Conditions: Diabetic Gastroparesis Idiopathic Gastroparesis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 161
Healthy volunteers: no

Brief summary:
The purpose of this study is to assess the safety and efficacy of various dose levels of NG101 compared with placebo in adult participants with gastroparesis during 12 weeks of treatment.

Detailed description:
This is a randomized, double-blind, parallel-group , placebo-controlled, multicenter US-based study to evaluate the safety and efficacy of 3 dose levels of NG101 (Metopimazine mesylate) compared with placebo in participants with diabetic or idiopathic gastroparesis.

The study will enroll approximately 140 participants. Following the Screening Period, there is a 2-week Pretreatment Period during which participants will complete an electronic daily diary. Participants eligible for the clinical study will be randomly assigned (in a 1:1:1:1 ratio) to receive either NG101 5 mg, 10 mg, or 20 mg, or matching placebo during a 12-week Treatment Period. All participants will be asked to take one capsule 30 minutes before a meal 3 times a day and 30 minutes before bedtime for a total of 4 capsules daily (QID). The total duration of the study for each participant will be approximately 20 weeks.

Arms:
arm 1: NG101 5 mg, capsules, orally, QID (4 times a day) for up to 12 weeks arm 2: NG101 10 mg, capsules, orally, QID (4 times a day) for up to 12 weeks arm 3: NG101 20 mg, capsules, orally, QID (4 times a day) for up to 12 weeks arm 4: Placebo-matching, capsules, orally, QID (4 times a day) for up to 12 weeks

Interventions: intervention 1: NG101 intervention 2: Placebo
Intervention descriptions: intervention 1: Capsules intervention 2: Capsules

Protocol document:
Prot_SAP_000.pdf: 
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Title Page 
Protocol Title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Parallel-Group 
Study of the Safety and Efficacy of NG101 Administered Orally to Patients with 
Gastroparesis 
Protocol Number: NG101-201 
Amendment Number: Not applicable 
Compound: NG101 (metopimazine mesylate) 
Study Phase: 2  
Acronym: Not applicable 
Sponsor Name: Neurogastrx, Inc. 
Legal Registered Address: 600 Unicorn Park Drive, Woburn, MA 01801, USA 
Regulatory Agency Identifier Number(s): 
 
Approval Date: 08 November 2019 
Protocol Version: Original 
 
 




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Study Contact Information  
Sponsor 
Neurogastrx, Inc. 
600 Unicorn Park Avenue 
First Floor 
Woburn, MA 01801 
Medical Monitor 
 
 
 
  
Contract Research 
Organization (CRO) Medical 
Monitor 
 
 
 
 
Clinical Laboratory 
 
 
 
 
 
CRO Contact 
 
 
 
 
Neurogastrx Contact 
 
 
 
  
Dedicated SAE Telephone, 
Facsimile, and Email 
  
  
 
 
  
  
 
 
 
 


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Table of Contents 
1. 
Protocol Summary ..........................................................................................................8 
1.1. 
Synopsis ............................................................................................................................8 
1.2. 
Schema ............................................................................................................................12 
1.3. 
Schedule of Activities (SoA) ..........................................................................................13 
2. 
Introduction ...................................................................................................................20 
2.1. 
Nonclinical ......................................................................................................................20 
2.2. 
Clinical Experience .........................................................................................................20 
2.2.1. 
Phase 1 Studies ...............................................................................................................20 
2.2.2. 
Previous Human Experience ...........................................................................................24 
2.3. 
Study Rationale ...............................................................................................................25 
2.4. 
Background .....................................................................................................................25 
2.5. 
Benefit / Risk Assessment ..............................................................................................26 
2.5.1. 
Risk Assessment .............................................................................................................27 
2.5.2. 
Benefit Assessment .........................................................................................................30 
2.5.3. 
Overall Benefit: Risk Conclusions..................................................................................30 
3. 
Objectives and Endpoints ............................................................................................31 
4. 
Study Design ..................................................................................................................34 
4.1. 
Overall Design ................................................................................................................34 
4.2. 
Scientific Rationale for Study Design ............................................................................35 
4.2.1. 
Participant Input into Design ..........................................................................................36 
4.3. 
Justification for Dose ......................................................................................................36 
4.4. 
End of Study Definition ..................................................................................................37 
5. 
Study Population ...........................................................................................................38 
5.1. 
Inclusion Criteria ............................................................................................................38 
5.2. 
Exclusion Criteria ...........................................................................................................40 
5.3. 
Lifestyle Considerations .................................................................................................43 
5.3.1. 
Meals and Dietary Restrictions .......................................................................................43 
5.3.2. 
Caffeine, Alcohol, and Tobacco .....................................................................................43 
5.3.3. 
Activity ...........................................................................................................................43 
5.4. 
Screen Failures ................................................................................................................43 
5.5. 
Pretreatment Period Failures ...........................................................................................44 
6. 
Study Drug ....................................................................................................................45 
6.1. 
Study Drug(s) Administered ...........................................................................................45 
6.2. 
Preparation / Handling / Storage / Accountability ..........................................................46 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ............................................47 
6.4. 
Study Compliance ...........................................................................................................47 
6.5. 
Concomitant Therapy .....................................................................................................48 
6.5.1. 
Rescue Medicine .............................................................................................................48 
6.6. 
Dose Modification ..........................................................................................................49 
6.7. 
Intervention after the End of the Study ...........................................................................49 
7. 
Discontinuation of Study Drug and Participant 
Discontinuation / Withdrawal......................................................................................50 


