Conditions: Diabetic Gastroparesis
Allocation: RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 2
Healthy volunteers: no

Brief summary:
This is a randomized, double-blind, placebo-controlled scintigraphy study to investigate the effect of oral CIN-102 on gastric emptying and antral contractility in adults with diabetic gastroparesis.

Detailed description:
This is a randomized, double-blind, placebo-controlled scintigraphy study to investigate the effect of oral CIN-102 on gastric emptying and antral contractility in adults with diabetic gastroparesis. The population for this study is adult patients 18 to 70 years old with Type 1 or Type 2 diabetes and a diagnosis of diabetic gastroparesis. The study will consist of two cohorts with approximately 15 subjects in each cohort.

Arms:
arm 1: CIN-102 tablets by mouth twice daily for 14 days arm 2: Placebo tablets by mouth twice daily for 14 days arm 3: CIN-102 tablets by mouth twice daily for 14 days arm 4: Placebo tablets by mouth twice daily for 14 days

Interventions: intervention 1: CIN-102 Dose 1 intervention 2: CIN-102 Dose 2 intervention 3: Placebo for CIN-102
Intervention descriptions: intervention 1: Deuterated domperidone (deudomperidone) intervention 2: Deuterated domperidone (deudomperidone) intervention 3: Placebo

Protocol document:
Prot_SAP_001.pdf: 
 
Confidential & Proprietary 
1 
Version 1.0, 21 October 2019 
 
 
 
CLINICAL STUDY PROTOCOL 
 
A Randomized, Double-Blind Placebo-Controlled Scintigraphy Study 
to Investigate the Effect of CIN-102 on Gastric Emptying and Antral 
Contractility in Adults with Diabetic Gastroparesis 
Investigational Product: CIN-102 
Protocol Number: CIN-102-122 
 
 
 
Sponsor: 
CinDome Pharma, Inc. 
5375 Medpace Way 
Cincinnati, OH 45227 
United States 
 
 
 
 
Version Number: 1.0 
Date: 21 October 2019 
 
 
 
 
Confidentiality Statement 
The information in this document is confidential and is not to be disclosed without the written consent 
of CinDome Pharma, Inc. except to the extent that disclosure would be required by law and for the 
purpose of evaluating and/or conducting a clinical study for CinDome Pharma, Inc. You are allowed 
to disclose the contents of this document only to your Institutional Review Board and study personnel 
directly involved with conducting this protocol. Persons to whom the information is disclosed must 
be informed that the information is confidential and proprietary to CinDome Pharma, Inc. and that it 
may not be further disclosed to third parties. 




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INVESTIGATOR AGREEMENT 
By signing below I agree that: 
I have read this protocol. I approve this document and I agree that it contains all necessary details for 
carrying out the study as described. I will conduct this study in accordance with the design and 
specific provision of this protocol and will make a reasonable effort to complete the study within the 
time designated. I will provide copies of this protocol and access to all information furnished by 
CinDome Pharma, Inc. to study personnel under my supervision. I will discuss this material with 
them to ensure they are fully informed about the study product and study procedures. I will let them 
know that this information is confidential and proprietary to CinDome Pharma, Inc. and that it may 
not be further disclosed to third parties. I understand that the study may be terminated or enrollment 
suspended at any time by CinDome Pharma, Inc., with or without cause, or by me if it becomes 
necessary to protect the best interests of the study subjects. 
I agree to conduct this study in full accordance with Food and Drug Administration Regulations, 
Institutional Review Board/Ethic Committee Regulations and International Council for 
Harmonisation Guidelines for Good Clinical Practices. 
 
 
 
 
 
 
______________________________________________  
____________________ 
Investigator’s Signature 
 
 
 
 
 
Date 
 
 
 
______________________________________________ 
Investigator’s Printed Name 
 


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SYNOPSIS 
TITLE:  A Randomized, Double-Blind, Placebo-Controlled Scintigraphy Study to Investigate the 
Effect of Oral CIN-102 on Gastric Emptying and Antral Contractility in Adults with Diabetic 
Gastroparesis 
PROTOCOL NUMBER:  CIN-102-122 
INVESTIGATIONAL PRODUCT:  CIN-102 
PHASE:  2a 
INDICATION(S):  Treatment and relief of symptoms associated with acute and recurrent 
gastroparesis 
OBJECTIVES: 
The objectives of this study are the following: 
 To evaluate the change from baseline in gastric percentage retention of a radiolabeled 
meal after dosing CIN-102 in patients with diabetic gastroparesis. 
 To evaluate the safety and tolerability of CIN-102 in patients with diabetic gastroparesis.
 To assess the effect of CIN-102 on antral contractility as measured by Dynamic Antral 
Scintigraphy (DAS). 
 To assess the effect of CIN-102 on gastric accommodation. 
 To assess the effect of CIN-102 on symptom severity as measured by 
patient/investigator-reported outcomes. 
POPULATION: 
The population for this study is adult patients 18 to 70 years old with Type 1 or Type 2 diabetes 
mellitus, according to the American Diabetes Association criteria, and a diagnosis of diabetic 
gastroparesis defined by upper gastrointestinal symptoms felt to be consistent with gastroparesis 
AND previously documented delayed gastric emptying within the past 3 years by scintigraphy. 
SELECTION AND WITHDRAWAL OF PATIENTS: 
Inclusion Criteria: 
Patients who meet all of the following criteria will be eligible to participate in the study: 
1. Male and female patients 18 to 70 years old, inclusive. 
2. Has Type 1 or Type 2 diabetes mellitus, according to the American Diabetes Association 
criteria. 
3. Current diagnosis of diabetic gastroparesis as defined by the following: 




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13. Able to understand and willing to comply with all study visits, procedures, restrictions, 
discontinuation of medications, including those to treat gastroparesis (as specified in the 
protocol), and provide written informed consent according to institutional and regulatory 
guidelines. 
Exclusion Criteria 
Patients who meet any of the following criteria will be excluded from participation in the study: 
1. History of, or current, clinically significant arrhythmias as judged by the Investigator, 
including ventricular tachycardia, ventricular fibrillation, atrial fibrillation, and Torsades 
de Pointes. Patients with minor forms of ectopy (eg, premature atrial contractions) are not 
necessarily excluded. 
2. Clinically significant bradycardia with a resting heart rate under 50 beats per minute, sinus 
node dysfunction, or heart block. 
3. Prolonged heart rate-corrected QT interval using Fridericia’s formula (QTcF) (QTcF 
>450 msec for males or QTcF >470 msec for females) based on the average of triplicate 
ECGs. 
4. A personal or family history of long QT syndrome, Torsades de pointes, or other complex 
ventricular arrhythmias or family history of sudden death; 
5. Evidence (based on Screening or Baseline assessments) or history of clinically significant 
immunologic, hematologic, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, 
hepatic, psychiatric, neurologic, or allergic disease (including drug allergies); surgical 
conditions; cancer (with the exception of basal or squamous cell carcinoma of the skin and 
cancer that resolved or has been in remission for >5 years prior to the Screening Visit); or 
any condition that, in the Investigator’s opinion, might significantly interfere with the 
absorption, distribution, metabolism, or excretion of the study drug.  
Note: Cholecystectomy and appendectomy are allowed. 
6. History of prolactin-releasing pituitary tumor (ie, prolactinoma). 
7. Serum prolactin greater than the upper limit of normal. 
Note: Patients who are on domperidone with an elevated prolactin at the time of Screening 
may be considered for this study, provided prolactin is within normal limits at time of 
randomization. 
8. Known or suspected hypogonadism, current clinically significant menstrual abnormalities 
(eg, oligomenorrhea or amenorrhea), gynecomastia, galactorrhea, or other clinical features 
that in the Investigator’s opinion may be consistent with hyperprolactinemia. 
9. Pyloric injection of botulinum toxin within 6 months of Screening and during the course 
of the study. 
10.  Has a serum creatinine level greater than 1.5 × the upper limit of normal or has an 
estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 using the Chronic Kidney 
Disease Epidemiology Collaboration (CKD-EPI) equation at Screening.  














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TABLE OF CONTENTS 
Signature Page ................................................................................................................................. 2 
Investigator Agreement ................................................................................................................... 3 
Synopsis ........................................................................................................................................... 4 
Table of Contents........................................................................................................................... 13 
List of Tables ................................................................................................................................. 17 
List of Abbreviations and Definition of Terms ............................................................................. 18 
1 Introduction and Background Information .............................................................................. 21 
1.1 
Indication and Treatment Options ................................................................................. 21 
1.2 
CIN-102 ......................................................................................................................... 22 
1.3 
Study Rationale .............................................................................................................. 23 
1.4 
Risk/Benefit ................................................................................................................... 23 
2 Study Objectives ...................................................................................................................... 26 
2.1 
Objectives ...................................................................................................................... 26 
3 Study Description .................................................................................................................... 27 
3.1 
Summary of Study Design ............................................................................................. 27 
3.2 
Study Indication ............................................................................................................. 28 
3.3 
Dose Escalation and Review Committee ....................................................................... 28 
3.3.1 Criteria for Temporary Suspension of Dosing ................................................... 29 
3.3.2 Criteria to Cease Dose Escalation ...................................................................... 30 
4 Selection and Withdrawal of Subjects ..................................................................................... 31 
4.1 
Inclusion Criteria ........................................................................................................... 31 
4.2 
Exclusion Criteria .......................................................................................................... 32 
4.3 
Randomization Criteria .................................................................................................. 34 
4.4 
Withdrawal Criteria ....................................................................................................... 35 
5 Study Treatments ..................................................................................................................... 36 
5.1 
Treatment Groups .......................................................................................................... 36 
5.2 
Rationale for Dosing ...................................................................................................... 36 
5.3 
Randomization and Blinding ......................................................................................... 37 
5.4 
Breaking the Blind ......................................................................................................... 37 
5.5 
Drug Supplies ................................................................................................................. 37 
5.5.1 Formulation and Packaging ............................................................................... 37 


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5.5.2 Study Drug Preparation and Dispensing ............................................................ 37 
5.5.3 Study Drug Administration ................................................................................ 37 
5.5.4 Treatment Compliance ....................................................................................... 38 
5.5.5 Storage and Accountability ................................................................................ 38 
5.6 
Prior and Concomitant Medications and/or Procedures ................................................ 38 
5.6.1 Excluded Medications and/or Procedures .......................................................... 38 
5.6.2 Restricted Medications and/or Procedures ......................................................... 39 
5.6.3 Allowed Medications and/or Procedures ........................................................... 39 
5.6.4 Documentation of Prior and Concomitant Medication Use ............................... 40 
6 Study Procedures ..................................................................................................................... 41 
6.1 
Informed Consent ........................................................................................................... 41 
6.2 
Screening Visit (Days -28 to -6) .................................................................................... 41 
6.3 
Baseline Scintigraphy Test Visit (Days -5 to -1) ........................................................... 42 
6.4 
Treatment Period – Day 1 through Day 14 (+ 1 Day) ................................................... 43 
6.4.1 Day 1 (Randomization) ...................................................................................... 43 
6.4.2 Day 2… .............................................................................................................. 44 
6.4.3 Day 3 (± 1 Day) ................................................................................................. 44 
6.4.4 Days 4, 5, 6 ........................................................................................................ 45 
6.4.5 Day 7 (± 1 Day) ................................................................................................. 45 
6.4.6 Days 8 and 9 ....................................................................................................... 46 
6.4.7 Day 10 (± 1 Day) ............................................................................................... 46 
6.4.8 Days 11, 12, 13 .................................................................................................. 47 
6.4.9 Day 14 (+ 1 Day) ............................................................................................... 47 
6.5 
Follow-up Visit (Day 20 ± 1 Day) ................................................................................. 48 
6.6 
Early Termination Visit and Withdrawal Procedures .................................................... 48 
7 Efficacy Assessments .............................................................................................................. 50 
7.1 
Efficacy Assessments ..................................................................................................... 50 
7.2 
Pharmacokinetics ........................................................................................................... 52 
8 Safety Assessments.................................................................................................................. 53 
8.1 
Adverse Events .............................................................................................................. 53 
8.1.1 Adverse (Drug) Reaction ................................................................................... 54 
8.1.2 Unexpected Adverse Drug Reaction .................................................................. 54 
8.1.3 Assessment of Adverse Events by the Investigator ........................................... 54 


