Clinical trial NCT05270460
Conditions: Gastroparesis
Keywords: Idiopathic Gastroparesis Diabetic Gastroparesis
Sponsor: Processa Pharmaceuticals
Start date: 2022-03-09; Completion date: 2022-10-06
Enrollment: 25 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a randomized, double-blind, placebo-controlled study that will compare the effect of 2 different dosage regimens of PCS12852 on gastric emptying time to placebo in both idiopathic gastroparesis (IG) and diabetic gastroparesis (DG) patients.

Detailed description:

Arms: arm 1: PCS12852 0.1mg tablet arm 2: PCS12852 0.5mg tablet arm 3: Similar in appearance to active study drug
Interventions: intervention 1: PCS12852 intervention 2: Placebo
Intervention descriptions: intervention 1: PCS12852 oral tablet administered once daily intervention 2: Placebo comparator oral tablet administered once daily

Protocol documents:
Prot_SAP_000.pdf: 
 
 Protocol Title:  
A Phase 2A, Placebo-controlled, Randomized, 
Dose Response Study of the Safety, 
Pharmacokinetics and Efficacy of PCS12852 
on Gastric Emptying Rate Assessed by 13C 
Spirulina GEBT in Patients with Moderate to 
Severe Gastroparesis  
Protocol Version and Date 
Version 3.0, 20 April 2022 
NCT Number 
NCT05270460 
 


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Title Page 
Protocol Title: 
A Phase 2A, Placebo-controlled, Randomized, Dose Response 
Study of the Safety, Pharmacokinetics and Efficacy of PCS12852 
on Gastric Emptying Rate Assessed by 13C Spirulina GEBT in 
Patients with Moderate to Severe Gastroparesis 
Compound: 
PCS12852 
Indication: 
Moderate to Severe Gastroparesis 
Study Sponsor: 
Processa Pharmaceuticals, Inc. 
7380 Coca Cola Drive, Suite 106 
Hanover MD 21076 
Protocol Number.: 
PCS12852-GP-01 
Study Phase: 
2A 
IND number 
154163 
Version: 
3.0 
Approval Date: 
20 April 2022 
 
 




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Table of Contents 
 
Title Page ........................................................................................................................................ 1 
Table of Contents ............................................................................................................................ 3 
List of Tables ................................................................................................................................... 5 
1 
Protocol Summary .................................................................................................................... 6 
1.1 
Synopsis ................................................................................................................................ 6 
1.2 
Schedule of Activities (SoA) .............................................................................................. 17 
2 
Introduction............................................................................................................................. 20 
2.1 
Study Rationale................................................................................................................... 21 
2.2 
Background ......................................................................................................................... 22 
2.3 
Benefit/Risk Assessment .................................................................................................... 26 
3 
Objectives and Endpoints ....................................................................................................... 28 
4 
Study Design ........................................................................................................................... 30 
4.1 
Overall Design .................................................................................................................... 30 
4.2 
Scientific Rationale for Study Design ................................................................................ 31 
4.3 
Justification for Dose .......................................................................................................... 32 
4.4 
End of Study Definition ...................................................................................................... 32 
5 
Study Population ..................................................................................................................... 33 
5.1 
Inclusion Criteria ................................................................................................................ 33 
5.2 
Exclusion Criteria ............................................................................................................... 34 
5.3 
Lifestyle Considerations ..................................................................................................... 36 
5.3.1 
Meals and Dietary Restrictions ...................................................................................... 36 
5.4 
Screen Failures ................................................................................................................... 36 
6 
Study Treatment and Concomitant Therapy ........................................................................... 37 
6.1 
Treatments Administered .................................................................................................... 37 
6.2 
Preparation, Handling, Storage, and Accountability .......................................................... 37 
6.3 
Measures to Minimize Bias: Randomization and Blinding ................................................ 38 
6.4 
Study Treatment Compliance ............................................................................................. 39 
6.5 
Continued Access to Study Treatment After the End of the Study ..................................... 39 
6.6 
Treatment of Overdose ....................................................................................................... 40 
6.7 
Concomitant Therapy ......................................................................................................... 40 
6.7.1 
Prohibited Treatments ..................................................................................................... 40 
6.7.2 
Permitted Treatments ...................................................................................................... 41 
6.7.3 
Rescue Medicine ............................................................................................................ 42 
7 
Discontinuation/Withdrawal Criteria ...................................................................................... 42 
7.1.1 
Stopping Criteria ............................................................................................................ 43 


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7.2 
Loss to Follow-Up/Early Discontinuation from Study Drug ............................................. 44 
8 
Study Assessments and Procedures ........................................................................................ 44 
8.1 
Efficacy Assessments.......................................................................................................... 45 
8.1.1 
Primary Efficacy Assessment – Gastric Emptying Breath Test ...................................... 45 
8.1.2 
Secondary Efficacy Assessment – ANMS GCSI-DD..................................................... 46 
8.1.3 
Exploratory Efficacy Assessments ................................................................................. 47 
8.1.3.1 
PAGI-SYM and PAGI-QOL ....................................................................................... 47 
8.1.3.2 
CGI-S and CGI-I ......................................................................................................... 48 
8.1.3.3 
PGI-S and PGI-C ........................................................................................................ 48 
8.2 
Safety Assessments ............................................................................................................. 49 
8.2.1 
Physical Examinations .................................................................................................... 49 
8.2.2 
Vital Signs ...................................................................................................................... 50 
8.2.3 
Electrocardiograms ......................................................................................................... 50 
8.2.4 
Clinical Safety Laboratory Tests .................................................................................... 50 
8.2.5 
Pregnancy Testing ........................................................................................................... 51 
8.2.6 
Suicidal Ideation and Behavior Risk Monitoring ........................................................... 51 
8.3 
Adverse Events, Serious Adverse Events, and Other Safety Reporting ............................. 52 
8.3.1 
Time Period and Frequency for Collecting AE and SAE Information ........................... 52 
8.3.2 
Method of Detecting AEs and SAEs .............................................................................. 52 
8.3.3 
Follow-up of AEs and SAEs ........................................................................................... 53 
8.3.4 
Regulatory Reporting Requirements for SAE ................................................................ 53 
8.3.5 
Pregnancy ....................................................................................................................... 53 
8.4 
Pharmacokinetics ................................................................................................................ 54 
9 
Statistical Considerations........................................................................................................ 55 
9.1 
Analysis Sets....................................................................................................................... 55 
9.2 
Statistical Analyses ............................................................................................................. 55 
9.2.1 
General Considerations .................................................................................................. 55 
9.2.2 
Primary Efficacy Analysis .............................................................................................. 55 
9.2.3 
Secondary Efficacy Analysis .......................................................................................... 57 
9.2.4 
Other Patient-reported outcomes (PRO) Assessments – Exploratory Endpoints ........... 57 
9.2.5 
Safety Analyses .............................................................................................................. 58 
9.3 
Sample Size Determination ................................................................................................ 59 
10 Supporting Documentation and Operational Considerations ................................................. 60 
10.1 Appendix 1: Regulatory, Ethical, and Study Oversight Considerations ............................. 60 
10.1.1 
Regulatory and Ethical Considerations .......................................................................... 60 
10.1.2 
Informed Consent Process .............................................................................................. 61 
10.1.3 
Data Protection ............................................................................................................... 61 
10.1.4 
Dissemination of Clinical Study Data ............................................................................ 62 


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10.1.5 
Data Quality Assurance .................................................................................................. 62 
10.1.6 
Source Documents .......................................................................................................... 63 
10.1.7 
Study and Site Start and Closure .................................................................................... 63 
10.1.8 
Protocol Approval and Amendment ............................................................................... 64 
10.1.8.1 
Access to Source Data ................................................................................................ 64 
10.2 Appendix 2: Clinical Laboratory Tests ............................................................................... 66 
10.3 Appendix 3: AEs and SAEs: Definitions and Procedures for Recording, Evaluating, 
Follow-up, and Reporting ................................................................................................... 68 
10.3.1 
Definition of AE ............................................................................................................. 68 
10.3.2 
Definition of SAE ........................................................................................................... 69 
10.3.3 
Recording and Follow-up of AE and SAE ..................................................................... 71 
10.3.4 
Reporting of SAE ........................................................................................................... 74 
10.4 Appendix 4: Contraceptive Guidance and Collection of Pregnancy Information .............. 76 
Definitions..................................................................................................................................... 76 
10.5 Appendix 5: Abbreviations ................................................................................................. 80 
11 References............................................................................................................................... 83 
12 Declaration of the Investigator ............................................................................................... 85 
 
List of Tables 
Table 1 
Schedule of Activities (SoA) ................................................................................ 17 
Table 2 
Objectives and Endpoints ..................................................................................... 28 
Table 3 
Study Treatments Administered ............................................................................ 37 
Table 4 
Measures to Minimize Bias .................................................................................. 38 
Table 5 
Analysis Data Sets ................................................................................................ 55 
Table 6 
Protocol-required Safety Laboratory Tests ........................................................... 66 
 


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1 Protocol Summary 
1.1 Synopsis 
Name of Sponsor/Company: Processa Pharmaceuticals, Inc. 
Name of Investigational Product: PCS12852 
Name of Active Ingredient: PCS12852 
Title of Study: A Phase 2A Placebo-controlled, Randomized Dose Response Study of the 
Safety, Pharmacokinetics and Efficacy of PCS12852 on Gastric Emptying Rate Assessed by 
13C Spirulina GEBT in Patients with Moderate to Severe Gastroparesis. 
Study center(s): Approximately 8 centers in the United States (US) 
Phase of Development: Phase 2a 
Objectives: 
Primary Objective: 
• To evaluate the effect of different doses of PCS12852 on the gastric emptying rate, as 
measured by the Gastric Emptying Breath Test (GEBT), in patients with moderate to 
severe idiopathic gastroparesis (IG) or diabetic gastroparesis (DG). 
• To evaluate the safety and tolerability of different doses of PCS12852 in IG and DG 
patients. 
• To evaluate the PK profile of PCS12852 at different dose levels. 
Secondary Objective: 
• To evaluate the effect of different doses of PCS12852 on symptoms, as measured by the 
American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom 
Index Daily Diary (ANMS GCSI-DD), in patients with moderate to severe IG or DG. 
Methodology: 
This is a randomized, double-blind, placebo-controlled study that will compare the effect of 
2 different dosage regimens of PCS12852 on gastric emptying time to placebo in both IG and 
DG patients. 
In this Phase 2A study, gastroparesis patients who have successfully completed Screening 
criteria (Visit 1) will return for a second Screening Visit (Visit 2) where the 
inclusion/exclusion criteria will be re-evaluated. Visit 1 will include all safety labs and 
procedures (including an electrocardiogram [ECG]). The investigator will complete the 
Columbia-Suicide Severity Rating Scales (C-SSRS) to confirm that there are no suicidal 
tendencies or ideation. If the patients still meet study criteria when returning for Visit 2, 
patients will have a GEBT performed and will be educated on completion of the ANMS 


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Name of Sponsor/Company: Processa Pharmaceuticals, Inc. 
Name of Investigational Product: PCS12852 
Name of Active Ingredient: PCS12852 
GCSI-DD. Patients will complete the ANMS GCSI-DD for 7 days. The results from both the 
GEBT and the ANMS GCSI-DD during the Screening period will be considered the baseline 
values for these assessments. 
Patients will return to the site for Visit 3 (Randomization) where patients who meet the 
criteria based on having moderate to severe symptoms based on the ANMS GCSI-DD and 
moderate to severe delay in gastric emptying will be randomized in a 1:1:1 ratio into three 
treatment groups, PCS12852 0.1 mg, PCS12852 0.5 mg or placebo. 
At Visit 3, patients will answer a series of assessments including the following: Patient 
Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM), Patient 
Assessment of Upper Gastrointestinal Disorders – Quality of Life (PAGI-QOL), Patient 
Global Impression of Severity (PGI-S) and the Patient Global Impression of Change (PGI-C). 
Patients will arrive fasting and have PK samples drawn prior to receiving the first dose and at 
the following times after the first dose: 0.5, 1, 2, 4, 6, and 8 hours. The investigator will 
assess the patient through the C-SSRS as well as the Clinical Global Impression- Severity 
scale (CGI-S) and Clinical Global Impression – Improvement scale (CGI-I). 
Patients will take their assigned treatment for 28 days. During the treatment period, the 
patients will also complete the ANMS GCSI-DD. Each patient will be told to take one tablet 
from their assigned kit at approximately the same time each morning, at least 30 minutes 
prior to a meal (actual dosing times will be captured via a dosing diary), starting on Day 1 for 
28 days. Patients will return to the clinic on Day 7 and Day 14 to be assessed in a blinded 
manner for safety and tolerability of the study treatment as well as have the investigator 
assess the patient for suicidal tendencies or ideations via the C-SSRS.  
On the morning of Day 28, after fasting overnight, the patient will return to the site for 
Visit 6. At Visit 6, the patient will again complete the patient assessments and will have a PK 
sample drawn prior to receiving their final dose of PCS12852 or placebo and then have PK 
samples drawn at 0.5, 1, 2, 4, 6, and 8 hours post-dose. The ECG should be performed prior 
to the 4-hour PK draw between the 2- and 4- hour samples. The patient’s fasting blood 
glucose (FBG) of ≤ 275 mg/dL is required to proceed with the GEBT. If the patient’s FBG is 
not within range, the patient will be sent home with an additional dose of study drug and 
asked to return the next day to perform the GEBT. The GEBT test will be performed for 4 
hours and will be administered approximately 30-60 minutes after the patient’s final dose of 
study treatment. During the GEBT test, the site will prioritize taking the GEBT samples and 
then the PK samples. After the test is complete the patients will be discharged and will return 
approximately 48-72 hours after Day 28 (Visit 6) to have a PK blood sample drawn. The 
patient will also return to the site 1 week after the Day 28 visit for a follow-up visit (Day 
35/Visit 8). 


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Name of Sponsor/Company: Processa Pharmaceuticals, Inc. 
Name of Investigational Product: PCS12852 
Name of Active Ingredient: PCS12852 
The GEBT at Visit 2 and Visit 6 will be performed at the sites. Patients will be told to fast 
overnight prior to coming to the site for the test. The patient will have their glucose tested via 
fingerstick both before and after the GEBT. The patient must have a fasting blood glucose 
(FBG) of ≤ 275 mg/dL to proceed with the GEBT. If the patient does not have a FBG of ≤ 
275 mg/dL prior to the GEBT, the patient may come in the following day to take the GEBT. 
The GEBT is a nonradioactive, noninvasive test that measures gastric emptying. Patients 
provide baseline (premeal) breath samples and then consume a standardized 230 kCal 
(kilocalorie) 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 
post meal 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 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 total study duration for each patient will be approximately 8 weeks. 
Number of patients (planned):  
Total number randomized into this study: 24 patients with moderate to severe gastroparesis 
who have documented delayed gastric emptying. The randomization to treatment groups will 
be stratified by type (IG, DG), enrolling at least 2 patients of each type in each treatment 
group. 
Diagnosis and Main criteria for Eligibility: 
Inclusion criteria: 
1. Has a documented diagnosis of moderate to severe IG or DG according to the ANMS 
GCSI-DD score during the Screening Period (Score of > 2 on average of the 
screening days). 
2. Moderate to severe delay in gastric emptying rate as measured by GEBT at Screening 
defined as GE half-time (t1/2) ≥ the 80th percentile of normative data as determined 
by Cairn Diagnostics. 
3. Male or female patients 18 to 80 years of age, inclusive, at baseline. 
4. Has continuous moderate to severe symptoms for gastroparesis (that is, chronic 
postprandial fullness, abdominal pain, postprandial nausea, vomiting, loss of appetite 
and/or early satiety) as assessed by the investigator for at least the past 3 months. 


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Name of Sponsor/Company: Processa Pharmaceuticals, Inc. 
Name of Investigational Product: PCS12852 
Name of Active Ingredient: PCS12852 
5. Has hemoglobin A1c (HbA1c) less than (<) 11%. 
6. Has Body Mass Index (BMI) range between 18- 40. 
7. Women of childbearing potential must have a negative serum pregnancy test at the 
Screening Visit and a negative urine pregnancy test at baseline before dosing. 
8. Women of childbearing potential must use one of the following acceptable methods 
of contraception throughout the study (from 1 month prior to Screening through 1 
month after last dose of study medication): oral contraceptive medication, intrauterine 
device (IUD), hormonal implants, injectable contraceptive medications, 
double-barrier methods, or tubal ligation. 
9. Females who are postmenopausal (age-related amenorrhea ≥ 12 consecutive months 
and increased follicle-stimulating hormone [FSH] > 40 mIU/mL. If necessary, to 
confirm postmenopausal status, an FSH will be drawn at Screening) or who have 
undergone hysterectomy or bilateral oophorectomy are exempt from pregnancy 
testing. 
10. Male patients must be willing to use acceptable contraceptive measures such as 
vasectomy or double barrier method and refrain from sexual activity with any female 
who is pregnant or lactating. Female partners of male participants should use 
acceptable methods of contraception stated in Inclusion #8 above. 
11. Patient must be willing and able to swallow whole tablets. 
12. Patient must be willing and able to comply with study procedures. 
13. Compliance with the completion of the ANMS GCSI-DD, defined as approximately 
80% diary completions, during the screening period. For those patients whose 
compliance is measured to be <80%, the final decision to randomize a patient will be 
made by the Investigator and the Sponsor (or designee). 
14. Patient must be willing and able to provide signed, informed consent. 
Exclusion criteria: 
1. Has acute, severe gastroenteritis and pronounced dehydration in the past 48 hours 
prior to Screening, chronic parenteral feeding or persistent severe vomiting. 
2. Has known hypersensitivity to Spirulina, egg, milk products or wheat allergens. 
3. Has a known disturbance of small intestinal absorption, exocrine pancreatic function, 
liver metabolism or pulmonary function. 
4. Has a history of anorexia nervosa or bulimia. 