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7.1. 
Discontinuation of Study Drug .......................................................................................50 
7.1.1. 
Temporary Interruption ...................................................................................................51 
7.1.2. 
Reinitiation ......................................................................................................................51 
7.2. 
Participant Discontinuation / Withdrawal from the Study..............................................51 
7.3. 
Lost to Follow up ............................................................................................................52 
8. 
Study Assessments and Procedures.............................................................................53 
8.1. 
Total Volume of Blood ...................................................................................................53 
8.2. 
Gastric Emptying Test ....................................................................................................55 
8.3. 
Efficacy Assessments .....................................................................................................55 
8.3.1. 
Diabetic and Idiopathic Gastroparesis Symptoms Daily Diary 
(DIGS-DD) .....................................................................................................................55 
8.3.2. 
Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD) .................................56 
8.3.3. 
Patient Assessment of Upper Gastrointestinal Disorders -
Symptoms Questionnaire ................................................................................................56 
8.3.4. 
Patient Assessment of Upper Gastrointestinal Disorders -Quality 
of Life Questionnaire ......................................................................................................56 
8.3.5. 
Nausea Profile .................................................................................................................57 
8.3.6. 
Patient Global Impression of Severity Questionnaire .....................................................57 
8.3.7. 
Patient Global Impression of Change Questionnaire ......................................................57 
8.3.8. 
Treatment Satisfaction Assessment ................................................................................57 
8.3.9. 
Nausea Improvement ......................................................................................................57 
8.4. 
Safety Assessments .........................................................................................................58 
8.4.1. 
Physical Examinations ....................................................................................................58 
8.4.2. 
Vital Signs .......................................................................................................................58 
8.4.3. 
Electrocardiograms .........................................................................................................59 
8.4.4. 
Clinical Safety Laboratory Assessments ........................................................................59 
8.5. 
Adverse Events and Serious Adverse Events .................................................................60 
8.5.1. 
Time Period and Frequency for Collecting AE and SAE 
Information .....................................................................................................................60 
8.5.2. 
Method of Detecting AEs and SAEs ..............................................................................60 
8.5.3. 
Follow-up of AEs and SAEs ...........................................................................................60 
8.5.4. 
Regulatory Reporting Requirements for SAEs ...............................................................60 
8.5.5. 
Pregnancy ........................................................................................................................61 
8.5.6. 
Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs .............................................................................................61 
8.5.7. 
Adverse Events of Special Interest .................................................................................62 
8.6. 
Treatment of Overdose ...................................................................................................63 
8.7. 
Pharmacokinetics ............................................................................................................64 
8.7.1. 
Pharmacokinetic Assessment Methods and Timing .......................................................64 
8.8. 
Pharmacodynamics .........................................................................................................66 
8.9. 
Genetics ..........................................................................................................................67 
8.10. 
Biomarkers ......................................................................................................................67 
8.11. 
Immunogenicity Assessments.........................................................................................67 
8.12. 
Healthcare Resource Utilization .....................................................................................68 
9. 
Statistical Considerations .............................................................................................69 


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9.1. 
Sample Size Determination ............................................................................................69 
9.2. 
Populations for Analyses ................................................................................................69 
9.3. 
Statistical Analyses .........................................................................................................69 
9.3.1. 
General considerations ....................................................................................................69 
9.3.2. 
Efficacy Endpoints ..........................................................................................................70 
9.3.3. 
Key Secondary Efficacy Endpoints ................................................................................71 
9.3.4. 
Additional Secondary Efficacy Endpoints ......................................................................71 
9.3.5. 
Exploratory Endpoint(s) ..................................................................................................72 
9.3.6. 
Safety Endpoints .............................................................................................................73 
9.4. 
Interim Analyses .............................................................................................................73 
9.5. 
Data Monitoring Committee (DMC) and Data Safety Monitoring 
Board (DSMB) ................................................................................................................73 
10. 
Supporting Documentation and Operational Considerations ..................................74 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ................................................................................................................74 
10.1.1. Regulatory and Ethical Considerations ...........................................................................74 
10.1.2. Financial Disclosure ........................................................................................................74 
10.1.3. Informed Consent Process ..............................................................................................75 
10.1.4. Data Protection................................................................................................................75 
10.1.5. Committees Structure......................................................................................................75 
10.1.6. Dissemination of Clinical Study Data .............................................................................75 
10.1.7. Data Quality Assurance ..................................................................................................76 
10.1.8. Source Documents ..........................................................................................................76 
10.1.9. Study and Site Start and Closure ....................................................................................77 
10.1.10. Publication Policy ...........................................................................................................77 
10.2. 
Appendix 2: Prohibited and Permitted Medications .......................................................78 
10.3. 
Appendix 3: Clinical Laboratory Tests ...........................................................................81 
10.4. 
Appendix 4: Patient Reported Outcomes for Efficacy 
Assessments ....................................................................................................................83 
10.5. 
Appendix 5: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting .........................................................85 
10.5.1. Definition of AE .............................................................................................................85 
10.5.2. Definition of SAE ...........................................................................................................86 
10.5.3. Recording and Follow-Up of AE and/or SAE ................................................................87 
10.5.4. Reporting of SAEs ..........................................................................................................89 
10.6. 
Appendix 6: Contraceptive Guidance and Collection of 
Pregnancy Information ...................................................................................................90 
10.7. 
Appendix 7: Estimated Glomerular Filtration Rate ........................................................93 
10.8. 
Appendix 8: Genetics......................................................................................................94 
10.9. 
Appendix 9: Abbreviations .............................................................................................95 
11. 
References ......................................................................................................................97 
 
 
 


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List of Tables 
Table 1: 
Study Drugs ....................................................................................................... 45 
Table 2: 
Total Volume of Blood Required for Each Assay ............................................ 54 
Table 3: 
Adverse Events of Special Interest: Rationale for Inclusion and Criteria for 
Diagnosis .......................................................................................................... 62 
Table 4: 
Pharmacokinetic Sampling Times ..................................................................... 65 
Table 5: 
Serum Prolactin Sampling Times ...................................................................... 67 
Table 6: 
Protocol-Required Safety Laboratory Assessments .......................................... 81 
 






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• 
Association of exposure and clinical 
response 
• 
Association of PK parameters and changes 
in gastroparesis symptom PRO scores. 
• 
Association of PK parameters and safety 
assessments 
• 
Additional analyses of clinical response in 
gastroparesis symptoms 
• 
Achievement of threshold levels of 
improvement or worsening in each of the 
components of the DIGS-DD (nausea, 
vomiting, early satiety, post-prandial 
fullness, and abdominal pain) 
• 
Composite symptom severity scores 
• 
Healthcare resource utilization 
• 
Number of visits to healthcare providers 
• 
Association of serum glucose with clinical 
response 
• 
Association of serum glucose levels and 
HgbA1c with gastroparesis symptom PRO 
scores 
Abbreviations: DIGS-DD = Diabetic and Idiopathic Gastroparesis Symptoms Daily Diary; 
ECG = electrocardiogram; GCSI-DD = Gastroparesis Cardinal Symptom Index Daily Diary; 
PAGI-SYM = Patient Assessment of Upper Gastrointestinal Disorders -Symptoms Questionnaire; 
PAGI-QOL = Patient Assessment of Upper Gastrointestinal Disorders -Quality of Life; PGI-C = Patient Global 
Impression of Change; PGI-S = Patient Global Impression of Severity; PD = pharmacodynamic; 
PK = pharmacokinetic; PRO = patient-reported outcomes; TEAEs = treatment-emergent adverse events; 
TEAESIs = treatment-emergent adverse events of special interest; TESAEs = treatment-emergent serious adverse 
events.  
Overall Design 
This is a randomized, double-blind, parallel-group (4 arms), placebo-controlled, multicenter 
study to evaluate the safety and efficacy of 3 dose levels of NG101 compared with placebo in 
participants with diabetic or idiopathic gastroparesis. 
Following a Screening Period of up to 4-weeks, eligible participants will enter a 2-week 
Pretreatment Period, during which time they will complete specified gastroparesis symptom 
assessments to establish baseline data and to determine compliance with completion of these 
assessments. Following completion of the Pretreatment Period, a participant’s randomization 
eligibility will be determined (based on all inclusion/exclusion criteria, including the 
participant’s compliance with eDiary completion).  
Participants who do not initially meet study screening criteria (ie, are screen failures) may be 
rescreened (no more than 1 additional screening) after consultation with and approval by the 
sponsor. A participant’s eligibility for the study must be confirmed by the sponsor’s Medical 
Monitor, or designee, prior to randomization. 
Participants eligible for the clinical study will be randomized in a 1:1:1:1 ratio to receive either 
NG101 treatment arms of 5 mg, 10 mg, or 20 mg, or matching placebo during a 12-week 
Treatment Period. Randomization will be stratified on the following factors: gastroparesis 
etiology (diabetes vs idiopathic), sex (male vs female), and cannabinoid use (yes vs no). 
Determination of diabetes etiology will be done according to the medical history data at 
Screening. 