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8.2 
Serious Adverse Events ................................................................................................. 55 
8.3 
Serious Adverse Event Reporting − Procedures for Investigators ................................. 56 
8.4 
Pregnancy Reporting ...................................................................................................... 57 
8.5 
Clinical Laboratory Evaluations .................................................................................... 57 
8.6 
Vital Signs ...................................................................................................................... 58 
8.7 
Electrocardiograms ........................................................................................................ 58 
8.8 
Physical Examinations ................................................................................................... 59 
8.9 
Height and Weight ......................................................................................................... 59 
9 Statistics ................................................................................................................................... 60 
9.1 
Analysis Populations ...................................................................................................... 60 
9.2 
Statistical Methods ......................................................................................................... 60 
9.2.1 Analysis of Efficacy ........................................................................................... 60 
9.2.2 Pharmacokinetic Analysis .................................................................................. 60 
9.2.3 Pharmacokinetic-Pharmacodynamic Analysis ................................................... 61 
9.2.4 Analysis of Safety .............................................................................................. 61 
9.2.5 Sample Size Determination ................................................................................ 61 
10 Data Management and Record Keeping .................................................................................. 62 
10.1 Data Management .......................................................................................................... 62 
10.1.1 Data Handling .................................................................................................... 62 
10.1.2 Computer Systems ............................................................................................. 62 
10.1.3 Data Entry .......................................................................................................... 62 
10.1.4 Medical Information Coding .............................................................................. 62 
10.1.5 Data Validation .................................................................................................. 62 
10.2 Record Keeping ............................................................................................................. 63 
11 Investigator Requirements and Quality Control ...................................................................... 64 
11.1 Ethical Conduct of the Study ......................................................................................... 64 
11.2 Institutional Review Board/Independent Ethics Committee .......................................... 64 
11.3 Informed Consent ........................................................................................................... 64 
11.4 Study Monitoring Requirements .................................................................................... 65 
11.5 Disclosure of Data .......................................................................................................... 65 
11.6 Retention of Records ...................................................................................................... 65 
11.7 Publication Policy .......................................................................................................... 66 
11.8 Financial Disclosure ....................................................................................................... 66 


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12 Study Administrative Information ........................................................................................... 67 
12.1 Protocol Amendments .................................................................................................... 67 
13 References ............................................................................................................................... 68 
Appendix A:  Schedule of Procedures ........................................................................................... 70 
Appendix B:  Clinical Laboratory Analytes .................................................................................. 73 
Appendix C: Electrocardiogram Alert Criteria Guidance ............................................................. 75 


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LIST OF TABLES 
Table 1.     CTCAE Severity Assessment of Adverse Events .......................................................... 54 
 
 


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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS  
Abbreviation            Definition 
AE
Adverse Event
ALT
Alanine Aminotransferase
 
 
AST
Aspartate Aminotransferase
AUC
Area Under the Plasma-Time Curve
AV
Atrioventricular
BID
Twice Daily
BMI
Body Mass Index
BPM
Beats Per Minute
C
Carbon
CFR
Code of Federal Regulations
CKD-EPI
Chronic Kidney Disease Epidemiology Collaboration
Cmax
Maximum Plasma Concentration
CNS
Central Nervous System
CO2
Carbon Dioxide
 
CRA
Clinical Research Associate
CT
Computed Tomography
CTCAE
Common Terminology Criteria for Adverse Events
CYP
Cytochrome P450
DAS
Dynamic Antral Scintigraphy
DGE
Delayed Gastric Emptying
dL
Deciliter(s)
DRC
Data Review Committee
ECG
Electrocardiogram
eCRF
Electronic Case Report Form
EDC
Electronic Data Capture
eGFR
Estimated Glomerular Filtration Rate
EIU
Exposure In Utero
FDA
Food and Drug Administration
g
Gram(s)
GCP
Good Clinical Practice
GI
Gastrointestinal
HBsAg
Hepatitis B Surface Antigen
HCV
Hepatitis C Virus


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Abbreviation            Definition 
HIV
Human Immunodeficiency Virus
ICF
Informed Consent Form
ICH
International Conference for Harmonisation
IRB
Institutional Review Board
ITT
Intent-to-Treat
IV
Intravenous
keV
Kiloelectron Volt(s)
kPCD
Percent Dose Excreted * 1000
LBBB
Left Bundle Branch Block
MAD
Multiple Ascending Dose
MBQ
Megabecquerel(s)
MCI
Millicurie(s)
mg
Milligram(s)
mITT
Modified Intent-to-Treat
mL
Milliliter(s)
mm
Millimeter(s)
mREM
Millirem(s)
MSEC
Millisecond(s)
mSv
Millisievert(s)
MTT
Mean Transit Time
ng
Nanogram(s)
 
PD
Pharmacodynamics(s)
PEG
Percutaneous Endoscopic Gastrostomy
PI
Principal Investigator
PK
Pharmacokinetic(s)
POC
Point-of-Care
QTcF
Heart rate-corrected QT interval using Fridericia’s formula
ROI
Region(s) of Interest
SAD
Single Ascending Dose
SAE
Serious Adverse Event
 
SVT
Supraventricular Tachycardia
T1/2
Terminal Phase Elimination Half-Life
TAC
Time-Activity Curve(s)
Tc-99
Technetium-99
TEAE
Treatment-Emergent Adverse Event
THC
Tetrahydrocannabinol
TSH
Thyroid-Stimulating Hormone
TWA
Time-Weighted Average


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Abbreviation            Definition 
ULN
Upper Limit(s) of Normal
USA
United States of America
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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1 
INTRODUCTION AND BACKGROUND INFORMATION  
1.1 
Indication and Treatment Options 
Gastroparesis is defined as impaired gastric emptying in the absence of physical gastric outlet 
obstruction. Symptoms include early satiety, postprandial fullness, nausea, vomiting, and abdominal 
pain.1 The disease is often associated with diabetes or may occur after gastric surgery; it may also 
be idiopathic from unknown etiologies.2 Gastroparesis affects the patient’s nutritional state, 
especially in diabetics, and severe symptoms of gastroparesis can lead to other complications such 
as malnutrition, esophagitis, and Mallory-Weiss tears.3,4  Gastroparesis negatively impacts a 
patient’s quality of life, causing decreased social interaction, poor work functionality, and 
development of anxiety or depression.3 
The first-line treatment for gastroparesis involves nutritional management and support, including 
fluid and electrolyte replacement. Pharmacologic therapy is directed at increasing gastric emptying 
and  accelerating intestinal  transit  time.  Currently,  metoclopramide,  a dopamine D2 receptor 
antagonist, is the only United States Food and Drug Administration (FDA)-approved agent for the 
treatment of gastroparesis. While effective, this agent readily crosses the blood-brain barrier resulting 
in central nervous system (CNS) side effects in up to 40% of patients.5 Common CNS effects 
associated with metoclopramide treatment include restlessness, drowsiness, fatigue, and lassitude; 
however, the major safety concern with metoclopramide treatment is the development of tardive 
dyskinesia. Tardive dyskinesia is a disorder characterized by involuntary movements of the face, 
tongue, or extremities and is often irreversible. Increased risk of developing tardive dyskinesia 
correlates to treatment duration; therefore, it is recommended that therapy with metoclopramide not 
exceed 12 weeks.6 
Domperidone is a peripheral dopamine D2 receptor antagonist that acts as an antiemetic and a 
prokinetic agent through its effects on the chemoreceptor trigger zone in the area postrema and the 
motor function in the stomach and small intestine.7,8 Domperidone has been available worldwide 
outside of the United States since 1978 as a treatment for gastroparesis as well as a general 
antiemetic. It is currently available in 58 countries, including Canada. In those countries where 
domperidone is approved, the current recommended daily dose is up to 30 mg/day (10 mg 
administered orally 3 times a day) for nausea and vomiting. While available in many countries 
worldwide,   domperidone   is   only   available   to   patients   in   the   United   States   through a 
physician-initiated Investigational New Drug application at doses up to 120 mg/day (30 mg 
administered orally 4 times per day) for the treatment of gastroparesis and any condition causing 
chronic nausea and vomiting.8 Current treatment guidelines recommend the use of domperidone for 
patients unable to use metoclopramide.9 
Unlike metoclopramide, domperidone does not cross the blood-brain barrier and seldom causes 
extrapyramidal side effects. Similar to other dopamine D2 receptor antagonists, domperidone has 
been shown to raise prolactin levels with chronic administration, but prolactin levels return to 
normal upon discontinuation of the drug.7,10 Use of domperidone has also been associated with QT 
prolongation. Due to reports of cardiac arrest with the use of intravenous (IV) domperidone, the IV 
dose form was removed from the market. Given the low oral bioavailability of domperidone 
(approximately 13% to 17% of the administered dose),8 oral doses in excess of 1000 mg/day would 
correlate with the IV doses administered to patients at the time when the cardiac issues were 


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reported.11 When QT prolongation has been reported with oral domperidone, it has primarily been 
in patients over 60 years of age, in patients taking more than 30 mg/day, in patients with cardiac 
predispositions, or in patients who were also receiving other QT-prolonging drugs or potent 
cytochrome P450 (CYP) 3A4 inhibitors, such as ketoconazole. However, there have been reports 
of cases of QT prolongation among patients taking domperidone with none of these additional risk 
factors.12,13  The potential for QT prolongation is believed to be related to increased plasma 
concentrations of domperidone. It is suggested that the mean effect on QT of 10 msec (the definition 
of QT prolongation) may occur when the domperidone plasma concentration reaches approximately 
65 ng/mL.14,15  Therefore, limiting the maximum plasma concentration (Cmax) of domperidone to 
approximately 60 ng/mL may significantly lower the risk of QT prolongation. 
 
1.2 
CIN-102 
CinDome Pharma, Inc. is currently developing CIN-102, a deuterated form of domperidone. 
A new process was developed to synthesize a deuterated version of domperidone 
 
 
 
 
 
 Given that the 
pharmacological properties of CIN-102 are similar to those of domperidone, CIN-102 is intended 
to provide an alternative for the treatment and relief of symptoms associated with acute and recurrent 
gastroparesis that may have less potential for QT prolongation. 
Two clinical studies of CIN-102 in healthy subjects have completed to date: a single-ascending 
dose (SAD) study (Study CIN-102-111) and a multiple-ascending dose (MAD) study (Study CIN-
102-112). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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A Phase 2 study to evaluate the effect of CIN-102 in diabetic patients with gastroparesis is ongoing 
(Protocol CIN-102-121). The CIN-102-121 protocol will enroll patients in a similar manner as this 
current protocol CIN-102-122 and will start at the same 
 BID starting dose. Instead of utilizing 
scintigraphy as in this current protocol, the CIN-102-121 protocol will evaluate the patient’s gastric 
emptying via the Gastric Emptying Breath Test, a nonradioactive stable isotope breath test, in which 
the ratio of exhaled 13CO2/12CO2 is used to determine the rate of gastric emptying after consumption 
of a standardized, 13C-enriched meal. Data from the CIN-102-121 protocol will be shared with the 
investigators in the CIN-102-122 protocol as available, and vice versa. 
1.3 
Study Rationale 
To date, the PK, pharmacodynamics (PD; based on increases in prolactin), and safety of CIN-102 
have been evaluated in a SAD study and a MAD study in healthy subjects. The current study is the 
second study to commence in patients with gastroparesis. As such, this study is intended to evaluate 
the effect of CIN-102 on gastric emptying in patients with diabetic gastroparesis over a range of 
doses. The safety, PD, and effect of CIN-102 on symptoms of gastroparesis in these patients will 
also be assessed in this study. The results of this study will be used to support dose selection for 
future studies. 
1.4 
Risk/Benefit 
Side effects that have been reported by 1% of patients treated in clinical trials with traditional 
domperidone with a median total daily dose of 80 mg include the following: depression, anxiety, 
loss of libido, headache, somnolence, akathisia, diarrhea, rash, pruritus, gynecomastia, breast 
tenderness, galactorrhea, amenorrhea, breast pain, irregular menstruation, lactation disorders, and 
asthenia.7 
Less frequently reported adverse events that occurred in <1% of treated patients include 
hypersensitivity, urticaria, breast  discharge, and  breast swelling.7  Rare or very rare adverse 
reactions that have been estimated from spontaneous reporting include anaphylactic reactions, 
agitations, nervousness, extrapyramidal disorders, convulsions, sudden cardiac death, ventricular 
arrhythmias, angioedema, urinary retention, abnormal liver tests, and increased blood prolactin.7 
As noted previously, domperidone has been associated with prolongation of the QT interval on 
electrocardiograms (ECGs).16 During postmarketing surveillance, there have been very rare cases 
(<1/10,000 cases) of QT prolongation and QT prolongation-induced Torsades de Pointes in patients 
taking oral domperidone.16,17  These reports included patients with confounding risk factors, 




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A goal of this study is to assess the effect of CIN-102 on gastric emptying in patients with diabetic 
gastroparesis. Given the known antiemetic and prokinetic effects of domperidone, it is possible that 
patients may experience improvement in their symptoms during the course of this study.  