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Name of Sponsor/Company: Processa Pharmaceuticals, Inc. 
Name of Investigational Product: PCS12852 
Name of Active Ingredient: PCS12852 
5. Previous history of bezoars (the presence of retained liquid, bile, or small amounts of 
poorly organized food residue is permitted). 
6. Prior surgery involving any gastrointestinal (GI) surgery, including the luminal GI 
tract (cholecystectomy and appendectomy, are permitted if performed greater than 3 
months prior to the baseline GEBT test). 
7. Any abdominal or pelvic surgery within the past 3 months. 
8. Known or history of the following GI conditions: inflammatory bowel disease; 
irritable bowel syndrome with diarrhea; or any other active disorder that could explain 
symptoms in the opinion of the investigator. 
9. Has active diverticulitis, diverticular stricture, and other intestinal strictures. 
10. Has feeding or decompression tubes and/or a gastric pacemaker. 
11. Has had Botox pyloric injections within the prior 3 months. 
12. Has had diabetic ketoacidosis (within the prior 4 weeks). 
13. Currently taking Glucagon-like peptide-1 (GLP-1) agonists, e.g. exenatide, 
liraglutide, semaglutide or dulaglutide; or pramlintide. 
14. Has severe psychiatric illness (including suicidal tendencies or ideation) or 
neurological illness. 
15. History or suspicion of alcohol, barbiturate, amphetamine or narcotic abuse. 
16. Use of narcotics/opioids, drugs used to treat gastroparesis within 3 days of the 
Screening GEBT test. 
17. Anticipated concurrent use of a strong Cytochrome P450 (CYP) inhibiting or 
inducing drug (listed in Section 6.7.1) that would significantly alter the metabolism of 
PCS12852 and/or its metabolites during the course of the study (after Screening) 
18. Fever (>38°C), or chronic, persistent, or recurring infection(s) at Screening or 
baseline. 
19. Clinically significant cardiac disease including but not limited to unstable angina, 
acute myocardial infarction within 6 months of baseline, and arrhythmia requiring 
therapy. 
20. Patient has QTcF interval ≥ 480 milliseconds on Screening ECG; a second Screening 
ECG may be done at the Investigator’s discretion but the average of the two QTcF 
screening intervals must not be ≥ 480 milliseconds. 


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Name of Investigational Product: PCS12852 
Name of Active Ingredient: PCS12852 
21. History of cerebral hemorrhage, cerebrovascular accident, transient ischemic attack, 
gastrointestinal bleeding, or retinal hemorrhage within 6 months of baseline. 
22. Patient has active or history of neoplastic disease (except for adequately treated non-
invasive basal cell and/or squamous cell carcinoma of the skin or carcinoma in situ of 
the cervix) within the past 5 years prior to baseline. 
23. Presence of clinically significant medical condition(s) including but not limited to: 
renal, hepatic, cardiovascular, hematological, gastrointestinal, endocrine, pulmonary, 
neurological, psychiatric, substance abuse, and/or any other clinically significant 
disease or disorder, which in the opinion of the Investigator (by its nature or by being 
inadequately controlled), may put the patient at risk due to participation in the study, 
influence the results of the study, and/or affect the patient’s ability to complete the 
study. 
24. History of or current diagnosis of active tuberculosis (TB); undergoing treatment for 
latent TB infection (LTBI); untreated LTBI (as determined by documented results 
within 3 months of the Screening Visit of a positive TB skin test with purified protein 
derivative with induration >= 5 mm, a positive QuantiFERON-TB test or positive or 
borderline T-SPOT [Elispot] test); or positive TB test at Screening.  Patients with 
documented completion of appropriate LTBI treatment would not be excluded and are 
not required to be tested. 
25. Vaccination with live or live-attenuated virus vaccine within 1 month prior to 
baseline. Vaccines for COVID-19 are allowed. 
26. The results of the following laboratory tests performed at the central laboratory at 
Screening meet any of the criteria below: 
a. Hemoglobin < 8.0 g/dL (International System of Units: < 80 g/L) 
b. White blood cells < 3.0 x 10^3 cells/mm^3 (SI: < 3.0 x 10^9 cells/L) 
c. Neutrophils < 1.0 x 10^3 cells/mm^3 (SI: < 1.0 x 10^9 cells/L) 
d. Lymphocytes < 0.5 x 10^3 cells/mm^3 (SI: < 0.5 x 10^9 cells/L) 
e. Platelets < 100 x 10^3 cells/mm^3 (SI: < 100 x 10^9 cells/L) 
f. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and/or 
alkaline phosphatase (ALP) ≥ 2 x upper limit of normal (ULN) 
g. Total bilirubin level ≥ 2 x ULN unless the individual has been diagnosed with 
Gilbert's disease and this is clearly documented 
h. Estimated glomerular filtration rate < 40 mL/min/1.73 m^2 based on the 
Modification of Diet in Renal Disease formula 
i. Creatinine ≥ 3 mg/dL 
j. Positive human immunodeficiency virus serology 
k. Evidence of active Hepatitis B Virus infection 


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Name of Sponsor/Company: Processa Pharmaceuticals, Inc. 
Name of Investigational Product: PCS12852 
Name of Active Ingredient: PCS12852 
l. Evidence of active Hepatitis C Virus infection 
27. Women who are pregnant or breastfeeding. 
28. Any other medical condition, serious intercurrent illness, or extenuating circumstance 
that, in the opinion of the Investigator, would preclude participation in the study. 
29. Use of any investigational product within 30 days prior to baseline or currently 
enrolled in another study that involves clinical intervention. 
30. Currently taking known P-gp and BCRP inhibitors or inducers and gastric acid 
reducing agents. e.g., proton pump inhibitors or H2 receptor antagonists. 
 
 Investigational product, dosage and mode of administration  
Patients in each assigned treatment group, will take one tablet, once daily by mouth at 
approximately the same time each morning, and at least 30 minutes prior to a meal) during 
the treatment period of the study. The patient will be asked to complete a dosing diary to 
document actual dosing times. 
Group 
Dosage Forms 
PCS12852 
0.1 mg tablet  
PCS12852 
0.5 mg tablet 
Placebo 
Matching tablet 
Criteria for Evaluation: 
Primary Endpoints 
• Change in gastric emptying rate from baseline as determined by the AUC of the gastric 
emptying rate over time as assessed by the GEBT at Visit 6 (Day 28) after administration 
of the PCS12852 or placebo. 
• Change in gastric emptying rate from baseline using the t10 and t50 metric for gastric 
emptying rate. 
• Concentrations of PCS12852 in plasma; PK parameters will be estimated from 
concentration-time data using noncompartmental methods, as data permit. 
Secondary Endpoints 
• Change from baseline in the ANMS GCSI-DD (i.e., Day-7 to Day -1) (predose) and Day 
7 (Day 1 to Day 7). 


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Name of Sponsor/Company: Processa Pharmaceuticals, Inc. 
Name of Investigational Product: PCS12852 
Name of Active Ingredient: PCS12852 
• Change from baseline in the ANMS GCSI-DD (i.e., Day-7 to Day -1) (predose) and Day 
14 (Day 8 to Day 14). 
• Change from baseline in the ANMS GCSI-DD (i.e., Day-7 to Day -1) (predose) and Day 
21 (Day 15 to Day 21). 
• Change from baseline in the ANMS GCSI-DD (i.e., Day-7 to Day -1) (predose) and Day 
28 (Day 22 to Day 28). 
Exploratory Endpoints 
• Change from baseline in ANMS GCSI-DD score over time (Day 7, 14, 21, 28) by 
comparing Day 7 to Day 14, Day 14 to Day 21 and Day 21 to Day 28. 
• Change from baseline in the subscores (nausea, early satiety, postprandial fullness, 
upper abdominal pain and number of vomiting episodes) of the ANMS-GCSI-DD 
over time (Day 7, 14 ,21, 28) by comparing Day 7 to Day 14, Day 14 to Day 21 and 
Day 21 to Day 28. 
• Change from baseline in PAGI-SYM and PAGI-QOL scores over time by comparing 
Day 1 to Day 28. 
• Change from baseline in Clinical Global Impression-Severity (CGI-S) and Clinical 
Global Impression-Improvement (CGI-I) scores over time by comparing Day 1 to 
Day 28. 
• Change from baseline in PGI-S and PGI-C scores over time by comparing Day 1 to 
Day 28. 
Safety Endpoints 
• Adverse Events (AEs) (by type, severity, and relatedness) at each visit. 
• Changes in safety clinical laboratory testing and vital signs at each site visit. 
• Changes in ECGs at each site visit and the potential correlation of the PK with changes in 
the ECG. 
• Change from baseline in the C-SSRS scores over time by comparing Day 1 to Day 28. 
STATISTICAL ANALYSES: 
Analysis Sets: 
• Safety Set: All patients enrolled in the study who received at least 1 dose of treatment.  
• PK Analysis Population: Patients in the Safety Set with at least 1 plasma sample with a 
quantifiable concentration of PCS12852. 


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Name of Sponsor/Company: Processa Pharmaceuticals, Inc. 
Name of Investigational Product: PCS12852 
Name of Active Ingredient: PCS12852 
• Full Analysis Set (FAS): All patients who are randomized. 
Other populations (e.g., Per Protocol) may be defined and used as supportive evidence of 
treatment benefit. 
Patient Characteristics: 
Baseline demographics and disease characteristics will be presented for each treatment group 
by descriptive statistics. All descriptive summary statistics of continuous variables will 
include n, mean, median, standard deviation (SD), minimum and maximum. All descriptive 
summaries presenting frequencies and incidences will include n, percent of total, and N, 
where N is the total number of patients with recorded values in the corresponding group. 
Patient completion status and exposure outcomes will be similarly presented. 
Primary Efficacy Analyses: 
The change in the gastric emptying rate AUC from baseline to Day 28 will be analyzed in the 
FAS using an analysis of covariance (ANCOVA) model with treatment group (three levels) 
and types (IG, DG) as a factor and the baseline GEBT as a covariate. Each of the two 
primary comparisons (0.1 mg versus placebo, 0.5 mg versus placebo) will be conducted 
using a two-sided Dunnett’s test at the overall alpha=0.05 significance level.  
Other efficacy analyses: 
All secondary endpoints will be analyzed using the same types of ANCOVA models as 
described for the primary analysis. Each treated group will be compared to placebo. All 
secondary analyses will be conducted with no adjustment for multiplicity. 
Subgroup analysis: 
A subgroup analysis of idiopathic gastroparesis patients compared to diabetic gastroparesis 
patients will be performed for all efficacy analysis endpoints.  
Pharmacokinetic Assessment 
Plasma concentrations will be used to estimate the pharmacokinetic parameters for 
PCS12852 on Day 1 and Day 28 using noncompartmental methods in WinNonlin®. The 
following parameters will be calculated as data permit: 
• Cmax: maximum observed plasma concentration 
• Tmax: time at which the maximum plasma concentration was observed 
• t½: (the apparent first-order terminal elimination half-life) 


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Name of Sponsor/Company: Processa Pharmaceuticals, Inc. 
Name of Investigational Product: PCS12852 
Name of Active Ingredient: PCS12852 
• AUC0-last: the area under the plasma concentration versus time curve, from time 0 to the 
last measurable concentration 
• AUC∞: the area under the plasma concentration vs. time curve from time 0 to infinity 
• λz: apparent first order terminal elimination rate constant 
A dose proportionality analysis will be conducted for log-transformed Cmax, AUC0-last, and 
AUC∞ using the power model.  In addition, the relationship between gastric emptying rate and 
drug exposure will be assessed, as data permit.  Exposure-response for safety measures may 
also be explored.  Details of these analysis will be provided in the Statistical Analysis Plan.  
In addition, a population PK model may be used to describe the PK of PCS12852, if 
appropriate based on the data collected.   A previously developed population PK model 
describing the PK of PCS12852 in patients with functional constipation, using a two-
compartment model with first order absorption, may be used to predict the PK in patients in 
this study.  
 
Safety Analyses: 
The safety analyses will be performed using the Safety Population and include AEs, changes 
in physical exam findings, vital signs, ECGs and clinical laboratory values. 
Adverse events will be coded using the current version of the Medical Dictionary for 
Regulatory Activities (MedDRA version 23.0 or higher). The number and percent of patients 
reporting at least one AE will be summarized by System Organ Class (SOC) and Preferred 
Term (PT) and presented by severity, relationship to study treatment, amount of drug 
exposure, and time. Each patient will contribute only once (i.e., first occurrence) to each of 
the incidence rates, regardless of the number of occurrences. Severity of AEs will be assessed 
based on the National Cancer Institute (NCI) CTCAE Version 5.0. For reporting of AE 
severity in patients with more than one occurrence of the same AE, the patient will only be 
reported once based on the highest severity of the AE observed. Patients who have a serious 
adverse event (SAE) or who discontinue the study due to an AE deemed to be related to 
study treatment will be described in patient narratives. 
Vital signs, clinical laboratory, and ECG results will also be presented and summarized by 
dose level and summarized by descriptive statistics with change from baseline values 
calculated.  All safety data collected in the clinical database, including physical exam 
findings and abnormal ECG results, will be presented in data listings. 
 


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Name of Sponsor/Company: Processa Pharmaceuticals, Inc. 
Name of Investigational Product: PCS12852 
Name of Active Ingredient: PCS12852 
SAMPLE SIZE CALCULATION: 
Based on the results of a prior study (Study 102), estimates of the SD of the AUC of the 
gastric emptying rate over time as assessed by the GEBT change from baseline range from 10 
to 35. Assuming a true SD of 15 and based on a two-sided test at the alpha=0.025 level of 
significance, a sample size of 8 patients per arm (24 total patients) will provide 80% power to 
detect a between-group mean difference of 25. 


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1.2 Schedule of Activities (SoA) 
Table 1 
Schedule of Activities (SoA) 
Procedure 
Visit 1 
(Screening) 
 
Visit 2 
(Screening) 
(Baseline) 
Visit 3  
(Randomization) 
Day 1 
Visit 4 
Day 7  
 
Visit 5 
Day 14  
 
Visit 6 
Day 28 
  
Visit 7 
48-72 hrs after 
Day 28 visit 
Visit 8/ET  
Day 35 
 
Visit Window 
Days -21 to -1 
±2 days 
+3 days 
+1 day 
±1 day 
Informed consent 
X 
 
 
 
 
 
 
 
Demographic 
information 
X 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
Inclusion/ 
Exclusion criteria 
X 
X 
X 
 
 
 
 
 
Screening Lab 
testing (inc. Hep 
B/C, HIV and TB) 
X 
 
 
 
 
 
 
 
Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
 
X 
Vital signs 
X 
X 
X 
X 
 
X 
 
X 
Physical examg 
X 
 
X 
X 
X 
X 
 
X 
13C GEBT 
 
X 
 
 
 
Xd 
 
 


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Procedure 
Visit 1 
(Screening) 
 
Visit 2 
(Screening) 
(Baseline) 
Visit 3  
(Randomization) 
Day 1 
Visit 4 
Day 7  
 
Visit 5 
Day 14  
 
Visit 6 
Day 28 
  
Visit 7 
48-72 hrs after 
Day 28 visit 
Visit 8/ET  
Day 35 
 
Visit Window 
Days -21 to -1 
±2 days 
+3 days 
+1 day 
±1 day 
ANMS GCSI-DDa 
 
X 
X 
X 
X 
X 
 
 
Safety laboratory 
testing 
 
 
 
X 
 
X 
 
X 
Pregnancy testb 
X 
 
X 
X 
X 
X 
 
X 
ECGh 
X 
 
Xi 
Xj 
Xj 
X 
 
X e 
C-SSRS 
X 
 
X 
X 
X 
X 
 
X 
PGI-S 
 
 
X 
 
 
X 
 
X 
PGI-C 
 
 
X 
 
 
X 
 
X 
PAGI-SYM 
 
 
X 
 
 
X 
 
 
PAGI-QOL 
 
 
X 
 
 
X 
 
 
CGI-S  
 
 
X 
 
 
X 
 
X 
CGI-I 
 
 
X 
 
 
X 
 
X 
Adverse  
Events 
X 
X 
X 
X 
X 
X 
 
X 
Study Drug 
Dispensed 
 
 
X 
X 
X 
X 
 
 


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a. 
ANMS GCSI-DD will be collected for 7 consecutive days after Screening Visit 2, but prior to randomization (i.e. from Days -7 to -1) as well as from Day 1 to Day 28. 
b. 
For WOCBP: Serum β-HCG at Screening Visit 1; Urine pregnancy test at subsequent visits 
c. 
Patients will take the dose of PCS12852 or placebo in clinic on Day 28. 
d. 
A blood glucose finger stick will be taken both before and at the completion of the GEBT. 
e. 
Repeat ECG at Visit 8, only if ECG at Visit 6 was abnormal. 
f. 
PK blood samples will be drawn at both Visit 3 (Day 1) and Visit 6 (Day 28) at the following timepoints: pre-dose (trough) and at 0.5h, 1h, 2h, 4h, 6h and 8h post dose. Clinical staff are 
encouraged to take the blood samples for PK analysis at the scheduled time point; however, deviations from the scheduled sample times are not considered protocol deviations.  The exact 
time and date of the blood draw must be recorded. 
g. 
A symptom driven physical exam will be done on Visit 3 (Day 1), Visit 4 (Day 7), Visit 5 (Day 14) and Visit 8 (Day 35). 
h. 
Clinical staff are encouraged to perform ECGs prior to any blood draws at a given visit. 
i. 
ECGs should be performed prior to the 4 hour PK draw. 
j. 
ECGs should be performed approximately 4 hours after patient’s dose. 
k. 
The single PK sample drawn between 48-72 hours after the Day 28 visit can either be done in the office or by a home health nurse.
Procedure 
Visit 1 
(Screening) 
 
Visit 2 
(Screening) 
(Baseline) 
Visit 3  
(Randomization) 
Day 1 
Visit 4 
Day 7  
 
Visit 5 
Day 14  
 
Visit 6 
Day 28 
  
Visit 7 
48-72 hrs after 
Day 28 visit 
Visit 8/ET  
Day 35 
 
Visit Window 
Days -21 to -1 
±2 days 
+3 days 
+1 day 
±1 day 
Study Drug 
Instructions 
X 
X 
X 
 
 
 
 
 
Study Drug 
Administered 
 
 
X 
 
 
Xc 
 
 
PK samplef 
 
 
X 
 
 
X 
Xk 
 
Drug Accountability 
 
 
 
X 
X 
X 
 
 


