discontinuation will be followed to an adequate resolution, as determined by the Investigator. 
Any medical condition that is present at the time that the patient is screened will be 
considered as medical history and not reported as an AE. However, if the patient’s condition 
deteriorates at any time during the study, it will be recorded as an AE. 
Changes in the severity of an AE will be documented to allow an assessment of the duration 
of the event at each level of severity to be performed. The AEs characterized as intermittent 
require documentation of onset and duration of each episode. 
6.12.1 
Reporting Timelines 
The Investigator will record all reportable events with start dates occurring any time after 
informed consent and continue through clinical study completion or, in the case of 
withdrawal, until the outcome is determined. The AEs will be assessed at each visit and/or 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 39 
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through telephone contact with the patient. A neutral question, such as “How have you been 
feeling since your last visit?” may be asked.  
All SAEs should be reported after the patient signs the informed consent and followed until 
resolution, stabilization, or until the Investigator provides sufficient evidence that no further 
information can be obtained. 
All SAEs and pregnancies (in a patient or partner of a male patient) occurring while the 
patient is on the study or within 30 (±3) days after the patient received the last dose of study 
drug must be reported within 24 hours of the knowledge of the event by study personnel 
whether or not considered to be related to study drug. 
Deaths that occur ≥30 (±3) days after the patient’s last study dose must be reported within 
24 hours of knowledge of the event, if deemed related to study drug by the Investigator. 
Although pregnancy is not considered an AE or SAE by regulatory definition, for this study 
pregnancies must be processed following SAE timelines (e.g., within 24 hours of knowledge 
of the pregnancy) for data transmission purposes. In the event that a pregnancy complication 
occurs, or elective termination of a pregnancy is required for medical reasons, then the 
complication will be recorded as an AE or SAE, as appropriate. 
While elective and uncomplicated induced abortion not required for medical reasons does not 
constitute an AE or SAE (even if the patient or patient’s partner is hospitalized to undergo 
abortion), spontaneous abortion is considered a fatal event and must be reported as an AE 
and SAE, as appropriate. 
Any pregnancy and/or suspected pregnancy that occurs during the study in a female patient 
should be reported using Pregnancy Reporting Form within 24 hours of knowledge of the 
event by study personnel. Any pregnancy and/or suspected pregnancy will be followed for 
outcome. 
If the patient has received the investigational drug prior to becoming pregnant, the patient 
will continue the efficacy assessment and Follow-up periods and measures of safety and 
efficacy will be obtained. 
The patient will be followed until the outcome of the pregnancy is determined. It is the 
responsibility of the Investigator to obtain and document pregnancy information on the most 
recent Pregnancy Report Form. Furthermore, any SAE occurring as an outcome of the 
pregnancy must be reported according to the procedures outlined for SAE reporting. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 40 
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6.12.2 
Severity 
The intensity of each AE will be graded as follows: 
Mild: 
Events require minimal or no treatment and do not interfere with the 
patient’s daily activities.  
Moderate: 
Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning.  
Severe: 
Events interrupt a patient’s usual daily activity and may require systemic 
drug therapy or other treatment. Severe events are usually potentially 
life-threatening or incapacitating.  
 
It is important to distinguish between serious and severe AEs. Severity is a measure of 
intensity; however, an AE of severe intensity need not necessarily be considered serious. For 
example, nausea that persists for several hours may be considered severe nausea but may not 
be considered an SAE. Alternatively, a stroke that results in only a limited degree of 
disability may be considered only a mild stroke but would be considered an SAE. 
6.12.3 
Relationship 
The Investigator’s assessment of causality must be provided for all AEs (serious and 
nonserious). An Investigator’s causality assessment is the determination of whether there 
exists a reasonable possibility that the study drug caused or contributed to an AE. For 
purposes of consistency, guidelines for assessing causality are provided below: 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 41 
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Not Related 
The AE is completely independent of study drug administration, and/or 
evidence exists that the event is definitely related to another etiology. There 
must be an alternative, definitive etiology documented by the clinician. 
No relationship between the experience and the administration of study 
drug; related to other etiologies such as concomitant medications or 
patient’s clinical state. 
Unlikely to be 
Related 
A clinical event, including an abnormal laboratory test result, whose 
temporal relationship to drug administration makes a causal relationship 
improbable (e.g., the event did not occur within a reasonable time after 
administration of the trial medication) and in which other drugs or chemicals 
or underlying disease provides plausible explanations (e.g., the patient’s 
clinical condition, other concomitant treatments). 
Possibly 
Related 
There is some evidence to suggest a causal relationship (e.g., the event 
occurred within a reasonable time after administration of the trial 
medication). However, other factors may have contributed to the event 
(e.g., the patient’s clinical condition, other concomitant events). Although 
an AE may rate only as “possibly related” soon after discovery, it can be 
flagged as requiring more information and later be upgraded to “probably 
related” or “definitely related,” as appropriate. 
Probably 
Related 
There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely. The clinical event, including an abnormal laboratory test 
result, occurs within a reasonable time after administration of the drug, is 
unlikely to be attributed to concurrent disease or other drugs or chemicals, 
and follows a clinically reasonable response on withdrawal (dechallenge). 
Rechallenge information is not required to fulfill this definition.  
Definitely 
Related 
There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an 
abnormal laboratory test result, occurs in a plausible time relationship to 
drug administration and cannot be explained by concurrent disease or other 
drugs or chemicals. The response to withdrawal of the drug (dechallenge) 
should be clinically plausible. The event must be pharmacologically or 
phenomenologically definitive, with use of a satisfactory rechallenge 
procedure if necessary.  
 
These criteria, in addition to good clinical judgment, should be used as a guide for 
determining the causal assessment. If the event is believed to be unrelated to study drug 
administration, then an alternative explanation should be provided, if available. 
6.12.4 
Expectedness 
An AE or suspected adverse reaction is considered “unexpected” if it is not listed in the 
Investigators’ Brochure or is not listed at the specificity or severity that has been observed; 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 42 
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or, if an Investigators’ Brochure is not required or available, is not consistent with the risk 
information described in the general investigational plan or elsewhere in the protocol. 
The drug safety medical reviewer will be responsible for determining whether an AE is 
expected or unexpected. An AE will be considered unexpected if the nature, severity, or 
frequency of the event is not consistent with the risk information previously described for the 
study agent (e.g., Investigators’ Brochure). 
6.12.5 
Clinical Laboratory Adverse Events 
Laboratory abnormalities should not be recorded as AEs or SAEs unless they are associated 
with clinical signs or symptoms or require medical intervention, as determined by the 
Investigator. However, each laboratory abnormality (e.g., clinically significant changes 
detected in hematology, serum chemistry panel, urinalysis, urine microscopic, and HbA1c 
evaluations) independent from any underlying medical condition that requires medical or 
surgical intervention, or that leads to study drug interruption or discontinuation, must be 
recorded as an AE, or SAE if applicable. If the laboratory abnormality is part of a clinical 
condition or syndrome, it should be recorded as the syndrome or diagnosis rather than as the 
individual laboratory abnormality. In addition, laboratory abnormalities or other abnormal 
test assessments (e.g., vital signs) performed that are associated with signs or symptoms must 
be recorded as AEs or SAEs if they meet the definition of an AE (or SAE) as described 
below. 
6.12.6 
Serious Adverse Events 
6.12.6.1 
Definition 
An SAE is defined as an AE or suspected adverse reaction occurring at any dose that results 
in any of the following outcomes: death, life-threatening AE, inpatient hospitalization or 
prolongation of existing hospitalization, a persistent or significant disability/incapacity or a 
substantial disruption of the ability to conduct normal life functions, or a congenital 
anomaly/birth defect. 
An AE or suspected adverse reaction is considered ‘‘life-threatening’’ if, in the view of either 
the Investigator or Sponsor, its occurrence places the patient at immediate risk of death. It 
does not include an AE or suspected adverse reaction that, had it occurred in a more severe 
form, might have caused death. 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical judgment, 
they may jeopardize the patient and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. Examples of such medical events include 
allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of 
drug dependency or drug abuse. Medical and scientific judgment should be exercised in 
deciding whether expedited reporting is appropriate in these other situations. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 43 
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6.12.6.2 
Suspected Unexpected Serious Adverse Reaction (SUSAR) 
The Sponsor must submit a safety report for any suspected adverse reaction to study 
treatment that is both serious and unexpected. Before submitting a safety report, the Sponsor 
needs to ensure that the event meets all 3 of the definitions: 
• Suspected adverse reaction 
• Serious 
• Unexpected 
If the AE does not meet all 3 of the definitions, it should not be submitted as a safety report. 
6.12.6.3 
Reporting Serious Adverse Events 
The Investigator will report all SAEs to the designated drug safety team within 24 hours of 
knowledge of the event whether or not considered to be related to study drug using the SAE 
Report Form provided. 
Although not all information required for a complete SAE Report Form may be readily 
available at the time of the event, the Investigator must include sufficient information on the 
SAE Report Form to allow for a complete medical assessment. This should include at a 
minimum the patient number, site number, detailed description of the event, seriousness 
criteria, causality/relationship to study drug, and Investigator signature. 
The designated drug safety team will acknowledge the receipt of the SAE via email to the 
clinical site. After submission of the initial report, the Investigator will provide follow-up 
information to the drug safety team as requested (e.g., concomitant medications, hospital 
discharge summary) to further evaluate the event and assure that all appropriate information 
is received. Once all information is received and the SAE has been deemed appropriate for 
closure, the SAE Report Form must be signed and dated by the Investigator. 
The Investigator is responsible for informing the Institutional Review Board (IRB) of the 
SAE in accordance with institutional policies and procedures including relevant initial and 
follow-up information about the SAE. 
Treatment-related SAEs or events leading to discontinuation of study drug will be followed 
for outcome information until resolution or stabilization. Other supporting documentation of 
the event may be requested by Censa Pharmaceuticals (or designee) and should be provided 
as soon as possible. The Medical Monitor should be contacted when the Investigator 
considers an SAE to be treatment-related. 
6.12.7 
Treatment-Emergent Adverse Events 
Those AEs that start at the time of or after the first dose of study drug are TEAEs. Those AEs 
that worsen at or after the time of first dose of study drug are also considered 
treatment-emergent. All AEs that occur on or after the ICF has been signed, including all 
TEAEs, through Day 29 will be recorded in the eCRF. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 44 
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All SAEs through Day 44 ±3 days [30 ±3 days after the patient received last dose of study 
drug] will be recorded in the eCRF and reported as described in Section 6.12.6.3. 
6.13 
Prior and Concomitant Medication Assessments 
All prescription and over-the-counter medications (including herbal medications) taken by a 
patient starting from the 30-day period before Screening through Day 28 (±1 day) before the 
patient leaves the clinic after completion of all EOS evaluations will be recorded. Any 
concomitant medications added or discontinued during the study will be recorded at each 
visit. 
6.14 
Removal of Patients From the Trial or Study Drug 
6.14.1 
Early Discontinuation From Study Drug Administration 
Premature discontinuation of study drug administration is defined as the discontinuation of 
study drug for an individual patient before the required full course of study drug is 
completed. Reasons for premature discontinuation from study drug administration should be 
recorded on the appropriate page(s) of the eCRF and may include, but are not limited to the 
following: 
• Occurrence of an AE, SAE, or clinically significant laboratory abnormality that, in the 
opinion of the Investigator, warrants the patient’s permanent discontinuation from study 
drug administration 
• In the judgment of the Investigator, the patient experiences a general or specific 
change(s) that renders the patient unsuitable for continued study drug administration 
• There is a need for concomitant medication that makes the patient ineligible for further 
study drug administration 
• Pregnancy 
• Specific reasons related to adverse events that have been observed in pre- and post-
marketing treatment with the same drug class of CNSA-001 (i.e., sapropterin): 
o Hypersensitivity reactions including anaphylaxis  
o Gastritis  
o Abnormal liver function tests in patients with liver impairment  
o Unexplained hyperactivity 
Given the requirement for pregnancy testing in women of childbearing potential at Screening 
and the requirement for highly effective methods of contraception during the study, it is 
unlikely that pregnancies will occur during study conduct. However, study drug will be 
discontinued should suspected or confirmed pregnancy or nursing during the study drug 
administration period occur. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 45 
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Patients who prematurely discontinue study drug due to any of the above reasons will 
complete the EOT assessments within 24 hours of withdrawal.  
6.14.2 
Withdrawal From the Study 
Patients may withdraw from the study for any reason or be withdrawn at the request of the 
Investigator or Sponsor. The reason for a patient’s withdrawal must be recorded on the 
appropriate page(s) of the eCRF. Reasons for withdrawal from the study may include, but are 
not limited to: 
• Withdrawal of consent  
• AEs or SAEs 
• Significant patient noncompliance, defined as refusal or inability to adhere to the protocol 
requirements 
• The Investigator determines that it is in the best interest of the patient to withdraw from 
study participation, due to a reason other than safety 
Each patient who withdraws from the study after receipt of any amount of study drug will be 
asked to undergo EOT assessments. However, patients may withdraw consent to participate 
in this study at any time without penalty. Withdrawn patients who receive any amount of 
study drug, will not be replaced. Withdrawn patients who do not receive any study drug will 
be replaced. 
6.14.3 
Study Stopping Criteria 
The study may be terminated if significant violations of Good Clinical Practice (GCP) that 
compromise the ability to achieve the study objectives or compromise patient safety are 
observed at any time during the study. With regard to safety, the study may be temporarily 
suspended or terminated should the Investigator, Sponsor, or IRB determine that the safety of 
patients is significantly jeopardized. The decision for a temporary or permanent study hold 
will depend on the nature, frequency, and severity of AEs that were observed in all enrolled 
patients to date. For example, the study will be temporarily or permanently halted should 
either of the following occur: 
• The presence of the same system organ class (e,g., gastrointestinal, cardiac, etc.) 
severe AE for which no other alternative etiology can be identified, considered 
related to study drug, in 2 or more patients (Severity defined in Section 6.12.2). 
• The presence of life-threatening AE or AE requiring urgent intervention in 1 or more 
patients. 
• Death related to Adverse Event. 
 