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2 
STUDY OBJECTIVES 
2.1 
Objectives 
The objectives of this study are to evaluate the following: 
 To evaluate the change from baseline in gastric percentage retention of a radiolabeled meal after 
dosing CIN-102 in patients with diabetic gastroparesis. 
 To evaluate the safety and tolerability of CIN-102 in patients with diabetic gastroparesis. 
 To assess the effect of CIN-102 on antral contractility as measured by Dynamic Antral 
Scintigraphy. 
 To assess the effect of CIN-102 on gastric accommodation. 
 To assess the effect of CIN-102 on symptom severity as measured by patient/investigator-
reported outcomes. 
 


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3 
STUDY DESCRIPTION 
3.1 
Summary of Study Design 
This is a randomized, double-blind, placebo-controlled study to investigate the effect of oral CIN-102 
on gastric emptying in adults with diabetic gastroparesis. The safety, tolerability and 
pharmacodynamics (PD) of multiple doses of CIN-102 will also be assessed in this population.  
The study will begin by randomizing patients in Cohort 1 to either CIN-102 
 BID or placebo 
BID in a ratio such that approximately 10 patients receive CIN-102 and 5 patients receive placebo. 
The Data Review Committee (DRC) will review emerging safety and/or efficacy data throughout the 
study. After approximately 12 patients in Cohort 1 complete the study, the data from Cohort 1 will 
be reviewed by the DRC to determine if it is safe and appropriate to continue the study with the 
currently planned dose levels or if further refinement of the proposed dose levels is warranted. 
Currently planned dose level for Cohort 2 is 
 BID, with 10 patients receiving the study drug 
and 5 patients receiving placebo. However, this dosing cohort may be modified based on emerging 
information from the prior cohort as well as other ongoing studies. The highest dose will not exceed 
 BID without a protocol amendment. Further details regarding the role, responsibilities, and 
procedures of the DRC will be provided in the DRC Charter. 
The dosing regimens for this study have been chosen based upon the safety, tolerability, and PK 
profile established in healthy subjects in single-ascending and multiple-ascending dose studies as 
well as modelling and simulation.  
At the Screening Visit, all patients will sign informed consent prior to any study procedures being 
performed. Patients must meet all of the inclusion criteria and none of the exclusion criteria to be 
eligible for study participation. 
Patients will be evaluated as follows: 
 Days -28 to Day -6: Screening procedures will be performed. 
 
 
 
 Day -5 to Day -1:  Scintigraphic gastric emptying and Dynamic Antral Scintigraphy (DAS) will 
be performed on a single day within this window for baseline determination. 
 
 
 
 
 Patients 
may be randomized at any point during the baseline period once all procedures have been 
performed and all eligibility criteria are met. 
 Days 1 to 14: Study drug will be administered (CIN-102 or placebo BID for 14 [+1 day]) and 
safety assessments and PK, will be completed. 
 
  
o Day 14 (+1 day): The patient will present after an overnight (>8-hour) fast. 
 
 Study drug will be administered and the patient will 
consume the radiolabeled meal 30 minutes after study drug administration. The 


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radiolabeled meal should be consumed by the patient in <10-minutes. Scintigraphic gastric 
emptying and DAS will be administered following completion of the radiolabeled meal. 
 
 Blood glucose will be measured by glucometer prior to the 
meal and at the 2 hour and 4 hour timepoints.  
 Day 20 (±1 day): Patients will have a follow up phone call 5 to 7 days following the last dose of 
study drug to assess adverse events and changes to concomitant medications (including use of 
rescue medication). 
On days of the scintigraphy, patients will present after an overnight (>8-hour) fast and should take 
regular medications, including any treatment for diabetes, with the exception of any prohibited 
concomitant medication. Patients should be instructed to bring in their medication. Patients should 
self-administer their usual morning insulin injection, (calculated considering their fasting status). 
Fasting blood glucose will be assessed before study drug administration and gastric emptying 
assessments to ensure a blood glucose of ≤275 mg/dL. Additional insulin may be given to ensure a 
blood glucose of ≤275 mg/dL prior to the gastric emptying procedure. 
Patients will be given a meal consisting of 120 cc of egg beaters labeled with Tc-99m sulfur colloid 
at a dosage of 2 mCi (74 MBq) and 2 pieces of white wheat bread toast, 30 g of strawberry jam and 
120 mL of water as a standardized meal recommended by a Joint Consensus of the Society of Nuclear 
Medicine and American Neurogastroenterology and Motility Society for GES. On Day 14, the meal 
will be taken 30 minutes after study drug administration and should be consumed in <10-minutes. 
During the period of time from immediately prior to the meal to 4 hours after the meal, patients will 
be asked about symptoms 
 
. Additionally, 
finger stick blood sugars will be monitored over this period. 
For the baseline scintigraphy, patients who ingest <50% of the meal or who vomit before the 2 hour 
scintigraphy data point may be excluded. Patients who have demonstrated delayed gastric emptying 
at the 2 hour data point but vomit before the 4 hour data point may continue to randomization. 
Safety will be evaluated through assessments of adverse events, vital signs, physical examinations, 
clinical laboratory evaluations, and electrocardiogram (ECG) findings. 
Patients will have a final follow-up phone call 5 to 7 days after the final dose of study drug to assess 
adverse events and changes to concomitant medications (including use of rescue medications), 
unscheduled visits and/or additional follow-up may be required at the discretion of the Investigator. 
For example, patients with clinically significant abnormal laboratory findings, unresolved treatment-
emergent adverse events, serious adverse events that require follow-up laboratories and review, and 
clinically significant adverse events may necessitate further assessments. 
3.2 
Study Indication 
CIN-102 is being developed for the treatment and relief of symptoms associated with acute and 
recurrent gastroparesis. 
3.3 
Dose Escalation and Review Committee 
A DRC consisting of at least three members, including a cardiologist, a clinical pharmacologist, 
and an independent clinician experienced in the treatment of patients with diabetic gastroparesis 


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will be formed to review emerging safety and efficacy data in a blinded manner to determine if it 
is safe and appropriate to continue the study with the currently planned dose level of 
 BID 
or if further refinement of the proposed dose level is warranted.  
Upon each DRC review, the following may occur: 
 Proceed to the next protocol-specified dose level, or 
 Proceed to alternate dosing regimen(s) not to exceed the next protocol-specified dose level 
Further detail on DRC conduct will be described in the DRC Charter. 
3.3.1 
Criteria for Temporary Suspension of Dosing 
Dosing within a cohort or between cohorts will be temporarily suspended until a full cumulative data 
review is completed if any of the following occur: 
 Any study drug-related SAE grade 3 or higher based on Common Terminology Criteria for 
Adverse Events (CTCAE) Version 5.0. 
 Any single subject whose ECG (average triplicate ECGs  as interpreted by central read) 
demonstrates a heart-rate corrected QTcF interval (QTcF) >500 msec or in whom there is an 
increase in QTcF >60 msec from baseline (confirmed by repeat ECG). 
 Any new ECG abnormality deemed clinically significant by the investigator. 
 Any study drug-related cardiac adverse event.  In the event that a patient experiences a vasovagal 
or near-syncopal episode, dosing within a cohort or subsequent cohort may proceed as planned 
unless the episode is associated with ECG abnormality or the event is deemed to be severe in 
intensity (severity) by the Investigator. 
 A study drug-related adverse event from a single System Organ Class deemed to be of moderate 
intensity (severity) in 4 or more patients. 
 Any of the following laboratory abnormalities that are thought to be study drug-related or in 
which an alternative explanation is not reasonable: 
o ALT or AST >8 × the upper limit of normal (ULN), or 
o ALT or AST >5 × ULN and persist for more than 2 weeks, or 
o ALT or AST >3 × ULN  in  conjunction  with  elevated  total  bilirubin  >2 × ULN or 
international normalized ratio >1.5, or 
o ALT or AST >3 × ULN with appearance of fatigue, nausea, vomiting, right upper quadrant 
pain or tenderness, fever, rash, and/or eosinophilia (>5%). 
 Any single patient who develops serious study drug-related electrolyte abnormalities due to 
vomiting and/or inability to maintain adequate oral hydration that impacts cardiac stability. 
 Other conditions as deemed medically appropriate based on the Investigator’s judgement. 
The Sponsor and/or DRC may also suspend dosing for any other reason based on emerging 
data from this or other ongoing studies. Should dosing be temporarily suspended, the DRC can 
review and discuss all available safety and PK data from all patients participating in the study 
up until the time of the event. The DRC will decide whether knowledge of the treatment 


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assignment of any patient(s) is(are) necessary to make an appropriate decision about 
continuation of the study. If so, a request to unblind will be made and relevant data will be 
reviewed in an unblinded manner. All unblinding Standard Operating Procedures will be 
followed and documented as appropriate. 
Upon completion of the cumulative data review (whether fully blinded or partially unblinded), 
the DRC may elect to terminate the study or to resume study conduct. If study conduct is 
resumed, the DRC may elect to do one of the following: 
 Continue dosing in the current cohort with the same number of patients originally planned. 
 Expand the current cohort with additional patients to obtain more information at that dose level. 
 Escalate to a higher dose level. 
 Increase the frequency of dosing at the current dose level (if the protocol-specified number of 
subjects at the current dose level have already completed). 
 De-escalate to a lower dose level. 
 Decrease the frequency of dosing at the current dose level. 
If additional cohorts or expansion cohorts are added at the discretion of the Sponsor and DRC, 
no more than 30 additional patients (ie, a study total of 60 patients) will be added without a 
protocol amendment. 
3.3.2 
Criteria to Cease Dose Escalation 
Dosing within a cohort or between cohorts will cease if either of the following occurs: 
 Any two grade 3 or 1 grade 4 or higher study drug-related SAE based on CTCAE Version 5.0. 
 Any 2 patients with an ECG (average of triplicate ECGs as determined by central read) 
demonstrating QTcF >500 msec or a change in QTcF >60 msec from baseline (confirmed by 
repeat ECG with central read). 
Should one of the above occur, consideration may still be given to continued study of an alternate 
dose level or frequency (either expansion of a previously studied cohort or addition of a lower dose 
level). 