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2 Introduction 
Gastroparesis is a disorder characterized by delayed gastric emptying of solid food in the absence 
of a mechanical obstruction, particularly pyloric stenosis ( Camilleri, 2013). This delay may 
result in the cardinal symptoms of early satiety, postprandial fullness, nausea, vomiting, belching 
and bloating. The syndrome is caused by neuromuscular dysfunction that leads to delayed gastric 
emptying (Camilleri, 2018). 
Gastroparesis can be idiopathic, associated with diabetes mellitus, can occur after a medical 
intervention (iatrogenic or post-surgical), may be associated with neurological disorders or may 
occur after a bacterial or viral infection. In one series of 146 patients, the etiology of 
gastroparesis was 36% idiopathic, 29% diabetic, 13% postsurgical, 7.5% Parkinson’s Disease, 
4.8% collagen vascular disorders, 4.1% intestinal pseudo obstruction and 6% miscellaneous 
(Soykan, 1998). The majority of patients (up to 80%) with gastroparesis are women (Parkman, 
2019). 
The symptoms of gastroparesis are nonspecific and may mimic other disorders such as functional 
dyspepsia. 
Treatment of symptomatic gastroparesis generally follow these principles (Quigley, 2001): 
1. 
Dietary recommendations to correct fluid, electrolyte or nutritional deficiencies; 
2. 
Identify and rectify the underlying cause of gastroparesis, if possible; and 
3. 
Reduce the symptoms of gastroparesis. 
For diabetic patients with gastroparesis, improvement of glucose control has been shown to 
increase antral contractility, correct gastric dysrhythmias and accelerate gastric emptying 
although there have been no long-term studies confirming the beneficial effects of maintaining 
euglycemia on gastroparetic symptoms (Parkman, 2004). 
Treatments are based on the symptom presentation and usually include antiemetic agents or 
prokinetic agents. Currently the only treatment approved in the United States (US) for 
gastroparesis is metoclopramide (Prescribing information for Reglan, ANI Pharmaceuticals, Inc., 
Baudette, MN 2017; Prescribing information for Gimoti, Evoke Pharma, 2021). The currently 
approved indication for metoclopramide oral or nasal spray is relief of symptoms in adults with 
acute and recurrent diabetic gastroparesis (DG), although this medication has a black-box 
warning limiting treatment to no more than 12 weeks because of the risk of related side effects 


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including tardive dyskinesia. The 5-HT4 agonist, cisapride, was previously used for the treatment 
of gastroparesis but was removed from the US market in 2000 because of cardiovascular risks. 
Gastroparesis is a disease that affects a large number of people and can significantly impact the 
quality of life for those patients. With the limitation on currently approved treatments for 
gastroparesis there still is a need for new, effective treatments for this disorder. 
2.1 Study Rationale 
PCS12852 is a novel, potent, and highly selective 5-HT4 receptor agonist. Approximately 80% of 
the total body 5-HT is found in the gut where it plays a central role in the initiation of the 
peristaltic reflex on enteric neurons. Serotonergic drugs have been developed for gastric motility 
disorders, but these products were not selective, e.g. cisapride and tegaserod were withdrawn 
from the market due to adverse events (AEs). PCS12852 has a high binding affinity for the 5-
HT4 receptor with more than 200-fold selectivity over other 5-HT receptors. It has also been 
shown to have more potent 5-HT4 agonistic activity than other 5-HT agonists, e.g. prucalopride. 
In vitro pharmacological models have shown that PCS12852 was able to induce a 
concentration-dependent contraction of guinea pig colon, confirming its agonistic effects on the 
5-HT4 receptor. In vivo models have also demonstrated the effect of PCS12852 on gastric 
motility, showing significant increases in the gastric emptying rate in rats, restoring gastric 
emptying in clonidine-induced gastroparesis in male beagle dogs and decreasing the gastric 
emptying time at all dose levels in cynomolgus monkeys. 
Cardiovascular effects were reported with earlier 5-HT4 agonists (prolonged QTc increasing risk 
for arrythmias) resulting in the withdrawal of these products from the market possibly due to 
their off target effects. The safety pharmacology studies conducted with PCS12852 showed a low 
risk of any off-target effects on the cardiovascular, central or respiratory systems. 
A previous study (Study 102) evaluated the single and multiple dose pharmacokinetics (PK) and 
pharmacodynamics (PD) in healthy patients and in patients with functional constipation. 
Study 102 was a randomized, double-blind/open label, placebo/active controlled study. 
Prucalopride was the active control included in the 102 study. An immediate release (IR) and a 
modified release formulation (DR) of PCS12852 were studied over the 0.3 mg to 3 mg dose 
range for the IR and 0.5 mg to 2 mg for the DR. Systemic exposures following administration of 
the IR formulation increased linearly over the 0.3 mg to 3 mg dose range. Steady state 
concentrations were achieved by approximately Day 5, consistent with the half-life of 


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approximately 24 hours. Only the IR formulation is currently being evaluated in the development 
of PCS12852. 
In terms of PD, PCS12852 resulted in pharmacologic activity related to stool assessments. There 
was a trend in improvement over placebo and comparable to prucalopride in terms of average 
weekly spontaneous bowel movements over the 2-week treatment period. PCS12852 was safe 
and generally well-tolerated with single and multiple doses under fasted and fed conditions in the 
healthy male and female patients and in patients with functional constipation. 
In the 102 study, an exploratory evaluation was also performed to investigate the change from 
baseline in gastric emptying measured by the GEBT on Day 7 for the low dose-immediate 
release cohort (IRM) at 0.05 mg and 0.1 mg, as well as the delayed release multiple dose cohort 
(DRM) at the various doses between 0.5 to 2 mg doses. The gastric emptying rate was estimated 
from the GEBT for each patient over time (45, 90, 120, 150, 180, and 240 minutes). The Area 
Under the Curve (AUC) for gastric emptying for each patient was determined as well as the 
change in the AUC from baseline for each patient. The time for 10% and 50% of the gastric 
emptying was also estimated from the GEBT. In the IRM cohort, the change from baseline in 
gastric emptying rate increased in both PCS12852 IR 0.05 mg and 0.1 mg groups. Additionally, 
the AUC of the 13C-Spirulina rate showed a statistically significant change from baseline in the 
PCS12852 IR 0.1 mg group. The IR 0.05 mg group showed a difference from baseline that was 
not statistically different. All the DRM treatment groups showed a significant difference from 
baseline.  These results along with the pharmacology data provide the rationale for looking 
further into PCS12852 as a treatment for gastroparesis. 
The efficacy of PCS12852 in gastroparesis will be investigated in this Phase 2A study. 
Preliminary data from the PCS12852-102 study showed a significant effect of PCS12852 at the 
0.1 mg QD dose level on the gastric emptying rate assessed by the Gastric Emptying Breath Test 
(GEBT), but less effect was noted with the 0.05 mg daily dose. Safety for multiple dosing up to 
3 mg daily has been well tolerated in the Phase 1 studies. This Phase 2A study will evaluate the 
effects of PCS12852 at the 0.1 and 0.5 mg dose levels vs. placebo on gastric emptying rate after 
28 days of treatment. The study will also evaluate the effects of PCS12852 treatment on the 
symptoms of gastroparesis assessed by the AMNI-GCSI-DD scale. 
2.2 Background 
PCS12852 (formerly known as YH12852) was previously developed by Yuhan Corporation 
(Korea) for the treatment of gastrointestinal motility disorders including chronic constipation, 
constipation-predominant irritable bowel syndrome, functional dyspepsia and gastroparesis. 


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Recently the product was acquired by Processa Pharmaceuticals, Inc. (Processa) and is being 
further developed for the treatment of gastroparesis. 
Although there have been advances in understanding the mechanisms and pathophysiology of 
gastroparesis, there are still significant gaps in knowledge, inconsistencies across studies, and 
potential differences between different etiological groups (for example, diabetic versus 
idiopathic). Currently, the only FDA approved treatment for gastroparesis is metoclopramide. 
However, it carries a black box warning, as it is generally not well-tolerated and chronic use 
(>12 weeks) may lead to extrapyramidal side effects and potential irreversible tardive dyskinesia. 
Based on the limitations in currently available products for the treatment of gastroparesis, there 
still remains an unmet need for new treatments for these patients. 
In support of the clinical development program for PCS12852, in vitro, ex vivo and in vivo 
pharmacology, safety pharmacology, pharmacokinetic and toxicology studies have been 
conducted. PCS12852 has been shown to have a high binding affinity for the 5-HT4 receptor 
with more than 200-fold selectivity over other 5-HT receptors, as well as for 80 targets including 
receptors, ion channels and transporters. PCS12852 also exhibits 3.4 times more potent agonistic 
activity than tegaserod to human 5-HT4A receptors stably expressed in Chinese hamster ovaries 
(CHO). In studies of ex vivo contractile activity in guinea pig colon, PCS12852 was found to be 
17 times more potent than 5-HT. 
The in vivo prokinetic effects of PCS12852 in the upper GI tract were evaluated in various 
models including rat, dog and monkey. Single oral administration of PCS12852 at doses of 3 to 
10 mg/kg in rats significantly increased the gastric emptying rate and PCS12852 at 3 mg/kg 
showed a comparable effect to that of another selective 5-HT4 agonist, mosapride at 10 mg/kg. In 
rat models of delayed gastric emptying and feeding inhibition induced by restraint stress, single 
oral administration of PCS12852 at doses of 1, 2 and 3 mg/kg dose-dependently improved 
gastric emptying, and doses of 1 and 2 mg/kg led to significant restoration of food intake. Single 
oral administration of PCS12852 at 1.0 μg/kg, significantly restored gastric emptying up to 
normal levels under conditions of clonidine-induced delayed gastric emptying in conscious 
beagle dogs. Single oral administration of PCS12852 at doses of 0.2, 0.4 and 1 mg/kg also 
significantly shortened the gastric emptying time as measured by real-time fluoroscopy imaging 
in monkeys. In addition to the efficacy shown in the gastroparesis models, PCS12852 
significantly increased fecal pellet output at 0.1, 0.3, 1, 3 and 10 mg/kg in male guinea pigs as 
well as significantly shortening the time to the first giant migrating contraction at 3, 10 and 30 
μg/kg and significantly increased giant migrating contraction frequency at 30 μg/kg in female 
dogs. These data demonstrate that PCS12852 possesses excellent prokinetic effects in the upper 
and lower GI tracts. 


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In cardiovascular safety studies, PCS12852 decreased hERG K+ currents in a dose-dependent 
manner, with an IC50 value of 0.71 μM in CHO cells and increased action potential duration 
(APD) at concentrations of 4.52 μM in isolated rabbit Purkinje fibers. Considering the affinity of 
PCS12852 for the human 5-HT4A receptor (IC50, 0.05 nM) and the expected Cmax at doses up to 
10 mg in human subjects, (free-drug Cmax = 2.89 nM, total-drug Cmax = 72.26 nM), it is estimated 
that there is little risk of hERG inhibition, action potential duration (APD) prolongation or 
cardiovascular contractility exists at the projected therapeutic clinical dose levels. In a telemetry 
study conducted with conscious monkeys, there were no abnormal electrocardiograms (ECG), 
blood pressure or heart rate findings after administration of single oral doses up to 60 mg/kg. In 
addition, no abnormalities were detected in ECG findings in 4-week and 13-week repeat-dose 
oral toxicity studies in monkeys treated with doses up to 60 mg/kg/day. Additionally, in a 
telemetry study performed in conscious dogs, there were no abnormal changes in heart rate or 
ECG parameters after single intravenous administration up to 1 mg/kg. Additional safety 
pharmacology studies did not show any significant effects on neurobehavioral function or 
respiratory function. 
Non-clinical toxicology studies of PCS12852 conducted so far include single-dose (rats and 
monkeys) and repeat-dose (rats and monkeys up to 13 weeks) toxicity studies, as well as in 
vitro/in vivo genetic toxicology studies, carcinogenicity studies, developmental and reproductive 
studies. In the 13-week toxicology study in rats there were no treatment-related findings up to 
100 mg/kg/day. The No Observable Adverse Effect Level (NOAEL) was determined to be 
100 mg/kg/day for both sexes. A 13-week repeat-dose oral toxicity study in monkeys, 
demonstrated treatment-related clinical signs including vomiting and soft/watery feces with 
increased neutrophil counts in both sexes at 60 mg/kg/day. Based on these findings, the NOAEL 
was determined to be 60 mg/kg/day for both sexes. No evidence for genotoxicity has been 
observed for PCS12852. In the carcinogenicity studies in rats and mice, no PCS12852-related 
neoplasms were noted. In fertility and early embryonic developmental toxicology studies in rats, 
there were no abnormal outcomes of mating, fertility or pregnancy. In addition, in embryo–fetal 
development studies in rats and rabbits, there has been no evidence suggesting that PCS12852 is 
dysmorphogenic. 
Two clinical phase 1 studies that include pharmacokinetic (PK) and pharmacodynamic (PD) 
information for PCS12852 have been conducted in healthy volunteers and patients. The first 
study, Study 101 was a randomized, double-blind, placebo/active-controlled, single/multiple 
dose Phase 1 study. This study evaluated the PK and PD of single and multiple ascending doses 
of PCS12852 over the range of 0.5 mg to 10 mg and 0.5 mg to 3 mg, respectively. In addition, 
the effect of food was evaluated over the 0.5 mg to 3 mg single dose range. The systemic 
exposure for PCS12852 increased in a dose-proportional manner following single and multiple 


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administrations under fed conditions; although peak exposure was increased in a slightly greater 
than dose-proportional manner at multiple doses of 0.5 to 3 mg. Food intake decreased 
PCS12852 Cmax by 75% and AUC(0-τ) by 61%, and delayed Tmax from 1.5 to 6 hours in females 
with no change in t½. In terms of PD, PCS12852 increased the frequency of defecation and 
decreased the stool consistency with fast onset of spontaneous bowel movements following 
single and multiple doses. 
A second study, Study 102, evaluated the single and multiple dose PK and PD in healthy patients 
and in patients with functional constipation. This was a randomized, double-blind/open label, 
placebo/active controlled study. Prucalopride was the active control. An immediate release (IR) 
and a delayed release formulation (DR) of PCS12852 were studied over the 0.3 mg to 3 mg dose 
range for the IR and 0.5 mg to 2 mg for the DR. Systemic exposures following administration of 
the IR formulation increased linearly over the 0.3 mg to 3 mg dose range. Steady state 
concentrations were achieved by approximately Day 5, consistent with the half-life of 
approximately 24 hours. In the groups that evaluated the modified release formulation (DR), a 
delay in Tmax for PCS12852 was noted, as expected. In terms of PD, PCS12852 resulted in 
pharmacologic activity related to stool assessments. There was a trend in improvement over 
placebo and comparable to prucalopride in terms of average weekly spontaneous bowel 
movements over the 2-week treatment period. PCS12852 was safe and generally well-tolerated 
with single and multiple doses under fasted and fed conditions in the healthy male and female 
patients and in patients with functional constipation. 
In the 102 study, an exploratory evaluation was also performed to investigate the change from 
baseline in gastric emptying measured by GEBT on Day 7 (for the low dose-immediate release 
cohort (IRM) and the delayed release multiple dose cohort (DRM) only). The time for 10% and 
50% gastric emptying was analyzed, along with the area under the curve (AUC) of the 13C rate 
measured in breaths and the analysis of the gastric emptying rate over time (45, 90, 120, 150, 
180, and 240 minutes). In the IRM cohort, the change from baseline in gastric emptying rate 
increased in both PCS12852 IR 0.1 mg and 0.05 mg groups. Additionally, the AUC of the 13C 
rate showed a statistically significant change from baseline in the PCS12852 IR 0.1 mg group. 
Similar results were noted for DRM cohort. 
All doses of PCS12852 in both of the clinical studies were well tolerated and no serious adverse 
events (SAEs) occurred. The most frequent treatment-emergent adverse events were diarrhea, 
headache, and nausea. There were no changes in vital signs, platelet aggregation or ECG 
parameters including no sign of QTc prolongation in time-matched ECGs monitored in the single 
ascending dose cohort. 


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The non-clinical and limited clinical safety and efficacy data accumulated thus far support 
further investigation on the efficacy, safety and tolerability of multiple doses of PCS12852 IR 
formulation for the treatment of gastroparesis. 
2.3 Benefit/Risk Assessment 
The clinical benefit/risk profiles of these 5-HT4 receptor agonists, some of which exhibit poor 
5-HT4 receptor selectivity, have been complicated by the occurrence of rare but serious side 
effects related to the binding of the agonists to unintended target receptors or channels. For 
example, the marketing of both cisapride and tegaserod was discontinued due to cardiovascular 
concerns (cardiac arrhythmias with cisapride and ischemic events with tegaserod, respectively). 
Tegaserod, which is used for the treatment of irritable bowel syndrome-constipation and chronic 
constipation, was also found to be an agonist for the 5-HT1B and 5-HT1D receptors, as well as an 
antagonist for 5-HT2B receptors. This nonselectivity may explain its association with rare, but 
serious, instances of ischemic AEs, including stroke and angina. Therefore, more highly selective 
5-HT4 receptor agonists are expected to exhibit favorable safety profiles with a lower risk of 
cardiovascular side effects ( Manabe, 2010; FDA Briefing Document, 2011). Prucalopride, a 
recently developed selective 5-HT4 receptor agonist, is intended to be used by laxative 
non-responders (NICE, 2010). However, it has been found that in several clinical trials, the most 
common reason for discontinuation of prucalopride medication was its poor response rate 
(Movetis, 2008 [PRU-USA-22]; Movetis, 2008 [PRU-INT-17]; Movetis, 2008 [PRU-INT-10]). 
This implies that a significant number of refractory patients still exist. In addition, recently-
developed IBS and chronic constipation drugs such as linaclotide are considered expensive 
compared to traditional laxatives. Linaclotide at 1,000 μg doses had no effect on upper 
gastrointestinal motility, as measured by gastric emptying and small bowel transit. 
A series of in vitro and in vivo safety pharmacology studies were conducted to assess PCS12852 
for evidence of off-target receptor binding and adverse effects on the central nervous, 
cardiovascular and respiratory systems. Exposure multiples were estimated based on the human 
Cmax (free-drug Cmax = 2.89 nM, total-drug Cmax 72.26 nM) at the highest dose of 10 mg in the 
SAD study. PCS12852 decreased hERG K+ current in a dose-dependent manner with an IC50 
value of 710 nM, obtained using the whole-cell patch clamp technique to measure peak hERG 
tail current in CHO cells (G12070). An isolated rabbit Purkinje fiber assay (G12171), revealed 
that PCS12852 increased APD at a concentration of 4.52 μM. Ex vivo contractility testing using 
tissue chambers with isolated rat aorta and canine coronary artery demonstrated that PCS12852 
did not significantly influence canine coronary artery or aorta isometric tone in sham-operated or 
DOCA-salt hypertensive rats at concentrations of 0.1 to 100 μM. Considering the affinity of 
PCS12852 for the human 5-HT4A receptor (IC50, 0.05 nM) and Cmax (free-drug Cmax = 2.89 nM, 


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total-drug Cmax = 72.26 nM) at 10 mg in the SAD study, it is estimated that little or no risk of 
hERG inhibition, APD prolongation or cardiovascular contractility exists at the projected 
therapeutic clinical dose levels. 
In summary, PCS12852 at the doses of 3 and 10 mg/kg significantly increased solid gastric 
emptying rates in rats, and its effect appears to be comparable to that of mosapride, indicating 
that PCS12852 may accelerate gastric emptying in patients with gastroparesis or functional 
dyspepsia. 
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs associated with PCS12852 are provided in the Investigator’s Brochure. 