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Two weeks following the Week 12 Visit, participants will return to the clinic for an End of Study 
(EoS) Visit / Follow-up Visit.  
If a participant permanently discontinues study medication (for any reason) prior to the Week 12 
Visit, the participant must attend the Early Discontinuation Visit as soon as possible, and then 
the Safety Follow-up Visit 2 weeks later.  
Study Assessments: 
Study assessments will be performed at the times specified in the Schedule of Activities (SoA – 
see Section 1.3).  
The primary efficacy objective is to determine the efficacy of NG101 to reduce nausea severity 
in participants with gastroparesis. The primary endpoint is the change from baseline at Weeks 7 
through 12 for the nausea severity score in the Diabetic and Idiopathic Gastroparesis Symptoms 
Daily Diary (DIGS-DD). Key secondary efficacy endpoints will also be assessed by the 
DIGS-DD and include changes from baseline at Weeks 7 through 12 in the DIGS-DD number of 
discrete episodes of vomiting, early satiety severity score, post-prandial fullness severity score, 
abdominal pain severity score, and total severity score (nausea, early satiety, post-prandial 
fullness, abdominal pain). An eDiary will be used to collect information for the primary and key 
secondary endpoints. 
In addition, blood samples will be obtained from all participants to measure plasma levels of 
metopimazine and metopimazine acid following single-dose administration (Day 1) and at 
steady-state after multiple-dose administration (Week 2). Blood samples for PK will be collected 
at the Day 1 and Week 2 visits for all participants (up to 3 hours after the first dose on each 
occasion). In a subset of participants (8 to 10 participants per treatment arm; 32 to 40 participants 
total), intensive sampling will be performed (up to 6 hours after the first dose at the Day 1 and 
Week 2 visits, as well as 1 and 2 hours after the second dose at the Day 1 visit). 
Disclosure Statement:  
This is a parallel group treatment study with 4 arms that is participant, investigator, and sponsor 
blinded. 
Number of Participants: 
A total of approximately 280 participants will be randomized to achieve an estimated 
224 participants completing the 12-week Treatment Period (and approximately 56 participants 
per treatment arm). At least 120 randomized participants will have diabetic gastroparesis and at 
least 120 randomized participants will have idiopathic gastroparesis. Up to approximately 
140 participants can be cannabinoid users, and of these, up to approximately 56 can be marijuana 
users. 
Intervention Groups and Duration: 
The total duration of the study for each participant will be approximately 20 weeks. 
On Day 1 of the Treatment Period, eligible participants will be randomized in a 1:1:1:1 ratio to 
receive either NG101 5 mg, 10 mg, or 20 mg, or matching placebo. Study drug will be 
administered orally 4 times per day (QID) for 12 weeks. The 20 mg arm will initiate dosing on 


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Day 1 with 5 mg QID for 4 days, followed by 10 mg QID for 3 days, and then 20 mg QID 
through Week 12. No titration will occur in the 5 mg and 10 mg arms. 
The study drug should be taken by participants approximately 30 minutes before a meal 3 times a 
day and 30 minutes before bedtime, with a minimum interval of 4 hours between doses. 
Data Monitoring Committee and Data Safety Monitoring Board: 
A Data Monitoring Committee (DMC) comprised of representatives from the sponsor and CRO 
will review blinded data on an ongoing basis.  
An unblinded independent safety review conducted by a Data Safety Monitoring Board (DSMB) 
will be triggered if any of the following conditions are met: 3 or more participants in the study 
exhibit extrapyramidal symptoms (EPS); 1 or more participants have neuroleptic malignant 
syndrome (NMS); 3 or more participants are discontinued due to orthostatic hypotension-related 
adverse events (AEs); other events considered of high clinical significance by the sponsor are 
observed. The DSMB will then make any recommendations to the sponsor regarding conduct of 
the study. 
1.2. 
Schema 
 
 
















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2. 
Introduction 
NG101 is a potent and selective, peripherally-restricted (ie, very limited ability to penetrate the 
brain), human Ether-à-go-go-related gene (hERG) negative (ie, no hERG inhibition at expected 
human plasma exposures), dopamine D2/D3 receptor antagonist being evaluated for the treatment 
of gastroparesis. It is also an antagonist with lower affinity for dopamine D1, adrenergic alpha-1, 
histamine H1, and serotonin 5-HT2A/5-HT2B receptors.  
2.1. 
Nonclinical 
A complete battery of studies has been conducted to support the safety of the proposed clinical 
trial in accordance with International Conference of Harmonisation (ICH) M3(R2). Based upon 
the metabolism and pharmacologic properties of NG101, the rat and dog were considered 
appropriate models for pivotal nonclinical safety studies. NG101 was administered by the oral 
route in pivotal toxicology studies, as it is the intended route of administration for clinical trials 
and marketing.  
Briefly, the nonclinical program confirmed that metopimazine (tested as NG101) is a 
P-glycoprotein substrate with limited penetration of the blood-brain barrier. NG101 is not 
metabolized via the cytochrome P450 pathway, thereby minimizing potential for drug-drug 
interactions. Unlike domperidone, NG101 does not produce hERG channel inhibition at expected 
human plasma exposures. There is a > 100-fold window between expected free plasma 
concentrations in the proposed Phase 2 study and the hERG half maximal inhibitory 
concentration (IC50) determined in vitro. Nonclinical studies also demonstrated that 
metopimazine acid has > 100-fold lower affinity to D2 and D3 receptors as compared to the 
parent drug metopimazine. 
Effects seen in the toxicology studies were anticipated given the mechanism of action of 
metopimazine, and are able to be monitored in the clinic. These include effects related to 
increased prolactin levels (see Section 2.5.1). 
See the NG101 Investigator’s Brochure (IB) for further details. 
2.2. 
Clinical Experience 
2.2.1. 
Phase 1 Studies 
Two phase 1 studies have been conducted by the sponsor with metopimazine in healthy 
volunteers: Study NG100-101 and Study NG101-102. A summary of both studies is provided 
below and further details can be found in the NG101 IB. 