 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 46 
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In a temporary study hold, no additional patients will be enrolled into the study or dosed with 
study drug until the study team members (including the Investigator and the Medical 
Monitor) decide it is safe to proceed with the study. 
  
6.15 
Appropriateness of Measurements 
Safety will be measured by AEs (including SAEs), vital signs, physical examinations, and 
clinical laboratory and HbA1c tests.  
Because treatment with BH4 is hypothesized to restore nNOS function in the control of 
gastric accommodation, the nutrient satiety test (Section 6.7) was chosen for the primary 
endpoint for this study. Gastric accommodation has been measured using ultrasonography 
(Undeland et al, 1998), single-photon emission computed tomography (Bredenoord et al, 
2003), and barostat testing (Coulie et al, 1998; Sarnelli et al, 2001). Barostat studies have 
been shown to be reproducible (Sarnelli et al, 2001) but are invasive and not widely 
available. Satiety testing using a nutrient liquid has been shown to be reproducible (Kindt et 
al, 2008) and correlate with impairment in gastric accommodation but not gastric emptying 
or visceral sensitivity (Tack et al, 2003). 
The GEBT is nonradioactive, noninvasive test of gastric emptying rate that has been 
validated against the reference method of gastric scintigraphy. It has been accepted by the 
United States Food and Drug Administration (FDA) for use in the measurement of the rate of 
gastric emptying of solids and as an aid in the diagnosis of delayed gastric emptying 
(gastroparesis) in adult humans who are symptomatic for gastroparesis. The GEBT can 
determine how fast the stomach empties a standardized meal with a 13C-labeled egg 
component by measuring the ratio of 13CO2 to carbon-12 dioxide (12CO2) collected in breath 
samples at multiple time points after the meal is consumed compared to baseline. The breath 
samples are collected in capped glass tubes and sent to a specified local laboratory for 
analysis. By measuring the change in the ratio of 13CO2 to 12CO2 over time in comparison to 
the premeal value, the rate of 13CO2 excretion can be calculated and the gastric emptying rate 
determined. The GEBT does not require administration by specially trained health care 
professionals or special precautions related to radiation-emitting compounds (Section 6.10).  
The GCSI (Section 6.8, Appendix 2), consisting of a subset of items from the PAGI-SYM 
instrument (Section 6.9, Appendix 2) (described below), is based on reviews of the medical 
literature and results from clinician interviews and patient focus groups. Its reliability and 
validity were examined in 169 gastroparesis patients from 7 clinical centers in the US. 
Patients completed the GCSI, SF-36 Health Survey, and disability day questions at baseline 
and again at 8 weeks. Clinicians independently rated the severity of the patients' symptoms, 
and both clinicians and patients rated the changes in gastroparesis-related symptoms over the 
8weeks. For the GCSI total score, the internal consistency reliability was 0.84, and the test-
re-test reliability was 0.76. Significant relationships were observed between the clinician-
assessed symptom severity and the GCSI total score, and significant associations were found 
between the GCSI scores and SF-36 physical and mental component summary scores and 
restricted activity and bed disability days. Patients with greater symptom severity, as rated by 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 47 
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clinicians, reported greater symptom severity on the GCSI. The GCSI total scores were 
responsive to changes in overall gastroparesis symptoms as assessed by clinicians 
(p = 0.0002) and patients (p = 0.002) (Revicki et al, 2003). 
The PAGI-SYM (Section 6.9, Appendix 2) is a 20-item upper GI symptom severity 
instrument with 6 subscales: heartburn/regurgitation, fullness/early satiety, nausea/vomiting, 
bloating, upper abdominal pain, and lower abdominal pain. To develop the instrument, 
patients with GERD (n = 810), dyspepsia (n = 767), or gastroparesis (n = 169) from the US, 
France, Germany, Italy, the Netherlands, and Poland completed the PAGI-SYM, the SF-36 
Health Survey, a disease-specific health-related quality of life measure (Patient Assessment 
of Upper Gastrointestinal Disorders-Quality of Life [PAGI-QOL]), and disability day 
questions. Two-week reproducibility was evaluated in 277 stable patients. Construct validity 
was evaluated by correlating subscale scores with SF-36, PAGI-QOL and global symptom 
severity scores and disability days. Internal consistency reliability ranged from 0.79 to 0.91, 
and test-retest reliability ranged from 0.60 to 0.82 for the PAGI-SYM subscales. The 
PAGI-SYM subscale scores correlated significantly with SF-36 scores (all p <0.0001), 
PAGI-QOL scores (all p <0.0001), disability days (p <0.0001), and global symptom severity 
(p <0.0001). Mean PAGI-SYM scores varied significantly in groups defined by disability 
days (all p <0.0001), in which greater symptom severity was associated with more disability 
days (Rentz et al, 2004; Revicki et al, 2004). 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 48 
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7 
STUDY ACTIVITIES 
7.1 
Screening Procedures (Day –28 to Day -1) 
The following will be performed/collected during the Screening Period from Day -28 to 
Day -1 after obtaining informed consent with a properly signed ICF (Section 10.4): 
• Obtain demographic data (age, gender, self-reported race/ethnicity) 
• Obtain medical/surgical history, including specific information related to any prior or 
existing medical conditions or surgical procedures involving the dermatologic, HEENT, 
lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and neurological systems 
(Section 6.2) 
• Obtain vital signs (blood pressure, pulse, respiratory rate, and temperature) prior to 
collection of any laboratory samples and after patients have rested for 5 minutes in a 
supine position; obtain the patient’s weight (as necessary to determine the response to 
Exclusion Criterion #5 [Section 4.3] and on Day -1) and height (Section 6.3) 
• Conduct a complete physical examination, including assessments of general appearance, 
dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and 
neurological parameters (Section 6.4) 
• Collect blood samples for clinical chemistry, hematology, and HbA1c after the patient 
has fasted overnight (a minimum of 8 hours before blood sample collection) and a urine 
sample for urinalysis (Section 6.5) 
• Perform a serum pregnancy test for all women who are of childbearing potential  
• Obtain 12-lead ECGs in triplicate, with 1 minute separating the first and second 
recordings and 1 minute separating second and third recordings (Section 6.6) 
• Administer the GCSI (Section 6.8, Appendix 2) 
• Record all prescription and over-the-counter medications (including herbal medications) 
taken within 30 days before the Screening 
• Assess/record AEs from the time of informed consent 
• Administer the nutrient satiety test (Section 6.76.10) after the patient has fasted overnight 
and after any medications that can alter GI sensation or accommodation or gastric 
emptying have been held overnight 
• Confirm patient meets inclusion criteria and no exclusion criteria (Section 4.2 and 
Section 4.3, respectively) 
• Administer the GEBT (Section 6.10) on Day -1 after the patient has fasted overnight (a 
minimum of 8 hours before test administration with the exception of 4 ounces of water up 
to 1 hour before the test) 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 49 
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• Instruct the patient regarding fasting overnight before blood is drawn for the clinical 
laboratory evaluations (Section 6.5) and the nutrient satiety test (Section 6.7) is 
administered on Day 1 predose 
• Instruct the patient regarding not taking any medications that can alter GI sensation or 
accommodation or gastric emptying overnight before the days of the nutrient satiety test 
(Section 6.7)  
• Randomize patient on Day -1 
7.2 
Day 1 Predose 
The following will be performed/collected on Day 1 in the clinic before the patient receives 
study drug: 
• Obtain medical/surgical history since Screening, including specific information related to 
any prior or existing medical conditions or surgical procedures involving the 
dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and 
neurological systems (Section 6.2) 
• Obtain vital signs (blood pressure, pulse, respiratory rate, and temperature) prior to 
collection of any laboratory samples and after patients have rested 5 minutes in a supine 
position (Section 6.3) 
• Conduct a complete physical examination, including assessments of general appearance, 
dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and 
neurological parameters (Section 6.4) 
• Collect blood samples for clinical chemistry, and hematology after the patient has fasted 
overnight (a minimum of 8 hours before blood sample collection) and a urine sample for 
urinalysis (Section 6.5) 
• Perform a urine pregnancy test for all women who are of childbearing potential; confirm 
any positive urine pregnancy test by performing a serum pregnancy test 
• Record all prior prescription and over-the-counter medications (including herbal 
medications) taken since Screening 
• Assess/record AEs since Screening 
• Administer:  
o Nutrient satiety test (Section 6.76.10) 
o GCSI (Section 6.8, Appendix 2) 
o PAGI-SYM (Section 6.9, Appendix 2) 
7.3 
Day 1 After Baseline Evaluations Through Day 13 
7.3.1 
Day 1  
• Administer first dose of study drug in the clinic 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 50 
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• Obtain vital signs (blood pressure, pulse, respiratory rate, and temperature) 2 hours 
postdose after patients have rested 5 minutes in a supine position (Section 6.3) 
• Dispense study drug and instruct the patient on its preparation and administration BID 
starting with the second dose on Day 1 and continuing through Day 14 (Section 5.2 and 
Section 6.11) 
• Dispense dosing diary and instruct the patient on its completion (Section 5.8.1) 
• Instruct the patient not to take any Day 14 doses of study drug before the Day 14 clinic 
visit, and to bring the dosing diary and all study drug supplies to the Day 14 visit 
• Record all medications the patient received since the predose assessment 
• Assess/record AEs since the predose assessment 
• Instruct the patient regarding fasting overnight before blood is drawn for the clinical 
laboratory evaluations, the nutrient satiety test (Section 6.7), and the GEBT 
(Section 6.10) on Day 14 and/or on Day 15  
• Instruct the patient regarding not taking any medications that can alter GI sensation or 
accommodation or gastric emptying overnight before the Day 14 visit (for the nutrient 
satiety test)  
7.4 
Early Termination Procedures 
If a patient discontinues study drug early (Section 6.14.1), the patient should return to the 
study site within 24 hours of withdrawal and complete all of the procedures outlined for the 
EOT (Section 7.5). If a patient withdraws early from the study (Section 6.14.2), the patient 
will be asked to return to the study site within 24 hours of withdrawal and complete all of the 
procedures outlined for the EOT (Section 7.5). All study drug and supplies and the dosing 
diary will be collected.  
7.5 
End of Treatment Visits (Day 14 and Day 15) 
Patients will complete EOT visit(s) at early termination (Section 7.4) or on Day 14 and 
Day 15. During the EOT visits, the following will be completed: 
• Obtain vital signs (blood pressure, pulse, respiratory rate, and temperature), prior to 
collection of any laboratory samples and after patients have rested 5 minutes in a supine 
(Section 6.3) on Day 14 or Day 15 
• Conduct a complete physical examination, including assessments of general appearance, 
dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and 
neurological parameters (Section 6.4) on Day 14 or Day 15 
• Collect blood samples for clinical chemistry, hematology, and HbA1c after the patient 
has fasted overnight (a minimum of 8 hours before blood sample collection) and a urine 
sample for urinalysis (Section 6.5) on Day 14 or Day 15 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 51 
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• Perform a urine pregnancy test for all women who are of childbearing potential; confirm 
any positive urine pregnancy test by performing a serum pregnancy test on Day 14 or 
Day 15 
• Administer:  
o Nutrient satiety test (Section 6.76.10) on Day 14 
o GCSI (Section 6.8, Appendix 2) on Day 14 or Day 15 
o PAGI-SYM (Section 6.9, Appendix 2) on Day 14 or Day 15 
o GEBT (Section 6.10) on Day 15 
• Administer first Day 14 dose of study drug on Day 14; administer the second Day 14 
dose of study drug on Day 14 or instruct patient to take second Day 14 dose of study drug 
on Day 14 after the patient leaves the clinic 
• Record all prescription and over-the-counter medications (including herbal medications) 
taken since the Day 1 visit through Day 15 before the patient leaves the clinic 
• Assess/record AEs since last visit through Day 15 before the patient leaves the clinic 
• Collect study drug, dosing diary, and assess study drug compliance on Day 14 if the 
patient takes the last dose of study drug on Day 14 while in the clinic or, if the patient 
takes the last dose of study drug on Day 14 after leaving the clinic, on Day 15 
• Instruct the patient regarding fasting overnight before blood is drawn for the clinical 
laboratory evaluations on Day 28 (±1 day), the nutrient satiety test (Section 6.7) on 
Day 28, and the GEBT (Section 6.10) on Day 27 or Day 29 
• Instruct the patient regarding not taking any medications that can alter GI sensation or 
accommodation or gastric emptying overnight before the Day 28 visit (for the nutrient 
satiety test) 
7.6 
End of Study (Day 28 ±1 Day) 
Patients will complete the EOS assessments on Days 27 through Day 29. The following EOS 
assessments will be completed: 
• Obtain vital signs (blood pressure, pulse, respiratory rate, and temperature), prior to 
collection of any laboratory samples and after patients have rested 5 minutes in a supine 
position (Section 6.3) on Day 28 (±1 day) 
• Conduct a complete physical examination, including assessments of general appearance, 
dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and 
neurological parameters (Section 6.4) on Day 28 (±1 day) 
• Collect blood samples for clinical chemistry, hematology, and HbA1c after the patient 
has fasted overnight (a minimum of 8 hours before blood sample collection) and a urine 
sample for urinalysis (Section 6.5) on Day 28 (±1 day) 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 52 
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• Perform a urine pregnancy test for all women who are of childbearing potential; confirm 
any positive urine pregnancy test by performing a serum pregnancy test on Day 28 
(±1 day) 
• Administer:  
o Nutrient satiety test (Section 6.76.10) on Day 28 
o GCSI (Section 6.8, Appendix 2) on Day 28 (±1 day) 
o PAGI-SYM (Section 6.9, Appendix 2) on Day 28 (±1 day) 
o GEBT (Section 6.10) on Day 27 or Day 29 
• Collect study drug, dosing diary, and assess study drug compliance on Day 28 (±1 day) 
(if not done on Day 14 or Day 15)  
• Record all prescription and over-the-counter medications (including herbal medications) 
taken since the last visit through Day 28 (±1 day) before the patient leaves the clinic after 
completion of all EOS evaluations  
• Assess/record AEs since last visit through Day 28 (±1 day) before the patient leaves the 
clinic after completion of all EOS evaluations 
7.7 
Telephone Follow-up Day 44 (±3 Days) (30 ±3 Days After Last Dose) 
During telephone Follow-up on Day 44 (±3 days), the following will be completed: 
• Call the patient to see if any SAEs were experienced during the 30 ±3 days after the last 
dose of study drug  
• Record SAEs in the eCRF, if applicable 
• Report SAEs following SAE reporting timelines per Section 6.12.1 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 53 
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8 
QUALITY CONTROL AND ASSURANCE 
Regular monitoring and an independent audit, if conducted, must be performed according to 
International Council on Harmonisation (ICH)-GCP (Section 10.6). 
Quality control procedures will be implemented beginning with the data entry system and 
data quality control checks that will be run on the database will be generated. Any missing 
data or data anomalies will be communicated to the site(s) for clarification/resolution. 
Following written Standard Operating Procedures, the monitors will verify that the clinical 
trial is conducted and data are generated, documented (recorded), and reported in compliance 
with the protocol, GCP, and the applicable regulatory requirements (e.g., GLPs, Good 
Manufacturing Practices). 
The investigational site will provide direct access to all trial-related sites, source 
data/documents (including patient diaries), and reports for the purpose of monitoring and 
auditing by Censa Pharmaceuticals (or designee), and inspection by local and regulatory 
authorities. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 54 
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9 
PLANNED STATISTICAL METHODS 
9.1 
General Considerations 
Descriptive statistics, including numbers and percentages for categorical variables, and 
numbers, means, standard deviations, medians, minimums, and maximums for continuous 
variables will be provided. Exploratory analyses may also be performed. Listings of 
individual patient data will be produced. Additional details can be found in the statistical 
analysis plan. 
9.2 
Determination of Sample Size 
The primary objective of this study is to assess the impact of CNSA-001 on gastric 
accommodation, as measured by nutrient satiety testing (Section 6.7), in women with 
moderate to severe diabetic gastroparesis. A total of 10 patients will be enrolled in each 
treatment group. If it is assumed that the standard deviation for the change from baseline in 
nutrient meal volume ingested is approximately 235 mL (data on file), and using a one-sided 
t-test at the 0.025 significance level, this trial has 80% power to detect a treatment difference 
greater than 288 mL (i.e., an effect size of 1.23) in the CNSA-001group. The study also has 
90% power to detect a treatment difference greater than 330 mL (i.e., an effect size of 1.41) 
in the CNSA-001 group. 
9.3 
Analysis Populations 
Two study populations will be analyzed: 
• Safety population: all patients who were randomized and received any amount of study 
drug (CNSA-001 or placebo) 
• Efficacy population: all patients who were randomized, received any amount of study 
drug (CNSA-001 or placebo), and had available Day 1 predose and Day 14 nutrient 
satiety test (Section 6.7) maximum tolerated volume results 
9.4 
Demographics, Baseline Characteristics, Enrollment, Protocol Deviations, 
and Patient Disposition 
Enrollment, protocol deviations, demographics (age, sex, race/ethnicity), prior and 
concomitant medications, and medical history will be summarized by treatment group using 
descriptive statistics. Discontinuations from study drug and the study will be summarized by 
treatment group as well and the reasons for discontinuation will be listed. 
9.5 
Statistical Analysis of Efficacy Variables 
Efficacy will be assessed in the Efficacy population.  
The primary efficacy measure will be the changes in maximal tolerated volume consumed 
during the nutrient satiety test (Section 6.7) from Day 1 to Day 14 and Day 28. The changes 
from Day 1 to Day 14 and from Day 1 to Day 28 in maximal tolerated volume consumed 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 55 
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during the nutrient satiety test will be compared between treatment groups using a student’s 
t-test.  
Secondary efficacy measures will consist of changes in the following from baseline through 
Day 14 (±1 day) and through Day 28 (±1 day):  
• PAGI-SYM (Section 6.9, Appendix 2) subscale (heartburn/regurgitation, fullness/early 
satiety, nausea/vomiting, bloating, upper abdominal pain, and lower abdominal pain) 
scores 
• Gastric emptying as measured by the GEBT (Section 6.10) 
The primary and secondary measures will be summarized by treatment group at each visit as 
well as changes from baseline using summary statistics (number of patients, mean, standard 
deviation, median, and range) including 95% confidence intervals for changes from baseline. 
Additional analyses may be conducted, and details will be provided in the statistical analysis 
plan (SAP). 
9.6 
Safety Analysis 
Safety will be assessed in the Safety population. The AEs will be coded using the Medical 
Dictionary for Regulatory Activities (MedDRA®). The number and percentage of patients 
with TEAEs will be tabulated by system organ class, preferred term, and treatment group. 
Severity of AEs and SAEs will be summarized similarly. Those AEs leading to premature 
discontinuation from the study drug and the serious TEAEs will be presented in a table or a 
listing. Clinical laboratory and HbA1c test results and vital signs will be summarized at each 
visit as will changes from baseline for each treatment group. A frequency distribution of 
abnormal physical examination results will be provided. Additional details will be provided 
in the SAP. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 56 
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10 
ADMINISTRATIVE CONSIDERATIONS 
10.1 
Investigators and Study Administrative Structure 
Table 1 summarizes the administrative structure for this study. 
Table 1: 
Administrative Structure for GAS-001 Study 
Contract Research Organization 
InClin, Inc.  
2655 Campus Drive, Suite 100 
San Mateo, CA, 94403 
Phone: 
 