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4 
SELECTION AND WITHDRAWAL OF SUBJECTS  
4.1 
Inclusion Criteria 
Patients who meet all of the following criteria will be eligible to participate in the study: 
1. Male and female patients 18 to 70 years old, inclusive. 
2. Has Type 1 or Type 2 diabetes mellitus, according to the American Diabetes Association criteria. 
3. Current diagnosis of diabetic gastroparesis as defined by the following: 
 Upper gastrointestinal (GI) symptoms felt to be consistent with gastroparesis (eg, 
postprandial nausea/vomiting, postprandial fullness, early satiety, anorexia, bloating, 
epigastric or abdominal pain) within the 6 months prior to screening; AND 
 Delayed gastric emptying (DGE) within the past 3 years as defined by >
 gastric 
retention at 4 hours based on scintigraphy.  
4. Has a body mass index (BMI) between 18 and 40 kg/m2, inclusive. 
5. Glycosylated hemoglobin level ≤11%. 
6. Male patients with female partners of child-bearing potential must agree to use 2 medically 
accepted, highly effective methods of birth control from Day 1 through 60 days following the 
final dose of study drug.  
Medically accepted, highly effective methods of birth control for male patients with female 
partners of child-bearing potential include the following: latex condom with spermicide, 
diaphragm with intravaginal spermicide, cervical cap with spermicide, indwelling intrauterine 
device (hormonal or nonhormonal), implanted contraceptives, and oral contraceptives.  
7. Male patients must agree to abstain from sperm donation from Day 1 through 60 days following 
the final dose of study drug. 
8. Female patients with male partners must be surgically sterile (hysterectomy and/or bilateral 
oophorectomy), postmenopausal for at least 1 year (with confirmed follicle-stimulating hormone 
in postmenopausal range at the Screening Visit), or agree to use 2 medically accepted, highly 
effective methods of birth control from Day -14 until 60 days following the final dose of study 
drug.  
Medically accepted, highly effective methods of birth control for female patients with male 
partners include the following: latex condom with spermicide, diaphragm with intravaginal 
spermicide, cervical cap with spermicide, and nonhormonal indwelling intrauterine device. 
9. Negative alcohol and drug screen at Screening and Randomization Visits.  
NOTE: Patients who utilize medical marijuana or THC-containing products may be considered 
for this study if they are able to discontinue within 14 days prior to baseline scintigraphy until 
the end of the study. 
10. Willing to abstain from tobacco or nicotine-containing products use after midnight on the day of 
the DAS test and throughout the time that gastric emptying is being imaged. 
11. 
 
 


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12. 
 
 
 
13. Able to understand and willing to comply with all study visits, procedures, restrictions, 
discontinuation of medications, including those to treat gastroparesis (as specified in the 
protocol), and provide written informed consent according to institutional and regulatory 
guidelines. 
4.2 
Exclusion Criteria 
Patients who meet any of the following criteria will be excluded from participation in the study: 
1. History of, or current, clinically significant arrhythmias as judged by the Investigator, including 
ventricular tachycardia, ventricular fibrillation, and Torsades de Pointes. Patients with minor 
forms of ectopy (eg, premature atrial contractions) are not necessarily excluded. 
2. Clinically significant bradycardia with a resting heart rate under 50 beats per minute, sinus node 
dysfunction, or heart block. 
3. Prolonged heart rate-corrected QT interval using Fridericia’s formula (QTcF) (QTcF >450 msec 
for males or QTcF >470 msec for females) based on the average of triplicate ECGs. 
4. A personal or family history of long QT syndrome, Torsades de pointes, or other complex 
ventricular arrhythmias or family history of sudden death; 
5. Evidence (based on screening or baseline assessments) or history of clinically significant 
immunologic, hematologic, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, 
hepatic, psychiatric, neurologic, or allergic disease (including drug allergies); surgical 
conditions; cancer (with the exception of basal or squamous cell carcinoma of the skin and cancer 
that resolved or has been in remission for >5 years prior to the Screening Visit); or any condition 
that, in the Investigator’s opinion, might significantly interfere with the absorption, distribution, 
metabolism, or excretion of the study drug.  
Note: Cholecystectomy and appendectomy are allowed. 
6. History of prolactin-releasing pituitary tumor (ie, prolactinoma). 
7. Serum prolactin greater than the upper limit of normal. 
Note: Patients who are on domperidone with an elevated prolactin at the time of Screening may 
be considered for this study, provided prolactin is within normal limits at time of randomization. 
8. Known or suspected hypogonadism, current clinically significant menstrual abnormalities 
(eg, oligomenorrhea or amenorrhea), gynecomastia, galactorrhea, or other clinical features that 
in the Investigator’s opinion may be consistent with hyperprolactinemia. 
9. Pyloric injection of botulinum toxin within 6 months of Screening and during the course of the 
study. 
10.  Creatinine levels greater than 1.5 × the upper limit of normal at Screening, or has an estimated 
glomerular filtration rate (eGFR) <30 mL/min/1.73m2 using the Chronic Kidney Disease 
Epidemiology Collaboration (CKD-EPI) equation at Screening.  


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11. Has bilirubin, alkaline phosphatase, aspartate aminotransferase or alanine transaminase greater 
than 2 × the upper limit of normal at Screening or has a Child-Pugh classification grade of B or 
C. 
12. Has a hemoglobin level <10 g/dL at Screening. 
13. Thyroid-stimulating hormone (TSH) levels that are abnormal at Screening, as judged by the 
Investigator. 
14. Allergic to egg or intolerant to gluten. 
15. Use of investigational, prescription, or over-the-counter medications as follows: 
 Actively participating in an experimental therapy study; received experimental therapy with 
a small molecule within 30 days of Day -1, or 5 half-lives, whichever is longer; or received 
experimental therapy with a large molecule within 90 days of Day -1, or 5 half-lives, 
whichever is longer. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
16. History of alcoholism or drug abuse within 2 years prior to dosing as defined by the Diagnostic 
and Statistical Manual of Mental Disorders, 4th Edition. 
17. Typical consumption of 14 alcoholic drinks weekly. 
18. History or evidence of illicit drug use within the past two years. 
19. Positive for human immunodeficiency virus (HIV), Hepatitis C virus (HCV) by RNA, or 
Hepatitis B surface antigen (HBsAg) at the Screening Visit. 
20. Donated blood or blood products within 30 days prior to dosing. 
21. Currently undergoing treatment with weight loss medication or prior weight loss surgery (eg, 
gastric bypass surgery). 
22. Pregnant, breastfeeding, or planning to become pregnant during the course of study. 
23. Inability to swallow medication. 
24. Currently receiving parenteral feeding or presence of a nasogastric or other enteral tube 
(eg, percutaneous endoscopic gastrostomy tube [PEG]) for feeding or decompression. 
25. Known or suspected gastric outlet obstruction (eg, peptic stricture) or other gastrointestinal 
mechanical obstruction.  
26. Known history or current diagnosis of intestinal malabsorption or pancreatic exocrine disease. 


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27. History of gastric surgery such as fundoplication, gastrectomy, gastric pacemaker placement, 
vagotomy, pyloroplasty, or bariatric procedure.  
Note: A history of diagnostic endoscopy is not exclusionary. Cholecystectomy and 
appendectomy are allowed. 
28. History or presence of any medical condition or psychiatric disease, which, in the opinion of the 
Investigator, could interfere with the conduct of the study or would put the patient at unacceptable 
risk. 
29. Known hypersensitivity to domperidone or any of the excipients in the CIN-102 formulation. 
30. Judged by the Investigator, after reviewing medical and psychiatric history, physical 
examination, and laboratory evaluation, to be unsuitable for any other reason that may either 
place the patient at increased risk during participation or interfere with the interpretation of the 
study outcomes. 
4.3 
Randomization Criteria 
In addition to the inclusion/exclusion criteria listed in Sections 4.1 and 4.2, in order to be 
randomized into the study, patients must meet the following criteria at the Randomization Visit: 
 Continues to satisfy all Inclusion/Exclusion criteria. 
 Has been off all motility agents and antiemetics for at least 14 days and is willing to remain off 
such medications (except for protocol-specified antiemetic rescue medication) during the course 
of the clinical trial. 
 Demonstrates evidence of delayed gastric emptying by gastric retention
 at 2 hours or 
 
at 4 hours by DAS. 
 


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4.4 
Withdrawal Criteria 
Participation of a patient in this clinical study may be discontinued for any of the following reasons: 
 The subject withdraws consent or requests discontinuation from the study for any reason. 
 Occurrence of any medical condition or circumstance that exposes the subject to substantial risk 
and/or does not allow the subject to adhere to the requirements of the protocol. 
 Any serious adverse event (SAE), clinically significant adverse event, severe laboratory 
abnormality, intercurrent illness, or other medical condition which indicates to the Investigator 
that continued participation is not in the best interest of the subject. 
 Pregnancy. 
 Requirement of prohibited concomitant medication. 
 Subject failure to comply with protocol requirements or study-related procedures. 
 Termination of the study by the Sponsor or the regulatory authority. 
If a patient withdraws prematurely from the study due to the above criteria or any other reason, 
study staff should make every effort to complete the full panel of assessments scheduled for the 
Early Termination Visit. The reason for patient withdrawal must be documented in the electronic 
case report form (eCRF). 
Study enrollment will continue until approximately 30 patients (approximately 10 patients per 
treatment) have completed the treatment period, unless the DRC and Sponsor have expanded a 
cohort or added a cohort. Withdrawn patients will not be replaced. 


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5 
STUDY TREATMENTS 
5.1 
Treatment Groups 
This study is planned to include 3 treatment groups with approximately 10 patients each: CIN-102 
 BID, CIN-102 
 BID, or placebo BID. 
At randomization, patients who meet all eligibility criteria (based on inclusion/exclusion and 
randomization criteria) will be randomized to in Cohort 1 to either CIN-102 
 BID or placebo 
BID in a ratio such that approximately 10 patients receive CIN-102 and 5 patients receive 
placebo. After approximately 12 patients in Cohort 1 complete the study, the data from Cohort 1 
will be reviewed by the DRC. The DRC will review emerging safety and/or efficacy data 
throughout the study to determine if it is safe and appropriate to continue the study with the 
currently planned dose levels or if further refinement of the proposed dose levels is warranted. 
Currently planned dose level for Cohort 2 is 
 BID, with 10 patients receiving the study 
drug and 5 patients receiving placebo. However, this dosing cohort may be modified based on 
emerging information from the prior cohort as well as other ongoing studies. The highest dose 
will not exceed 
 BID without a protocol amendment and no more than 30 additional 
patients (ie, a study total of 60 patients) will be enrolled without an amendment. Further details 
regarding the role, responsibilities, and procedures of the DRC will be provided in the DRC 
Charter. 
The duration of the double-blind treatment period will be 14 days (+1 day) of study drug 
administration. 
5.2 
Rationale for Dosing 
The dosing regimens for this study have been chosen based upon the safety, tolerability, and PK 
profile established in healthy subjects in single-ascending and multiple-ascending dose studies. 
Two clinical studies of CIN-102 in healthy subjects have commenced to date: a SAD study (study 
CIN-102-111) and a MAD study (study CIN-102-112). 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 


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5.3 
Randomization and Blinding 
Patients who have completed the Screening Visit and meet all of the inclusion, none of the 
exclusion criteria, and all of the additional criteria based on randomization procedures, including 
safety laboratory tests (see Section 6.5), will be randomized into the study. Randomization will 
occur on Day 1. Randomization assignments will be provided by the 
 
. Following randomization, study drug will be dispensed in a double-blind manner 
on Day 1. The Sponsor and all clinical personnel will be blinded to the treatment group for each 
patient. Patients will also be blinded to the treatment they receive. 
Bioanalytical staff involved in analysis of PK samples will be unblinded to treatment either via 
receipt of the randomization code to allow for analysis of samples from patients receiving CIN-102 
only (and possibly limited analysis of samples from patients receiving placebo), or by the nature 
of the results of sample analysis. The PK data will be de-identified before being provided to any 
other individuals, including those involved in calculating PK parameters and associated descriptive 
statistics, performing any modelling or simulations, and/or plotting PK data, in order to maintain 
blinding. 
5.4 
Breaking the Blind 
Blinding is not to be broken during the study unless considered necessary by the Investigator for 
emergency situations for reasons of patient safety or as determined by the DRC or Sponsor. 
Unblinding at the site for any other reason will be considered a protocol deviation. The 
Investigator should contact the Medical Monitor before breaking the blind, if time permits. When 
the blind is broken, the reason must be fully documented. The Investigator will be informed of 
treatment assignment via blinding envelopes provided to the Investigator. 
5.5 
Drug Supplies 
5.5.1 
Formulation and Packaging 
 
 
 
 
 
 
 
 
5.5.2 
Study Drug Preparation and Dispensing 
CIN-102 and matching placebo capsules will be provided to the site by the Sponsor or designee. 
5.5.3 
Study Drug Administration 
All patients will take a dose of blinded study drug (CIN-102 or placebo capsules) orally at 
AM 
hours) and 
PM (
 hours). A 
 interval will be maintained between each dose for 


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a given individual.  On Day 14 [+1 day] patients will fast for a minim of 8 hours before the morning 
dose of study drug and for a minimum of 4 hours following completion of the radiolabeled meal. 
. Patients will 
be provided study drug for self-administration for doses not administered at the site. 
5.5.4 
Treatment Compliance 
Study drug will be administered at the site by site staff during patient confinement and at all 
outpatient visits. A hand and mouth check will be performed by site staff to ensure study drug 
compliance. Dosing compliance will be recorded by the Investigator or designee at the site. The 
date and time of study drug administration will be recorded. 
For all protocol-specified doses when the patient is not at the site, patients will self-administer 
study drug and will record the date and time of study drug administration. Compliance to study 
drug will also be assessed by clinical site personnel via tablet counts of study drug and by 
questioning the patient, if necessary, upon return to the site on Days 3 [±1 day], 7 [±1 day], 10 [±1 
day], and 14 [+1 day]. A patient who is not compliant (compliance being defined as having taken 
75% of study drug) will be counseled at each visit on the importance of taking study drug as 
instructed. 
If a patient withdraws from the study or does not comply with the study protocol procedures, the 
patient can cease participation in the study but will still be considered evaluable for safety 
purposes. If a patient withdraws from the study or does not comply with the protocol after receiving 
study drug but before Day 14 procedures have been performed, they will be requested to undergo 
the Early Termination procedure. 
5.5.5 
Storage and Accountability 
Records will be maintained indicating the receipt and dispensation of all study drug supplies. At 
the conclusion of the study, any unused study drug will be returned to the Sponsor or designee for 
final drug accountability and destruction. A certificate of destruction will be provided. If no study 
drug remains, this will be indicated in the Drug Accountability Log. 
 