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2.2.1.1. 
Study NG100-101 (SAD / MAD Study) 
Study Design 
Study NG100-101 was a phase 1 double-blind, placebo-controlled, single-ascending and 
multiple-ascending dose (SAD and MAD) study of the safety, tolerability, and PK of 
metopimazine administered orally to healthy adult participants ages 18 to 45 years at a single 
study center in France. The investigational medicinal product administered in this study was the 
French approved and marketed brand of metopimazine, Vogalene. 
In the SAD portion of the study a total of 4 cohorts were enrolled and single ascending doses of 
15, 30, 45, and 60 mg were tested. A total of 32 participants (16 females, 16 males) were 
randomized, and all participants completed the SAD portion of the study. 
In the MAD portion of the study, sequential multiple-ascending doses were evaluated in 
3 cohorts of 8 participants. Dosing regimens of 15, 30, and 45 mg, were administered every 
6 hours (Q6H) for 5 days, followed by a single dose on Day 6. A total of 24 participants 
(12 females, 12 males) were randomized, and 23 participants completed part 2 (12 females, 
11 males). 
Results 
Pharmacokinetics 
Following dosing with metopimazine, maximum plasma concentration (Cmax) occurred at a 
median time of 0.8 to 1.1 hours after dosing with median lag time from 0.1 to 0.25 hours after 
dosing. A high inter-individual variability was observed for Cmax of metopimazine with 
coefficient of variations (%CV) ranging from 46 to 75%. The area under the plasma 
concentration-time curve (AUC) from time 0 to infinity (AUC0-inf) and derived pharmacokinetic 
(PK) parameters of metopimazine (terminal half-life [t1/2], total clearance [Cl/F] and Vz/F) could 
be estimated at doses of 30 mg and above. The mean t1/2 ranged from 2 to 2.3 hours, Vz/F ranged 
from 430 to 860 L and Cl/F ranged from 170.5 to 335 L/h. Mean PK parameters of 
metopimazine showed an increase of Cmax and AUC with dose from 15 to 60 mg. However, dose 
proportionality may have been obscured by inter-subject variability. Mean PK parameters 
increased with higher doses in a manner that was close to dose-proportional over a dose range of 
15 to 60 mg for single doses and 15 to 45 mg for multiple doses.   
Following administration of multiple doses every 6 hours (Q6H), steady-state conditions 
appeared to be reached by the end of Day 1. After continued Q6H dosing through Day 6, 
metopimazine accumulated 30 to 40% based on AUC.   
Metopimazine was rapidly metabolized to metopimazine acid, with metopimazine acid Cmax 
occurring at median times ranging from 2 to 3 hours after dosing across cohorts. The mean 
metopimazine acid elimination t1/2 ranged from 2.7 to 3.5 hours. Relative to parent 
metopimazine, plasma metopimazine acid exposure was generally 3- to 4-fold higher for Cmax 
and 6- to 11-fold higher for AUC. For metopimazine, a close to dose proportional increase was 
observed for Cmax, AUC from time 0 to the last measurable concentration (AUC0-last) and 
AUC0-inf. Accumulation of metopimazine acid was observed after repeated doses (Q6H) with a 
mean accumulation ratio of 1.6 to 1.7 based on Cmax and 1.7 to 1.9 based on AUC0-6. 


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Safety 
No serious adverse events (SAEs) were observed during the study, and no participants withdrew 
due to adverse events (AEs). All adverse events (AEs) were reported to be mild or moderate in 
severity. No symptoms suggestive of neuroleptic malignant syndrome (NMS) or extrapyramidal 
symptoms (EPS) were observed and there were no clinically relevant changes in 
electrocardiogram (ECG) time intervals. No notable trends were observed in changes in 
laboratory tests. 
An increased risk of orthostatic hypotension (OH) was observed with metopimazine, likely due 
to inhibition of peripheral adrenergic alpha-1 receptors. Orthostatic changes in vital signs 
considered to be clinically significant were defined as a decrease in systolic or diastolic blood 
pressure (BP) of at least 20 mm Hg or 10 mm Hg, respectively, or heart rate increase of at least 
30 beats/minute and/or heart rate above 120 beats/minute (Freeman et al. 2011; NIH-NINDS 
Postural Tachycardia Syndrome Information Page 2019).  
In the 15 mg and 30 mg groups of the SAD portion of the study, 1 to 2 participants (out of 6 in 
each dose group) were reported to have “dizziness in standing position”. No vital sign 
measurements were obtained at the time of these events; however, the preferred term of OH was 
recorded. A protocol amendment was implemented after cohort 2 (30 mg) of the SAD portion of 
the study to require vital sign measurements lying, sitting, and standing at prescribed timepoints 
after dosing. In the 45 mg and 60 mg groups of the SAD, 4 participants (out of 6 in each dose 
group) experienced OH.   
Two participants in the MAD 15 mg Q6H group experienced OH (on Day 1 at Hour 1 after the 
first dose) and 1 participant in the MAD 30 mg Q6H group experienced OH (on Day 1 at Hour 1 
after the first dose). No other episodes of OH occurred with subsequent dosing in these 
participants, and no other participants in these dose groups experienced OH. On the other hand, 
most participants in the MAD 45 mg Q6H group experienced OH, and more than half 
experienced episodes on multiple days during the dosing period. A similar trend was noted for 
orthostatic tachycardia. 
Based on these results, the risk of OH appeared to be dose dependent, with the 45 mg and 60 mg 
doses associated with a higher risk for OH than the 15 mg and 30 mg doses. These data also 
suggest that with repeat dosing, participants adapt to the alpha-adrenergic inhibition, which is 
consistent with the literature on alpha-1 receptor antagonists approved for use in hypertension 
and benign prostatic hyperplasia (Achari et al. 1998). 
2.2.1.2. 
Study NG101-102 (Comparative PK Study) 
Study Design 
Study NG101-102 was a phase 1 two-cohort, partial crossover, open-label, randomized, single-
dose study to assess the relative bioavailability between NG101 (metopimazine mesylate) and 
the reference metopimazine formulation (Vogalene) in healthy participants at a single study 
center in France. The NG101 dose (15 mg) for Cohort 2 of the study was determined from the 
PK results from Cohort 1 of the study. The reference metopimazine was administered either 
orally as a 15 mg capsule or via a diluted intravenous (IV) infusion of a 10 mg/mL solution 
administered as 7.5 mg over 60 minutes. 