 
10.2 
Institutional Review Board Approval 
The Investigator will submit this protocol, any protocol modifications, and the patient 
consent form to be utilized in this study, to the appropriate IRB for review and approval. This 
committee must operate in accordance with the ICH GCP. Documentation of approval of the 
protocol and the informed consent document must be forwarded to Censa Pharmaceuticals 
(or designee) prior to initiation of this study. 
The Investigator is responsible for assuring continuing review and approval of the clinical 
study. The Investigator must also promptly report all changes in the research activity and all 
unanticipated problems involving risk to the patients or others to his/her IRB. The 
Investigator will not make any changes in the protocol without IRB approval except as 
necessary to eliminate apparent immediate hazards to the patients. The Investigator will 
provide progress reports to the IRB as required by the IRB. If the study remains in progress 
for >1 year, the Investigator must obtain annual renewal and re-approval from the IRB. 
Documentation of renewal must be submitted to Censa Pharmaceuticals (or designee). The 
Investigator will provide notice to the IRB of completion of participation in the study. 
10.3 
Ethical Conduct of the Study 
This study will be conducted in compliance with the protocol; GCPs, including ICH 
Technical Requirements for Registration of Pharmaceuticals for Human Use Guidelines; 
applicable regional regulatory requirements (i.e., ICH E6); and in accordance with the ethical 
principles of the Declaration of Helsinki. 
10.4 
Patient Information and Consent 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate 
in the study and continues throughout the individual’s study participation. Discussion in 
understandable terms of the purposes, procedures, risks and possible benefits of participation, 
and rights of study patients will be conducted with patients, and, as appropriate, their legally 
authorized representatives (LARs; henceforth in the discussion of informed consent, study 
patient means “patient and/or LAR”) and family members. The study patients should have 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 57 
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the opportunity to discuss the study with their surrogates or think about it prior to agreeing to 
participate. Study patients will be asked to carefully review the ICF approved by Censa 
Pharmaceuticals (or designee) and the IRB. After any needed discussion and consideration of 
study participation and before undergoing any procedures specifically for the study, the 
patient will sign the ICF. The ICF will be retained in the study patient’s study records, and a 
copy of the ICF will be given to the study patient. 
Patients may decline to participate in the study and withdraw consent at any time or for any 
reason throughout the course of the study without AEs on the quality of their medical care. 
10.5 
Confidentiality 
The Investigator must assure that patients’ anonymity is strictly maintained and that their 
identities are protected from unauthorized parties. This extends to testing of biological 
samples and genetic tests in addition to the clinical information relating to participants. Only 
an identification code (i.e., not names) should be recorded on any form or document 
submitted to Censa Pharmaceuticals, the Contract Research Organization (CRO), or the IRB. 
The Investigator must keep logs on screened and enrolled patients. In addition, the 
Investigator must have a list where the identity of all treated patients can be found. 
The Investigator agrees that all information received from Censa Pharmaceuticals, including, 
but not limited to, the Investigator’s Brochure, this protocol, CRFs, and any other 
information related to the protocol-specified treatment of the study, remain the sole and 
exclusive property of Censa Pharmaceuticals during the conduct of the study and thereafter. 
This information is not to be disclosed to any third party (except employees or agents directly 
involved in the conduct of the study or as required by law) without prior written consent from 
Censa Pharmaceuticals. The Investigator further agrees to take all reasonable precautions to 
prevent the disclosure by any employee or agent of the study center to any third party or 
otherwise into the public domain. 
The study monitor, other authorized representatives of Censa Pharmaceuticals, and 
representatives of the IRB may inspect all documents and records required to be maintained 
by the Investigator, including but not limited to, medical records (office, clinic, and hospital) 
and pharmacy records for the participants in this study. The clinical study site’s research staff 
will permit access to such records. 
The study patient’s contact information will be securely stored at each clinical site for 
internal use during the study. At the end of the study, all records will be kept in a secure 
location for as long a period as dictated by local IRB and Institutional regulations. 
10.6 
Study Monitoring 
A clinical monitor authorized to represent Censa Pharmaceuticals will conduct site visits to 
inspect study data, patient’s medical records, and eCRFs in accordance with ICH guidelines 
GCP, and applicable regulations and guidelines. The clinical monitor will also monitor 
ongoing drug accountability and adherence to protocol procedures. Details of clinical site 
monitoring are specified in a Clinical Monitoring Plan. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 58 
AMENDMENT 3: 21 Feb 2019 
 