 
 
5.6 
Prior and Concomitant Medications and/or Procedures 
5.6.1 
Excluded Medications and/or Procedures 
Use of the following investigational, prescription, or over-the-counter medications is not permitted 
during the study: 
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considering their fasting status). Fasting blood glucose will be assessed before study drug 
administration and gastric emptying assessments to ensure a blood glucose of ≤275 mg/dL. 
Additional insulin may be given to ensure a blood glucose of ≤275 mg/dL prior to the gastric 
emptying procedure. 
5.6.4 
Documentation of Prior and Concomitant Medication Use 
Any medications administered 28 days prior to the first dose of study drug and/or during the study 
period must be recorded. 


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6 
STUDY PROCEDURES 
6.1 
Informed Consent 
Written informed consent for the study will be obtained from all patients before any study 
procedures are performed. See Section 11.3 for details on informed consent. 
6.2 
Screening Visit (Days -28 to -6) 
Screening procedures, including vital sign assessments, may be repeated no more than 2 times for 
eligibility purposes. Patients who are screened but failed to meet inclusion/exclusion criteria 
(despite potentially having undergone repeated Screening assessments, if relevant) may be 
considered for rescreening with prior written sponsor approval. 
For all patients, the Screening Visit will occur up to 28 days prior to randomization (between 
Days -28 and -6). 
The screening prolactin should be performed at the local lab to determine eligibility. 
The following procedures will be performed at the Screening Visit: 
 Obtain informed consent. 
 Assess eligibility based on inclusion/exclusion criteria. 
 Record demographics and medical/surgical history. 
 Record prior medications. 
 Perform a complete physical examination (general appearance, skin, head, eyes, ears, 
mouth, oropharynx, neck, heart, lungs, abdomen, extremities, and neuromuscular system). 
 Measure height and weight and calculate BMI. 
 Perform breath alcohol test. 
 Collect urine samples for the following: 
o Urinalysis, 
o Urine drug screen. 
 Obtain vital signs (including heart rate, blood pressure, respiration rate, and temperature) 
while patient is sitting after a minimum of 5-minute rest. 
 Perform 12-lead ECG (in triplicate approximately 1 minute apart after the patient has been 
resting in the supine position for at least 10 minutes). 
Note: Screening 12-lead ECGs will be printed and will be interpreted as soon as possible 
by the Investigator or Sub-Investigator. 
 Collect blood samples for the following: 
o Chemistry, hematology, coagulation, and prolactin, 


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o FSH (only for females who have been postmenopausal for at least 1 year and are 
not surgically sterile), 
o TSH, 
o Serum pregnancy test (only for females who are not surgically sterile or 
postmenopausal for at least 1 year [with confirmed FSH in postmenopausal range]), 
o HIV, HBsAg, and HCV screen. 
 
 
 
. 
6.3 
Baseline Scintigraphy Test Visit (Days -5 to -1) 
Baseline scintigraphy will be performed between Days -5 and -1 after a minimum 14-day 
washout from motility agents with the exception of the protocol-specified rescue medication. 
The following procedures will be performed at the Baseline scintigraphy Visit (Days -5 to -1): 
 
 
 
 
 Record medical/surgical history. 
 Record prior medications. 
 Obtain vital signs (including heart rate, blood pressure, respiration rate, and temperature) 
while patient is sitting after a minimum of 5-minute rest. 
 Assess fasting blood glucose before gastric emptying assessments to ensure a blood 
glucose of <275 mg/dL. Blood glucose will be measured at 2 hours (+/-15 min) and 4 hours 
(+/-15 min) after the start of the gastric emptying assessment. 
 Collect blood sample for a serum pregnancy test (females). 
 Patient will consume standardized meal after an ≥8-hour fast. 
 Obtain scintigraphy following completion of standardized meal.  
Note: patients should fast for 4 hours after the completion of the standardized meal. If the 
patient or Investigator determine that food should be consumed by the patient (ie, due to low 
blood glucose levels or symptoms of hypoglycemia), it is permissible to break the specified 
fast to ensure patient safety.      
 
 
. 
 
 


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6.4 
Treatment Period – Day 1 through Day 14 (+ 1 Day) 
For outpatient visits, patients will report to the clinic before taking their morning dose of study 
drug.  
6.4.1 
Day 1 (Randomization) 
Eligible patients will be randomized to receive CIN-102 or placebo. Randomization will occur on 
the morning of Day 1, although randomization procedures may also be performed at a separate 
outpatient visit 1 day prior to taking the morning dose of study drug (Day -1) to allow adequate 
turnaround time for test results if necessary. The safety laboratory tests (ie, chemistry, hematology, 
coagulation, and urinalysis) from Day -1 or Day 1 will be processed at local laboratories for 
verifying patient eligibility.  Other than the Screening prolactin which should be performed at the 
local lab to determine eligibility, prolactin will be sent to the central laboratory for analysis to 
maintain the site blind. A point-of-care (POC) urine pregnancy test and urine drug screen will be 
used to assess eligibility for the purpose of randomization. 
The following procedures will be performed: 
 Assess eligibility based on inclusion/exclusion and randomization criteria. 
 Record medical/surgical history. 
 Measure weight and calculate BMI using height from Screening Visit. 
 Perform limited physical examination (minimum of general appearance, skin, heart, lungs, 
and abdomen). 
 Obtain vital signs (including heart rate, blood pressure, respiration rate, and temperature) 
while patient is sitting after a minimum 5-minute rest. 
 Perform 12-lead ECGs 
 
in triplicate approximately 1 minute apart after the patient has been 
resting in the supine position for at least 10-minutes. 
Note: 12-lead ECGs will be printed and will be interpreted as soon as possible by the 
Investigator. A digital recording of each ECG will be submitted to a central reviewer. 
 Perform breath alcohol test. 
 Record concomitant medications (prior to each dose).  
 Collect blood samples for the following: 
o Chemistry, hematology, coagulation, prolactin. Sample to be collected predose. 
o PK analysis.  
Note: 
 
 
 
 Collect urine samples for the following: 


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o Urinalysis, 
o Urine drug screen, 
o POC urine drug screen. 
 If the patient continues to meet all eligibility criteria, the patient will be randomized,  
treatment assigned, and study drug will be dispensed. 
 Administer study drug (all patients will take a dose of blinded study drug [CIN-102 or 
placebo capsules] orally at 
AM 
 and 
PM 
with approximately 
240 mL of water. 
 
 
  The evening dose will be self-administered by the 
patient. 
 Record adverse events following fist dose of study drug.  
 
 
 
6.4.2 
Day 2 
The following procedures will be performed by the patient on Day 2: 
 Patient will record concomitant medications and adverse events. 
 
 
 Patient will self-administer study drug (all patients will take a dose of blinded study drug 
[CIN-102 or placebo capsules] orally at 
 AM 
and 
 PM 
 with 
approximately 240 mL of water. 
 
 
 
6.4.3 
Day 3 (± 1 Day) 
The following procedures will be performed at Day 3: 
 Record concomitant medications (prior to each dose) and adverse events. 
 Obtain vital signs (including heart rate, blood pressure, respiration rate, and temperature) 
while patient is sitting after a minimum 5-minute rest. 
 Perform 12-lead ECGs in triplicate approximately 1 minute apart after the patient has been 
resting in the supine position for at least 10-minutes. 
Note: 12-lead ECGs will be printed and will be interpreted as soon as possible by the 
Investigator. A digital recording of each ECG will be submitted to a central reviewer. 
 Collect blood samples for the following: 
o Chemistry, hematology, coagulation, prolactin. Sample to be collected predose. 


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o PK analysis.  
Note: The PK samples will be collected within ±15 minutes of the corresponding ECG.  
 Collect urine samples for urinalysis. 
 Administer study drug (all patients will take a dose of blinded study drug [CIN-102 or 
placebo capsules] orally at 
 AM 
 and 
PM 
with approximately 
240 mL of water. 
 
 
 The evening dose will be self-administered by the 
patient.  
 Perform study drug accountability. Verify that the patient has the necessary amount of study 
drug for self-administration for the remainder of the treatment period. 
 
 
 
6.4.4 
Days 4, 5, 6 
The following procedures will be performed by the patient on Days 4, 5, and 6 respectively: 
 Patient will record concomitant medications and adverse events. 
 
 
 Patient will self-administer study drug (all patients will take a dose of blinded study drug 
[CIN-102 or placebo capsules] orally at 
 AM [
 and 
PM 
 
with 
approximately 240 mL of water. 
 
 
 
6.4.5 
Day 7 (± 1 Day) 
The following procedures will be performed at Day 7: 
 Record concomitant medications (prior to each dose) and adverse events 
 Obtain vital signs (including heart rate, blood pressure, respiration rate, and temperature) 
while patient is sitting after a minimum 5-minute rest. 
 Perform 12-lead ECGs in triplicate approximately 1 minute apart after the patient has been 
resting in the supine position for at least 10-minutes. 
Note: 12-lead ECGs will be printed and will be interpreted as soon as possible by the 
Investigator. A digital recording of each ECG will be submitted to a central reviewer. 
 Collect blood samples for the following 
o Chemistry, hematology, coagulation, prolactin. Sample to be collected predose. 
o PK analysis.  


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Note: The PK samples will be collected within ±15 minutes of the corresponding ECG.  
 Collect urine samples for urinalysis. 
 Administer study drug (all patients will take a dose of blinded study drug [CIN-102 or 
placebo capsules] orally at 
 AM 
 and 
 PM 
with approximately 
240 mL of water. 
 
 
 The evening dose will be self-administered by the 
patient.  
 Perform study drug accountability. Verify that the patient has the necessary amount of study 
drug for self-administration for the remainder of the treatment period. 
 
 
 
6.4.6 
Days 8 and 9 
The following procedures will be performed by the patient on Days 8 and 9, respectively: 
 Patient will record concomitant medications and adverse events. 
 
 
 Patient will self-administer study drug (all patients will take a dose of blinded study drug 
[CIN-102 or placebo capsules] orally at 
AM 
and 
PM 
 with 
approximately 240 mL of water. 
 
 
 
 
6.4.7 
Day 10 (± 1 Day) 
The following procedures will be performed at Day 10: 
 Record concomitant medications (prior to each dose) and adverse events 
 Obtain vital signs (including heart rate, blood pressure, respiration rate, and temperature) 
while patient is sitting after a minimum 5-minute rest. 
 Perform 12-lead ECGs in triplicate approximately 1 minute apart after the patient has been 
resting in the supine position for at least 10-minutes. 
Note: 12-lead ECGs will be printed and will be interpreted as soon as possible by the 
Investigator. A digital recording of each ECG will be submitted to a central reviewer. 
 Collect blood samples for the following 
o Chemistry, hematology, coagulation, prolactin. Sample to be collected predose. 
o PK analysis.  