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Cohort 1 was a 3-period, partial crossover in the fasted state with 3 administrations of NG101 
7.5 mg PO, Vogalene 15 mg PO, or Vogalene 7.5 mg IV. There was a wash-out period of 
48 hours between each administration. A total of 8 participants were enrolled and received each 
of the 3 treatments.  
Cohort 2 was a 3-period, cross-over design with 3 administrations of 15 mg of each of the 
following: oral formulation of NG101 fasting, oral formulation of NG101 after a high-fat 
breakfast, oral formulation of the reference metopimazine fasting. There was a wash-out period 
of 48 hours between each administration. Fifteen participants were enrolled and received each of 
the 3 treatments. 
Results 
Relative Bioavailability and Food Effect 
Based upon geometric least squares mean ratio, preliminary estimates of the relative 
bioavailability of NG101 compared to Vogalene, each under fasting conditions, were 109% for 
AUClast and 86.4% for Cmax, but the 90% confidence intervals (CIs) were too wide to conclude 
equivalence. A high degree of inter-subject variability was observed for these PK parameters and 
several participants had plasma concentrations below the limit of quantification (5 ng/mL) within 
the first 6 hours after dosing. An elimination t1/2 for metopimazine could not be determined for 
any participant; therefore, AUC0-inf could not be calculated. Given that the time of last 
measurable plasma metopimazine concentration varied within participants for the different study 
treatments, an additional exploratory PK in which AUClast was uniformly truncated at the time of 
last measurable concentration showed a relative bioavailability of 98%. For metopimazine acid, 
the 2 formulations met bioequivalence criteria with geometric mean ratios of 92.2% and 93.1% 
for AUClast and Cmax respectively. 
Overall, NG101 provided generally similar exposure to metopimazine compared to Vogalene 
under fasting conditions, although the current limit of quantification for metopimazine (5 ng/mL) 
limited some of the PK objectives.  
For metopimazine, administration of NG101 with a high-fat breakfast resulted in an approximate 
15% reduction in Cmax and an approximate 5% reduction in AUClast with 90% CIs outside of the 
bioequivalence range. An additional exploratory PK analysis was performed in which AUClast 
was uniformly truncated at the time of last measurable concentration for each participant, which 
showed a 12% reduction in AUClast with a high-fat breakfast. For metopimazine acid, NG101 
given with a high fat breakfast resulted in a 30% reduction in Cmax and a 27% reduction in 
AUClast. Overall, these PK differences are unlikely to be of clinical significance. 
Pharmacokinetics 
For the NG101 7.5 mg dose, few timepoints after Cmax were quantifiable above the limit of 
quantification (5 ng/mL) with the time of the last measurable concentration (Tlast) ranging from 
1.25 to 2 hours. As such, the terminal elimination rate constant (Lambda z) and the derived 
parameters (t1/2, AUCinf, Cl/F and Vd/F) could not be reliably determined. For the 15 mg 
Vogalene dose, Tlast ranged from 2 to 6 hours and terminal t1/2 for metopimazine was determined 
for 2/6 participants.     
For Cohort 1, the dose-adjusted metopimazine Cmax for participants administered NG101 was 
similar compared to those administered Vogalene. Based on AUClast, NG101 appeared to result 


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in approximately 50% lower and absolute relative bioavailability; however, this determination 
was influenced by the duration of quantifiable metopimazine exposure. When the AUC was 
limited uniformly to 2 hours post-dose, metopimazine dose-adjusted AUC in participants 
administered NG101 was approximately 91% compared to those administered Vogalene. For the 
metopimazine acid metabolite, the relative bioavailability based on dose-adjusted AUClast was 
approximately 86%.  The absolute bioavailability of Vogalene was approximately 19% (also 
based on AUClast), which is consistent with published studies (Herrstedt et al. 1990). The results 
from Cohort 1 indicated that plasma metopimazine exposure for NG101 was generally similar 
compared to Vogalene and an NG101 dose of 15 mg was selected for Cohort 2. 
Following oral administration of 15 mg of metopimazine as NG101 in fasted conditions, 
metopimazine plasma peaks occurred at a median time of 0.75 hours after dosing. Mean 
metopimazine Cmax and AUC0-last values were 20.6 ng/mL and 39.9 ng.h/mL, respectively. A lag 
time of 0.25 hours (median) was observed after dosing. The terminal elimination rate constant 
(Lambda z) and the derived parameters (t1/2, AUCinf, Cl/F and Vd/F) could not be reliably 
determined. A high inter-individual variability was observed with %CV between 60.4 and 
82.6%. Metopimazine Cmax and AUC0-2h appeared to be approximately dose proportional 
between the 7.5 mg dose of NG101 in Cohort 1 and the 15 mg dose in Cohort 2. 
Safety 
No serious adverse events (SAEs) were observed during the study, and no participants withdrew 
due to adverse events (AEs). All adverse events (AEs) were reported to be mild or moderate in 
severity. In each of the three 15-participant treatment groups, 2 to 4 participants reported AEs 
that were related to postural change (consistent with results observed in the SAD / MAD study). 
However, no consistent pattern was observed within individual participants across the treatments 
(ie, some participants had the AEs with 1 treatment but not another). A small increased risk of 
orthostatic related AEs was observed upon fasting (ie, 3 fasting versus 1 fed). All OH events 
occurred at 1 hour after dosing, with the exception of 1 OH event that occurred at hour 8. There 
were no other trends indicative of clinically important treatment-related laboratory abnormalities.  
2.2.2. 
Previous Human Experience 
Metopimazine (Vogalene®) has been used extensively as an antiemetic for over 40 years in 
France. In a dose-ranging open-label safety and tolerability study involving 38 patients 
undergoing chemotherapy, metopimazine was administered orally every 4 hours at increasing 
doses (Herrstedt et al. 1997a). A total of 36 patients completing 46 cycles of chemotherapy 
received 20, 30, 40, 50 and 60 mg oral metopimazine every 4 hours over a 44-hour period. The 
metopimazine dose-limiting toxicity was moderate to severe dizziness caused by OH, as seen in 
0, 0, 17%, 42% and 50% of the patients at the respective dose levels. No information was 
provided on the timing of the occurrence of dizziness during the 44-hour period. Few other side 
effects were reported, and most were mild. A single possible extrapyramidal AE was observed in 
a patient in the 60 mg x 11 dose group. Metopimazine was demonstrated to be safe at a dosage of 
30 mg, 6 times (180 mg) daily.  
Further, in a randomized, double-blind comparison of ondansetron vs ondansetron plus 
metopimazine as antiemetic prophylaxis during platinum-based chemotherapy in patients with 
cancer, metopimazine was administered at 35 mg/m2 IV followed by 30 mg, 4 times a 