CONFIDENTIAL 
Independent audits may be conducted to ensure that monitoring practices are performed 
consistently across all participating sites and that monitors are following the Clinical 
Monitoring Plan. 
The Investigator will allow representatives of the Censa Pharmaceuticals and regulatory 
authorities to inspect facilities and records relevant to this study. 
10.7 
Case Report Forms and Study Records 
The eCRFs will be supplied by Censa Pharmaceuticals or designee for the recording of all 
information and study data as specified by this protocol. Original eCRF data should be 
handled in accordance with instructions from Censa Pharmaceuticals or designee. All eCRFs 
must be completed by the clinical study site’s research staff authorized to do so by the 
Investigator. The Investigator is responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported. 
Data reported in the eCRF derived from source documents should be consistent with the 
source documents. Source documents are defined as records of documentation related to 
original observations and activities of a clinical investigation. Source documents may 
include, but are not limited to, study progress notes, study- or patient-specific email 
correspondence, computer printouts, laboratory data, and recorded data from automated 
instruments. All source documents produced in this study will be maintained by the 
Investigator and made available for inspections by Censa Pharmaceuticals or designee and by 
regulatory authorities. The original ICF for each participating patient shall be filed with 
records kept by the Investigator, and copies shall be given to the patient. 
Once all data queries and issues have been resolved for each patient the Investigator will 
electronically sign each patient’s eCRF. This signature will indicate that the data have been 
thoroughly inspected and will thereby certify the contents of the eCRF. 
Clinical data will be entered into a 21 Code of Federal Regulations (CFR) Part 11-compliant 
electronic data capture system. The data system includes password protection and internal 
quality checks, such as automatic range checks, to identify data that appear inconsistent, 
incomplete, or inaccurate. Clinical data will be entered by the clinical study site’s research 
staff directly from the source documents. 
10.8 
Protocol Violations/Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol requirements. The 
noncompliance may be either on the part of the patient, the Investigator, or the study site 
staff. Because of deviations, corrective actions are to be developed by the site and 
implemented promptly. This is consistent with the following sections in ICH E6: 
• 4.5 Compliance with Protocol, Sections 4.5.1, 4.5.2, and 4.5.3 
• 5.1 Quality Assurance and Quality Control, Section 5.1.1 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 59 
AMENDMENT 3: 21 Feb 2019 
 
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• 5.20 Noncompliance, Sections 5.20.1, and 5.20.2. 
10.9 
Access to Source Documentation 
The Investigator agrees by his/her participation that the results of this study may be used for 
submission for national or international registration. If required, national or international 
authorities will be provided with the name of the Investigator and his or her address, full 
disclosure of his or her qualifications, any potential conflicts of interests, payments, and 
extent of involvement. 
During site visits, the clinical monitor will review original patient records, drug 
accountability records, and additional documents as needed. During the course of the study, 
Censa Pharmaceutical’s (or designee’s) Quality Assurance personnel may conduct an on-site 
audit visit. The Investigator will provide direct access to and allow verification and copying 
of all trial-related documents (e.g., source data) for trial-related monitoring, audits, IRB 
reviews, and regulatory inspections. 
10.10 
Data Generation and Analysis 
Some or all of the obligations of implementing or conducting this study may be transferred 
from Censa Pharmaceuticals to the CRO. 
A case report, comprised of individual eCRFs, will be completed for every patient who signs 
an ICF and is enrolled into the study. 
All original source documentation (laboratory results, treatment records, audit query 
responses, etc.) will be retained by the Investigator or institution unless specified otherwise 
by the protocol. The results as they become available will be entered on the appropriate 
eCRFs. Legible reproductions of the original laboratory reports for selected tests or variables 
will be submitted to Censa Pharmaceuticals or CRO as requested. 
The eCRFs will be reviewed by a clinical monitor who will evaluate the completeness and 
accuracy of the data. Queries will be generated for omissions, corrections, and clarifications. 
Data may also be reviewed in-house by a clinical auditor and data management or other 
personnel. 
Data analyses will be performed after database lock, when all queries have been resolved. 
10.11 
Retention of Data 
Study documents should be retained for a minimum of 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region or until at least 2 years have elapsed since the 
formal discontinuation of clinical development of the investigational product. These 
documents should be retained for a longer period, however, if required by local regulations. 
No records will be destroyed without the written consent of Censa Pharmaceuticals, if 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 60 
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CONFIDENTIAL 
applicable. It is the responsibility of Censa Pharmaceuticals to inform the Investigator when 
these documents no longer need to be retained. 
10.12 
Financial Disclosure 
Each Investigator must submit to Censa Pharmaceuticals (or designee) financial disclosure 
information according to national law and/or local regulations. 
10.13 
Publication and Disclosure Policy 
The data generated in this clinical study are the exclusive property of Censa Pharmaceuticals 
and are confidential. Authorship on any publication of the results from this study will be 
based on contributions to study design, patient enrollment, data analysis, interpretation of 
results, and drafting and editing of any publication in accordance with published authorship 
ethical guidelines for publication of research studies. Independent analysis and/or publication 
of these data by the Investigator(s) or any member of their staff is not permitted without the 
prior, written consent of Censa Pharmaceuticals. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 61 
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11 
REFERENCE LIST 
Anaparthy R, Pehlivanov N, Grady J, et al. Gastroparesis and gastroparesis-like syndrome: 
response to therapy and its predictors. Dig Dis Sci. 2009 May;54(5):1003-10. 
Arts J, Caenepeel P, Verbeke K, et al. Influence of erythromycin on gastric emptying and 
meal related symptoms in functional dyspepsia with delayed gastric emptying. Gut. 2005 
Apr;54(4):455-60. 
Bredenoord AJ, Chial HJ, Camilleri M et al. Gastric accommodation and emptying in 
evaluation of patients with upper gastrointestinal symptoms. Clin Gastroenterol Hepatol. 
2003 Jul;1(4):264-72 
Cairn Diagnostics™. Interpreting Cairn Gastric Emptying Breath Test results. Available 
from https://cairndiagnostics.com/wp-
content/uploads/2016/08/interpretation_of_cairn_gebt_test_results_101915.pdf. Accessed 
2018 Aug 15. 
Camilleri M, Parkman HP, Shafi MA, et al. Clinical Guideline: Management of 
Gastroparesis. Clinical Guideline: Management of Gastroparesis. The American journal of 
gastroenterology. 2013;108(1):18-38. 
Coulie B, Tack J, Peeters T, et al. Involvement of two different pathways in the motor effects 
of erythromycin on the gastric antrum in humans. Gut. 1998 Sep;43(3):395-400. 
Fass R. Treatment Options for Diabetic Gastroparesis. Gastroenterology and Hepatology 
Volume 6, Issue 6, Supplement 9 June 2010. 
Feldman M, Schiller LR. Disorders of gastrointestinal motility associated with diabetes 
mellitus. Ann Intern Med. 1983 Mar;98(3):378-84. 
Gangula PR, Maner WL, Micci MA, et al. Diabetes induces sex-dependent changes in 
neuronal nitric oxide synthase dimerization and function in the rat gastric antrum. Am J 
Physiol Gastrointest Liver Physiol. 2007 Mar;292(3):G725-33. 
Gastric Emptying Breath Test (GEBT) [package insert]. Brentwood TN: ADVANCED 
BREATH DIAGNOSTICS LLC; 2015 Apr. 
Hoogerwerf WA, Pasricha PJ, Kalloo AN, et al. Pain: the overlooked symptom in 
gastroparesis. Am J Gastroenterol. 1999 Apr;94(4):1029-33. 
Horowitz M, O'Donovan D, Jones KL, et al. Gastric emptying in diabetes: clinical 
significance and treatment. Diabet Med. 2002 Mar;19(3):177-94. 
Ishiguchi T, Nakajima M, Sone H, et al. Gastric distension-induced pyloric relaxation: 
central nervous system regulation and effects of acute hyperglycaemia in the rat. J Physiol. 
2001 Jun 15;533(Pt 3):801-13. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 62 
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CONFIDENTIAL 
Karamanolis G, Caenepeel P, Arts J, et al. Determinants of symptom pattern in idiopathic 
severely delayed gastric emptying: gastric emptying rate or proximal stomach dysfunction? 
Gut. 2007 Jan;56(1):29-36. 
Khoury V, Dubois, D. GCSI Gastroparesis Cardinal Symptom Index information booklet. 
2nd ed. Lyon, France: Mapi Research Trust; 2015. p 30. 
Kindt S, Coulie B, Wajs E, Janssens J, Tack J. Reproducibility and symptomatic predictors 
of a slow nutrient drinking test in health and in functional dyspepsia. Neurogastroenterol 
Motil. 2008 Apr;20(4):320-9. 
Kumar A, Attaluri A, Hashmi S, et al. Visceral hypersensitivity and impaired 
accommodation in refractory diabetic gastroparesis. Neurogastroenterol Motil. 2008 
Jun;20(6):635-42. 
Mayer B, Werner ER. In search of a function for tetrahydrobiopterin in the biosynthesis of 
nitric oxide. Naunyn Schmiedebergs Arch Pharmacol. 1995;351(5):453-463. 
Park MI. How to Interpret Nutrition Drink Test. Journal of Neurogastroenterology and 
Motility. 2011;17(1):88-90. 
Parkman HP, Hasler WL, Fisher RS, et al, American Gastroenterological Association 
technical review on the diagnosis and treatment of gastroparesis. Gastroenterology. 2004 
Nov;127(5):1592-622.   
Prakash A, Wagstaff AJ. Domperidone. A review of its use in diabetic gastropathy. Drugs. 
1998 Sep;56(3):429-45. 
Rentz AM, Kahrilas P, Stanghellini V, et al. Development and psychometric evaluation of 
the Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM) in 
patients with upper gastrointestinal disorders. Qual Life Res. 2004 Dec;13(10):1737-49. 
Revicki DA, Rentz AM, Dubois D, et al. Development and validation of a patient-assessed 
gastroparesis symptom severity measure: the Gastroparesis Cardinal Symptom Index. 
Aliment Pharmacol Ther. 2003 Jul 1;18(1):141-50.  
Revicki DA, Rentz AM, Tack J, et al. Responsiveness and interpretation of a symptom 
severity index specific to upper gastrointestinal disorders. Clin Gastroenterol Hepatol. 2004 
Sep;2(9):769-77. 
Sarnelli G, Vos R, Cuomo R, et al. Reproducibility of gastric barostat studies in healthy 
controls and in dyspeptic patients. Am J Gastroenterol. 2001 Apr;96(4):1047-53. 
Sawabe K, Yamamoto K, Kamata T, et al. (2002) Sepiapterin Administration Raises Tissue 
BH4 Levels More Efficiently Than BH4 Supplement in Normal Mice. In: Milstien S, et al. 
(eds) Chemistry and Biology of Pteridines and Folates. Springer Science+Business Media 
New York. 