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Note: The PK samples will be collected within ±15 minutes of the corresponding ECG.  
 Collect urine samples for urinalysis. 
 Administer study drug (all patients will take a dose of blinded study drug [CIN-102 or 
placebo capsules] orally at 
 AM 
and 
 PM 
with approximately 
240 mL of water. 
 
  
The evening dose will be self-administered by the patient.  
 Perform study drug accountability. Verify that the patient has the necessary amount of study 
drug for self-administration for the remainder of the treatment period. 
 
 
 
6.4.8 
Days 11, 12, 13 
The following procedures will be performed by the patient on Days 11, 12, and 13, respectively: 
 Patient will record concomitant medications and adverse events. 
 
. 
 Patient will self-administer study drug (all patients will take a dose of blinded study drug 
[CIN-102 or placebo capsules] orally at 
 AM 
 
and 
PM 
 
with 
approximately 240 mL of water. 
 
 
 
6.4.9 
Day 14 (+ 1 Day) 
The following procedures will be performed at Day 14: 
 
 
 
. 
 Record concomitant medications (prior to each dose) and adverse events. 
 Obtain vital signs (including heart rate, blood pressure, respiration rate, and temperature) 
while patient is sitting after a minimum 5-minute rest. 
 Perform a complete physical examination (general appearance, skin, head, eyes, ears, mouth, 
oropharynx, neck, heart, lungs, abdomen, extremities, and neuromuscular system). 
 Perform 12-lead ECGs 
 
 in triplicate approximately 1 minute apart after 
the patient has been resting in the supine position for at least 10-minutes. 
Note: 12-lead ECGs will be printed and will be interpreted as soon as possible by the 
Investigator. A digital recording of each ECG will be submitted to a central reviewer. 


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 Collect blood samples for the following: 
o Chemistry, hematology, and coagulation, and prolactin. Sample collected predose. 
o PK analysis 
 
 
 
 
o Serum pregnancy test (only for females who are not surgically sterile or postmenopausal 
for at least 1 year [with confirmed FSH in postmenopausal range]), 
 Collect urine samples for the following: 
o Urinalysis, 
o Urine drug screen. 
 Assess fasting blood glucose before gastric emptying assessments to ensure a blood glucose 
of <275 mg/dL. Blood glucose will be measured at 2 hours (+/-15 min) and 4 hours (+/-15 
min) after the start of the gastric emptying assessment. 
 Administer the final dose of study drug (all patients will take a dose of blinded study drug 
[CIN-102 or placebo capsules] orally at 
 AM 
with approximately 240 mL of 
water. Patients will fast for a minimum of 8 hours before the morning dose and 4 hours after 
the completion of the standardized meal. If the patient or Investigator determine that food 
should be consumed by the patient (ie, due to low blood glucose levels or symptoms of 
hypoglycemia), it is permissible to break the specified fast to ensure patient safety.      
 Obtain scintigraphy following completion of standardized meal. 
 
 
 
 
 
 
 Perform study drug accountability and collect unused study drug. 
6.5 
Follow-up Visit (Day 20 ± 1 Day) 
The following procedures will be performed via telephone call to the patient: 
 Record concomitant medications and adverse events. 
6.6 
Early Termination Visit and Withdrawal Procedures 
For patients who are withdrawn from the study prior to completion, an attempt should be made to 
perform the following procedures at the Early Termination Visit: 
  Record concomitant medications and adverse events. 


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 
 
 
 
 Perform a complete physical examination (general appearance, skin, head, eyes, ears, mouth, 
oropharynx, neck, heart, lungs, abdomen, extremities, and neuromuscular system). 
 Obtain vital signs (including heart rate, blood pressure, respiration rate, and temperature) 
while patient is sitting after a minimum 5-minute rest. 
 Perform 12-lead ECGs in triplicate approximately 1 minute apart after the patient has been 
resting in the supine position for at least 10-minutes. 
Note: 12-lead ECGs will be printed and will be interpreted as soon as possible by the 
Investigator. A digital recording of each ECG will be submitted to a central reviewer. 
 Collect blood samples for the following: 
o Chemistry, hematology, coagulation, prolactin. Sample to be collected predose if 
applicable. 
o PK analysis.  
Note: The PK samples will be collected within ±15 minutes of the corresponding ECG.  
o Serum pregnancy test (only for females who are not surgically sterile or postmenopausal 
for at least 1 year [with confirmed FSH in postmenopausal range]) 
 Collect urine samples for the following: 
o Urinalysis, 
o Urine drug screen. 
 Patient will consume standardized meal after an ≥8-hour fast. 
 Obtain scintigraphy following completion of standardized meal. 
 
 
 
 
 
 Perform study drug accountability and collect unused study drug. 


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7 
EFFICACY ASSESSMENTS 
7.1 
Efficacy Assessments 
The efficacy variables are as follows: 
 The change from baseline in gastric percentage retention of a radiolabeled meal at 2 and 4 
hours after dosing CIN-102 in patients with diabetic gastroparesis. 
 The change from baseline in antral contractility as measured by Dynamic Antral Scintigraphy 
at Day 14. 
 The change from baseline in gastric accommodation at Day 14. 
 
 
 
 
 
 
 
 
 
 
 
. 
Dynamic antral scintigraphy (DAS), a non-invasive technique for the assessment of post-prandial 
peristaltic gastric contraction frequency and contraction amplitude of the distal antrum will be used 
to evaluate antral motility at study timepoints that demonstrate a sufficient count rate (labeled food 
content). 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 


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7.2 
Pharmacokinetics 
Blood samples for measurement of plasma concentrations of deuterated domperidone (and 
possibly metabolites) will be collected each  time a triplicate ECG is obtained.   
 


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8 
SAFETY ASSESSMENTS 
8.1 
Adverse Events 
An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation 
patient administered a pharmaceutical product, which does not necessarily have a causal 
relationship with this treatment. An adverse event can therefore be any unfavorable and/or 
unintended sign (including an abnormal laboratory finding), symptom, or disease temporally 
associated with the use of an investigational medicinal product whether or not related to the 
investigational medicinal product. All adverse events, including observed or volunteered 
problems, complaints, or symptoms, are to be recorded on the appropriate eCRF. 
Adverse events, which include clinical laboratory test variables, will be monitored and 
documented from the time of first dose of study drug until participation is complete. Patients 
should be instructed to report any adverse event that they experience to the Investigator and/or 
relevant site staff whether or not they think the event is due to study treatment. Beginning at the 
time of first dose of study drug, Investigators should make an assessment for adverse events at 
each visit and record the event on the appropriate adverse event eCRF. 
Wherever possible, a specific disease or syndrome rather than individual associated signs and 
symptoms should be identified by the Investigator and recorded on the eCRF. However, if an 
observed or reported sign or symptom is not considered a component of a specific disease or 
syndrome by the Investigator, it should be recorded as a separate adverse event on the eCRF. 
Additionally, the condition that led to a medical or surgical procedure (eg, surgery, endoscopy, 
tooth extraction, or transfusion) should be recorded as an adverse event, not the procedure itself.  
Any medical condition already present at the time of first dose of study drug should be recorded 
as medical history and not be reported as an adverse event unless the medical condition or signs 
or symptoms present at baseline changes in severity, frequency, or seriousness at any time during 
the study. In this case, it should be reported as an adverse event. 
Clinically significant abnormal laboratory or other examination (eg, ECG) findings that are 
detected during the study or are present at the time of first dose of study drug and significantly 
worsen during the study should be reported as adverse events, as described below. The Investigator 
will exercise his or her medical and scientific judgment in deciding whether an abnormal 
laboratory finding, or other abnormal assessment is clinically significant. Clinically significant 
abnormal laboratory values occurring during the clinical study will be followed until repeat tests 
return to normal, stabilize, or are no longer clinically significant. Abnormal test results that are 
determined to be an error should not be reported as an adverse event. Laboratory abnormalities or 
other abnormal clinical findings (eg, ECG abnormalities) should be reported as an adverse event 
if any of the following are applicable: 
 If an intervention is required as a result of the abnormality 
 If action taken with the study drug is required as a result of the abnormality 
 Based on the clinical judgment of the Investigator 


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8.1.1 
Adverse (Drug) Reaction 
All noxious and unintended responses to a medicinal product related to any dose should be 
considered an adverse drug reaction. “Responses” to a medicinal product means that a causal 
relationship between a medicinal product and an adverse event is at least a reasonable possibility, 
ie, the relationship cannot be ruled out. 
8.1.2 
Unexpected Adverse Drug Reaction 
An Unexpected Adverse Drug Reaction is defined as an adverse reaction, the nature or severity of 
which is not consistent with the applicable product information. 
8.1.3 
Assessment of Adverse Events by the Investigator 
The Investigator will assess the severity (intensity) of all adverse events (serious and non-serious) 
and will be graded using the CTCAE Version 5.0 criteria as shown in Table 1. The Investigator 
will also categorize each adverse event as to its potential relationship to study drug using the 
categories of yes or no. 
Table 1.     CTCAE Severity Assessment of Adverse Events 
Grade 
Severity 
Description 
1 
Mild 
Asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated 
2 
Moderate 
Minimal, local or noninvasive intervention indicated; limiting age-appropriate 
instrumental activities of daily living* 
3 
Severe 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting 
self-care activities of daily living** 
4 
Life Threatening 
Life threatening consequences; urgent intervention indicated 
5 
Death 
Death related to AE 
*Instrumental activities of daily living refer to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc. 
**Self-care activities of daily living refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not 
bedridden.
Ref: https://ctep.cancer.gov/protocolDevelopment/electronic applications/docs/CTCAE v5 Quick Reference 5x7.pdf
 
Causality assessment: 
The relationship of an adverse event to the administration of the study drug is to be assessed 
according to the following definitions 
No (unrelated, not related, unlikely to be related) – The time course between the administration of 
study drug and the occurrence or worsening of the adverse event rules out a causal relationship 
and another cause (concomitant drugs, therapies, complications, etc.) is suspected. 


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Yes (possibly, probably, or definitely related) – The time course between the administration of 
study drug and the occurrence or worsening of the adverse event is consistent with a causal 
relationship and no other cause (concomitant drugs, therapies, complications, etc.) can be 
identified. 
The definition implies a reasonable possibility of a causal relationship between the event and the 
study drug. This means that there are facts (evidence) or arguments to suggest a causal relationship. 
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. 
8.2 
Serious Adverse Events 
An adverse event or adverse reaction is considered serious if, in the view of either the Investigator 
or Sponsor, it results in any of the following outcomes: 
 Death 
 A life-threatening adverse event 
Note: An adverse event or adverse reaction is considered “life-threatening” if, in view of either 
the Investigator or Sponsor, its occurrence places the subject at immediate risk of death. It does 
not include an event that, had it occurred in a more severe form, might have caused death. 
 Requires hospitalization or prolongation of existing hospitalizations 


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Note: Any hospital admission with at least one overnight stay will be considered an inpatient 
hospitalization. An emergency room or urgent care visit without hospital admission will not 
be recorded as a SAE under this criterion, nor will hospitalization for a procedure scheduled 
or planned before signing of informed consent, or elective treatment of a pre-existing condition 
that did not worsen from Baseline. However, unexpected complications and/or prolongation 
of hospitalization that occur during elective surgery should be recorded as adverse events and 
assessed for seriousness. Admission to the hospital for social or situational reasons (ie, no place 
to stay, live too far away to come for hospital visits, respite care) will not be considered 
inpatient hospitalizations.  
 A persistent or significant disability/incapacity or substantial disruption of the ability to 
conduct normal life functions. 
 A congenital anomaly/birth defect 
 An important medical event. 
Note: Important medical events that do not meet any of the above criteria may be considered 
an SAE when, based upon appropriate medical judgment, they may jeopardize the subject and 
may require medical or surgical intervention to prevent one of the outcomes listed above. 
Examples of such medical events include allergic bronchospasm requiring intensive treatment 
in an emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalizations, or the development of drug dependency. 
8.3 
Serious Adverse Event Reporting − Procedures for Investigators 
Initial Reports 
All SAEs occurring from the time of first dose of study drug until 30 days following the final dose 
of study drug must be reported to 
 within 24 hours of the knowledge of 
the occurrence. After the 30-day reporting window, any SAE that the Investigator considers related 
to study drug must be reported to 
 or the Sponsor/designee. Of note, 
reporting of SAEs after the follow-up phone call 72 hours after discharge is dependent on 
spontaneous reporting by the patient. The Investigator is not required to have further contact to 
elicit this information after completion of the follow-up phone call but should instruct the patient 
to contact the site to report any such events. 
To report the SAE, complete the SAE form electronically in the electronic data capture (EDC) 
system for the study. When the form is completed, 
 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 e-mail to 
 at 
 or call the 
 SAE reporting line (phone 
number listed below), and fax/e-mail the completed paper SAE form to 
 (fax number 
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. 
Safety Contact Information: 
 
 reporting line – USA: 