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day (120 mg daily), for 4 days. A total of 94 patients completed the crossover study. Results 
suggested that metopimazine plus ondansetron was significantly superior to ondansetron alone 
on all efficacy parameters assessed. Reported adverse reactions were mild and without 
significant differences between the 2 treatments. However, an asymptomatic decrease in standing 
BP was observed when patients received the combination antiemetic therapy 
(Herrstedt et al. 1997a).  
In a randomized, double-blind trial assessing the efficacy and safety of sublingual metopimazine 
compared to ondansetron in chemotherapy-induced delayed emesis, patients received either 
45 mg/day of metopimazine (15 mg every 8 hours) or 16 mg/day of ondansetron (8 mg every 
12 hours). Metopimazine was comparable in efficacy to ondansetron. Furthermore, the incidence 
of gastrointestinal (GI) disorders was significantly lower in the metopimazine group, particularly 
abdominal pain and constipation (Herrstedt et al. 1997b; Bethune-Volters et al. 2006).  
Since metopimazine market approval as an antiemetic in France (10 January 1977), a number of 
other open-label or randomized, placebo-controlled efficacy studies involving oral or IV 
administration of metopimazine have been published. These studies conclude that metopimazine 
is safe and well tolerated with no reports of severe central nervous system (CNS) or 
cardiovascular (CV) AEs (Paradis and Brault 1967; Guerin et al. 1969; Arbus and Parente 1971; 
Berry et al. 1971; Arnaud and Sportouch 1972; Bertrand and Thillier 1975; Barale et al. 1977; 
Israel 1978; Rodary et al. 1979; Ballester et al 1980; Gosselin et al 1981; Badji et al 1988; 
Herrstedt et al. 1990; Herrstedt et al. 1997b; Lebeau et al. 1997; Sigsgaard et al. 2001; 
Croom and Keating 2006).  
Generally, studies in chemotherapy-induced nausea and vomiting suggest that doses of 
metopimazine higher than approved for common nausea and vomiting conditions tend to be 
more efficacious while remaining safe and well tolerated. Doses ranging from 45 to 120 mg per 
day were evaluated in these studies (Israel and Rodary 1978; Herrstedt et al. 1997b; 
Lebeau et al. 1997; Sigsgaard et al. 2001; Bethune-Volters et al. 2006). 
2.3. 
Study Rationale 
The purpose of this study is to evaluate the safety and efficacy of NG101 when administered 
orally across a range of 3 doses to participants aged 18 years or older with diabetic or idiopathic 
gastroparesis. Results of this study will guide optimal dose selection for phase 3. 
2.4. 
Background 
Gastroparesis is a chronic disorder of the stomach characterized by delayed gastric emptying 
without evidence of mechanical obstruction (Camilleri et al. 2013; Stein et al. 2015). The core 
set of symptoms of gastroparesis include nausea, vomiting, early satiety, post-prandial fullness, 
and abdominal pain (Food and Drug Administration [FDA] 2019; Camilleri et al. 2013). The 
most common etiologies of gastroparesis are of idiopathic and diabetic origin (Parkman 2018; 
Camilleri et al. 2013). While the overall incidence of gastroparesis is not well understood, the 
10-year incidence in Olmsted County Minnesota, United States (US), was 5.2% in patients with 
type 1 diabetes, 1% in patients with type 2 diabetes, and 0.2% among non-diabetic controls 
(Choung et al. 2012). Evidence suggests gastroparesis is associated with increased healthcare 
costs, including an increased frequency of hospitalizations (Wadhwa et al. 2017; 


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Camilleri et al. 2013). Overall, gastroparesis adversely affects the lives of patients, and there is 
urgent need to develop treatments with a favorable risk-benefit profile. 
Neurogastrx, Inc. is developing NG101, a mesylate salt of metopimazine, a potent and selective, 
peripherally-restricted (ie, very limited ability to penetrate the brain), hERG negative (ie, no 
hERG inhibition at expected human plasma exposures), dopamine D2/D3 receptor antagonist for 
the treatment of gastroparesis. Metopimazine (oral capsules, orally disintegrating tablet, 
suppositories, liquid drops or syrup) has been approved in France for over 40 years under the 
current trade name Vogalene® (15 mg oral capsule; 7.5 mg orally disintegrating tablet) for the 
short-term symptomatic treatment of nausea and vomiting.  An IV formulation (10 mg) is 
approved and is almost exclusively used for the treatment of chemotherapy-induced nausea and 
vomiting in adults and children. The vast majority of prescriptions for adults and 
infants / children are for seasonal gastroenteritis or acute nausea and vomiting of various 
etiologies. Metopimazine is also available as an over-the-counter medication (Vogalib®, 7.5 mg 
orally disintegrating tablets). 
Dopamine antagonism has been well validated as an effective treatment for gastroparesis. 
Metoclopramide and domperidone, existing D2 antagonists, have gastroprokinetic properties as 
well as anti-nausea/anti-emetic effects. However, these agents are associated with limiting CNS 
and CV side effects, respectively. Although metopimazine belongs to the chemical family of 
phenothiazines (most of which are associated with CNS and/or CV side effects), its use is rarely 
associated with CNS side effects, and has not been associated with significant cardiac risk when 
used at the current marketed doses in France. As such, NG101 is a promising candidate for the 
treatment of gastroparesis.   
A detailed description of the chemistry, pharmacology, efficacy, and safety of metopimazine is 
provided in the NG101 IB. 
2.5. 
Benefit / Risk Assessment 
A summary of the benefit-risk assessment for conducting Study NG101-201 is provided in the 
following sections (Section 2.5.1, Section 2.5.2, and Section 2.5.3). 
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of NG101 may be found in the IB. 