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 63 
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CONFIDENTIAL 
Snape WJ, Jr., Battle WM, Schwartz SS, et al. Metoclopramide to treat gastroparesis due to 
diabetes mellitus: a double-blind, controlled trial. Ann Intern Med. 1982 Apr;96(4):444-6. 
Soykan I, Sivri B, Sarosiek I, et al. Demography, clinical characteristics, psychological and 
abuse profiles, treatment, and long-term follow-up of patients with gastroparesis. Dig Dis 
Sci. 1998 Nov;43(11):2398-404. 
Stacher G. Diabetes mellitus and the stomach. Diabetologia. 2001 Sep;44(9):1080-93. 
Sutton KL, Sims CD, Honeywell MS. et al. Gastric Emptying Breath Test. 2015 Dec 14. 
Available from https://www.uspharmacist.com/article/diagnostic-spotlight-gastric-emptying-
breath-test. Accessed 2018 Aug 15. 
Tack J, Caenepeel P, Piessevaux H, et al. Assessment of meal induced gastric 
accommodation by a satiety drinking test in health and in severe functional dyspepsia. Gut. 
2003 Sep;52(9):1271-7. 
Takahashi T. Pathophysiological significance of neuronal nitric oxide synthase in the 
gastrointestinal tract. J Gastroenterol. 2003;38(5):421-30. 
Takahashi T, Nakamura K, Itoh H, et al. Impaired expression of nitric oxide synthase in the 
gastric myenteric plexus of spontaneously diabetic rats. Gastroenterology. 1997 
Nov;113(5):1535-44. 
Talley NJ, Verlinden M, Jones M. Can symptoms discriminate among those with delayed or 
normal gastric emptying in dysmotility-like dyspepsia? The American journal of 
gastroenterology. 2001 May;96(5):1422-8. 
Undeland KA, Hausken T, Gilja OH, et al. Gastric meal accommodation studied by 
ultrasound in diabetes. Relation to vagal tone. Scand J Gastroenterol. 1998 Mar;33(3):236-
41. 
United States Food and Drug Administration. Gastroparesis: Clinical Evaluation of Drugs for 
Treatment Guidance for Industry. 2015 Jul. Available from 
https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/
ucm455645.pdf. Accessed 2018 Jun 4. 
Werner ER, Gorren AC, Heller R, et al. Tetrahydrobiopterin and nitric oxide: mechanistic 
and pharmacological aspects. Exp Biol Med (Maywood). 2003 Dec;228(11):1291-302. 
Wood JD, Alpers DH, Andrews PL. Fundamentals of neurogastroenterology. Gut. 1999 
Sep;45 Suppl 2:II6-II16. 
Xu J, Wu Y, Song P, et al. Proteasome-dependent degradation of guanosine 5'-triphosphate 
cyclohydrolase I causes tetrahydrobiopterin deficiency in diabetes mellitus. Circulation. 2007 
Aug 21;116(8):944-53 


CNSA-001 (sepiapterin) 
 
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Clinical Trial Protocol: GAS-001 
 
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CONFIDENTIAL 
APPENDIX 1 
SCHEDULE OF EVENTS 
Evaluation 
Screening Period 
Treatment Period 
Follow-up Period 
EOT 
EOS 
Telephone 
Follow-up 
-28 to -1 
Day 1 
(Predose) 
Day 1 
Through 
Day 13 
Day 14a 
Day 14a Day 15 
Day 28 (±1 
Day)  
Day 44 (±3 
Days) 
Informed consent 
X 
 
 
 
 
 
 
 
Confirm inclusion/exclusion criteria eligibility 
X 
 
 
 
 
 
 
 
Randomization 
Xb 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical historyc 
X 
X 
 
 
 
 
 
 
Vital signs, weight, and heightd 
X 
X 
X 
 
X 
X 
 
Physical examinatione 
X 
X 
 
 
X 
X 
 
Clinical laboratory testsf 
X 
X 
 
 
X 
X 
 
HbA1cg 
X 
 
 
 
X 
X 
 
Serum/urine pregnancy testh 
X 
X 
 
 
X 
X 
 
ECGi 
X 
 
 
 
 
 
 
 
Prior/concomitant medicationsj 
X 
X 
X 
X 
X 
 
X 
 
AEsk 
X 
X 
X 
X 
X 
 
X 
Xl 
Nutrient satiety testm 
Xn 
X 
 
 
X 
 
X 
 
GCSIo 
Xp 
X 
 
 
X 
X 
 
PAGI-SYMq 
 
X 
 
 
X 
X 
 
GEBTr 
Xw 
 
 
 
 
X 
X 
 
GES 
Xw 
 
 
 
 
 
 
 
Dispense study drug 
 
 
X 
 
 
 
 
 
Dispense dosing diary 
 
 
Xs 
 
 
 
 
 
Study drug dosingt 
 
 
Xu 
X 
 
 
 
 
Collect study drug, dosing diary, assess 
compliance 
 
 
 
 
Xv 
Xv 
Xv 
 
a Study Day 14 is included both in the Treatment Period and EOT. 


CNSA-001 (sepiapterin) 
 
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Clinical Trial Protocol: GAS-001 
 
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b Randomize patient on Day -1. 
c Includes specific information related to any prior or existing medical conditions or surgical procedures involving the following systems: dermatologic, HEENT, lymphatic, 
cardiovascular, respiratory, GI, musculoskeletal, and neurological.  
d Includes blood pressure, pulse, respiratory rate, and temperature. Obtain vital signs before collection of any laboratory samples and after patients have rested for 5 minutes in a 
supine position. Obtain vital signs both predose and 2 hours postdose on Day 1; for all other timepoints, obtain at any time during the indicated visits. Obtain height only at 
Screening. Obtain weight at Screening to determine response to Exclusion Criterion #5 (Section 4.3) and on Day -1 (Section 6.3). 
e Conduct a complete physical examination of general appearance, dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and neurological 
parameters.  
f Includes clinical chemistry panel (ALB, AP, ALT, AST, BUN, Ca, CO2, Cl, creatinine, GGT, glucose, LDH, phosphorus, K, Na, total bilirubin, direct bilirubin, total cholesterol, 
total protein, uric acid); hematology panel (HCT, HGB, platelet count, RBC count, WBC count, and WBC differential); and urinalysis (bilirubin, glucose, ketones, occult blood, 
pH, protein, specific gravity, urobilinogen and microscopic examination of WBC, RBC, and epithelial cells). Patients will fast overnight before blood sample collections. 
g Patients will fast overnight before blood sample collections. 
h Serum and urine pregnancy tests required for all women of childbearing potential; serum testing is to occur during the Screening Period, and urine testing is to occur before 
dosing on Day 1 and at an EOT visit on Day 28 (±1 day). Any positive urine pregnancy test should be confirmed by a serum pregnancy test. 
i Obtain 12-lead ECG recordings in triplicate with 1 minute separating the first and second and second and third recordings. 
j Record all treatments and over-the-counter medications (including herbal medications) received from 30 days prior to Screening (to determine responses to Inclusion Criterion 
#9 [Section 4.2] and Exclusion Criteria #11 through #14 and #21 [Section 4.3] concerning medications) and through Day 28 ±1 day before the patient leaves the clinic after 
completion of all EOS evaluations. 
k Collect AEs from the time of informed consent through Day 28 ±1 day before the patient leaves the clinic after completion of all EOS evaluations and SAEs from the time of 
informed consent through telephone Follow-up. 
l Telephone Follow-up is to assess SAEs only. 
m Administer the nutrient satiety test (Section 6.7) at Screening, on Day 1 (predose), and on Day 14 and Day 28 after overnight fasts and after any medications that can alter GI 
sensation or accommodation or gastric emptying have been held overnight. 
n Administer the nutrient satiety test at Screening to determine the response to Inclusion Criterion #6 (Section 4.2) 
o Administer the GCSI (Section 6.8, Appendix 2) at Screening, on Day 1 (predose), on Day 14 (+1 day) and on Day 28 (±1 day). 
p Administer the GCSI (Section 6.8, Appendix 2) to determine response to Inclusion Criterion #5 (Section 4.2). 
q Administer the PAGI-SYM (Section 6.9, Appendix 2) in the clinic on Day 1 (predose), on Day 14 (+1 day), and on Day 28 (±1 day). 
r Administer the GEBT on Day -1, on Day 15, and on Day 27 or Day 29. For the GEBT (Section 6.10), patients will fast overnight before the GEBT (a minimum of 8 hours 
before test administration with the exception of 4 ounces of water up to 1 hour before the test). Collect a premeal breath sample and then provide a standardized 230 kCal meal, 
consisting of a proprietary standardized 13C-labeled egg component (which is rehydrated and then microwaved for 1.5 minutes) and 6 saltine crackers, accompanied by 6 ounces 
of water. Encourage the patient to consume the meal within 10 minutes. Collect single postmeal breath samples in capped glass tubes at 45, 90, 120, 150, 180, and 240 minutes 
after the meal is consumed and send the samples to the specified local laboratory for analysis. 
s Dispense a dosing diary with instructions to record times all doses of study drug are taken. 
t If a patient vomits after taking a dose of study drug, the patient should wait until the next scheduled timepoint to take another dose. A missed dose should be taken as soon as 
possible, but >2 doses should not be taken on the same day. 
u Patients will take their first doses of study drug (CNSA-001 or placebo) on Day 1 while in the clinic. 
v Collect study drug, dosing diary, assess compliance on Day 14 if the patient takes the last dose of study drug on Day 14 while in the clinic or, if the patient takes the last dose of 
study drug on Day 14 after leaving the clinic, on Day 15 or Day 28 (±1 day). 
w GES or GEBT may be performed at Screening is historical confirmation of gastric emptying is >2 years prior to enrollment into the study. 
 


CNSA-001 (sepiapterin) 
 
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Clinical Trial Protocol: GAS-001 
 
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AMENDMENT 3: 21 Feb 2019 
 
CONFIDENTIAL 
Abbreviations: AE = adverse event; ALB = albumin; ALT = alanine aminotransferase (serum glutamic pyruvic transaminase [SGPT]); AP = alkaline phosphatase; AST = aspartate 
aminotransferase (serum glutamic oxaloacetic transaminase [SGOT]); BUN = blood urea nitrogen; 13C = carbon-13; Ca = calcium; CO2 = carbon dioxide; Cl = chloride; 
ECG = electrocardiogram; EOS = End of Study; EOT = End of Treatment; GCSI = Gastroparesis Cardinal Symptom Index; GES = Gastric Emptying Scintigraphy; 
GEBT = Gastric Emptying Breath Test; GI = gastrointestinal; GGT = gamma glutamyl transferase; HCT = hematocrit; HGB = hemoglobin; HEENT = head, eyes, ears, nose, and 
throat; HbA1c = glycosylated hemoglobin A1c; K = potassium; LDH = lactate dehydrogenase; Na = sodium; PAGI-SYM = Patient Assessment of Upper Gastrointestinal 
Disorders-Symptom Severity; RBC = red blood cell; SAE = serious adverse event; WBC = white blood cell.


CNSA-001 (sepiapterin)                                                                                                       Censa Pharmaceuticals 
Clinical Trial Protocol: GAS-001                                                                                                                 Page 67 
AMENDMENT 3: 21 Feb 2019 
 
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APPENDIX 2 
GCSI AND PAGI-SYM ASSESSMENT INSTRUMENTS  
Gastroparesis Cardinal Symptom Index Questionnaire (English Version):  
  
Khoury V, Dubois, D. GCSI Gastroparesis Cardinal Symptom Index information booklet. 
2nd ed. Lyon, France: Mapi Research Trust; 2015. p 30. 
 