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Telephone: 
 
Fax: 
 
E-mail: 
 
Follow-Up Reports 
The Investigator must continue to follow the patient until the SAE has subsided or until the 
condition becomes chronic in nature, stabilizes (in the case of persistent impairment), or the patient 
dies. 
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 
(eg, patient discharge summary or autopsy reports) to 
 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. 
8.4 
Pregnancy Reporting 
If a patient becomes pregnant during the study or within the safety follow-up period defined in the 
protocol, the Investigator is to stop dosing with study drug(s) immediately and the patient should 
be withdrawn from the study. Early termination procedures should be implemented at that time.  
A pregnancy is not considered to be an adverse event or SAE; however, it must be reported to 
 within 24 hours of knowledge of the event. 
 will 
then provide the Investigator/site the Exposure In Utero (EIU) form for completion. The 
Investigator/site must complete the EIU form and fax or e-mail it back to 
.  
If the female partner of a male patient becomes pregnant while the patient is receiving study drug 
or within the safety follow-up period defined in the protocol, the Investigator should notify 
 as described above.  
The pregnancy should be followed until the outcome of the pregnancy, whenever possible. Once 
the outcome of the pregnancy is known, the EIU form should be completed and faxed/e-mailed to 
. If the outcome of the pregnancy meets the criteria for immediate 
classification as an SAE (ie, postpartum complication, spontaneous abortion, stillbirth, neonatal 
death, or congenital anomaly), the Investigator should follow the procedures for reporting an SAE. 
8.5 
Clinical Laboratory Evaluations 
Safety laboratory tests will include chemistry, hematology, coagulation, prolactin, and urinalysis. 
See Appendix B for a complete list of analytes.  
Safety laboratory tests will be evaluated at the times indicated in the Schedule of Procedures table 
in Appendix A.  
Abnormal Screening laboratory tests may be repeated no more than 2 times for eligibility purposes.  
If, in the opinion of the Investigator, any patient has a clinically significant abnormal laboratory 
finding in comparison to the value at the time of randomization or unresolved treatment-emergent 


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adverse event(s) (TEAE), additional follow-up visits will be scheduled. Patients will be followed 
approximately once a week (or more frequently as deemed appropriate) until the Investigator 
determines that repeat laboratory findings are clinically unremarkable in comparison to baseline, 
or unresolved adverse events return to prestudy levels or clinically acceptable levels. 
If a patient experiences an SAE for which follow-up laboratories and review are required, the 
Investigator will schedule additional postdose visits as necessary. 
If, in the opinion of the Investigator, any patient has a clinically significant adverse event at the 
follow-up call, the Investigator will provide additional follow-up until the adverse event returns to 
clinically acceptable levels. 
The safety laboratory sample collection times may be refined based on emerging data to ensure 
study objectives are met. 
8.6 
Vital Signs 
Vital signs, including heart rate, blood pressure, respiration rate, and temperature, will be measured 
at the times indicated in the Schedule of Procedures table in Appendix A using the following 
standardized procedures: 
 Prior to measuring vital signs, the patient should be sitting for a minimum of 5 minutes 
with his/her back supported, feet flat on the floor, and his/her measurement arm supported 
so that the midpoint of the manometer cuff is at heart level. 
 An appropriately sized cuff should be used with the bladder centered over the brachial 
artery. 
 The cuff size and arm used for the measurement should be recorded. Whenever possible, 
the same arm should be used for all vital sign assessments throughout the study. 
8.7 
Electrocardiograms 
Twelve-lead ECGs will be performed at the times indicated in the Schedule of Procedures table in 
Appendix A.  
Every effort will be made to eliminate any sources of physical (including any movement, eating, 
or drinking) or electrical interference. During these assessments, patients are not permitted to use 
cell phones, iPods, laptop computers, tablets, or any type of battery-operated or electrical device, 
and all of these devices must be turned off during the assessments. 
All 12-lead ECGs will be performed in triplicate approximately 1 minute apart after the patient 
has been resting in the supine position for at least 10 minutes. The average QTcF will be used for 
eligibility and safety assessments. Twelve-lead ECGs will be printed and will be interpreted as 
soon as possible by an Investigator (or Subinvestigator for Screening Visit only). All ECGs 
collected at the time of randomization and throughout the treatment period must be evaluated for 
the presence of abnormalities by a qualified physician. A digital recording of all ECGs for 
randomized subjects will be submitted to a central reviewer. The central overread ECG data will 
be utilized for all safety assessments and analyses. 


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Standard ECG parameters will be measured, and the following ECG parameters will be recorded: 
 QRS interval 
 Heart rate 
 RR interval 
 QT interval 
 QTc (QTcF) 
Investigators should contact the Sponsor or designee if any clinically meaningful changes from 
baseline are noted on review. Please refer to Appendix C for ECG alert criteria guidance. 
8.8 
Physical Examinations 
Complete physical examinations will be performed at the times indicated in the Schedule of 
Procedures table in Appendix A. A complete physical examination will consist of general 
appearance, skin, head, eyes, ears, mouth, oropharynx, neck, heart, lungs, abdomen, extremities, 
and neuromuscular system. 
Brief limited physical examinations will be performed at the times indicated in the Schedule of 
Procedures table in Appendix A. A limited physical examination will consist of a minimum of 
general appearance, skin, heart, lungs, and abdomen. 
All complete and limited physical examination findings must be recorded. 
8.9 
Height and Weight 
Height and weight will be measured at the times indicated in the Schedule of Procedures table in 
Appendix A and will be used to calculate BMI. Height will be measured with the patient’s shoes 
off. Weight will be measured with the patient’s shoes off and after the patient’s bladder has been 
emptied. 
 


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9 
STATISTICS 
9.1 
Analysis Populations 
The Intent-to-Treat (ITT) Population: All patients who are randomized. 
Modified ITT (MITT) Population: All patients in the ITT Population who received any amount of 
study drug and have a baseline DAS and a post-baseline DAS. 
The primary analysis population will be the MITT Population. 
The Safety Population will consist of all randomized patients who receive any study drug. 
The PK Population will consist of all randomized patients who have at least one quantifiable 
plasma concentration following administration of CIN-102. 
9.2 
Statistical Methods 
The data from placebo patients of all cohorts will be pooled for efficacy and safety analysis.  
9.2.1 
Analysis of Efficacy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
9.2.2 
Pharmacokinetic Analysis 
Plasma concentrations of deuterated domperidone (and any measured metabolites) will be listed 
by individual.  


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9.2.3 
Pharmacokinetic-Pharmacodynamic Analysis 
If the data permit, an attempt may be made to correlate plasma concentrations  with select safety 
measures, prolactin data, and/or measures of gastric emptying time and symptoms of gastroparesis. 
9.2.4 
Analysis of Safety 
Safety data, including physical examinations, ECGs, vital sign assessments, clinical laboratory 
evaluations (including prolactin), and adverse events, will be summarized by treatment group 
(placebo patients from all dose levels will be pooled) and time of collection, when appropriate. 
Individual and mean time course of absolute prolactin values and change from baseline prolactin 
by treatment may also be generated. 
Descriptive statistics (arithmetic mean, standard deviation, median, minimum, and maximum) will 
be calculated for quantitative safety data, as well as for the difference from baseline, when 
appropriate. Absolute and change from baseline values in QT and QTc [using  Fridericia’s 
correction factor) will be plotted against time points by cohort, if applicable. 
Shift tables describing out-of-normal range shifts will be provided for clinical laboratory results. 
9.2.5 
Sample Size Determination 
A total of 30 patients (10 patients per group) will be randomized to CIN-102 
 BID or CIN-
102 
 BID or placebo BID. The sample size is considered adequate to provide the necessary 
data to evaluate the objectives of the study. No formal statistical assessment for sample size 
determination has been performed.   


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10 
DATA MANAGEMENT AND RECORD KEEPING 
10.1 
Data Management 
10.1.1 
Data Handling 
Data will be recorded at the site on eCRFs and reviewed by the clinical research associate (CRA) 
during monitoring visits. The CRAs will verify data recorded in the EDC system with source 
documents. All corrections or changes made to any study data must be appropriately tracked in an 
audit trail in the EDC system. An eCRF will be considered complete when all missing, incorrect, 
and/or inconsistent data has been accounted for. 
10.1.2 
Computer Systems 
Data will be processed using a validated computer system conforming to regulatory requirements. 
10.1.3 
Data Entry 
Data must be recorded using the EDC system as the study is in progress. All site personnel must 
log into the system using their secure user name and password in order to enter, review, or correct 
study data. These procedures must comply with Title 21 of the Code of Federal Regulations (21 
CFR Part 11) and other appropriate international regulations. All passwords will be strictly 
confidential. 
10.1.4 
Medical Information Coding 
For medical information, the following thesauri will be used: 
 Medical Dictionary for Regulatory Activities (latest) for medical history and adverse events 
 World Health Organization Drug Dictionary for prior and concomitant medications 
10.1.5 
Data Validation 
Validation checks programmed within the EDC system, as well as supplemental validation 
performed via review of the downloaded data, will be applied to the data in order to ensure 
accurate, consistent, and reliable data. Data identified as erroneous, or data that are missing, will 
be referred to the investigative site for resolution through data queries. 
The eCRFs must be reviewed and electronically signed by the Investigator. 


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10.2 
Record Keeping 
Records of subjects, source documents, monitoring visit logs, eCRFs, inventory of study product, 
regulatory documents, and other Sponsor correspondence pertaining to the study must be kept in 
the appropriate study files at the site. Source data is defined as all information in original records 
and certified copies of original records of clinical findings, observations, or other activities in a 
clinical study necessary for the evaluation and reconstruction of the clinical study. Source data are 
contained in source documents (original records or certified copies). These records will be retained 
in a secure file for the period as set forth in the Clinical Study Agreement. Prior to transfer or 
destruction of these records, the Sponsor must be notified in writing and be given the opportunity 
to further store such records.  
 


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11 
INVESTIGATOR REQUIREMENTS AND QUALITY CONTROL  
11.1 
Ethical Conduct of the Study 
Good Clinical Practice (GCP) is an international ethical and scientific quality standard for 
designing, conducting, recording, and reporting studies that involve human patients. Compliance 
with this standard provides public assurance that the rights, safety, and well-being of study patients 
are protected, consistent with the principles that have their origin in the Declaration of Helsinki, 
and that the clinical study data are credible. 
11.2 
Institutional Review Board/Independent Ethics Committee 
The Institutional Review Board (IRB) will review all appropriate study documentation in order to 
safeguard the rights, safety, and well-being of patients. The study will only be conducted at sites 
where IRB approval has been obtained. The protocol, Investigator’s Brochure, ICF, advertisements 
(if applicable), written information given to the patients, safety updates, annual progress reports, 
and any revisions to these documents will be provided to the IRB by the Investigator. 
Federal regulations and International Council for Harmonisation (ICH) Guidelines require that 
approval be obtained from an IRB prior to participation of patients in research studies. Prior to 
study onset, the protocol, any protocol amendments, ICFs, advertisements to be used for patient 
recruitment, and any other written information regarding this study to be provided to a patient or 
patient’s legal guardian must be approved by the IRB. 
No drug will be released to the site for dosing until written IRB authorization has been received 
by the Sponsor. 
11.3 
Informed Consent 
The ICF and any changes to the ICF made during the course of the study must be agreed to by the 
Sponsor or designee and the IRB prior to its use and must be in compliance with all ICH GCP, 
local regulatory requirements, and legal requirements.  
The Investigator must ensure that each study patient is fully informed about the nature and 
objectives of the study and possible risks associated with participation and must ensure that the 
patient has been informed of his/her rights to privacy. The Investigator will obtain written informed 
consent from each patient before any study-specific activity is performed and should document in 
the source documentation that consent was obtained prior to enrollment in the study. The original 
signed copy of the ICF must be maintained by the Investigator and is subject to inspection by a 
representative of the Sponsor, their representatives, auditors, the IRB, and/or regulatory agencies. 
A copy of the signed ICF will be given to the patient. 
On enrollment in the study, the subject will receive a subject card to be carried at all times. The 
subject card will state that the subject is participating in a clinical research study, type of treatment, 
number of treatment packs received, and contact details in case of an SAE. 