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3 Objectives and Endpoints 
Table 2 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
 
• 
To evaluate the effect of different doses of 
PCS12852 on the gastric emptying rate, as 
measured by the GEBT, in patients with 
moderate to severe idiopathic gastroparesis 
(IG) or DG 
• 
To evaluate the PK profile of PCS12852 at 
different dose levels. 
 
• 
Change in gastric emptying rate from baseline 
as determined by the AUC of the gastric 
emptying rate over time as assessed by the 
GEBT at Visit 6 (Day 28) after administration 
of the PCS12852 or placebo. 
• 
Change in gastric emptying rate from baseline 
using the t10 and t50 metric for gastric 
emptying rate. 
• 
Concentrations of PCS12852 in plasma; PK 
parameters will be estimated from 
concentration-time data using 
noncompartmental methods, as data permit. 
 
Secondary 
 
• 
To evaluate the effects of different doses of 
PCS12852 on symptoms, as measured by the 
American Neurogastroenterology and 
Motility Society Gastroparesis Cardinal 
Symptom Index Daily Diary (ANMS 
GCSI-DD), in patients with moderate to 
severe idiopathic and diabetic gastroparesis 
• 
Change from baseline in the ANMS 
GCSI-DD) (i.e., Day-7 to Day -1) (predose) 
and Day 7 (Day 1 to Day 7) 
• 
Change from baseline in the ANMS 
GCSI-DD (i.e., Day-7 to Day -1) (predose) 
and Day 14 (Day 8 to Day 14) 
• 
Change from baseline in the ANMS 
GCSI-DD (i.e., Day-7 to Day -1) (predose) 
and Day 21 (Day 15 to Day 21) 
• 
Change from baseline in the ANMS 
GCSI-DD (i.e., Day-7 to Day -1) (predose) 
and Day 28 (Day 22 to Day 28) 
Exploratory Efficacy 
• 
To evaluate the effects of different doses of 
PCS12852 on symptoms or QOL, as 
measured by the PAGI-SYM, PAGI-QOL, 
PGI-S, PGI-C, CGI-S and CGI-I, in patients 
with moderate to severe idiopathic or diabetic 
gastroparesis 
• 
Change from baseline in ANMS GCSI-DD 
score over time (Day 7, 14, 21, 28) by 
comparing Day 7 to Day 14, Day 14 to 
Day 21 and Day 21 to Day 28. 
• Change from baseline in the sub scores 
(nausea, early satiety, postprandial 
fullness, upper abdominal pain and 
number of vomiting episodes) of the 


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Objectives 
Endpoints 
 
ANMS-GCSI-DD over time (Day 7, 14, 
21, 28) by comparing Day 7 to Day 14, 
Day 14 to Day 21 and Day 21 to Day 
28. 
• 
Change from baseline in PAGI-SYM and 
PAGI-QOL scores over time by comparing 
Day 1 to Day 28. 
• 
Change from baseline in Clinical Global 
Impression-Severity (CGI-S) and Clinical 
Global Impression-Improvement (CGI-I) 
scores over time by comparing Day 1 to 
Day 28. 
• 
Change from baseline in PGI-S and PGI-C 
scores over time by comparing Day 1 to 
Day 28. 
Safety 
To evaluate the safety and tolerability of different 
doses of PCS12852 in idiopathic and diabetic 
gastroparesis patients. 
• 
Adverse Events (by type, severity, and 
relatedness) at each visit. 
• 
Changes in safety clinical laboratory testing 
and vital signs at each site visit. 
• 
Changes in ECGs at each site visit and the 
potential correlation of the PK with changes 
in the ECG. 
• 
Change from baseline in the C-SSRS scores 
over time by comparing Day 1 to Day 28. 


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4 Study Design 
4.1 Overall Design 
This is a Phase 2A, placebo-controlled, randomized dose response study of the safety, PK, and 
efficacy of PCS12852 on gastric emptying rate assessed by the GEBT in patients with moderate 
to severe gastroparesis. 
In this study, gastroparesis patients who have successfully completed Screening criteria (Visit 1) 
will return for a second Screening Visit (Visit 2) where the inclusion/exclusion criteria will be 
re-evaluated. 
Visit 1 will include all safety labs and procedures (including an ECG) as well as the 
Columbia-Suicide Severity Rating Scales (C-SSRS) assessed by the investigator to confirm that 
the patient does not have any suicidal tendencies or ideation. If patients still meet study criteria 
when returning for Visit 2, a GEBT will be performed and the patient will be educated on 
completion of the ANMS GCSI-DD. Patients will complete the ANMS GCSI-DD for 7 days. 
The results from both the GEBT and the ANMS GCSI-DD during the Screening period will be 
considered the baseline values for these assessments. 
The GEBT at Visit 2 and Visit 6 will be performed at the sites. Patients will be told to fast 
overnight (at least 8 hours) prior to coming to the site for the test. The patient will have their 
glucose tested both before and after the GEBT. The patient must have a fasting blood glucose of 
≤275 mg/dL to proceed with the GEBT. If the patient does not have a FBG ≤ 275 mg/dL, they 
are permitted to come in the following day to perform the GEBT test. If the patient’s FBG is not 
within range at Visit 6, the patient will be sent home with an additional dose of study medication 
and asked to return the next day to perform the GEBT.  
Patients will return to the site for Day 1 (Visit 3 [Randomization]) where patients who meet the 
criteria for having moderate to severe symptoms based on the ANMS GCSI-DD will be 
randomized in a 1:1:1 ratio into three treatment groups, PCS12852 0.1 mg, PCS12852 0.5 mg or 
placebo. At Visit 3, patients will answer a series of questionnaires including the Patient 
Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM), Patient 
Assessment of Upper Gastrointestinal Disorders – Quality of Life (PAGI-QOL), Patient Global 
Impression of Severity (PGI-S) and the Patient Global Impression of Change (PGI-C). Patients 
will arrive in a fasted condition and have PK samples drawn prior to receiving the first dose and 
at the following times after the first dose, 0.5, 1, 2, 4, 6, and 8 hours. The ECG should be 
performed prior to the 4-hour PK draw between the 2- and 4-hour samples. The investigator will 
assess the patient through the C-SSRS as well as the CGI-S and CGI-I. 
Patients will return to the site on Day 7 (Visit 4) and Day 14 (Visit 5) to undergo safety and 
tolerability assessments as per the Schedule of Assessments, along with the investigator 
assessing the patient for the C-SSRS to ensure the patient does not have any suicidal tendencies 


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or ideation.  Sites will be asked to schedule the patient’s visit so that the ECG can be performed 
approximately 4 hours after the patient’s dose.  
Patients will take their assigned treatment once daily for 28 days and will return to the site on 
Day 28 (Visit 6) for their final dose. On Visit 6, PK samples will be drawn and the GEBT will be 
repeated. During the treatment period, the patients will also complete the ANMS GCSI-DD. 
Each patient will be told to take one tablet from their assigned kit each day at approximately the 
same time each morning, at least 30 minutes prior to a meal (actual dosing times will be captured 
via a dosing diary), while fasting starting on Day 1 for 28 days. 
On the morning of Day 28, after fasting overnight (for at least 8 hours), the patient will return to 
the site for Visit 6. At Visit 6, the patient will again compete the patient assessments and will 
have a PK sample drawn prior to receiving the final dose of PCS12852 or placebo and then have 
PK samples drawn at 0.5, 1, 2, 4, 6, and 8 hours post-dose. The ECG should be performed prior 
to the 4-hour PK draw between the 2- and 4-hour samples. The patient must have a fasting blood 
glucose (FBG) of ≤275 mg/dL to proceed with the GEBT.  If the patient’s FBG is not within 
range, the patient will be sent home with an additional dose of study drug and asked to return the 
next day to perform the GEBT and PK sampling. The GEBT test will be performed for 4 hours 
and will be administered approximately 30-60 minutes after the patient’s final dose of study 
treatment. During the GEBT test, the site will prioritize taking the GEBT samples and then the 
PK samples. After the test is complete the patients will be discharged and then will return 
approximately 48-72 hours after Day 28 (Visit 6) to have a PK blood sample drawn. The patient 
will also return to the site 1 week after the Day 28 visit for a follow-up visit (Day 35/Visit 8). 
The total study duration for each patient is expected to be approximately 8 weeks (3 weeks for 
Screening, 4 weeks for treatment, and 1 week for follow-up). 
The SoA displaying assessments/tasks and time points is presented in Table 1. 
 
4.2 Scientific Rationale for Study Design 
This study has been designed to comply with recommendations in the FDA Guidance: 
Gastroparesis: Clinical Evaluation of Drugs for Treatment Guidance for Industry. 
Several design features have been incorporated in the study in an effort to minimize bias, 
including double-blind design and random assignment of patients, helping to ensure that both 
known and unknown risk factors are distributed evenly among treatment groups. The use of a 
placebo control permits prospective comparison between the PCS12852 0.1 mg group and the 
PCS12852 0.5 mg group. 


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4.3 Justification for Dose 
In the Phase 1 studies conducted with PCS12852, the product appeared to be safe and generally 
well-tolerated after both single (0.5 to 10 mg) and multiple doses (0.05 to 3 mg QD) 
(Section 2.1). The most frequently reported AE was headache. All AEs were generally mild and 
resolved without treatment. Therefore, the doses to be administered in the proposed Phase 2A 
study are 0.1 mg and 0.5 mg QD.   
Data from the PCS12852-102 study showed a significant effect of PCS12852 at the 0.1 mg QD 
dose level on the gastric emptying rate assessed by the GEBT, but less effect was noted with the 
0.05 mg daily dose.  Safety for multiple dosing up to 3 mg daily has been well tolerated in the 
Phase 1 studies. In this Phase 2A study the effects of PCS12852 at the 0.1 and 0.5 mg dose levels 
vs. placebo will be evaluated on gastric emptying rate after 28 days of treatment.   
4.4 End of Study Definition 
The end of the study is defined as the date of the last visit of the last patient in the study. 
A patient is considered to have completed the study if he/she has completed all 4 weeks of the 
study treatment and has had the last visit (Visit 8). 
Independent of the end of study definition, all laboratory tests with values considered clinically 
significantly abnormal during participation in the study or within 30 days after the last dose of 
study treatment should be repeated until the values return to normal or baseline or are no longer 
considered clinically significant by the Investigator or medical safety physician. 
The overall study will be stopped if ≥ 2 patients develop the same Grade 3 CTCAE (Common 
Terminology Criteria for Adverse Events) cardiac event or 1 patient develops a CTCAE ≥ Grade 
4 cardiac event. 
 
 


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5 Study Population 
The study population will consist of male and female patients 18 to 80 years of age with 
moderate to severe IG or DG. 
The patients must be able to provide written consent and meet all the inclusion criteria and none 
of the exclusion criteria based on Screening. 
5.1 Inclusion Criteria 
Patients are eligible to be included in the study only if all of the following criteria apply: 
1. Has a documented diagnosis of moderate to severe DG or IG according to the 
ANMS GCSI-DD score during the Screening period (Score of >2 on average of 
the screening days). 
2. Moderate to severe delay in gastric emptying rate as measured by the GEBT at 
Screening defined as GE half-time (t1/2) ≥ the 80th percentile of normative data as 
determined by Cairn Diagnostics. 
3. Male or female patients 18 to 80 years of age, inclusive, at baseline. 
4. Has continuous moderate to severe symptoms for gastroparesis (that is, chronic 
postprandial fullness, abdominal pain, postprandial nausea, vomiting, loss of 
appetite and/or early satiety) as assessed by the investigator for at least the past 3 
months. 
5. Has hemoglobin A1c (HbA1c) less than (<) 11 percent (%). 
6. Has Body Mass Index range between 18 - 40. 
7. Women of childbearing potential must have a negative serum pregnancy test at 
the Screening Visit and a negative urine pregnancy test at baseline before dosing. 
8. Women of childbearing potential must use one of the following acceptable 
methods of contraception throughout the study (1 month prior to Screening 
through 1 month after last dose of study medication): oral contraceptive 
medication, intrauterine device (IUD), hormonal implants, injectable 
contraceptive medications, double-barrier methods, or tubal ligation. 
9. Females who are postmenopausal (age-related amenorrhea ≥ 12 consecutive 
months and increased follicle-stimulating hormone [FSH] > 40 mIU/mL. If 
necessary, to confirm postmenopausal status, an FSH will be drawn at Screening) 
or who have undergone hysterectomy or bilateral oophorectomy are exempt from 
pregnancy testing. 
10. Male patients must be willing to use acceptable contraceptive measures such as 
vasectomy or double barrier method and refrain from sexual activity with any 


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female who is pregnant or lactating.  Female partners of study participants are 
asked to use acceptable methods of contraception as listed in Inclusion #8 above.  
11. Patient must be willing and able to swallow whole tablets. 
12. Patient must be willing and able to comply with study procedures. 
13. Compliance with the completion of the ANMS GCSI-DD, defined as 
approximately 80% diary completions, during the screening period. For those 
patients whose compliance is measured to be <80%, the final decision to 
randomize a patient will be made by the Investigator and the Sponsor (or 
designee). 
14. Patient must be willing and able to provide signed, informed consent. 
5.2 Exclusion Criteria 
Patients are excluded from the study if any of the following criteria apply: 
1. Has acute, severe gastroenteritis and pronounced dehydration in the past 48 hours 
prior to Screening, chronic parenteral feeding or persistent severe vomiting. 
2. Has known hypersensitivity to Spirulina, egg, milk products or wheat allergens. 
3. Has a known disturbance of small intestinal absorption, exocrine pancreatic 
function, liver metabolism or pulmonary function. 
4. Has a history of anorexia nervosa or bulimia. 
5. Previous history of bezoars (the presence of retained liquid, bile, or small amounts 
of poorly organized food residue is permitted). 
6. Prior surgery involving any gastrointestinal surgery, including the luminal 
gastrointestinal (GI) tract (cholecystectomy and appendectomy are permitted if 
performed greater than (>) 3 months prior to baseline GEBT). 
7. Any abdominal or pelvic surgery within the past 3 months. 
8. Known or history of the following GI conditions: inflammatory bowel disease; 
irritable bowel syndrome with diarrhea; or any other active disorder that could 
explain symptoms in the opinion of the investigator. 
9. Has active diverticulitis, diverticular stricture, and other intestinal strictures. 
10. Has feeding or decompression tubes and/or a gastric pacemaker. 
11. Has had Botox pyloric injections within the prior 3 months. 
12. Has had diabetic ketoacidosis (within the prior 4 weeks). 
13. Currently taking Glucagon-like peptide-1 (GLP-1) agonists, e.g. exenatide, 
liraglutide, semaglutide or dulaglutide, or pramlintide. 
14. Has severe psychiatric illness (including suicidal tendencies or ideation) or 
neurological illness. 
15. History or suspicion of alcohol, barbiturate, amphetamine or narcotic abuse. 


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16. Use of narcotics/opioids, drugs used to treat gastroparesis within 3 days of the 
Screening GEBT test. 
17. Anticipated concurrent use of a strong Cytochrome P450 (CYP) inhibiting or 
inducing drug (listed in Section 6.7.1) that would significantly alter the 
metabolism of PCS12852 and/or its metabolites during the course of the study 
(after Screening) 
18. Fever (> 38°C), or chronic, persistent, or recurring infection(s) at Screening or 
baseline. 
19. Clinically significant cardiac disease including but not limited to unstable angina, 
acute myocardial infarction within 6 months of baseline, and arrhythmia requiring 
therapy. 
20. Patient has QTcF interval ≥ 480 milliseconds on Screening ECG; a second 
Screening ECG may be done at the Investigator’s discretion but the average of the 
two QTcF screening intervals must not be ≥ 480 milliseconds. 
21. History of cerebral hemorrhage, cerebrovascular accident, transient ischemic 
attack, gastrointestinal bleeding, or retinal hemorrhage within 6 months of 
baseline. 
22. Patient has active or history of neoplastic disease (except for adequately treated 
non-invasive basal cell and/or squamous cell carcinoma of the skin or carcinoma 
in situ of the cervix) within the past 5 years prior to baseline. 
23. Presence of clinically significant medical condition(s) including but not limited 
to: renal, hepatic, cardiovascular, hematological, gastrointestinal, endocrine, 
pulmonary, neurological, psychiatric, substance abuse, and/or any other clinically 
significant disease or disorder, which in the opinion of the Investigator (by its 
nature or by being inadequately controlled), may put the patient at risk due to 
participation in the study, influence the results of the study, and/or affect the 
patient’s ability to complete the study. 
24. History of or current diagnosis of active tuberculosis (TB); undergoing treatment 
for latent TB infection (LTBI); untreated LTBI (as determined by documented 
results within 3 months of the Screening Visit of a positive TB skin test with 
purified protein derivative with induration > = 5 mm, a positive QuantiFERON-
TB test or positive or borderline T-SPOT [Elispot] test); or positive TB test at 
Screening. Patients with documented completion of appropriate LTBI treatment 
would not be excluded and are not required to be tested. 
25. Vaccination with live or live-attenuated virus vaccine within 1 month prior to 
baseline. Vaccines for COVID-19 are allowed. 


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26. The results of the following laboratory tests performed at the central laboratory at 
Screening meet any of the criteria below: 
a. Hemoglobin < 8.0 g/dL (International System of Units: < 80 g/L) 
b. White blood cells < 3.0 x 10^3 cells/mm^3 (SI: < 3.0 x 10^9 cells/L) 
c. Neutrophils < 1.0 x 10^3 cells/mm^3 (SI: < 1.0 x 10^9 cells/L) 
d. Lymphocytes < 0.5 x 10^3 cells/mm^3 (SI: < 0.5 x 10^9 cells/L) 
e. Platelets < 100 x 10^3 cells/mm^3 (SI: < 100 x 10^9 cells/L) 
f. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), 
and/or alkaline phosphatase (ALP) ≥ 2 x upper limit of normal (ULN) 
g. Total bilirubin level ≥ 2 x ULN unless the individual has been diagnosed 
with Gilbert’s disease and this is clearly documented 
h. Estimated glomerular filtration rate < 40 mL/min/1.73 m^2 based on the 
Modification of Diet in Renal Disease formula 
i. Creatinine ≥ 3 mg/dL 
j. Positive human immunodeficiency virus serology 
k. Evidence of active Hepatitis B Virus infection 
l. Evidence of active Hepatitis C Virus infection 
27. Women who are pregnant or breastfeeding. 
28. Any other medical condition, serious intercurrent illness, or extenuating 
circumstance that, in the opinion of the Investigator, would preclude participation 
in the study. 
29. Use of any investigational product within 30 days prior to baseline or currently 
enrolled in another study that involves clinical interventions. 
30. Currently taking known P-gp and BCRP inhibitors or inducers and gastric acid 
reducing agents. E.g., proton pump inhibitors or H2 receptor antagonists 
5.3 Lifestyle Considerations 
Abuse of alcohol, barbiturates, amphetamines or narcotics is restricted as indicated in 
Section 5.2. Smoking is prohibited at least 24 hours prior to the Screening GEBT and during the 
conduct of the study. There are no other specific lifestyle restrictions in the study. 
5.3.1 
Meals and Dietary Restrictions 
Please refer to Section 4.1 for details regarding the standardized low calorie meal that the 
patients will consume at Visits 2 and 6. Please refer to the SoA (Table 1) for timing of the GEBT. 
5.4 Screen Failures 
Screen failures are defined as patients who consent to participate in the clinical study but are not 
subsequently enrolled in the study. 