SAP_001.pdf: 


Censa Pharmaceuticals, Inc.
Protocol GAS-001
Statistical Analysis Plan, Version 0.1
July 29, 2019
CONFIDENTIAL
Page 2 of 22
STATISTICAL ANALYSIS PLAN APPROVAL
Protocol: GAS-001
Version 0.1
__________________
          
          
_______________________
Date
InClin, Inc.
_______________________
          
          
_______________________
Date
Censa Pharmaceuticals, Inc.
DocuSign Envelope ID: B1700D80-04C7-4184-A509-0C33CD494D9C

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Censa Pharmaceuticals, Inc.
Protocol GAS-001
Statistical Analysis Plan, Version 0.1
July 29, 2019
CONFIDENTIAL
Page 3 of 22
Table of Contents
LIST OF ABBREVIATIONS .......................................................................................................5 
1.0 
INTRODUCTION..............................................................................................................6 
2.0 
STUDY DESIGN................................................................................................................6 
3.0 
STUDY OBJECTIVES AND ENDPOINTS....................................................................7 
3.1 
Study Objectives ......................................................................................................7 
3.2 
Study Endpoints.......................................................................................................8 
3.3 
Study Duration and Dates........................................................................................8 
4.0 
ANALYSIS POPULATIONS ...........................................................................................9 
4.1 
Randomized Population...........................................................................................9 
4.2 
Safety Population.....................................................................................................9 
5.0 
STATISTICAL METHODS AND GENERAL CONSIDERATIONS .........................9 
5.1 
Sample Size..............................................................................................................9 
5.2 
Randomization and Masking ...................................................................................9 
5.3 
Interim Analysis.....................................................................................................10 
5.4 
Standard Calculations ............................................................................................10 
5.5 
General Comments on the Statistical Analyses .....................................................10 
5.6 
Handling of Missing Data......................................................................................11 
6.0 
STATISTICAL ANALYSES ..........................................................................................11 
6.1 
Subject Disposition................................................................................................11 
6.2 
Protocol Deviations................................................................................................12 
6.3 
Demographics and Baseline Characteristics..........................................................12 
6.4 
Medical History .....................................................................................................12 
6.5 
Prior and Concomitant Medications ......................................................................12 
6.6 
Extent of Exposure and Study Drug Treatment Compliance.................................13 
6.7 
Nutrient Satiety Test ..............................................................................................13 
6.8 
Gastroparesis Cardinal Symptom Index ................................................................14 
6.9 
Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity.......14 
6.10 
Gastric Emptying Breath Test (GEBT)..................................................................15 
6.11 
Adverse Events ......................................................................................................16 
6.12 
Clinical Laboratory Evaluations ............................................................................17 
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Censa Pharmaceuticals, Inc.
Protocol GAS-001
Statistical Analysis Plan, Version 0.1
July 29, 2019
CONFIDENTIAL
Page 4 of 22
6.13 
ECG Parameters.....................................................................................................18 
6.14 
Vital Signs..............................................................................................................18 
6.15 
Physical Examinations...........................................................................................18 
7.0 
CHANGES FROM PROTOCOL PLANNED ANALYSES........................................19 
APPENDIX A: 
SCHEDULE OF ASSESSMENTS AND PROCEDURES ..............20 
APPENDIX B: 
LABORATORY TESTING PARAMETERS ..................................22 
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CNSA-001 (sepiapterin)
Censa Pharmaceuticals
Clinical Trial Protocol: GAS-001
Page 5
AMENDMENT 3: 21 Feb 2019
July 29, 2019
CONFIDENTIAL
Page 5 of 22
LIST OF ABBREVIATIONS
AE
Adverse Event
ANCOVA
Analysis of Covariance
ATC
Anatomical/Therapeutic/Chemical
AUC
Area Under the Curve
BLQ
Below the Limit of Quantification
BMI
Body Mass Index
bpm 
Beats per minute 
CI
Confidence Interval
CFB
Change from Baseline
CSR
Clinical Study Report
CV
Coefficient of Variation
ECG
Electrocardiogram
eCRF
Electronic Case Report Form
EOS
End of study
EOT
End of treatment
GCSI
Gastroparesis Cardinal Symptom Index
GEBT
Gastric Emptying Breath Test
GM
Geometric Mean
ICH
International Council for Harmonisation 
ICF
Informed Consent Form
kg
Kilograms
kg/m2
Kilograms per meter squared
LSM
Least Squares Mean
MedDRA
Medical Dictionary For Regulatory Activities
PAGI-SYM
Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity
PRO
Patient reported outcomes
PT
Preferred term
QTcF 
QT with Fredericia’s correction
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SD
Standard deviation
SOC
System organ class
TEAE
Treatment-Emergent Adverse Event
WHO
World Health Organization
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CNSA-001 (sepiapterin)
Censa Pharmaceuticals
Clinical Trial Protocol: GAS-001
Page 6
AMENDMENT 3: 21 Feb 2019
July 29, 2019
CONFIDENTIAL
Page 6 of 22
1.0
INTRODUCTION
This Statistical Analysis Plan (SAP) provides the framework for the summarization and 
analysis of the clinical data from the study, “A Phase 2, Randomized, Double-Blind, 
Placebo-Controlled Pilot Study of CNSA-001 in Women With Moderate to Severe Diabetic
Gastroparesis.”  Changes made to the SAP after it has been signed but prior to the unblinding 
of the study following database lock will be documented in a SAP amendment and/or the 
clinical study report (CSR). 
2.0
STUDY DESIGN
Study GAS-001 is a Phase 2, randomized, double-blind, placebo-controlled pilot study of 
CNSA-001 (sepiapterin) powder for suspension administered 10 mg/kg twice a day orally in 
women with moderate to severe diabetic gastroparesis. This is an outpatient study in which 
up to 20 subjects will be enrolled at multiple centers. The study is comprised of five phases:
Screening Period (Day -28 Through Day 1 Predose)
An informed consent form (ICF) must be signed before any study-related procedures are 
performed. After providing consent, subjects will undergo Screening procedures to determine 
study eligibility, as indicated in the schedule of events (Appendix A). Subjects who are 
eligible based on Screening evaluations will undergo baseline evaluations before initiation of 
study drug (CNSA-001 or placebo), be randomized, and proceed to the Treatment Period. 
Treatment Period (Day 1 Through Day 14)
Following the Screening Period and completion of baseline evaluations, all randomized 
subjects will take their first dose of study drug (CNSA-001 or placebo) on Day 1 while in the 
clinic. Subjects will undergo procedures during the Treatment Period as indicated in 
Appendix A.
Study drug may be prematurely discontinued for safety reasons. Subjects may also withdraw
from the study for any reason. If a patient discontinues study drug early, the patient should 
return to the study site within 24 hours of withdrawal and complete all of the procedures 
outlined for the End of Treatment (EOT) (Appendix A). If a patient withdraws early from the 
study before undergoing EOT evaluations, the patient will be asked to return to the study site 
within 24 hours of withdrawal and complete all of the procedures outlined for the EOT 
(Appendix A). If a patient withdraws from the study before undergoing End of Study (EOS) 
evaluations, the patient will be asked to return to the study site within 24 hours of withdrawal 
and complete all of the procedures outlined for the EOS (Appendix A).
End of Treatment Period (Day 14 Through Day 15 Evaluations)
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Subjects will undergo EOT evaluations on Day 14 and Day 15 as indicated in Appendix A.
Preliminary efficacy will be assessed by the changes from baseline (Day 1) in the nutrient 
satiety on Day 14. The GCSI and the PAGI-SYM will also be administered on Day 14
(+1 day), and the GEBT will be conducted on Day 15.
End of Study Period (Day 15 After Evaluations Through Day 28 [±1 Day] Evaluations)
Subjects will undergo EOS evaluations on Day 28 (±1 day) as indicated in Appendix A.
Preliminary efficacy will be assessed by the changes from Day 1 in the nutrient satiety test on
Day 28. The GCSI and PAGI-SYM will also be administered on Day 28 ±1, and the GEBT
will be conducted on Day 27 or Day 29.
Follow-up Period (Day 28 [±1 Day] After Evaluations Through Day 44 [±3 Days])
Subjects will undergo telephone Follow-up on Day 44 ±3 days as indicated in Appendix A.
3.0
STUDY OBJECTIVES AND ENDPOINTS
3.1
Study Objectives
Primary objectives:
The primary objective of this study is to assess the impact of CNSA-001 on gastric 
accommodation, as measured by nutrient satiety testing, in women with moderate to severe 
diabetic gastroparesis.
Secondary objectives:
The secondary objectives of this study are, in women with moderate to severe diabetic 
gastroparesis:
x
To evaluate the effect of CNSA-001 on improvement of gastroparesis symptoms 
measured by the change from baseline in the global assessment of symptoms and 
symptom severity (Gastroparesis Cardinal Symptom Index [GCSI]).
x
To evaluate the effect of CNSA-001 on patient-reported outcomes (PROs) as 
measured by the change from baseline in the Patient Assessment of Upper 
Gastrointestinal Disorders-Symptom Severity (PAGI-SYM) 
x
To evaluate the effect of CNSA-001 on emptying of the stomach, as measured by the 
change from baseline in the Gastric Emptying Breath Test (GEBT)
x
To assess the safety and tolerability of CNSA-001 20 mg/kg/day
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3.2
Study Endpoints
Primary Efficacy Endpoint:
x
Changes in maximal tolerated volume consumed during the nutrient satiety test from Day 
1 to Day 14 and Day 1 to Day 28.
Secondary Efficacy Endpoints include
x
Observed maximal tolerated volume consumed during the nutrient satiety test
x
Observed and changes from baseline through Day 14 (±1 day) and through Day 28 (±1 
day) in the PAGI-SYM subscale (heartburn/regurgitation, fullness/early satiety, 
nausea/vomiting, bloating, upper abdominal pain, and lower abdominal pain) scores
x
Observed and changes from baseline through Day 14 (±1 day) and through Day 28 (±1 
day) in the gastroparesis symptoms measured by global assessment of symptoms and 
symptom severity (Gastroparesis Cardinal Symptom Index [GCSI])
x
Observed and changes from baseline through Day 14 (±1 day) and through Day 28 (±1 
day) in the patient-reported outcomes (PROs) as measured by the quality of life 
questionnaire Patient Assessment of Upper Gastrointestinal Disorders-Symptom 
Severity (PAGI-SYM)
x
Observed and changes from baseline through Day 14 (±1 day) and through Day 28 (±1 
day) in Gastric emptying, as measured by the Gastric Emptying Breath Test (GEBT)
The safety endpoints will be as follows: 
x
Observed and changes in hematology, chemistry, HbA1c, and urinalysis 
x
Observed and changes in vital signs 
x
Observed ECGs 
x
Observed and changes in Physical examination 
x
Severity and number of AEs and SAEs 
3.3
Study Duration and Dates
The study duration for each patient will be up to 75 days, extending from Screening (Day -28 
through Day -1) through the final assessments on Day 44 (±3 days). Duration of treatment 
will be 14 days.
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4.0
ANALYSIS POPULATIONS
4.1
Randomized Population
The Randomized Population will include all randomized subjects.  Subjects in the 
randomized population will be summarized based on the randomized study drug.
4.2
Safety Population
The Safety Population will consist of all subjects who received any amount of study drug 
(CNSA-001 or placebo).
visit.
5.0
STATISTICAL METHODS AND GENERAL CONSIDERATIONS
5.1
Sample Size 
The primary objective of this study is to assess the impact of CNSA-001 on gastric 
accommodation, as measured by nutrient satiety testing, in women with moderate to severe 
diabetic gastroparesis. A total of 10 subjects will be enrolled in each treatment group. If it is 
assumed that the standard deviation for the change from baseline in nutrient meal volume 
ingested is approximately 235 mL (data on file) and using a one-sided t-test at the 0.025 
significance level, this trial has 80% power to detect a treatment difference greater than 288
mL (i.e., an effect size of 1.23) in the CNSA-001group. The study also has 90% power to 
detect a treatment difference greater than 330 mL (i.e., an effect size of 1.41) in the 
CNSA-001 group.
5.2
Randomization and Masking
Subjects who fulfill the eligibility criteria and provide informed consent will be randomized 
in a ratio of 1:1 to the CNSA-001 or placebo group via the randomization scheme generated 
for the study. Subjects who are randomized will be considered enrolled. 
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As this is a double-blind study, blinding of the drug contents from the subjects, Investigator, 
and other study personnel at each site is necessary. The subject will be assigned with an 
identification number at Day 1 which will remain with the subject throughout the study. 