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Potential Risk of 
Clinical Significance 
Summary of Data /  
Rationale for Risk  
Mitigation Strategy 
continued AEs. Participants with recurrent postural AEs on subsequent days will 
return to the study site for further evaluation. 
Individual stopping criteria: 
Participants with OH (defined by a decrease in systolic BP of at least 20 mm Hg) 
and associated severe postural symptoms will be stopped and withdrawn from 
the study.   
These severe symptoms include presyncope, syncope, and other severe AEs that 
are considered of substantial clinical relevance by the investigator. Presyncope is 
defined as “feeling like one was going to pass out but without actual loss of 
consciousness” (Whitledge et al. 2019). Syncope is “the sudden loss of 
consciousness, associated with inability to maintain postural tone, with 
immediate and spontaneous recovery without requiring electrical or chemical 
cardioversion” (da Silva 2014). 
Participants meeting this discontinuation criterion while under observation 
during clinical visits must be monitored in the clinic until postural symptoms are 
no longer severe, and will be withdrawn from the study. Participants who 
develop severe postural symptoms at home will hold any further dosing and 
return to the study site as soon as possible for further evaluation. 
Other mitigation: 
Participants in the 20 mg treatment arm will be initiated with a dose titration, 
beginning with daily dosing with 5 mg 4 times daily (QID). 
Repeated dosing is associated with counter regulation to alpha blockade and 
reduction in blood pressure effects. 
Participants will be trained to recognize signs and symptoms of OH, and how to 
manage it should it occur. 
For the first 24 hours of dosing, participants should avoid situations in which 
injury might occur (eg, driving) should there be orthostatic symptoms. 
Neuroleptic malignant 
syndrome (NMS) 
Observed within the class of D2 
antagonists 
As a Pg-P substrate, metopimazine is not expected to have significant 
penetration of the CNS. Nevertheless, clinical assessment for early detection of 
NMS will be included in the study. 




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2.5.2. Benefit Assessment 
Patients with gastroparesis arising from diabetic or idiopathic origin may benefit from receiving 
NG101, which has the potential to alleviate the significant symptom burden associated with the 
condition. Use of metopimazine in France has been associated with benefit in the treatment of 
nausea and vomiting (Vogalene Summary of Product Characteristics, 2017). In addition, 
participants may benefit from the clinical monitoring and continuation of background 
medications during the study. 
2.5.3. Overall Benefit: Risk Conclusions 
Taking into account the measures taken to minimize risk to participants in this study, the 
potential risks identified in association with NG101 are justified by the potential benefits that 
may be afforded to participants with gastroparesis. In France, metopimazine is approved for the 
symptomatic treatment of nausea and vomiting, and has been prescribed for over 40 years. The 
body of evidence generated to date reflects a positive benefit risk balance in that indication. 
 






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PAGI-SYM = Patient Assessment of Upper Gastrointestinal Disorders -Symptoms Questionnaire; 
PAGI-QOL = Patient Assessment of Upper Gastrointestinal Disorders -Quality of Life; PGI-C = Patient Global 
Impression of Change; PGI-S = Patient Global Impression of Severity; PD = pharmacodynamic; 
PK = pharmacokinetic; PRO = patient-reported outcomes; TEAEs = treatment-emergent adverse events; 
TEAESIs = treatment-emergent adverse events of special interest; TESAEs = treatment-emergent serious adverse 
events.  


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4. 
Study Design 
4.1. 
Overall Design 
This is a randomized, double-blind, parallel-group (4 arms), placebo-controlled, multicenter 
study to evaluate the safety and efficacy of 3 dose levels of NG101 compared with placebo in 
participants with diabetic or idiopathic gastroparesis. 
The total duration of the study for each participant will be approximately 20 weeks. Following a 
Screening Period of up to 4-weeks, eligible participants will enter a 2-week Pretreatment Period 
during which time they will complete specified gastroparesis symptom assessments to establish 
baseline data and to determine compliance with completion of these assessments. Following 
completion of the Pretreatment Period, a participant’s randomization eligibility will be 
determined (based on all inclusion/exclusion criteria, including the participant’s compliance with 
eDiary completion).  
Participants who do not initially meet study screening criteria (ie, are screen failures) may be 
rescreened (no more than 1 additional Screening) after consultation with and approval by the 
sponsor. A participant’s eligibility for the study must be confirmed by the sponsor’s Medical 
Monitor, or designee, prior to randomization. 
Participants eligible for the clinical study will be randomized in a 1:1:1:1 ratio to receive either 
NG101 treatment arms of 5 mg, 10 mg, or 20 mg, or matching placebo during a 12-week 
Treatment Period. Randomization will be stratified on the following factors: gastroparesis 
etiology (diabetes vs idiopathic), sex (male vs female), and current cannabinoid use (yes vs no). 
Determination of diabetes etiology will be done according to the medical history data at 
Screening. 
NG101 will be administered orally (PO) QID for 12 weeks. The 20 mg arm will initiate dosing 
on Day 1 with 5 mg QID for 4 days, followed by 10 mg QID for 3 days, and then 20 mg QID 
through Week 12. No titration will occur in the 5 mg and 10 mg arms. The study drug should be 
taken by participants approximately 30 minutes before a meal 3 times a day and 30 minutes 
before bedtime, with a minimum interval of 4 hours between doses. 
Two weeks following the end of treatment / Week 12 Visit, participants will return to the clinic 
for an End of Study (EoS) Visit / Follow-up Visit.  
If a participant permanently discontinues study medication (for any reason) prior to the 
Week 12 Visit, the participant must attend the Early Discontinuation Visit as soon as possible, 
and then the Safety Follow-up Visit 2 weeks later.  
The sponsor will review blinded data on an ongoing basis. Independent reviews of safety data 
will be done if needed.    
Study Assessments: 
Study assessments will be performed at the times specified in the Schedule of Activities (SoA – 
Section 1.3).  
The primary efficacy objective is to determine the efficacy of NG101 to reduce nausea severity 
in participants with gastroparesis. The primary endpoint is the change from baseline at Weeks 7 
through 12 for the nausea severity score in the Diabetic and Idiopathic Gastroparesis Symptoms 