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Individuals who do not meet certain criteria (e.g. lab values) for participation in this study 
(screen failure) may be rescreened. The GEBT test will not be repeated on a patient that does not 
meet GEBT entry criteria. 
6 Study Treatment and Concomitant Therapy 
Study treatment is defined as any investigational treatments, marketed product, or placebo, or 
intended to be administered to a study patient according to the study protocol. 
6.1 Treatments Administered 
Table 3 
Study Treatments Administered 
Study Treatment 
PCS12852 
Placebo 
Dosage Formulation 
Tablet 
Tablet 
Unit Dose Strengths 
0.1 mg and 0.5 mg 
N/A  
Route of Administration 
Oral 
Oral 
Packaging and Labeling 
PCS12852 tablets and matching placebo tablets will be packaged in high density polyethylene 
bottles respectively.   
Each patient’s study medication will be packaged in a study-specific box (kit) and shipped to the 
study site by a central distribution site. 
 
Treatment Schedule 
Regardless of the patient’s assigned treatment group, each patient will take one tablet from their 
assigned kit at approximately the same time each morning and at least 30 minutes prior to a meal 
starting on Day 1 for 28 days.  For Day 28, the patients will be asked to fast overnight prior to the 
morning dose on Day 28 and the subsequent GEBT.  The patient will be asked to document the 
timing of each dosing via a dosing diary. 
 
6.2 Preparation, Handling, Storage, and Accountability 
The Investigator or designee must maintain a log to confirm appropriate temperature conditions 
have been maintained during transit for all study treatment received, and any discrepancies are 
reported and resolved before use of the study treatment. Study treatment must be stored in the 
original packaging between 20 to 25° C (68 to 77° F), with deviations permitted between 15 to 
30°C (59 to 86° F) and protected from extreme conditions of temperature, light, and humidity. 


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Only patients enrolled in the study may receive study treatment, and only authorized site staff 
may supply or administer study treatment. All study treatments must be stored in a secure, 
environmentally controlled, and monitored (manual or automated) area in accordance with the 
labeled storage conditions with access limited to the Investigator and authorized site staff. 
The Investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study treatment accountability, reconciliation, and record maintenance (e.g., 
receipt, reconciliation, and final disposition records). 
Further guidance and information for the final disposition of unused study treatment are provided 
in the Study Reference Manual. 
6.3 Measures to Minimize Bias: Randomization and Blinding 
Patients who have successfully completed Screening criteria (Visit 1 and Visit 2) will return for a 
Randomization visit (Visit 3) where the inclusion/exclusion criteria will be evaluated and 
patients who meet the criteria will be randomized in a 1:1:1 ratio into one of the three treatment 
groups, PCS12852 0.1mg, PCS12852 0.5mg or placebo via Interactive Response Technology 
(IRT).  The planned sample size to be randomized is 24 patients. The randomization to treatment 
groups will be stratified by type (IG, DG), enrolling at least 2 patients of each type in each 
treatment group. 
The list of treatment allocations will be kept in a secure location by the CRO until approval to 
unblind is provided for the final analysis.  Access to the treatment allocations will be monitored 
by Regulatory Affairs/Quality Assurance; any access to the allocations prior to unblinding the 
study will be documented by Regulatory Affairs/Quality Assurance and included in the Clinical 
Study Report.   
Table 4 
Measures to Minimize Bias 
Study using IRT 
All patients will be centrally randomized using an Interactive Response 
Technology (IRT). Each patient will be assigned a unique number 
(randomization number) that encodes the patient’s assignment to one of the 3 
arms of the study, according to the randomization schedule using a validated 
computer program. Details of the procedure are described in the IRT Manual 
provided to all sites. 
Study treatment will be administered/dispensed at the study visits as summarized 
in the SoA (Table 1). 
Returned study treatment should not be re-dispensed to the patients. 


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Blind break (IRT) 
This is a double-blind study in which patients are blinded to study treatment. 
The IRT will be programmed with blind-breaking instructions. In case of an 
emergency, the Investigator has the sole responsibility for determining if 
unblinding of a patient’s study treatment assignment is warranted. Patient safety 
must always be the first consideration in making such a determination. If the 
Investigator decides that unblinding is warranted, the Investigator should make 
every effort to contact the Medical Monitor prior to unblinding a patient’s study 
treatment assignment unless this could delay emergency treatment for the 
patient. If a patient’s study treatment assignment is unblinded, the Sponsor must 
be notified within 24 hours of this occurrence. The date and reason for the 
unblinding must be recorded. 
 
The Sponsor may unblind the treatment assignment for any patient with an SAE. If the SAE 
requires that an expedited regulatory report be sent to one or more regulatory agencies, a copy of 
the report, identifying the patient’s treatment assignment, may be sent to Investigators in 
accordance with local regulations and/or Sponsor policy. 
6.4 Study Treatment Compliance 
When patients are dosed at the site, study treatment will be administered directly by the 
Investigator or designee. All dosing by the patient throughout the treatment period will also be 
documented in the patient’s dosing diary. The date and time of each dose administered in the 
clinic will be recorded in the source documents. The dose of study treatment and study patient 
identification will be confirmed at the time of dosing by a member of the study site staff other 
than the person administering the study treatment. 
For self-administration of the study treatment at home by the patient, compliance with study 
treatment will be assessed at each visit. Compliance will be assessed by direct questioning and 
counting returned tablets during the site visits and documented in the source documents and 
relevant form. Deviations from the prescribed dosage regimen should be recorded. Final drug 
accountability will be done by counting returned tablets at the patient’s final visit. 
A record of the quantity of study treatment dispensed to and administered by each patient must 
be maintained and reconciled with study treatment and compliance records. Treatment start and 
stop dates, including dates for treatment delays and/or dose reductions will also be recorded. 
6.5 Continued Access to Study Treatment After the End of the Study 
The study treatment will not be available to the patients at the end of the study. 


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6.6 Treatment of Overdose 
For this study, any dose of study treatment greater than 20 tablets within a 24-hour time period 
will be considered an overdose. 
In the event of an overdose, the Investigator should: 
• Contact the medical monitor immediately. 
• Evaluate the patient to determine, in consultation with the medical monitor, whether study 
treatment should be interrupted or whether the dose should be reduced. 
• Closely monitor the patient for any AE/SAE and laboratory abnormalities until study 
treatment can no longer be detected systemically. 
6.7 Concomitant Therapy 
Any medication or vaccine (including over-the-counter or prescription medicines, recreational 
drugs, vitamins, and/or herbal supplements) that the patient is receiving at the time of enrollment 
or receives during the study must be recorded along with: 
• reason for use 
• dates of administration including start and end dates 
• dosage information including dose and frequency 
As much as possible, the dose and frequency of all concomitant medications taken for chronic 
conditions except for diabetes mellitus (see Section 6.7.2) should be held stable during the study. 
The Medical Monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
6.7.1 
Prohibited Treatments 
The class of drugs prohibited in the study are those that affect GI motility, either positively or 
negatively, and therefore could confound the assessment of the efficacy of the study treatment on 
the signs and symptoms of gastroparesis. 
Prohibited concomitant treatment includes cannabis, opioids, GLP-1 agonists (e.g. exenatide, 
liraglutide, semaglutide or dulaglutide, or pramlintide), cisapride, tegaserod, prucalopride, 
metoclopramide, bethanechol, domperidone and erythromycin or any other medications that are 
contraindicated for patients with gastroparesis. 


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IMPORTANT:  Patients should be instructed to consult with the Investigator before taking 
any new medication or changing medications and/or dosing regimens throughout the study.   
Drugs that are known to be strong inhibitors or inducers of Cytochrome P450 (CYP) (most likely 
CYP3A4 and CYP1A2) may significantly alter exposure to the investigational product, and as 
such, are strictly prohibited while on the study.    Examples of CYP inhibitors include 
cimetidine, ciprofloxacin, fluvoxamine, clarithromycin, diltiazem, grapefruit juice, and 
itraconazole. Examples of CYP inducers include carbamazepine, phenobarbital, tobacco, and St. 
John’s wort.  
P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and gastric acid 
reducing agents may also significantly alter the exposure of the investigational 
product and as such, are strictly prohibited while on study. Examples of P-gp 
inhibitors include cyclosporine, amiodarone, and itraconazole as well as BCRP inhibitors 
include novobiocin, sulfasalazine and cyclosporine A which may potentially increase the 
systemic exposure. Examples of P-gp inducers include carbamazepine, phenytoin and 
rifampin.  Examples of BCRP inducers and gastric acid reducing agents include 
venlafaxine, apalutamide and dovitinib as well as PPIs (esomeprazole, lansoprazole, 
omeprazole, etc), H2 blockers (ranitidine, famotidine, nizatidine) which may potentially 
decrease the systemic exposure.  
 
6.7.2 
Permitted Treatments 
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins, 
and/or herbal supplements) that the patient is receiving at the time of enrollment or receives 
during the study must be recorded in the eCRF along with: 
• 
indication 
• 
dates of administration including start and end dates 
• 
dosage information including dose and frequency 
 
Diabetic gastroparesis patients enrolled in the study will likely consist mostly of patients 
receiving one or more prescription medications for blood-glucose control. Good clinical practice 
allows for frequent adjustment of medication by patients and their health care providers to 
minimize large fluctuations in glycemia, and this practice is encouraged in this study. 
It should be remembered that certain diabetic drugs (see Section 6.7.1) delay gastric emptying 
and are prohibited during this study. Other therapy considered necessary for the patient’s welfare 


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may be given at the discretion of the Investigator. If the permissibility of a specific 
medication/treatment is in question, please contact the Medical Monitor. 
The Medical Monitor or designee should be contacted if there are any questions regarding 
concomitant or prior therapy. 
6.7.3 
Rescue Medicine 
Use of medications that may impact efficacy evaluations is strongly discouraged at any time after 
Visit 1 in the study. However, patients who experience severe symptoms of gastroparesis after 
entering the Treatment Period may receive a single day of treatment per week with an 
anti-emetic drug, but should avoid such treatment, if possible, on the day prior to and day of 
treatment visits. If a patient requires an anti-emetic drug (e.g., 5-HT3 receptor antagonists, NK1 
receptor antagonists) for more than 1 day a week, or requires an antiemetic drug once weekly 
repeatedly (i.e., more than 2 weeks while on study), the Investigator should contact the Medical 
Monitor to discuss the safety of the patient continuing in the study. 
The following rescue medications may be used: 
• ondansetron or promethazine (tablet, syrup or suppositories) for emesis 
• loperamide for diarrhea 
• Tramadol for pain 
 
 
The date and time of rescue medication administration as well as the name and dosage regimen 
of the rescue medication must be recorded. 
 
7 Discontinuation/Withdrawal Criteria 
It may be necessary for a patient to permanently discontinue study treatment. Reasons for 
discontinuation from study treatment and/or the study may include the following: 
• Adverse event 
• Death 
• Failure to meet randomization criteria 
• Lack of efficacy 
• Lost to follow-up 
• Investigator decision 
• Pregnancy 


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• Protocol deviation 
• Screen failure 
• Site terminated by the Sponsor 
• Study terminated by the Sponsor 
• Withdrawal by the patient 
 
The reason for discontinuation should be clearly documented on the appropriate eCRF. 
Discontinuation of study treatment also requires discontinuation from the study. If study 
treatment is permanently discontinued, the patient will not remain in the study. See the SoA 
(Table 1) for data to be collected at the time of discontinuation of study treatment and follow-up 
and for any further evaluations that need to be completed. 
A patient may withdraw from the study at any time at their own request or may be withdrawn at 
any time at the discretion of the Investigator for safety, behavioral, or compliance reasons. The 
patient will be permanently discontinued from the study treatment and the study at that time. 
If the patient withdraws consent for disclosure of future information, the Sponsor may retain and 
continue to use any data collected before such a withdrawal of consent. 
If a patient withdraws from the study, he/she may request destruction of any samples taken and 
not tested, and the Investigator must document this in the site study records. 
At the time of discontinuing from the study, if possible, an early discontinuation visit should be 
conducted, as shown in the SoA (Table 1). Refer to the SoA for data to be collected at the time of 
study discontinuation and follow-up and for any further evaluations that need to be completed. 
7.1.1 
Stopping Criteria 
  
PCS12852 is a highly selective 5-hydroxytryptamine receptor 4 (5-HT4 receptor) agonist. As 
such, the stopping rules focus on the known cardiac safety concerns identified for the drug class 
of 5-HT4 receptor agonists. The overall study will be stopped if ≥ 2 patients develop the same 
Grade 3 CTCAE cardiac event or 1 patient develops a CTCAE ≥ Grade 4 cardiac event. 
For cardiac adverse events classified as CTCAE ≥ Grade 3, if the same cardiac safety concern is 
seen on two separate ECGs, the patient should be withdrawn from the study and will be referred 
to a cardiologist for the appropriate treatment. 


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7.2 Loss to Follow-Up/Early Discontinuation from Study Drug 
A patient will be considered lost to follow-up if they repeatedly fail to return for scheduled visits 
and are unable to be contacted by the study site. 
The following actions must be taken if a patient fails to return to the clinic for a required study 
visit: 
• The site must attempt to contact the patient and reschedule the missed visit as soon as 
possible (and within the visit window, where one is defined), counsel the patient on the 
importance of maintaining the assigned visit schedule, and ascertain whether the patient 
wishes to and/or should continue in the study. 
• In cases in which the patient is deemed lost to follow-up, the Investigator or designee must 
make every effort to regain contact with the patient (where possible, three telephone calls 
and, if necessary, a certified letter to the patient’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the patient’s medical 
record/eCRF. 
• Should the patient continue to be unreachable, he/she will be considered to have withdrawn 
from the study. 
If a patient discontinues study drug prior to study termination, the patient will be asked to return 
to the clinic for an Early Termination visit.  This visit will include all the study procedures of the 
Day 35/Visit 8 clinic visit.  The Day 35 study procedures and their timing are summarized in the 
SoA (Table 1). 
8 Study Assessments and Procedures 
Study procedures and their timing are summarized in the SoA (Table 1).  
Immediate safety concerns should be discussed with the Medical Monitor immediately upon 
occurrence or awareness to determine if the patient should continue or discontinue study 
treatment. 
Adherence to the study design requirements, including those specified in the SoA (Table 1), is 
essential and required for study conduct. 
All screening evaluations must be completed and reviewed to confirm that potential patients 
meet all eligibility criteria. The Investigator should maintain a screening log to record details of 
all patients screened and to confirm eligibility or record reasons for screening failure, as 
applicable. 


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Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the 
samples. 
Patient Identification Card 
All patients will be given a patient identification card identifying them as patients in a research 
study. The card will contain study site contact information (including direct telephone numbers) 
to be used in the event of an emergency. The Investigator or qualified designee will provide the 
patient with a patient identification card immediately after the patient provides written informed 
consent. At the time of treatment allocation/randomization, site personnel will add the 
treatment/randomization number to the patient identification card. 
Medical History 
A medical history will be obtained by the Investigator or qualified designee. The medical history 
will collect all active conditions and any condition diagnosed within the prior 5 years that the 
Investigator considers to be clinically relevant. Details regarding the disease for which the 
patient has enrolled in this study will be recorded separately and not listed as medical history. 
8.1 Efficacy Assessments 
8.1.1 
Primary Efficacy Assessment – Gastric Emptying Breath Test 
The GEBT is a nonradioactive noninvasive test that measures gastric emptying. Patients will 
provide baseline (premeal) breath samples and then consume 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 post meal 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 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 GEBT measures the rate of 13CO2 excretion after consumption of a 13C-enriched test meal. 
As the 13C enriched meal is emptied from the stomach it is digested, assimilated and 13CO2 is 
excreted in the breath. At any given measurement time t, the 13CO2 excretion rate is related to the 
rate of gastric emptying. A larger kPCD value means a faster 13CO2 excretion rate which is 
proportional to a faster rate of gastric emptying. 


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In subjects with normal gastric emptying, 13CO2 excretion rates obtained by GEBT generally rise 
to a maximum between 120 and 180 minutes and then start to decrease because nearly all of the 
of the 13C-labeled test meal has been emptied from the stomach. In subjects with delayed 
emptying, 13CO2 excretion rates likewise start to rise after ingestion of the meal, but rates are 
lower and rarely reach a maximum before the end of the evaluation period (240 minutes) as a 
significant portion of the meal remains in the stomach and digestion and assimilation are 
incomplete. 
Planned timepoints for all efficacy assessments are provided in the SoA (Table 1). 
8.1.2 
Secondary Efficacy Assessment – ANMS GCSI-DD 
The ANMS GCSI-DD is designed to assess gastrointestinal symptoms associated with IG and 
DG. The ANMS GCSI-DD symptom assessments are based on a 24-hour recall period to 
minimize bias in patient recall.  The instrument asks patients to rate the severity of five 
symptoms: bloating (feeling like you need to loosen your clothes), nausea, not able to finish a 
normal-sized meal, feeling excessively full after meals, and upper abdominal pain. The severity 
response is rated by the patient as the worst severity of the symptom over the previous 24 hours. 
The severity of symptom response scale ranges from 0 (“none”), 1 (“mild”), 2 (“moderate”), 3 
(“severe”) to 4 (“very severe”). In the scoring of vomiting episodes, the number of episodes of 
vomiting per day is used, with the episodes capped at 4, so that the scoring is similar to the 
symptom severity scores of the other items. Therefore, vomiting episodes are scored as 0=none; 
1=one episode; 2=two episodes; 3= three episodes and 4= four or more episodes. 
The ANMS GCSI-DD total gastroparesis symptom daily score is generated by summing the 
scores on each of the five symptom items and then dividing by 5, that is the number of items 
within the gastroparesis related symptom score.  Thus, the maximum total symptom score could 
be (5 symptoms * maximum score 4 divided by 5); hence, the maximum score is 20/5=4. The 
ANMS GCSI-DD gastroparesis symptom daily score can range from 0 to 4. High scores on the 
ANMS GCSI-DD reflect greater symptom severity.  The minimum clinically important 
difference in the ANMS GCSI-DD score has been estimated to be 0.50. 
In addition, overall severity of gastroparesis is assessed. The overall severity of gastroparesis 
takes into account that other symptoms might impact on a patient’s condition. 
In this study, the change from baseline over time for the ANMS-GCSI-DD score will be assessed 
by comparing the following: 
Change from baseline in the ANMS GCSI-DD) (i.e. Day-7 to Day -1) (predose) and Day 7 (Day 
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Change from baseline in the ANMS GCSI-DD (i.e., Day-7 to Day -1) (predose) and Day 14 (Day 
8 to Day 14) 
Change from baseline in the ANMS GCSI-DD (i.e., Day-7 to Day -1) (predose) and Day 21 (Day 
15 to Day 21) 
Change from baseline in the ANMS GCSI-DD (i.e., Day-7 to Day -1) (predose) and Day 28 (Day 
22 to Day 28) 
The ANMS-GCSI-DD sub scores will also be assessed as an Exploratory Endpoint: 
Change from baseline in the sub scores (nausea, early satiety, postprandial fullness, upper 
abdominal pain and number of vomiting episodes) of the ANMS-GCSI-DD over time (Day 7, 14, 
21, 28) by comparing Day 7 to Day 14, Day 14 to Day 21 and Day 21 to Day 28. 
The patients will complete these assessments using an electronic diary. 
 