5.3
Interim Analysis
No interim analyses are planned for this study.
5.4
Standard Calculations
Variables requiring calculation will be derived using the following formulas:
x
Baseline - A baseline value, unless specified otherwise, is the last non-missing value 
recorded prior to the first dose of study drug. If an assessment has both a date and time 
that exactly match the date and time of first dose of study drug, the assessment will be 
counted as baseline.
x
Change from Baseline - Change from baseline will be calculated for each subject at the 
specified time point as the value at the specified time point minus the baseline value.
x
Study day – For a given date, study day is calculated as days since the date of first dose 
of study drug within the dosing cohort:
ż
Study day = date – first dose date   ZKHUH GDWH  ILUVW dose date
ż
Study day = date – first dose date, where date < first dose date
x
Days – Durations, expressed in days, between one date (date1) and another later date 
(date2) are calculated using the following formula: duration in days = (date2 - date1 + 1).
x
Body Mass Index (BMI) - BMI (kg/m2) = weight (kg) / [[height (cm)/100]2]
x
Age will be computed from the informed consent date and birth date.
x
Unless otherwise stated, when summation is based on the Safety Population, N = Number 
of subjects in the Safety population, n = Number of subjects in the specific category. 
Percentages are calculated as 100 x (n/N).
5.5
General Comments on the Statistical Analyses
x
In general, the summary tables will be presented by treatment and Visit, as appropriate.
x
Continuous variables will be summarized using number (n), mean, standard deviation 
(SD), median, minimum, and maximum. 
x
Frequency counts and percentages will be reported for all categorical data. 
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x
All listings will be sorted by subject number and study day in ascending order. All 
relevant data captured on the electronic case report forms (eCRFs), including specific 
descriptions of ‘other’ and comments fields will be included on the listings. 
x
If a laboratory result is reported relative to a lower/upper range of detection for an assay,
for example, “<10”, the numeric portion of the result (10) will be used for statistical 
analyses and the full result, including any symbols, will be provided in the subject
listings.
x
Version 9.4 (or higher) of the SAS statistical software package will be used to provide all 
summaries, listings, figures and statistical analyses.
x
The analyses described in this plan are considered a priori, in that they have been defined 
prior to unblinding of the study following database lock. Any analyses performed 
subsequent to unblinding will be considered post-hoc and exploratory. Post-hoc analyses 
will be labeled as such on the output and identified in the CSR.
5.6
Handling of Missing Data
Missing data are handled as follows:
x
Missing values for individual data points will remain as missing. Missing values will not 
be imputed and only observed values will be used in data analyses and presentations. 
x
Where individual data points are missing, categorical data will be summarized based on 
reduced denominators (i.e., only subjects with available data will be included in the 
denominators).
x
All AEs with partial or missing dates and times will be considered treatment emergent 
unless a partial start date and/or time indicates the AE began prior to the start of study 
medication or a stop date indicates the AE ended prior to the start of study medication.
x
All medications with partial or missing dates and times recorded on the concomitant 
medication eCRF will be considered concomitant unless a partial stop date and time 
clearly indicates it was stopped before the first dose of study treatment.
6.0
STATISTICAL ANALYSES
6.1
Subject Disposition
Subject disposition information will be summarized for all subjects by treatment using the
Randomized Population. Summaries will include: the number of subjects in each population,
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the number of subjects completing the study and the primary reason for premature 
discontinuation of study drug and the study.
A listing of all subjects who prematurely discontinued from study drug or study will be 
presented, and the primary reason for discontinuation provided.
6.2
Protocol Deviations
In accordance with International Council for Harmonisation (ICH) E3, Sponsor-defined 
eligibility violations and important post-randomization protocol deviations will be identified 
and listed.
6.3
Demographics and Baseline Characteristics
Demographic data and baseline characteristics will be presented for the Safety Population. A
summary table will present the subject demographics (e.g., gender, age, ethnicity, race and 
diabetes mellitus type) and baseline characteristics of height (cm), weight (kg) and BMI 
(kg/m2), collected prior to the administration of study drug.
A demographic listing will also be provided.
6.4
Medical History
Medical and surgical history collected at screening will be coded using Medical Dictionary 
for Regulatory Activities (MedDRA), version 21.0. Medical and surgical history will be 
summarized by system organ class (SOC) and preferred term (PT) for the Safety Population.
Subjects who report 2 or more medical and surgical history items that are coded to the same 
SOC and/or PT will be counted only once by the unique coded term in the summary.
A listing of disease-specific medical and surgical history will be provided.
6.5
Prior and Concomitant Medications
Verbatim terms on case report forms will be mapped to Anatomical/Therapeutic/Chemical 
(ATC) class and generic drug name using the World Health Organization (WHO) drug 
dictionary, enhanced March 2018.
Prior medications are those medications started prior to the start of study drug. Concomitant 
medications are those medications taken after the start of study drug. As such, medications
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started before first dose of study drug and continued after the first dose of study drug are also 
considered concomitant medications.
Prior medications and concomitant medications will be summarized WHO ATC level 1 term, 
ATC level 3 term and generic drug name with the number and percentage of subjects. At 
each level of subject summarization, a subject is counted once if he/she reported one or more 
medications at that level. Each summary will be ordered alphabetically by each level of ATC 
class and generic drug name within each level of ATC class. The summaries of prior and 
concomitant medications will be provided for the Safety Population.
Prior and concomitant medications will also be listed. 
6.6
Extent of Exposure and Study Drug Treatment Compliance
Compliance for each subject will be determined by the number of doses received, divided by 
the number of expected dosing relative to the subject’s time on treatment. Descriptive 
statistics for the level of compliance (n, mean, SD, median, minimum, and maximum) with 
the number and percentage of subjects belonging to compliance categories (  
and <12 DQG 20%) will be provided by treatment group for the Safety Population.
Extent of exposure to study drug will be evaluated by summarizing each subject’s total time 
of exposure in days.
A listing of the study drug administration dosing diary will be provided. 
6.7
Nutrient Satiety Test 
For the nutrient satiety test, subjects consume 150 mL of Ensure™ every 5 minutes. At 
5-minute intervals, subjects score their fullness using a rating scale that combines verbal 
descriptors on a scale graded 0 to 5 (0: no symptoms, 1: first sensation of fullness [threshold], 
2: mild, 3: moderate, 4: severe and 5: maximum or unbearable fullness). Subjects are told to 
stop when a score of 5 is obtained. The actual volume of Ensure™ consumed at this point is 
the maximum tolerated volume. Symptoms are measured 30 minutes after completing the test 
with subjects scoring each symptom of bloating, fullness, nausea and pain on a visual 
analogue scale with 100-mm lines and the words “unnoticeable” and “unbearable” as 
anchors. 
Results from the visual analogue scale will be evaluated as percentages where the 
percentages will be calculated as the (VAS score)/(Scale length) *100.  
The sum of the four percentages provides an aggregate symptom
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score.
The nutrient satiety test will be administered in the clinic at Screening, on Day 1 (pre-dose), 
and on Day 14 and Day 28.
Using the Safety Population, the changes from baseline (Day 1) to Day 14 in maximal 
tolerated volume consumed during the nutrient satiety test will be compared between 
treatment groups using analysis of covariance (ANCOVA) with baseline tolerated volume as 
a covariate and treatment group as a factor. Other covariates such as site will be considered
for inclusion. A similar analysis will be performed for the change from baseline to Day 28.
Summary statistics for the values at each visit and changes from baseline will be presented
for the maximal tolerated volume, the aggregate symptom score, and the scores for each 
symptom (bloating, fullness, nausea, and pain).
All nutrient satiety scores will be listed.  
6.8
Gastroparesis Cardinal Symptom Index
The GCSI consists of 9 items which are a subset of items from the PAGI-SYM instrument.
The GCSI consists of 4 subscales: nausea/vomiting (Questions 1 to 3), Post-prandial 
fullness/early satiety (Questions 4 to 7) and bloating (Questions 8 and 9).
Each question is rated on a 5-point Likert scale (0 = None, 1 = Very Mild, 2 = Mild, 3 = 
Moderate, 4 = Severe and 5 = Very Severe). To obtain a patient-specific score on each 
subscale the scores on each question within the subscale will be summed for each subject and 
divided by the number of questions in the subscale. A GCSI total score will be similarly 
derived. The GCSI will be administered in the clinic on Day 1 (predose) and on Day 14
(+1 day), and Day 28 (±1 day). Using the Safety Population, summary statistics will be 
provided for each subscale and each time point. The change from baseline will be 
summarized for each of the subscales using summary statistics.
Using the Safety Population and for each subscale, the changes from baseline to Day 14 will 
be evaluated between treatment groups using ANCOVA with baseline as a covariate. Other 
covariates such as site will be considered for inclusion.  A similar analysis will be performed 
for the change from baseline to Day 28. All GCSI subscale scores and total scores will be 
listed.  
6.9
Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity
The PAGI-SYM is a 20-item upper GI symptom severity instrument with 6 subscales: 
nausea/vomiting (Questions 1 to 3), Post-prandial fullness/early satiety (Questions 4 to 7), 
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bloating (Questions 8 and 9), upper abdominal pain (Questions 10 and 11) and lower 
abdominal pain (Questions 12 and 13), heartburn/regurgitation (Questions 14 to 20).
Each question is rated on a 5-point Likert scale (0 = None, 1 = Very Mild, 2 = Mild, 3 = 
Moderate, 4 = Severe and 5 = Very Severe). To obtain a patient-specific score on each 
subscale and the Total PAGI-SYM, the scores on each question within the subscale will be 
summed for each subject and divided by the number of questions in the subscale. The PAGI-
SYM will be administered in the clinic on Day 1 (pre-dose) and on Day 14 (+1 day), and 
Day 28 (±1 day). Using the Safety Population, summary statistics will be provided for each 
subscale, Total PAGI-SYM and each time point. The change from baseline will be 
summarized using summary statistics.
Using the Safety Population and for each subscale and Total PAGI-SYM, the changes from 
baseline to Day 14 will be evaluated between treatment groups using ANCOVA with 
baseline as a covariate. Other covariates such as site will be considered for inclusion.  A 
similar analysis will be performed for the change from baseline to Day 28 (±1 day).
All PAGI-SYM scores will be listed.  
6.10
Gastric Emptying Breath Test (GEBT)
The GEBT is a nonradioactive non-invasive test, conducted over a four-hour evaluation 
period and is designed to show how rapidly the stomach empties solids by measuring carbon 
dioxide in a subject’s breath.
The Cairn Gastric Emptying Breath Test (GEBT) measures the rate of CO2 excretion after 
consumption of a C-enriched test meal. The subject’s CO2 excretion rate at any measurement 
time “t” is calculated and reported using the GEBT metric “kPCD.” The acronym kPCD
stands for “1000 X Percent Carbon-13 Dose (PCD) excreted per minute.” A kPCD value is
calculated at each measurement time and the calculations incorporate the subject’s gender, 
age, height and weight.
The GEBT will be administered in the clinic on Day -1, Day 15, and Day 27 or Day 29 after 
the subject has fasted overnight (a minimum of 8 hours before test administration with the 
exception of 4 ounces of water up to 1 hour before the test). At the clinic, the subject 
provides baseline (premeal) breath samples and then consumes a standardized 230 kCal 
meal, Single post-meal breath samples are collected in capped glass tubes at 45, 90, 120, 150, 
180, and 240 minutes after the meal is consumed. The GEBT kPCD value (13CO2 excretion 
rate) is proportional to the rate of gastric emptying. Increasing GEBT values represent 
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increasing rates of gastric emptying. Some subjects may have a GEBT in Screening as 
evidence of delayed gastric emptying.
Using the Safety Population, summary statistics of the GEBT kPCD values at each breath 
sample time will be provided along with the time matched change from baseline. In addition 
to individual plots, mean (SD) plots will also be provided. For each visit and timepoint the 
number and percentage of subjects with delayed gastric emptying will be determined. 
All GEBT values will be listed. 
GEBT area under the curve (AUC), maximum GEBT, time of maximum GEBT, and time to 
first normal gastric emptying will be derived, summarized and listed using the Safety 
Population.  The GEBT AUC will be calculated for each visit using a linear up, linear down 