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11.4 
Study Monitoring Requirements 
It is the responsibility of the Investigator to ensure that the study is conducted in accordance with 
the protocol, Declaration of Helsinki, ICH GCP, and applicable regulatory requirements, and that 
valid data are entered into the eCRFs. 
To achieve this objective, the CRA’s duties are to aid the Investigator and, at the same time, the 
Sponsor in the maintenance of complete, legible, well-organized and easily retrievable data. Before 
the enrollment of any patient in this study, the Sponsor or their designee will review with the 
Investigator and site personnel the following documents: protocol, Investigator’s Brochure, eCRFs 
and procedures for their completion, informed consent process, and the procedure for reporting 
SAEs. 
The Investigator will permit the Sponsor or their designee to monitor the study as frequently as 
deemed necessary to determine that data recording and protocol adherence are satisfactory. During 
the monitoring visits, information recorded on the eCRFs will be verified against source 
documents and requests for clarification or correction may be made. After the eCRF data is entered 
by the site, the CRA will review the data for safety information, completeness, accuracy, and 
logical consistency. Computer programs that identify data inconsistencies may be used to help 
monitor the clinical study. If necessary, requests for clarification or correction will be sent to the 
Investigators. The Investigator and his/her staff will be expected to cooperate with the monitor and 
provide any missing information, whenever possible. 
All monitoring activities will be reported and archived. In addition, monitoring visits will be 
documented at the investigational site by signature and date on the study-specific monitoring log. 
11.5 
Disclosure of Data 
Data generated by this study must be available for inspection by the FDA, the Sponsor or their 
designee, applicable foreign health authorities, and the IRB as appropriate. Subjects or their legal 
representatives may request their medical information be given to their personal physician or other 
appropriate medical personnel responsible for their welfare. 
Subject medical information obtained during the study is confidential and disclosure to third 
parties other than those noted above is prohibited. 
11.6 
Retention of Records 
To enable evaluations and/or audits from regulatory authorities or the Sponsor, the Investigator 
will keep records, including the identity of all participating patients (sufficient information to link 
records; eg, eCRFs and hospital records), all original signed ICFs, copies of all eCRFs, SAE forms, 
source documents, and detailed records of treatment disposition. The records should be retained 
by the Investigator according to specifications in the ICH guidelines, local regulations, or as 
specified in the Clinical Study Agreement, whichever is longer. The Investigator must obtain 
written permission from the Sponsor before disposing of any records, even if retention 
requirements have been met. 


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If the Investigator relocates, retires, or for any reason withdraws from the study, the Sponsor should 
be prospectively notified. The study records must be transferred to an acceptable designee, such 
as another Investigator, another institution, or to the Sponsor. 
11.7 
Publication Policy 
Following completion of the study, the data may be considered for publication in a scientific 
journal or for reporting at a scientific meeting. Each Investigator is obligated to keep data 
pertaining to the study confidential. The Investigator must consult with the Sponsor before any 
study data are submitted for publication. The Sponsor reserves the right to deny publication rights 
until mutual agreement on the content, format, interpretation of data in the manuscript, and journal 
selected for publication are achieved. 
11.8 
Financial Disclosure 
Investigators are required to provide financial disclosure information to the Sponsor to permit the 
Sponsor to fulfill its obligations under 21 CFR Part 54. In addition, Investigators must commit to 
promptly updating this information if any relevant changes occur during the study and for a period 
of 1 year after the completion of the study. 


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12 
STUDY ADMINISTRATIVE INFORMATION 
12.1 
Protocol Amendments 
Any amendments to the study protocol will be communicated to the Investigators by 
 or 
the Sponsor. All protocol amendments will undergo the same review and approval process as the 
original protocol. A protocol amendment may be implemented after it has been approved by the 
IRB, unless immediate implementation of the change is necessary for patient safety. In this case, 
the situation must be documented and reported to the IRB within 5 working days. 


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13 
REFERENCES 
1. Bielefeldt K. Gastroparesis: concepts, controversies, and challenges. Scientifica (Cairo). 
2012;2012:424802. 
2. Parkman HP, Jacobs MR, Mishra A, et al. Domperidone treatment for gastroparesis: 
demographic and pharmacogenetic characterization of clinical efficacy and side-effects. 
Dig Dis Sci. 2011;56(1):115-124. 
3. US Department of Health and Human Services, Food and Drug Administration, Center 
for Drug Evaluation and Research (CDER). Gastroparesis: clinical evaluation of drugs 
for treatment. Guidance for industry [draft guidance]. July 2015. 
4. Camilleri M, Bharucha AE, Farrugia G. Epidemiology, mechanisms, and management of 
diabetic gastroparesis. Clin Gastroenterol Hepatol. 2011;9(1):5-12. 
5. Ortiz A, Cooper CJ, Alvarez A, et al. Cardiovascular safety profile and clinical 
experience with high-dose domperidone therapy for nausea and vomiting. Am J Med Sci. 
2015;349(5):421-424. 
6. 
 
 
7. Motilium® (domperidone) [product information]. Macquarie Park, NSW, Australia. 
Janssen-Cilag Pty Ltd. 04 February 2019. 
8. Reddymasu SC, Soykan I, McCallum RW. Domperidone: review of pharmacology and 
clinical applications in gastroenterology. Am J Gastroenterol. 2007;102(9):2036-2045. 
9. Camilleri M, Parkman HP, Shafi MA, et al. Clinical guideline: management of 
gastroparesis. Am J Gastroenterol. 2013;108(1):18-37. 
10. Fitzgerald P, Dinan TG. Prolactin and dopamine: what is the connection? A review 
article. J Psychopharmacol. 2008;22(2 Suppl):12-19. 
11. Buffery PJ, Strother RM. Domperidone safety: a mini-review of the science of QT 
prolongation and clinical implications of recent global regulatory recommendations. 
N Z Med J. 2015;128(1416):66-74. 
12. European Medicines Agency, Pharmacovigilance Risk Assessment Committee (PRAC). 
Assessment report. Domperidone-containing medicinal products. March 2014. 
13. FDA Briefing Document (Domperidone). Pharmacy Compounding Advisory Committee 
Meeting. October 2015. 
14. Biewenga J, Keung C, Solanki B, et al. Absence of QTc prolongation with domperidone: 
a randomized, double‐blind, placebo‐ and positive‐controlled thorough QT/QTc study in 
healthy volunteers. Clin Pharmacol Drug Dev. 2015;4(1):41-48. 
15. US Department of Health and Human Services, Food and Drug Administration, Center 
for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and 
Research (CBER). E14 clinical evaluation of QT/QTc interval prolongation and 
proarrhythmic potential for non-antiarrhythmic drugs. Guidance for Industry. 
October 2005. 
16. Motilium® (domperidone) [datasheet]. Auckland, New Zealand. Janssen-Cilag 
(New Zealand) Ltd. 02 May 2016. 
17. Food and Drug Administration, Center for Drug Evaluation and Research. Pharmacy 
Compounding Advisory Committee (PCAC) Meeting transcript. 28 October 2015. 


CinDome Pharma, Inc. 
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18. Boyce MJ, Baisley KJ, Warrington SJ. Pharmacokinetic interaction between 
domperidone and ketoconazole leads to QT prolongation in healthy volunteers: a 
randomized, placebo-controlled, double-blind, crossover study. Br J Clin Pharmacol. 
2012;73(3):411-421. 
19. US Food and Drug Administration. How to request domperidone for expanded access 
use. 
https://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandappro
ved/approvalapplications/investigationalnewdrugindapplication/ucm368736.htm. 
Accessed 09 August 2018. 
20. International Commission on Radiological Protection. Radiation Dose to Patients from 
Radiopharmaceuticals. ICRP Publication 53. Ann. ICRP. 1988: 18(1-4). 
21. Mettler FA, Huda W, Yoshizumi TT, et al. Effective doses in radiology and diagnostic 
medicine: a catalog. Radiology. 2008;248(1):254-63. 
22. National Council on Radiation Protection and Measurements. Ionizing radiation exposure 
of the population of the United States. National Council on Radiation Protection report 
no. 160. Bethesda, MD: National Council on Radiation Protection Measurements, 2009. 
23. American College of Radiology. Practice Parameter for the Performance of 
Gastrointestinal Scintigraphy. 
http://www.acr.org/~/media/ACR/Documents/PGTS/guidelines/GI_Scintigraphy.pdf. 
2015. Accessed 23 August 2019.  
 








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APPENDIX B:  CLINICAL LABORATORY ANALYTES 
Standard Safety Chemistry Panel 
Alanine aminotransferase 
Albumin 
Alkaline phosphatase 
Amylase 
Aspartate aminotransferase 
Bicarbonate 
Blood urea nitrogen 
Calcium 
Chloride 
Creatine kinase 
Creatinine 
Estimated glomerular filtration rate 
Gamma-glutamyl transferase 
Glucose 
Inorganic phosphorus 
Lactate dehydrogenase 
Lipase 
Potassium 
Sodium 
Total bilirubin 
Total protein 
Uric acid 
 
 
Endocrinology 
Follicle-stimulating hormone [1] 
Thyroid-stimulating hormone 
Prolactin 
Glycosylated hemoglobin (HbA1c) 
1. Follicle-stimulating hormone will only be assessed in females who have been 
postmenopausal for at least 1 year and are not surgically sterile. 
 
Hematology 
Hematocrit 
Hemoglobin 
Platelets 
Red blood cell count 
White blood cell count and differential [1] 
 
1. Manual microscopic review is performed only if white blood cell count and/or 
differential values are out of reference range. 
 
Urinalysis 
Bilirubin 
Blood 
Glucose 
Ketones 
Leukocyte esterase 
Microscopy [1] 
Nitrite 
pH 
Protein 
Specific gravity 
Urobilinogen 
 
1. Microscopy is performed only as needed based on positive dipstick test 
results. 


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Serology 
Hepatitis B surface antigen 
Hepatitis C virus antibody 
Human immunodeficiency virus antibody 
 
 
Pregnancy Test 
Serum and point-of-care pregnancy tests will only be performed in females who are not 
surgically sterile (or postmenopausal for at least 1 year [with confirmed FSH in postmenopausal 
range at the Screening Visit]). 
 
Urine Drug Screen [1] 
Amphetamines 
Cocaine 
Cotinine 
Opiates 
Phencyclidine 
Tetrahydrocannabinol 
1. Urine drug screen point-of-care drug test on randomization day. 
 
Breath Alcohol Test 
 


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APPENDIX C: ELECTROCARDIOGRAM ALERT CRITERIA 
GUIDANCE 
Investigators should contact the Sponsor or designee if any clinically meaningful changes 
from baseline ECGs, including but not limited to those listed below, are noted upon review. 
 QTcF ≥450 msec (male) 
 QTcF ≥470 msec (female) 
 A > 60 msec increase in QTcF from baseline 
 A 6% or greater increase in QTcF from baseline 
New onset findings including but not limited to the following: 
 Second degree AV block (Mobitz II) 
 Third degree AV block (complete heart block) 
 Acute myocardial infarction 
 New left bundle branch block (LBBB) 
 Severe bradycardia (ventricular rate ≤40 bpm) 
 Supraventricular tachycardia (SVT) (ventricular rate ≥150 bpm) 
 Torsades de pointes 
 Ventricular tachycardia (Three or more beats regardless of rate) 
 Ventricular fibrillation 
 Atrial fibrillation/atrial flutter (ventricular rate ≥150 bpm)