8.1.3 
Exploratory Efficacy Assessments 
8.1.3.1 
PAGI-SYM and PAGI-QOL 
The PAGI-SYM will assess the patient’s severity of symptoms related to the GI problem. The 
PAGI-SYM is a 20-question assessment (Rentz, 2004).  The patient will circle the number that 
best describes how severe the symptom has been during the past 2 weeks. PAGI-SYM subscale 
scores are calculated by taking the mean of the items in each subscale; the subscale scores vary 
from 0 (none or absent) to 5 (very severe). The half-scale rule is applied for missing data (i.e., 
the subscale score is calculated using the mean of non-missing items; when more than 50% of 
items are missing, the score is set to missing). The total score is calculated by taking the mean of 
the subscales. If a subscale score is missing, the PAGI-SYM total score is set to missing. 
If the patient has not experienced the symptom, they would circle 0. If the symptom has been 
very mild, mild, moderate, or severe, they would circle 1, 2, 3 or 4, respectively. 
The PAGI-QOL will assess the patient’s current GI problems such as pain, discomfort or other 
problems and evaluate how these symptoms have affected the patient’s quality of life and 
well-being in the past 2 weeks. There are 30 questions in the assessment, with questions such as 
“Have you had to depend on others to do your daily activities?” and “Have you felt helpless?” 
with answer options including “none of the time,” “a little of the time,” “some of the time,” “a 
good bit of the time,” and “all of the time.” The PAGI-QOL contains 30 items covering five 
subscales: Daily Activities (10 items), Clothing (2 items), Diet and Food Habits (7 items), 
Relationships (3 items), and Psychological Well-Being (8 items).  Subjects are asked to respond 


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to each item on a 6-point Likert scale, ranging from 0 (none of the time) to 5 (all of the time). 
Subscale scores are calculated by averaging across the items within the specific subscale after 
reversing item scores. The range of scores is 0–5; higher scores indicate better HRQL (de la 
Loge, 2004) 
In this study, the change from baseline over time for the PAGI-SYM and PAGI-QOL scores will 
be assessed by comparing Day 1 to Day 28. The patients will complete these assessments using 
an electronic diary. 
8.1.3.2 
CGI-S and CGI-I 
The CGI-S provides an overall clinician-determined summary measure that takes into account all 
available information, including a knowledge of the patient’s history, psychosocial 
circumstances, symptoms, behavior, and the impact of the symptoms on the patient’s ability to 
function. The CGI actually comprises two companion one-item measures evaluating the 
following: (a) severity of psychopathology from 1 to 7 and (b) change from the initiation of 
treatment on a similar seven-point scale (Busner, 2007). 
The CGI-S asks the Investigator the question: “Considering your total clinical experience with 
this particular population, how mentally ill is the patient at this time? This is rated on the 
following 7-point scale: 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 
4=moderately ill; 5= markedly ill; 6=severely ill; and 7=among the most extremely ill patients. 
The rating is based upon observed and reported symptoms, behavior and function in the past 
7 days. 
The CGI-I will ask the Investigator the question: “Compared to the patient’s condition at 
admission to the study, this patient’s condition is 1=very much improved since the initiation of 
study treatment; 2=much improved; 3=minimally improved; 4=no change from baseline (the 
initiation of study treatment); 5=minimally worse; 6=much worse; and 7=very much worse since 
the initiation of study treatment. 
In this study, the change from baseline over time for the CGI-S and CGI-I scores will be assessed 
by comparing Day 1 to Day 28. The investigator will complete these assessments using an 
electronic diary. 
8.1.3.3 
PGI-S and PGI-C 
Consistent with the recommendations in the FDA Draft Guidance: Gastroparesis: Clinical 
Evaluation of Drugs for Treatment, 2019, multiple anchor scales will also be used to assess the 
impact of treatment on the patient’s disease. The patient global impression of severity (PGI-S) 


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and patient global impression of change (PGI-C) scales will be used in the proposed Phase 2A 
study, with the intent of providing accumulated evidence to help interpret a clinically meaningful 
within-patient score change.   
The PGI-S will assess the patient’s severity of symptoms. The choices are: “none,” “mild,” 
“moderate,” “severe” and “very severe.” 
The PGI-C will assess the patient’s impression of how their GI symptoms have changed. The 
patient will choose 1 of 7 answers, including: “very much improved,” “much improved,” 
“minimally improved,” “no change,” “minimally worse,” “much worse” and “very much worse.” 
In this study, the change from baseline over time for the PGI-S and PGI-C scores will be 
assessed by comparing Day 1 to Day 28. The patients will complete these assessments using an 
electronic diary. 
8.2 Safety Assessments 
Planned timepoints for all safety assessments are provided in the SoA (Table 1). 
• AEs (by type, severity, and relatedness) at each visit. 
• Changes in safety clinical laboratory testing and vital signs at each site visit. 
• Changes in ECGs at each site visit and the potential correlation of the PK with changes in the 
ECG. 
• Change from baseline in the C-SSRS scores over time by comparing Day 1 to Day 28. 
 
8.2.1 
Physical Examinations 
Complete physical examinations (excluding pelvic exam in women and genital exam in men, and 
rectal exam in both genders) are to be performed at Screening (Visit 1) and Day 28 (Visit 6). 
Symptom-directed (abbreviated) physical examinations may be conducted as required at Visit 3 
(Day 1) Visit 4 (Day 7), Visit 5 (Day 14), and Visit 8 (Day 35). 
Patients should be weighed with no shoes, in light clothing, without any outerwear. Height 
should be measured only at the first study visit. Any abnormality noted on the physical 
examination done at or following Visit 3 or the early termination visit that was not present on the 
physical examination at screening should be reported as an AE if considered by the Investigator 
to be clinically significant. 


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Investigators should pay special attention to clinical signs related to previous serious illnesses. 
8.2.2 
Vital Signs 
• Heart rate (HR), respiratory rate, systolic and diastolic blood pressure (BP), weight and 
temperature will be assessed; the method for measuring temperature will be per the site’s 
preference. 
• BP and HR measurements will be assessed in the sitting position with a completely 
automated device. Manual techniques will be used only if an automated device is not 
available. 
• BP and HR measurements should be preceded by at least 3 minutes of rest for the patient in a 
quiet setting without distractions (eg, television, cell phones). 
• Vital signs are to be taken before blood collection for laboratory tests. 
8.2.3 
Electrocardiograms 
A 12-lead ECG will be obtained as outlined in the SoA (Table 1) using an ECG machine after 
the patient has rested for 5 minutes in supine position. At Visit 3 (Randomization) and Visit 6 
(Day 28), the ECG will be performed prior to the 4-hour PK draw. At Visit 4 and Visit 5, the 
ECG will be performed approximately 4 hours after the patient’s dose. The Investigator will 
report whether the ECG is normal or abnormal and if the result is considered clinically 
significant or not. 
All clinically significant ECG abnormalities occurring during the study should be documented as 
AEs. The ECG performed at Screening will be recorded as the baseline assessment. Standard 
ECG parameters, including heart rate, QRS, PR, QT, Bazett’s correction for QT (QTcB), and 
Fridericia’s correction for QT (QTcF) intervals will be measured. The ECGs will be overread by 
the Investigator to assess any abnormalities. 
8.2.4 
Clinical Safety Laboratory Tests 
Refer to Appendix 2 for the list of clinical laboratory tests to be performed and the SoA (Table 1) 
for the timing and frequency. 
The Investigator must review the laboratory report, document this review, and record any 
clinically significant changes occurring during the study as an AE. The laboratory reports must 
be filed with the source documents. 


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Abnormal laboratory findings associated with the underlying disease are not considered 
clinically significant unless judged by the Investigator to be more severe than expected for the 
patient’s condition. 
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study or within 30 days after the last dose of study treatment should be repeated until the 
values return to normal or baseline or are no longer considered clinically significant by the 
Investigator or Medical Monitor. 
• If such values do not return to normal/baseline within a period of time judged reasonable by 
the Investigator, the etiology should be identified, where possible, and the Sponsor notified. 
• All protocol-required laboratory tests, as defined in Appendix 2, must be conducted in 
accordance with the laboratory manual and the SoA (Table 1). 
• If laboratory values from laboratory tests not specified in the protocol and performed at the 
institution’s local laboratory result in the need for a change in patient management or are 
considered clinically relevant by the Investigator (e.g., are considered to be an SAE or an AE 
or require dose modification), then the results must be recorded in the eCRF. 
8.2.5 
Pregnancy Testing 
Women of childbearing potential must have a negative serum pregnancy test at the Screening 
Visit and a negative urine pregnancy test at baseline before dosing. A serum β-HCG test will be 
performed at Screening (Visit 1) and a urine pregnancy test at subsequent visits. Refer to the 
SoA (Table 1) for testing timepoints. 
Details of all pregnancies in females and female partners of male patients will be collected after 
the start of study treatment and until the end of the study period (Visit 7). If a pregnancy is 
reported, the Investigator should inform the Sponsor within 24 hours of learning of the 
pregnancy and should follow the procedures outlined in Appendix 4. Abnormal pregnancy 
outcomes (e.g., spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic 
pregnancy) are considered to be SAEs. 
8.2.6 
Suicidal Ideation and Behavior Risk Monitoring 
Although no increased risk of suicide ideation or behavior has been documented with PCS12852, 
it is in a class of products that have an increased risk of suicidal ideation or behavior. 
Patients being treated with PCS12852 should be monitored appropriately and observed closely 
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the beginning and end of the course of study treatment. Patients who experience signs of suicidal 
ideation or behavior should undergo a risk assessment. All factors contributing to SIB should be 
evaluated and consideration should be given to discontinuation of the study treatment. 
Baseline assessment of SIB will be monitored during the study using the C-SSRS by comparing 
Day 1 to Day 7, Day 14 and Day 28 scores. Refer to the SoA (Table 1) for timepoints. 
8.3 Adverse Events, Serious Adverse Events, and Other Safety Reporting 
The definitions of AEs and SAEs can be found in Appendix 3. 
Adverse events will be reported by the patient or noted by the Investigator. 
The Investigator and any qualified designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE and remain responsible for following 
up AEs that are serious, considered related to the study treatment or the study, or that caused the 
patient to discontinue the study treatment (see Section 7). 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3. 
8.3.1 
Time Period and Frequency for Collecting AE and SAE Information 
All AEs will be collected from the signing of the ICF.  All SAEs will be collected and followed 
until 30 days after the final Visit (Visit 8), at the timepoints specified in the SoA (Table 1). 
All SAEs will be recorded and reported to the Sponsor or designee within 24 hours of awareness, 
as indicated in Appendix 3. The Investigator will submit any updated SAE data to the Sponsor 
within 24 hours of it being available. 
Investigators are not obliged to actively seek information on AEs or SAEs after the conclusion of 
study participation. However, if the Investigator learns of any SAE, including a death, at any 
time after a patient has been discharged from the study, and he/she considers the event to be 
reasonably related to the study treatment or study participation, the Investigator must promptly 
notify the Sponsor. 
8.3.2 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the patient is the preferred method to inquire about 
AE occurrence. 


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8.3.3 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each patient at 
subsequent visits/contacts. All AEs and SAEs, (as defined in Appendix 3), will be followed until 
resolution, stabilization, until the event is otherwise explained, or the patient is lost to follow-up 
(as defined in Section 7.2). Further information on follow-up procedures is given in Appendix 3. 
8.3.4 
Regulatory Reporting Requirements for SAE 
Prompt notification within 24 hours (see Appendix 3) by the Investigator to the Sponsor of an 
SAE is essential so that legal obligations and ethical responsibilities towards the safety of 
patients and the safety of a study treatment under clinical investigation are met. 
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study treatment under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, Institutional Review Board (IRB)/Independent Ethics Committee (IEC), 
and Investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
(SUSAR) according to local regulatory requirements and Sponsor policy and forwarded to 
investigators as necessary. 
An Investigator who receives an Investigator Safety Report describing an SAE or other specific 
safety information (e.g., summary or listing of SAEs) from the Sponsor will review and then file 
it along with the Investigator’s Brochure and will notify the IRB/IEC, if appropriate according to 
local requirements. 
8.3.5 
Pregnancy 
Details of all pregnancies in female patients and female partners of male patients will be 
collected after the start of study treatment and until 7 days after the last dose. 
If a pregnancy is reported, the Investigator will record pregnancy information on the appropriate 
form and submit it to the Sponsor within 24 hours of learning of the pregnancy and should 
follow the procedures outlined in Appendix 4. 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered to be SAEs and will be reported as such. 


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8.4 Pharmacokinetics 
Blood samples will be collected for measurement of PCS12852 in plasma via a specific and 
sensitive validation bioanalytical method, at timepoints as specified in the SoA (Table 1). 
Clinical staff are encouraged to take the blood samples for PK analysis at the scheduled time 
point; however, deviations from the scheduled sample times are not considered protocol 
deviations. The actual date and time (24-hour clock time) of sample collections will be recorded 
in the source document and transcribed into the eCRF. Instructions for the collection and 
handling of biological samples will be provided in the Study Manual.  
Samples will be used to evaluate the PK of PCS12852. Samples collected for analyses of 
PCS12852 plasma concentration may also be used to evaluate safety or efficacy aspects that 
address concerns arising during or after the study. 
Genetic analyses will not be performed on these blood samples. Subject confidentiality will be 
maintained.  
Any changes in the timing or addition of time points for any planned study assessments must be 
documented and approved by the relevant study team member and then archived in the Sponsor 
and site study files but will not constitute a protocol amendment. The IRB/IEC will be informed 
of any safety issues that require alteration of the safety monitoring scheme or amendment of the 
ICF. 
 
 


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9 Statistical Considerations 
The statistical analysis plan (SAP) will be developed and finalized before database lock and will 
include a more technical and detailed description of the statistical analyses described in this 
section. This section is a summary of the planned statistical analyses of the most important 
endpoints including primary and key secondary endpoints. 
9.1 Analysis Sets 
The analysis populations will consist of patients as defined in Table 5. 
Table 5 
Analysis Data Sets 
Analysis Data Sets 
Description 
Safety Analysis Set 
Patients enrolled in the study who received at least 1 dose of 
treatment. 
PK Analysis Set 
Patients in the Safety Set with at least 1 plasma sample with a 
quantifiable concentration of PCS12852. 
Full Analysis Set 
Patients who are randomized. 
9.2 Statistical Analyses 
9.2.1 
General Considerations 
Approximately 24 patients (approximately 8 patients in each of the three treatment groups) with 
moderate to severe gastroparesis who have documented delayed gastric emptying are planned to 
be randomized (1:1:1) in the study. The randomization to treatment groups will be stratified by 
type of gastroparesis (idiopathic, diabetic), enrolling at least 2 patients of each type of 
gastroparesis (idiopathic, diabetic) in each treatment group. 
9.2.2 
Primary Efficacy Analysis 
The change in the gastric emptying rate AUC as measured by the GEBT, from baseline to Day 28 
will be analyzed in the FAS using an analysis of covariance (ANCOVA) model with treatment 
group (three levels) as a factor and the baseline GEBT as a covariate. Each of the two primary 
comparisons (0.1 mg versus placebo, 0.5 mg versus placebo), will be conducted using a two-
sided Dunnett’s test at the overall alpha=0.05 significance level. 
Other efficacy analyses: 


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All secondary endpoints will be conducted using the same approach as described for the primary 
analysis. Each treated group will be compared to placebo using Dunnett’s test. All secondary 
analyses will be based on the use of two-sided tests at the alpha=0.05 overall level of 
significance, with no adjustment for multiplicity. 
Subgroup analysis: 
 
A subgroup analysis of idiopathic gastroparesis patients compared to diabetic gastroparesis 
patients will be done for all efficacy analysis endpoints.  
Pharmacokinetic analysis: 
Plasma concentrations will be used to estimate the pharmacokinetic parameters for PCS12852 on 
Day 1 and Day 28 using noncompartmental methods in WinNonlin®. The following parameters 
will be calculated as data permits: 
• 
Cmax: maximum observed plasma concentration 
• 
Tmax: time at which the maximum plasma concentration was observed 
• 
t½: (the apparent first-order terminal elimination half-life) 
• 
AUC0-last: the area under the plasma concentration versus time curve, from time 0 to 
 
the last measurable concentration 
• 
AUC∞: the area under the plasma concentration vs. time curve from time 0 to infinity 
• 
λz:  apparent first order terminal elimination rate constant 
 
A dose proportionality analysis will be conducted for log-transformed Cmax, AUC0-last, and 
AUC∞ using the power model. . In addition, the relationship between gastric emptying rate and 
drug exposure will be assessed, as data permit.  Exposure-response for safety measures may also 
be explored.   
In addition, a population PK model may be used to describe the PK of PCS12852, if appropriate 
based on the data collected.   A previously developed population PK model describing the PK of 
PCS12852 in patients with functional constipation, using a two-compartment model with first 
order absorption, may be used to predict the PK in patients in this study.  
Further details of all analyses will be described in the SAP. 