trapezoidal method. Maximum GEBT will be the maximum value within the 240 minute 
profile and will also be calculated for each visit.  Change from baseline for each parameter 
will also be calculated, summarized and listed. For the parameters to be calculated, the 
subject must have a complete 240-minute profile.
Using the GEBT Parameter Population and for the parameters AUC and the maximum, the 
changes from baseline to Day 14 will be compared between treatment groups using 
ANCOVA with baseline GEBT as a covariate. Other covariates such as site will be 
considered for inclusion. The difference in least squares means and the associated 95% 
confidence interval will be provided A similar analysis will be performed for the change 
from baseline to Day 28 (±1 day).
6.11
Adverse Events
Adverse events will be coded to system organ class (SOC) and preferred term (PT) using 
MedDRA, version 21.0. The coding process will be described in the Data Management Plan.
Summaries will be provided for AEs, with the number and percentage of subjects reporting 
each type of event presented. If a subject reports the same preferred term more than once, it 
is counted only once within that category. Similarly, if a subject has AEs of two or more 
preferred terms under the same SOC, then that subject only counts once for that SOC. 
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Furthermore, for a given summary, the preferred term will only be counted once at its worst 
severity and strongest relationship to study drug.
Pre-treatment adverse events are defined as adverse events that have an onset on or after the 
date the informed consent was signed but prior to the time of the first dose of study drug.
Treatment-emergent adverse events (TEAEs) are defined as AEs that started or worsened 
after the first dose of study drug.
The following summaries for TEAEs will be provided:
x
An overall summary table of TEAEs summarizing the number and percent of subjects, in 
the following categories: any AE, any TEAE, TEAEs by highest severity, TEAEs by 
relationship to study drug, serious TEAE, TEAEs leading to premature discontinuation of 
study drug, TEAEs leading to premature discontinuation from the study, and TEAEs with 
a fatal outcome.
x
Incidence of TEAEs by MedDRA SOC and PT.
x
Incidence of TEAEs by MedDRA SOC, PT, and worst severity.
x
Incidence of TEAEs by MedDRA SOC, PT, and strongest relationship to study drug.
x
Incidence of serious TEAEs (SAEs) by MedDRA SOC and PT.
x
Incidence of TEAEs (SAEs) Leading to Study Discontinuation by MedDRA SOC and 
PT. 
x
Listing of all AEs (with treatment-emergent events flagged)
x
Listing of subjects with SAEs.
Listing of all AEs for subjects who prematurely discontinued study drug due to an AE or 
discontinued from study due to an AE.
6.12
Clinical Laboratory Evaluations
Descriptive statistics for chemistry, hematology and (quantitative) urinalysis parameter 
values, as specified in Appendix B, and the change from baseline will be summarized for the 
Safety Population at each scheduled time points:
x
End of Treatment visit (if there is early termination) or Day 14/Day 15 if subjects stay 
enrolled in the study.
x
End of Study (Day 28 ±1 Day).
HbA1c values will be summarized similarly.
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Change from baseline will be calculated for each subject at the specified visit as the value at 
the specified visit minus the baseline value. 
Additionally, shifts from baseline at each post-baseline visit will be presented for 
hematology, chemistry, and HbA1c values based on the lab reference ranges for high, normal
and low. Shifts are summarized by visit and maximum and minimum post baseline values.
A listing of hematology, chemistry, urinalysis, and HbA1c labs measurements will be 
provided. Baseline pregnancy test results (serum and urine) will also be listed.
6.13
ECG Parameters
ECGs will be recorded in triplicate at the Screening Visit, where each reading will be taken 1
minute apart. The mean of available triplicate values will be calculated and reported.
ECG parameters of RR interval, PR interval, QRS interval, QT interval, and QTcF interval
will be summarized using descriptive statistics.
A listing of electrocardiogram data will also be provided and will include the tracing results 
of normal, abnormal and clinically significant status for these measurements.
6.14
Vital Signs
Systolic and diastolic blood pressures (mmHg), pulse rate (bpm), respiratory rate 
(breaths/minute), and temperature (oC), will be summarized using descriptive statistics at all 
scheduled time points:
x
Screening
x
Baseline
x
Day 1 two hours post-dose
x
Day 14 (or Day 15)
x
End of Study (Day 28 ±1 Day).
Descriptive statistics and changes from baseline to each post baseline time point will also be 
provided.
Vital signs results will also be presented in by-subject listings.
6.15
Physical Examinations
The number and percentage of subjects with normal, abnormal (not clinically significant) 
and abnormal (clinically significant) observations in physical examinations will be 
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summarized for the Safety Population separately for each body system at Baseline and each 
scheduled post-baseine visit.
Body systems to be included are: General appearance, Dermatologic, HEENT, Lymphatic, 
Cardiovascular, Respiratory, Gastrointestinal, Musculoskeletal, Neurological, and Other.
Physical examination results will also be presented in by-subject listings.
7.0
CHANGES FROM PROTOCOL PLANNED ANALYSES
x
Participants are referred to as ‘Subjects’ instead of ‘Patients’
x
The Randomized Population was added.
x
The definition of Safety Population removed the requirement of randomization.
x
The Efficacy Population is removed and the Safety Population will be used for all 
efficacy analyses.
x
The 95% confidence intervals are provided on the least squares treatment differences
of the change from baseline instead of the change from baseline within a treatment 
group.
x
VAS scores will be transformed into a percentage prior to analysis.
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CNSA-001 (sepiapterin)
Censa Pharmaceuticals
Clinical Trial Protocol: GAS-001
Page 20
AMENDMENT 3: 21 Feb 2019
July 29, 2019
CONFIDENTIAL
Page 20 of 22
Appendix A: Schedule of Assessments and Procedures 
Evaluation
Screening Period
Treatment Period
Follow-up Period
EOT
EOS
Telephone Follow-
up
-28 to -1
Day 1
(Predose)
Day 1
Through 
Day 13
Day 14a
Day 1
4a
Day 
15
Day 28 (±1 
Day) 
Day 44 (±3 Days)
Informed consent
X
Confirm inclusion/exclusion 
criteria eligibility
X
Randomization
Xb
Demographics
X
Medical historyc
X
X
Vital signs, weight, and heightd
X
X
X
X
X
Physical examinatione
X
X
X
X
Clinical laboratory testsf
X
X
X
X
HbA1cg
X
X
X
Serum/urine pregnancy testh
X
X
X
X
ECGi
X
Prior/concomitant medicationsj
X
X
X
X
X
X
AEsk
X
X
X
X
X
X
Xl
Nutrient satiety testm
Xn
X
X
X
GCSIo
Xp
X
X
X
PAGI-SYMq
X
X
X
GEBTr
Xw
X
X
GES
Xw
Dispense study drug
X
Dispense dosing diary
Xs
Study drug dosingt
Xu
X
Collect study drug, dosing 
diary, assess compliance
Xv
Xv
Xv
a
Study Day 14 is included both in the Treatment Period and EOT.
b
Randomize subject on Day -1.
c Includes specific information related to any prior or existing medical conditions or surgical procedures involving the 
following systems: dermatologic, HEENT, lymphatic, cardiovascular, respiratory, GI, musculoskeletal, and neurological.
d Includes blood pressure, pulse, respiratory rate, and temperature. Obtain vital signs before collection of any laboratory 
samples and after subjects have rested for 5 minutes in a supine position. Obtain vital signs both predose and 2 hours 
postdose on Day 1; for all other timepoints, obtain at any time during the indicated visits. Obtain height only at Screening. 
Obtain weight at Screening to determine response to Exclusion Criterion #5 (Section 4.3) and on Day -1 (Section 6.3).
e Conduct a complete physical examination of general appearance, dermatologic, HEENT, lymphatic, cardiovascular, 
respiratory, GI, musculoskeletal, and neurological parameters. 
f Includes clinical chemistry panel (ALB, AP, ALT, AST, BUN, Ca, CO2, Cl, creatinine, GGT, glucose, LDH, phosphorus, 
K, Na, total bilirubin, direct bilirubin, total cholesterol, total protein, uric acid); hematology panel (HCT, HGB, platelet 
count, RBC count, WBC count, and WBC differential); and urinalysis (bilirubin, glucose, ketones, occult blood, pH, 
protein, specific gravity, urobilinogen and microscopic examination of WBC, RBC, and epithelial cells). Subjectss will 
fast overnight before blood sample collections.
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CNSA-001 (sepiapterin)
Censa Pharmaceuticals
Clinical Trial Protocol: GAS-001
Page 21
AMENDMENT 3: 21 Feb 2019
July 29, 2019
CONFIDENTIAL
Page 21 of 22
g Subjects will fast overnight before blood sample collections.
h Serum and urine pregnancy tests required for all women of childbearing potential; serum testing is to occur during the 
Screening Period, and urine testing is to occur before dosing on Day 1 and at an EOT visit on Day 28 (±1 day). Any 
positive urine pregnancy test should be confirmed by a serum pregnancy test.
i Obtain 12-lead ECG recordings in triplicate with 1 minute separating the first and second and second and third 
recordings.
j Record all treatments and over-the-counter medications (including herbal medications) received from 30 days prior to 
Screening (to determine responses to Inclusion Criterion #9 [Section 4.2] and Exclusion Criteria #11 through #14 and #21 
[Section 4.3] concerning medications) and through Day 28 ±1 day before the subject leaves the clinic after completion of 
all EOS evaluations.
k Collect AEs from the time of informed consent through Day 28 ±1 day before the subject leaves the clinic after 
completion of all EOS evaluations and SAEs from the time of informed consent through telephone Follow-up.
l Telephone Follow-up is to assess SAEs only.
m Administer the nutrient satiety test (Section 6.7) at Screening, on Day 1 (predose), and on Day 14 and Day 28 after 
overnight fasts and after any medications that can alter GI sensation or accommodation or gastric emptying have been 
held overnight.
n Administer the nutrient satiety test at Screening to determine the response to Inclusion Criterion #6 (Section 4.2)
o Administer the GCSI (Section 6.8, Appendix 2) at Screening, on Day 1 (predose), on Day 14 (+1 day) and on Day 28 (±1 
day).
p Administer the GCSI (Section 6.8, Appendix 2) to determine response to Inclusion Criterion #5 (Section 4.2).
q Administer the PAGI-SYM (Section 6.9, Appendix 2) in the clinic on Day 1 (predose), on Day 14 (+1 day), and on 
Day 28 (±1 day).
r Administer the GEBT on Day -1, on Day 15, and on Day 27 or Day 29. For the GEBT (Section 6.10), subjects will fast 
overnight before the GEBT (a minimum of 8 hours before test administration with the exception of 4 ounces of water up 
to 1 hour before the test). Collect a premeal breath sample and then provide a standardized 230 kCal meal, consisting of a 
proprietary standardized 13C-labeled egg component (which is rehydrated and then microwaved for 1.5 minutes) and 6 
saltine crackers, accompanied by 6 ounces of water. Encourage the subject to consume the meal within 10 minutes. 
Collect single postmeal breath samples in capped glass tubes at 45, 90, 120, 150, 180, and 240 minutes after the meal is 
consumed and send the samples to the specified local laboratory for analysis.
s Dispense a dosing diary with instructions to record times all doses of study drug are taken.
t If a subject vomits after taking a dose of study drug, the subject should wait until the next scheduled timepoint to take 
another dose. A missed dose should be taken as soon as possible, but >2 doses should not be taken on the same day.
u Subjects will take their first doses of study drug (CNSA-001 or placebo) on Day 1 while in the clinic.
v Collect study drug, dosing diary, assess compliance on Day 14 if the subject takes the last dose of study drug on Day 14
while in the clinic or, if the subject takes the last dose of study drug on Day 14 after leaving the clinic, on Day 15 or 
Day 28 (±1 day).
w GES or GEBT may be performed at Screening is historical confirmation of gastric emptying is >2 years prior to 
enrollment into the study.
Abbreviations: AE = adverse event; ALB = albumin; ALT = alanine aminotransferase (serum glutamic pyruvic transaminase 
[SGPT]); AP = alkaline phosphatase; AST = aspartate aminotransferase (serum glutamic oxaloacetic transaminase [SGOT]);
BUN = blood urea nitrogen; 13C = carbon-13; Ca = calcium; CO2 = carbon dioxide; Cl = chloride;
ECG = electrocardiogram; EOS = End of Study; EOT = End of Treatment; GCSI = Gastroparesis Cardinal Symptom Index;
GES = Gastric Emptying Scintigraphy; GEBT = Gastric Emptying Breath Test; GI = gastrointestinal; GGT = gamma 
glutamyl transferase; HCT = hematocrit; HGB = hemoglobin; HEENT = head, eyes, ears, nose, and throat; 
HbA1c = glycosylated hemoglobin A1c; K = potassium; LDH = lactate dehydrogenase; Na = sodium; PAGI-SYM = Patient 
Assessment of Upper Gastrointestinal Disorders-Symptom Severity; RBC = red blood cell; SAE = serious adverse event; 
WBC = white blood cell.
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Censa Pharmaceuticals, Inc.
Protocol GAS-001
Sepiapterin
Statistical Analysis Plan, Version 0.1
27 March 2019
CONFIDENTIAL
Page 22 of 22
Appendix B: Laboratory Testing Parameters
Hematology:
Hematocrit (HCT)
Hemoglobin (HGB)
Platelet count
Red blood cell (RBC) count
White blood cell (WBC) count with differential 
(neutrophils, eosinophils, basophils, 
lymphocytes, and monocytes)
Urinalysis:
Bilirubin
Glucose
Ketones
Occult blood
pH
Protein
Specific gravity
Urobilinogen 
Microscopy:
WBCs
RBCs
Epithelial cells
Serum Chemistry:
Albumin (ALB)
Alkaline phosphatase (AP)
Alanine aminotransferase (ALT; serum 
glutamic pyruvic transaminase [SGPT])
Aspartate aminotransferase (AST; serum 
glutamic oxaloacetic transaminase [SGOT])
Blood urea nitrogen (BUN)
Calcium (Ca)
Carbon dioxide (CO2)
Chloride (Cl)
Creatinine
Gamma glutamyl transferase (GGT)
Glucose
Lactate dehydrogenase (LDH)
Phosphorus
Potassium (K)
Sodium (Na)
Total bilirubin
Direct bilirubin
Total cholesterol
Total protein
Uric acid
Other:
Glycosylated hemoglobin A1(HbA1c)
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