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9.2.3 
Secondary Efficacy Analysis 
This study will enroll gastroparesis patients with documented delayed gastric emptying and at 
least moderate symptom severity. The ANMS GCSI-DD scale will be used to assess the change 
from baseline in symptoms. 
The ANMS GCSI-DD symptom assessments are based on a 24-hour recall period to minimize 
bias in patient recall. The ANMS GCSI-DD total gastroparesis symptom daily score is generated 
by summing the scores on each of the five symptom items (nausea, early satiety, postprandial 
fullness, upper abdominal pain, and number of vomiting episodes) and then dividing by 5, that is 
the number of items within the gastroparesis related symptom score. Thus, the maximum total 
symptom score could be (5 symptoms x maximum score 4 divided by 5); hence, the maximum 
score is 20/5=4. The ANMS GCSI-DD gastroparesis symptom daily score can range from 0 to 4. 
High scores on the ANMS GCSI-DD reflect greater symptom severity. 
9.2.4 
Other Patient-reported outcomes (PRO) Assessments – Exploratory 
Endpoints 
The PAGI-SYM is a patient-reported outcome that asks patients the severity of their symptoms 
over the last 2 weeks. The PAGI-SYM was developed to measure symptom severity for 
gastroparesis, functional dyspepsia, and gastroesophageal reflux disease. The PAGI-SYM is 
composed of 20 items and 6 subscales: heartburn/regurgitation (7 items), nausea/vomiting (3 
items), postprandial fullness/early satiety (4 items), bloating (2 items), upper abdominal pain (2 
items), and lower abdominal pain (2 items). Subscale scores are calculated by averaging across 
items comprising the subscale; scores vary from 0 (none or absent) to 5 (very severe). The half-
scale rule is applied for missing data (i.e., the subscale score is calculated by using the mean of 
non-missing items; when more than 50% of items are missing, the score is set to missing). The 
change from baseline in the PAGI-SYM will be analyzed using the same statistical approach as 
described for other analyses. 
The PGI-C is a patient-reported questionnaire with a 7-point rating scale where the participant 
rates his/her own improvement in overall symptoms relative to the baseline assessment. It is 
rated as 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, 
minimally worse; 6, much worse; or 7, very much worse. 
The PGI-S is a patient reported questionnaire with a single question to measure disease severity 
on a 5-point rating scale. It is rated as “none,” “mild,” “moderate,” “severe,” and “very severe.” 


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The PAGI-QOL is a 30-item instrument assessing quality of life in patients with gastroparesis. 
The questionnaire covers 5 domains: Daily Activities, Clothing, Diet and Food Habits, 
Relationship, and Psychological Well-Being and Distress. The effect on overall quality of life 
and well-being over the past 2 weeks is rated on a scale of 0 (none of the time) to 5 (all of the 
time) for each item. 
Clinicians complete the CGI-S, which is a 7-point scale on which the clinician rates the severity 
of the patient’s gastroparesis at the time of assessment and refers to the degree of illness at the 
time of the visit and during the 2 weeks before the visit. The CGI-S is rated on the following 7-
point scale: 1: normal, not at all ill; 2: borderline ill; 3: mildly ill; 4: moderately ill; 5: markedly 
ill; 6: severely ill; 7: among the most extremely ill patients. 
The CGI-I is a 7-point scale in which the clinician rates the change from the initiation of 
treatment. The CGI-I is rated as: 1: very much improved since the initiation of study treatment; 
2: much improved; 3: minimally improved; 4: no change from baseline (the initiation of study 
treatment); 5: minimally worse; 6: much worse; and 7: very much worse since the initiation of 
study treatment. 
9.2.5 
Safety Analyses 
The safety analyses will be performed using the Safety Population and include AEs, changes in 
physical exam findings, vital signs, ECGs and clinical laboratory values. 
Adverse events will be coded using the current version of the Medical Dictionary for Regulatory 
Activities (MedDRA version 23.0 or higher). The number and percent of patients reporting at 
least one AE will be summarized by System Organ Class and Preferred Term and presented by 
severity, relationship to study treatment, amount of drug exposure, and time. Each patient will 
contribute only once (i.e., first occurrence) to each of the incidence rates, regardless of the 
number of occurrences. Severity of AEs will be assessed based on the National Cancer Institute 
(NCI) CTCAE Version 5.0. For reporting of AE severity in patients with more than one 
occurrence of the same AE, the patient will only be reported once based on the highest severity 
of the AE observed. Patients who have an SAE or who discontinue the study due to an AE 
deemed to be related to study treatment will be described in patient narratives. 
Vital signs, clinical laboratory, and ECG results will also be presented and summarized by dose 
level and summarized by descriptive statistics with change from baseline values calculated. All 
safety data collected in the clinical database, including physical exam findings and abnormal 
ECG results, will be presented in data listings. The safety categories will be summarized as 
appropriate (eg, categorial or continuous descriptives, shift tables) and will be fully defined in 


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the SAP. The potential relationship between abnormal ECG results and PK will also be evaluated 
and fully defined in the SAP.  
9.3 Sample Size Determination 
Based on the results of a prior study (Study 102), estimates of the standard deviation (SD) of the 
AUC change from baseline range from 10 to 35. Assuming a true SD of 15 and based on a 
two-sided test at the alpha=0.025 level of significance, a sample size of 8 patients per arm (24 
total patients) will provide 80% power to detect a between-group mean difference of 25. 


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10 Supporting Documentation and Operational Considerations 
10.1 Appendix 1: Regulatory, Ethical, and Study Oversight Considerations 
10.1.1 Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with: 
• Consensus ethical principles derived from international guidelines including the Declaration 
of Helsinki and Council for International Organizations of Medical Sciences international 
ethical guidelines. 
• Applicable ICH Good Clinical Practice (GCP) guidelines. 
• Applicable laws and regulations. 
The protocol, protocol amendments, ICF, Investigator’s Brochure, and other relevant documents 
(e.g., advertisements) must be submitted to an IRB/IEC by the Investigator and reviewed and 
approved by the IRB/IEC before the study is initiated. 
Any amendments to the protocol will require IEC/IRB approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study patients. 
Protocols and any substantial amendments to the protocol will require health authority approval 
prior to initiation except for changes necessary to eliminate an immediate hazard to study 
patients. 
The Investigator will be responsible for the following: 
• Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by the 
IRB/EC. 
• Notifying the IRB/IEC of SAE or other significant safety findings as required by IRB/IEC 
procedures. 
• Providing oversight of the overall conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH GCP guidelines, the IRB/IEC, and all other applicable local 
regulations. 


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10.1.2 Informed Consent Process 
The Investigator or his/her representative will explain the nature of the study, including the risks 
and benefits, to the patient and answer all questions regarding the study. 
Patients must be informed that their participation is voluntary. Patients will be required to sign a 
statement of informed consent that meets the requirements of 21 CFR 50, local regulations, ICH 
guidelines, privacy and data protection requirements, where applicable, and the IRB/IEC or 
study center. 
The medical record must include a statement that written informed consent was obtained before 
the patient was enrolled in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF. 
Patients must be re-consented to the most current version of the ICF(s) during their participation 
in the study. 
A copy of the ICF(s) must be provided to the patient. 
If a protocol amendment is required, the ICF may need to be revised to reflect the changes to the 
protocol. If the ICF is revised, it must be reviewed and approved by the appropriate IEC/IRB and 
signed by all patients subsequently enrolled in the study as well as those currently enrolled in the 
study. 
10.1.3 Data Protection 
Patients will be assigned a unique identifier by the Sponsor via the IRT system. Any patient 
records or datasets that are transferred to the Sponsor will contain the identifier only; patient 
names or any information which would make the patient identifiable will not be transferred. 
The patient must be informed that their personal study-related data will be used by the Sponsor 
in accordance with local data protection law. The level of disclosure must also be explained to 
the patient who will be required to give consent for their data to be used as described in the 
informed consent. 
The patient must be informed that their medical records may be examined by Clinical Quality 
Assurance auditors or other authorized personnel appointed by the Sponsor, by appropriate 
IRB/IEC members, and by inspectors from regulatory authorities. 


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10.1.4 Dissemination of Clinical Study Data 
A summary of the results of the clinical study together with a summary that is understandable to 
a layperson will be provided after the global end (or early termination) of the study in all 
countries concerned to ensure full availability of all clinical data under this protocol, within 
12 months. 
10.1.5 Data Quality Assurance 
All patient data relating to the study will be recorded on electronic CRFs unless transmitted to 
the Sponsor or designee electronically (e.g., laboratory data). The Investigator is responsible for 
verifying that data entries are accurate and correct by electronically signing the CRF. 
The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF. 
The Investigator must permit study-related monitoring, audits, IRB/IEC review, and Regulatory 
Agency inspections and provide direct access to source data documents. 
The Sponsor or designee is responsible for the data management of this study including quality 
checking of the data. 
The Sponsor assumes accountability for actions delegated to other individuals (e.g., contract 
research organizations). 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the eCRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of patients are being protected; and that the study is being 
conducted in accordance with the currently approved protocol and any other study agreements, 
ICH GCP, and all applicable regulatory requirements. 
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the Investigator for 2 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during the 
retention period without the written approval of the Sponsor. No records may be transferred to 
another location or party without written notification to the Sponsor. 
Data entered in the eCRF that are transcribed from source documents must be consistent with the 
source documents or the discrepancies must be explained. The Investigator may need to request 


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previous medical records or transfer records, depending on the study. Also, current medical 
records must be available. 
The specific procedures to be used for data entry and query resolution using the eCRF will be 
provided to study sites in a training manual. In addition, site personnel will receive training on 
the eCRF. 
10.1.6 Source Documents 
Source documents provide evidence for the existence of the patient and substantiate the integrity 
of the data collected. Source documents are filed at the Investigator’s site. 
Data reported in the eCRF that are transcribed from source documents must be consistent with 
the source documents or the discrepancies must be explained. The Investigator may need to 
request previous medical records or transfer records, depending on the study. Also, current 
medical records must be available. 
The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF. 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the eCRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of patients are being protected; and that the study is being 
conducted in accordance with the currently approved protocol and any other study agreements, 
ICH GCP, and all applicable regulatory requirements. 
10.1.7 Study and Site Start and Closure 
First Act of Recruitment 
The study start date is the date on which the clinical study will be open for recruitment of 
patients. 
The first act of recruitment is the first site open and will be the study start date. 
Study/Site Termination 
The Sponsor or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study site closure visit has been performed. 


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The Investigator may initiate study site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or Investigator may include but are 
not limited to: 
• Failure of the Investigator to comply with the protocol, the requirements of the IRB/IEC or 
local health authorities, the Sponsor’s procedures, or GCP guidelines. 
• Inadequate recruitment of patients by the Investigator. 
• Total number of patients included earlier than expected. 
• Discontinuation of further study treatment development. 
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
Investigators, the IECs/IRBs, the regulatory authorities, and any contract research 
organization(s) used in the study of the reason for termination or suspension, as specified by the 
applicable regulatory requirements. The Investigator shall promptly inform the patient and 
should assure appropriate patient therapy and/or follow-up. 
10.1.8 Protocol Approval and Amendment 
Before the start of the study, the study protocol and/or other relevant documents will be approved 
by the IEC/IRB/Competent Authorities, in accordance with local legal requirements. The 
Sponsor must ensure that all ethical and legal requirements have been met before the first patient 
is enrolled in the study. 
This protocol is to be followed exactly. To alter the protocol, amendments must be written, 
receive approval from the appropriate personnel, and receive IRB/IEC/Competent Authority 
approval prior to implementation (if appropriate). In the US: Following approval, the protocol 
amendment(s) will be submitted to the Investigational New Drug Application under which the 
study is being conducted. 
Administrative changes (not affecting the patient benefit/risk ratio) may be made without the 
need for a formal amendment. All amendments will be distributed to all protocol recipients, with 
appropriate instructions. 
10.1.8.1 Access to Source Data 
During the study, a monitor will make site visits to review protocol compliance, compare eCRF 
entries and individual patient’s medical records, assess drug accountability, and ensure that the 


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study is being conducted according to pertinent regulatory requirements. The eCRF entries will 
be verified with source documentation. The review of medical records will be performed in a 
manner to ensure that patient confidentiality is maintained. 
Checking of the eCRF entries for completeness and clarity, and cross-checking with source 
documents, will be required to monitor the progress of the study. Moreover, regulatory 
authorities of certain countries, IRBs, IECs, and/or the Sponsor’s Clinical QA Group may wish 
to carry out such source data checks and/or on-site audit inspections. Direct access to source data 
will be required for these inspections and audits; they will be carried out giving due 
consideration to data protection and medical confidentiality. The Investigator assures the 
Sponsor of the necessary support at all times. 
 
 


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10.2 Appendix 2: Clinical Laboratory Tests 
• All clinical laboratory tests should be done after patients have fasted for at least 8 hours. 
• The tests will be performed by the central laboratory, unless prior approval is received 
from the Sponsor. 
• Protocol-specific requirements for inclusion or exclusion of patients are details in 
Sections 5.1 and 5.2. 
• Additional tests may be performed at any time during the study as determined necessary 
by the Investigator or required by local regulations. 
• Investigators must document their review of each laboratory safety report. 
Table 6 
Protocol-required Safety Laboratory Tests 
Laboratory Tests 
Parameters 
Hematology 
Platelet count 
RBC count 
Hemoglobin 
Hematocrit 
RBC indices: 
Mean corpuscular volume (MCV) 
Mean corpuscular hemoglobin (MCH) 
% Reticulocytes 
WBC count with differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
Clinical chemistry 
BUN 
Potassium 
Creatinine 
Sodium 
Glucose, fasting 
Calcium 
Phosphorus 
Bicarbonate 
AST/SGOT 
Total and direct bilirubin 
ALT/SGPT 
Total protein 
Alkaline phosphatase 
Chloride 
Albumin  


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Routine urinalysis 
Specific gravity 
pH, glucose, protein, blood, ketones, by dipstick 
Microscopic examination (if blood or protein is abnormal) 
Pregnancy testing 
Highly sensitive serum and/or urine hCG pregnancy test (as needed for women 
of childbearing potential) at timepoints detailed in Section 8.3.5. 
Other screening 
tests 
HbA1c and TSH will be done at Screening only 
Follicle-stimulating hormone and estradiol (as needed in women of 
non-childbearing potential only) 
Urine alcohol and drug screen (to include at minimum: amphetamines, 
barbiturates, cocaine, opiates, THC and benzodiazepines) 
Serology (HIV antibody, hepatitis B surface antigen (HbsAg), and HCV 
antibody) [HCV PCR will be done for any HCV Ab positive result] 
All study required laboratory assessments will be performed by a central 
laboratory.  
 
NOTES: 
1. Local urine testing will be standard for the protocol unless serum testing is required by local 
regulation or IRB/IEC. 
ALT= alanine aminotransferase; AST= aspartate aminotransferase; BUN=blood urea nitrogen; hCG= human 
chorionic gonadotropin; HCV = hepatitis C; HIV = human immunodeficiency virus; IEC= independent ethics 
committee; INR= international normalized ration; IRB= institutional review board; RBC= red blood cell; 
SGOT= serum glutamic-oxaloacetic transaminase; SGPT= serum glutamic-pyruvic transaminase; THC = 
tetrahydrocannabinol; TSH = thyroid stimulating hormone; WBC= white blood cell. 
 
 


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10.3 Appendix 3: AEs and SAEs: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting 
10.3.1 Definition of AE 
AE Definition 
An AE is any untoward medical occurrence in a patient or clinical study patient, temporally 
associated with the use of a study treatment, whether or not considered related to the study 
treatment. 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the 
use of a study treatment. 
 
Events Meeting the AE Definition 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other 
safety assessments (e.g., ECG, radiological scans, vital signs measurements), including those 
that worsen from baseline, considered clinically significant in the medical and scientific 
judgment of the Investigator (e.g., not related to progression of underlying disease). 
Exacerbation of a chronic or intermittent pre-existing condition including either an increase in 
frequency and/or intensity of the condition. 
New condition detected or diagnosed after study treatment administration even though it may 
have been present before the start of the study. 
Signs, symptoms, or the clinical sequelae of a suspected treatment-treatment interaction. 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study treatment or 
a concomitant medication. Overdose per se will not be reported as an AE/SAE unless it is an 
intentional overdose taken with possible suicidal/self-harming intent. Such overdoses should 
be reported regardless of sequelae. 
Lack of efficacy or failure of expected pharmacological action per se will not be reported as an 
AE or SAE. Such instances will be captured in the efficacy assessments. However, the signs, 


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symptoms, and/or clinical sequelae resulting from lack of efficacy will be reported as AE or 
SAE if they fulfill the definition of an AE or SAE. 
 
Events NOT Meeting the AE Definition 
Any clinically significant abnormal laboratory findings or other abnormal safety assessments 
that are associated with the underlying disease, unless judged by the Investigator to be more 
severe than expected for the patient’s condition. 
The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the patient’s condition. 
Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that leads to the 
procedure is the AE. 
Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen. 
 
10.3.2 Definition of SAE 
An SAE is an AE that: 
a. Results in death 
b. Is life-threatening 
The term life-threatening in the definition of serious refers to an event in which the patient 
was at risk of death at the time of the event. It does not refer to an event, which hypothetically 
might have caused death, if it were more severe. 


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c. Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the patient has been admitted (usually involving at 
least an overnight stay) at the hospital or emergency ward for observation and/or treatment that 
would not have been appropriate in the physician’s office or outpatient setting. Complications 
that occur during hospitalization are AE. If a complication prolongs hospitalization or fulfills 
any other serious criteria, the event is serious. When in doubt as to whether hospitalization 
occurred or was necessary, the AE should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE. 
d. Results in persistent or significant disability/incapacity 
The term disability means a substantial disruption of a person’s ability to conduct normal life 
functions. 
This definition is not intended to include experiences of relatively minor medical significance 
such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma 
(e.g., sprained ankle) that may interfere with or prevent everyday life functions but do not 
constitute a substantial disruption. 
e. Is a congenital anomaly/birth defect 
f. Other situations 
Medical or scientific judgment should be exercised by the Investigator in deciding whether 
SAE reporting is appropriate in other situations such as significant medical events that may 
jeopardize the patient or may require medical or surgical treatment to prevent one of the other 
outcomes listed in the above definition. These events should usually be considered serious. 
Examples of such events are intensive treatment in an emergency room or at home for allergic 
bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; or 
development of drug dependency or drug abuse. 


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10.3.3 Recording and Follow-up of AE and SAE 
AE and SAE Recording 
When an AE/SAE occurs, it is the responsibility of the Investigator to review all 
documentation (e.g., hospital progress notes, laboratory, and diagnostics reports) related to the 
event. 
The Investigator will then record all relevant AE/SAE information. 
It is not acceptable for the Investigator to send photocopies of the patient’s medical records to 
the Sponsor in lieu of completion of the AE/SAE eCRF page. 
There may be instances when copies of medical records for certain cases are requested by the 
Sponsor. In this case, all patient identifiers, with the exception of the patient number, will be 
blinded on the copies of the medical records before submission to the Sponsor. 
The Investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information. In such cases, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE. 
 
Assessment of Intensity 
The clinical severity of an AE will be graded using the NCI CTCAE Version 5.0. 
 
The severity of all adverse events should be graded according to the Common Terminology 
Criteria for Adverse Events (CTCAE)  v.5.0.  These criteria can be found at 
http://ctep.cancer.gov/reporting/ctc.html.  For those adverse event terms not listed in the 
CTCAE, the following grading system should be used: 
• CTCAE Grade 1: Mild; asymptomatic or mild symptoms; clinical or 
diagnostic observations only; intervention not indicated.   
• CTCAE Grade 2:  Moderate; minimal local or noninvasive intervention 
indicated; limiting age-appropriate instrumental activities of daily 
living.  


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• CTCAE Grade 3: Severe or medically significant but not immediately 
life-threatening; hospitalization or prolongation of hospitalization 
indicated; disabling; limiting self-care activities of daily living 
• CTCAE Grade 4:  Life threatening consequences; urgent intervention 
indicated. 
• CTCAE Grade 5:  Death related to the adverse event.   
The investigator is to evaluate whether the AE meets serious criteria. An event is defined as 
‘serious’ when it meets at least one of the predefined outcomes as described in the definition 
of an SAE, NOT when it is rated as severe. 
Assessment of Causality 
The Investigator is obligated to assess the relationship between study treatment and each 
occurrence of each AE/SAE. The Investigator will use clinical judgment to determine the 
relationship. 
A reasonable possibility of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, 
as well as the temporal relationship of the event to study treatment administration will be 
considered and investigated. 
The Investigator will also consult the Investigator’s Brochure and/or Product Information, for 
marketed products, in their assessment. 
For each AE/SAE, the Investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
There may be situations in which an SAE has occurred, and the Investigator has minimal 
information to include in the initial report in the electronic data collection tool. However, it is 
very important that the Investigator always make an assessment of causality for every 
event before the initial transmission of the SAE data to the electronic data collection tool. 
The Investigator may change their opinion of causality in light of follow-up information and 
send an SAE follow-up report with the updated causality assessment. 


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The following “binary” decision choice will be used by the Investigator to describe the initial 
causality assessment: 
• Related: Reasonable possibility of a relatedness 
• Not related: No reasonable possibility of relatedness. 
The following factors should also be considered: 
• The temporal sequence from study drug administration- 
The event should occur after the study drug is given. The length of time from study drug 
exposure to event should be evaluated in the clinical context of the event. 
• Underlying, concomitant, intercurrent diseases- 
Each report should be evaluated in the context of the natural history and course of the 
disease being treated and any other disease the subject may have. 
• Concomitant drug- 
The other drugs the subject is taking or the treatment the subject receives should be 
examined to determine whether any of them might be recognized to cause the event in 
question. 
• Known response pattern for this class of study drug- 
Clinical and/or preclinical data may indicate whether a particular response is likely to be 
a class effect. 
• Exposure to physical and/or mental stresses- 
The exposure to stress might induce adverse changes in the recipient and provide a 
logical and better explanation for the event. 
• The pharmacology and pharmacokinetics of the study drug- 
The known pharmacologic properties (absorption, distribution, metabolism, and 
excretion) of the study drug should be considered. 
 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
 
Follow-up of AE and SAE 
The Investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the Sponsor to 
elucidate the nature and/or causality of the AE or SAE as fully as possible. This may include 
additional laboratory tests or investigations, histopathological examinations, or consultation 
with other health care professionals. 


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If a patient dies during participation in the study or during a recognized follow-up period, the 
Investigator will provide the Sponsor with a copy of any post-mortem findings including 
histopathology. 
New or updated information will be recorded in the originally completed form. 
The Investigator will submit any updated SAE data to the Sponsor within 24 hours of receipt 
of the information. 
10.3.4 Reporting of SAE 
SAE Reporting to the Sponsor via email, fax or telephone 
Initial Reports 
All SAEs occurring from the time of informed consent until 30 days following the last 
administration of study drug must be reported to Medpace Clinical Safety within 24 hours of 
the knowledge of the occurrence. After the 30-day reporting window, any SAE that the 
investigator considers related to study must be reported to Medpace Clinical Safety or the 
Sponsor/designee. 
 
To report the SAE, complete the SAE form electronically in the electronic data capture (EDC) 
system for the study. When the form is completed, Medpace Safety personnel will be notified 
electronically by the EDC system and will retrieve the form. If the event meets serious criteria 
and it is not possible to access the EDC system, send an email to Medpace Safety at medpace-
safetynotification@medpace.com or call the Medpace SAE hotline (phone number listed 
below), and fax/email the completed paper SAE form to Medpace (contact information listed 
below) within 24 hours of awareness. When the EDC system becomes available, the SAE 
information must be entered within 24 hours of the system becoming available. 
Medpace SAE hotline – USA: 
Telephone: +1-800-730-5779, dial “3” or +1-513-579-9911, dial “3” 
Facsimile: +1-866-336-5320 or +1-1-513-570-5196 
E-mail: medpace-safetynotification@medpace.com 
Follow-Up Reports 
The investigator must continue to follow the subject until the SAE has subsided or until the 
condition becomes chronic in nature, stabilizes (in the case of persistent impairment) or the 
subject dies. 


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Within 24 hours of receipt of follow-up information, the investigator must update the SAE 
form electronically in the EDC system for the study and submit any supporting documentation 
(e.g., subject discharge summary or autopsy reports) to Medpace Clinical Safety via fax or e-
mail. If it is not possible to access the EDC system, refer to the procedures outlined above for 
initial reporting of SAEs.  
 


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10.4 Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information 
Definitions 
Woman of Childbearing Potential 
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below). 
Women in the following categories are not considered WOCBP: 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
• Documented hysterectomy 
• Documented bilateral salpingectomy  
• Documented bilateral oophorectomy 
Note: Documentation can come from the site personnel’s: review of the patient’s medical 
records, medical examination, or medical history interview. 
3. Premenopausal female 
• A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. An FSH level in the postmenopausal range may be 
used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence 
of 12 months of amenorrhea, a single FSH measurement is insufficient. 
• Females on HRT and whose menopausal status is in doubt will be required to use 
one of the non-hormonal highly effective contraception methods if they wish to 
continue their HRT during the study. Otherwise, they must discontinue HRT to 
allow confirmation of postmenopausal status before study enrollment.


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Contraception Guidance 
Female Patients 
Female patients of childbearing potential are eligible to participate if they agree to use a highly 
effective or accepted effective method of contraception consistently and correctly as described 
below. 
Highly Effective Contraception Methods 
Highly Effective Contraceptive Methods That Are User Dependenta 
Failure rate of < 1% per year when used consistently and correctly. 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation 
• Oral 
• Intravaginal 
• Transdermal 
Highly Effective Contraceptive Methods That Are User Independenta 
Implantable progestogen-only hormonal contraception associated with inhibition of ovulation 
• Intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS) 
Bilateral tubal occlusion 
Vasectomized Partner 
A vasectomized partner is a highly effective contraception method provided that the partner is 
the sole male sexual partner of the woman of childbearing potential (WOCBP) and the 
absence of sperm has been confirmed. If not, an additional highly effective method of 
contraception should be used. 
Sexual Abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study treatment. 
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the 
study and the preferred and usual lifestyle of the patient. 
a Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent 
with local regulations regarding the use of contraceptive methods for patients participating in clinical studies. 
Accepted Effective Contraceptive Methods 
Acceptable birth control methods that result in a failure of more than 1% per year include: 
• Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the 
primary mode of action 


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• Male or female condom with or without spermicide 
• Cap, diaphragm, or sponge with spermicide 
• Nonhormonal intrauterine device 
A combination of male condom with either cap, diaphragm, or sponge with spermicide (double 
barrier methods) are also considered acceptable, but not highly effective, birth control methods. 
Pregnancy Testing 
At a minimum, a pregnancy test should be performed as per the SoA (Table 1). 
• Women of childbearing potential (WOCBP) should only be included in the study after a 
confirmed menstrual period and a negative highly sensitive serum pregnancy test 
Pregnancy testing will be performed whenever a menstrual cycle is missed or when pregnancy is 
otherwise suspected. 
Collection of Pregnancy Information 
Female Patients Who Become Pregnant 
• The Investigator will collect pregnancy information on any female patient who becomes 
pregnant while participating in this study. Information will be recorded on the appropriate 
form and submitted to the Sponsor within 24 hours of learning of a patient’s pregnancy. 
• The patient will be followed to determine the outcome of the pregnancy. The Investigator 
will collect follow-up information on the patient and the neonate, and the information 
will be forwarded to the Sponsor. Generally, follow-up will not be required for longer 
than 6 to 8 weeks beyond the estimated delivery date. Any termination of pregnancy will 
be reported, regardless of fetal status (presence or absence of anomalies) or indication for 
the procedure. 
• While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication will be reported as an AE or SAE. Abnormal pregnancy outcomes (eg, 
spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) or 
genetic abnormalities (whether leading to an elective abortion or not) are always 
considered to be SAEs and will be reported as such. Any post study pregnancy-related 
SAE considered reasonably related to the study treatment by the Investigator will be 


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reported to the Sponsor as described in Section 10.3.4. While the Investigator is not 
obligated to actively seek this information in former study patients, he or she may learn 
of an SAE through spontaneous reporting. 
• Any female patient who becomes pregnant while participating in the study will 
discontinue study treatment or be withdrawn from the study. 
 
 


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10.5 Appendix 5: Abbreviations 
Abbreviation 
Description 
AE 
adverse event 
ALT 
alanine aminotransferase 
ANCOVA 
analysis of covariance 
ANMS 
GCSI-DD 
American Neurogastroenterology and Motility Society Gastroparesis 
Cardinal Symptom Index Daily Diary 
APD 
action potential duration 
AST 
aspartate aminotransferase 
AUC 
Area Under the Curve 
AUC0-last 
the area under the plasma concentration versus time curve, from time 0 to 
the last measurable concentration 
AUC∞ 
the area under the plasma concentration vs. time curve from time 0 to 
infinity 
BP 
Blood Pressure 
BCRP 
Breast cancer resistance protein 
BMI 
Body mass index 
BUN 
Blood urea nitrogen 
Cmax 
maximum observed plasma concentration 
eCRF 
electronic case report form 
CGI-I 
Clinical Global Impression-Improvement 
CGI-S 
Clinical Global Impression-Severity 
CHO 
Chinese hamster ovary 
C-SSRS 
Columbia–Suicide Severity Rating Scale 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
Cytochrome P450 
DG 
diabetic gastroparesis 
DRM 
delayed release multiple dose cohort 
ECG 
electrocardiogram 
FAS 
full analysis set 
FBG 
Fasting blood glucose 
FDA 
Food and Drug Administration 
FGID 
Functional gastrointestinal disorders 
FSH 
follicle-stimulating hormone 


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GCP 
Good Clinical Practice 
GEBT 
Gastric Emptying Breath Test 
GI 
Gastrointestinal 
GLP-1 
Glucagon-like peptide 1 
hCG 
human chorionic gonadotropin 
HbA1c 
hemoglobin A1c 
HCV 
hepatitis C 
HIV 
Human immunodeficiency virus 
HR  
Heart rate 
HRT 
hormone replacement therapy 
ICF 
informed consent form 
ICH 
International Conference for Harmonisation 
IG 
idiopathic gastroparesis 
IEC 
Independent Ethics Committee 
IND 
Investigational New Drug 
INR 
international normalized ration 
IR 
immediate release 
IRB 
Institutional Review Board 
IRM 
Low dose immediate release cohort 
IRT 
interactive response technology 
IUD 
intrauterine device 
LTBI 
latent TB infection 
NCI 
National Cancer Institute 
NOAEL 
No Observable Adverse Effect Level 
PAGI-SYM 
Patient Assessment of Gastrointestinal Disorders Symptom Severity Index 
PAGI-QOL 
Patient Assessment of Upper Gastrointestinal Disorders – Quality of Life 
PD 
pharmacodynamic(s) 
PGI-C 
Patient Global Impression of Change 
PGI-S 
Patient Global Impression of Severity 
P-gp 
p-glycoprotein 
PK 
pharmacokinetic(s) 
PRO 
Patient-Reported Outcomes 
PT 
preferred term 
QD 
once daily 
QTcB 
Bazett’s correction for QT 


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QTcF 
Fridericia’s correction for QT 
RBC 
Red blood cell 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
standard deviation 
SGOT 
serum glutamic-oxaloacetic transaminase 
SGPT 
serum glutamic-pyruvic transaminase 
SIB 
suicidal ideation and behavior 
SoA 
schedule of activities 
SOC 
System organ class 
TB 
tuberculosis 
Tmax 
time at which the maximum plasma concentration was observed 
t½ 
the apparent first-order terminal elimination half-life 
ULN 
upper limit of normal 
US 
United States 
WBC 
White blood cell 
WOCBP 
woman of childbearing potential 
λz 
apparent first order terminal elimination rate constant 
5-HT receptor 
5-hydroxytryptamine receptor 
5-HT4 receptor 
5-hydroxytryptamine receptor 4 


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11 References 
1. 
Briefing Document for FDA Gastrointestinal Drugs Advisory Committee Meeting 
Regarding Serotonin (5-hydroxytryptamine) Receptor 4 Agonists. 2011. 
2. 
Busner J, Targum SD. The clinical global impressions scale: applying a research tool in 
clinical practice. Psychiatry (Edgmont). 2007;4(7):28-37. 
3. 
Camilleri M, Chedid V, Ford AC, et al. Gastroparesis. Nat Rev Dis Primers. 
2018;4(1):41. Published 2018 Nov 1. doi:10.1038/s41572-018-0038-z. 
4. 
Camilleri M, Parkman H, Shafi M, Abell T, Gerson L. American College of 
Gastroenterology clinical guideline: management of gastroparesis. Am J Gastroenterol. 
2013:108;18-37. 
5. 
de la Loge C, Trudeau E, Marquis P, et al. Cross-cultural development and validation of a 
patient self-administered questionnaire to assess quality of life in upper gastrointestinal 
disorders: the PAGI-QOL. Qual Life Res. 2004;13(10):1751-1762. doi:10.1007/s11136-
004-8751-3 
6. 
Kim S, Lee HA, Jang SB, Lee H. A population pharmacokinetic-pharmacodynamic 
model of YH12852, a highly selective 5-hydroxytryptamine 4 receptor agonist, in healthy 
subjects and patients with functional constipation. CPT Pharmacometrics Syst 
Pharmacol. 2021 Jun 4. doi: 10.1002/psp4.12664. Epub ahead of print. PMID: 34085769. 
7. 
Manabe N, Wong BS, Camilleri M, et al. Lower functional gastrointestinal disorders: 
evidence of abnormal colonic transit in a 287 patient cohort. Neurogastroenterol Motil 
2010; 22:293-e82. 
8. 
Movetis NV. Study PRU-USA-22. A study to evaluate the long-term tolerability, safety, 
patient satisfaction, pharmacokinetics, and use pattern of oral prucalopride tablets in 
patients with chronic constipation. Clinical study report. Data on file. 2008. 
9. 
Movetis NV. Study PRU-INT-17. A study to evaluate the long-term tolerability and 
safety and the pattern of use of prucalopride in patients with chronic pain (cancer and 
non-cancer), suffering from opioid-induced constipation. Clinical study report. Data on 
file. 2008   
10. Movetis NV. Study PRU-INT-10. A study to evaluate the long-term tolerability and 
safety of oral prucalopride administered to patients with chronic constipation. Clinical 
study report. Data on file. 2008. 
11. National Institute for Health and Clinical Excellence (NICE). Prucalopride (Resolor®) 
for the treatment of women with chronic constipation in whom standard laxative 
regimens  have failed to provide adequate relief. 2010. 
12. Parkman HP, Hasler WL, Fisher RS; American Gastroenterological Association. 
American Gastroenterological Association technical review on the diagnosis and 
treatment of gastroparesis. Gastroenterology. 2004;127(5):1592-1622. 
doi:10.1053/j.gastro.2004.09.055. 


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13. Parkman HP, Yamada G, Van Natta ML, et al. Ethnic, Racial, and Sex Differences in 
Etiology, Symptoms, Treatment, and Symptom Outcomes of Patients With Gastroparesis. 
Clin Gastroenterol Hepatol. 2019;17(8):1489-1499.e8. doi:10.1016/j.cgh.2018.10.050. 
14. Quigley EM, Hasler WL, Parkman HP. AGA technical review on nausea and vomiting. 
Gastroenterology. 2001;120(1):263-286. doi:10.1053/gast.2001.20516 
15. 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;13(10):1737-1749. 
doi:10.1007/s11136-004-9567-x 
16. Soykan I, Sivri B, Sarosiek I, Kiernan B, McCallum RW. Demography, clinical 
characteristics, psychological and abuse profiles, treatment, and long-term follow-up of 
patients with gastroparesis. Dig Dis Sci. 1998;43(11):2398-2404. 
doi:10.1023/a:1026665728213 
17. US Food and Drug Administration. Drug approval Package Reglan Tablets. 2017. 
REGLAN (metoclopramide) tablets (fda.gov) 
18. US Food and Drug Administration. Drug approval Package Gimoti Nasal Spray. 2021. 
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=95269b1f-779c-4ca0-9f86-
e74e677f9900  
 
 


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12 Declaration of the Investigator 
Title: A Phase 2A Placebo-controlled, Randomized Dose Response Study of the Safety, 
Pharmacokinetics and Efficacy of PCS12852 on Gastric Emptying Rate Assessed by 13C 
Spirulina GEBT in Patients with Moderate to Severe Gastroparesis. 
All documentation for this study that is supplied to me and that has not been previously 
published will be kept in the strictest confidence. This documentation includes this study 
protocol, Investigator's Brochure, electronic CRF (eCRF), and other scientific data. 
The study will not be commenced without the prior written approval of a properly constituted 
IRB or IEC. No changes will be made to the study protocol without the prior written approval of 
the Sponsor and the IRB or IEC, except where necessary to eliminate an immediate hazard to the 
patients. 
I have read and understood and agree to abide by all the conditions and instructions contained in 
this protocol. 
Responsible Investigator of the Local Study Center 
 
_____________________________________ 
_____________________ 
Signature Date 
_____________________________________ 
Name (print letters) 
_____________________________________ 
Title (print letters) 
_____________________________________ 
Institution (print letters) 
_____________________________________ 
Phone number