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Daily Diary (DIGS-DD). Key secondary efficacy endpoints will also be assessed by the 
DIGS-DD and include changes from baseline at Weeks 7 through 12 in the DIGS-DD number of 
discrete episodes of vomiting, early satiety severity score, post-prandial fullness severity score, 
abdominal pain severity score, and total severity score (nausea, early satiety, post-prandial 
fullness, abdominal pain). An eDiary will be used to collect information for the primary and key 
secondary endpoints. 
In addition, blood samples will be obtained to measure plasma levels of metopimazine and 
metopimazine acid following single-dose administration (Day 1) and at steady-state after 
multiple-dose administration (Week 2). Blood samples for PK will be collected at the Day 1 and 
Week 2 visits for all participants (up to 3 hours after the first dose on each occasion. In a subset 
of participants (8 to 10 participants per treatment arm; 32 to 40 participants total), intensive 
sampling will be performed (up to 6 hours after the first dose at the Day 1 and Week 2 visits, as 
well as 1 and 2 hours after the second dose at the Day 1 visit). 
4.2. 
Scientific Rationale for Study Design 
Patients with gastroparesis arising from either diabetic or idiopathic etiology will be enrolled in 
this study. Both subsets of patients may derive improvement in symptoms from D2 inhibition, 
and thus treatment with metopimazine. Documentation of delayed gastric emptying is required in 
order to confirm the diagnosis of gastroparesis. A minimum severity of symptoms is required in 
order to facilitate demonstration of study drug treatment effect. The 12-week duration of the 
Treatment Period will enable assessment of the durability of response to treatment with 
metopimazine.  
Dose selection for this study is based on the evaluation of a range of estimated target receptor 
(D2) occupancies, phase 1 study results, and the clinical experience with marketed metopimazine 
in France (see Section 4.3). The dose escalation in the 20 mg QID treatment arm is included as 
mitigation against potential OH AEs, and to assess adaptation to alpha-1 receptor inhibition.   
The primary endpoint of this study is the change in nausea severity. This endpoint was chosen 
since nausea is one of the most frequently reported symptoms of gastroparesis, and also has a 
major impact on patient quality of life (FDA 2019). Moreover, nausea is likely to be the most 
sensitive symptom of gastroparesis to facilitate detection of a treatment effect from D2 inhibition. 
A novel PRO tool to assess the signs and symptoms of gastroparesis, the DIGS-DD, is being 
developed and employed in this study since no qualified assessment tools for gastroparesis 
currently exist. The DIGS-DD will assess the impact of NG101 on the symptoms of 
gastroparesis in this study, and results will enable a determination of appropriateness and 
reliability of the DIGS-DD for use in future potentially pivotal studies.   
Rescue medication rules have been designed to balance the need to treat a participant’s 
symptoms and the ability to detect a treatment effect of metopimazine. Stratification factors were 
identified as potentially impacting the clinical course and/or treatment response, and have been 
incorporated into planned analyses. 






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5. 
Study Population 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
Note: "Enrolled" means a participant, or their legally acceptable representative, agreed to 
participate in a clinical study following completion of the informed consent process.  
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
Age 
1. Participant must be ≥ 18 years of age at the time of signing the informed consent. 
Type of Participant and Disease Characteristics 
2. Participant has a diagnosis of diabetic or idiopathic gastroparesis with: 
• Documented evidence of no mechanical obstruction, as determined by a 
gastroenterologist such as by esophagogastroduodenoscopy or upper gastrointestinal 
series, and in the investigator’s opinion there is no current indication of obstruction, 
and 
• Diagnosis and symptoms consistent with gastroparesis (eg, nausea, vomiting, early 
satiety, post-prandial fullness, and abdominal pain) for at least 6 consecutive months 
preceding the Screening Visit, and 
• Delayed gastric emptying of solids during the Screening Period or within 12 months 
prior to the Screening Visit as demonstrated on either the US FDA-approved breath 
test (demonstrating delayed gastric emptying at 4 hours) or scintigraphy 
(demonstrating ≥ 10% residual food remaining at 4 hours).  
Note: There must be a minimum of 7 days between the gastric emptying study and 
the start of the Pretreatment Period, and 
• No known cause other than diabetes (ie, participants with gastroparesis due to other 
causes such as surgery, Parkinson’s disease, post-abdominal irradiation, atrophic 
gastritis, suspected arterial occlusion, Crohn’s disease, Chagas disease, etc., would be 
excluded). 
Note: A minimum of 120 participants with diabetic gastroparesis and a minimum of 
120 participants with idiopathic gastroparesis will be randomized. 
3. Participants using a gastric stimulator must have had stable symptoms for at least 
3 months prior to the Screening Visit following either: 
• Discontinuation of the gastric stimulator, or 
• Initiation of a stable treatment regimen. The participant must agree to maintain the 
same stable treatment regimen for the duration of the clinical study. 


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4. Participant must have all of the following during each week of the Pretreatment Period on 
the DIGS-DD: 
• Sum of the mean severity scores for each of the 4 gastroparesis symptoms ≥ 12. 
(The 4 symptoms are: nausea, early satiety, post-prandial fullness, and abdominal 
pain.) 
• A mean nausea severity score that is ≥ 4 and also greater than the mean severity score 
for abdominal pain.   
• Compliance with eDiary completion, as measured by adequately responding to at 
least 5 of 7 days of eDiary questions for each of the 2 weeks in the Pretreatment 
Period. 
5. Participant is ambulatory (eg, not bed-ridden, nursing home resident, etc.). 
6. Participant agrees to refrain from making any major changes in diet, weight, exercise, or 
other major lifestyle patterns after signing the informed consent form (ICF) and through 
the EoS Visit. 
7. Participant must be able to independently complete PRO assessments without assistance 
from others. 
Sex 
8. Participant is male or female. 
Contraceptive use by women of childbearing potential (WOCBP) should be consistent with 
local regulations regarding the methods of contraception for those participating in clinical 
studies. 
Female participants are eligible if: 
• She is not pregnant (confirmed by negative serum pregnancy test at Screening and a 
negative urine pregnancy test prior to study drug administration on Day 1) or 
breastfeeding, and at least 1 of the following conditions applies: 
o She is not a WOCBP as defined in Appendix 10.6), or 
o She is a WOCBP who agrees to use 1 highly effective method of birth control 
during the study and at least 3 months after the last dose of study drug. A highly 
effective method of birth control is defined as that which results in a low failure 
rate (ie, less than 1% per year) when used consistently and correctly, such as 
implants, injectable or combined oral contraceptives, patches, intrauterine devices 
(IUDs), sexual abstinence or vasectomized partner (or partner who follows the 
specifications outlined below). 
Males participants are eligible if: 
• 
He is of procreative capacity (ie, surgically sterile) or of procreative capacity and agrees 
to use an acceptable method of contraception from randomization through 1 month 
following the last dose of study medication. (Examples of acceptable contraception for 


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males include abstinence, use of a barrier method, or sterilized or post-menopausal 
partner [or partner who follows the specifications outlined above].) 
Informed Consent 
9. Participant is capable of giving signed informed consent.  
10. Participant has signed an ICF before any study-specific procedures are performed. 
5.2. 
Exclusion Criteria  
Participants are excluded from the study if any of the following criteria apply: 
Medical History 
1. Participant has another active disorder that, in the opinion of the investigator, can cause 
abdominal pain or discomfort, nausea, vomiting, fullness, bloating, or other 
gastrointestinal symptoms that may confound the assessment of gastroparesis symptoms. 
2. Participant has been hospitalized within the 2 months prior to the Screening Visit for 
uncontrolled diabetes mellitus, gastroparesis, or associated malnutrition. 
3. Participant has had surgery that meets any of the following criteria: 
• Gastric surgery, including fundoplication, gastric banding, bypass, resection, or 
gastric per-oral endoscopic pyloromyotomy, at any time before the Screening Visit. 
• Surgery of the abdomen, pelvis, or retroperitoneal structures during the 6 months 
before the Screening Visit. 
• An appendectomy or cholecystectomy during the 3 months before the Screening 
Visit. 
• Other major surgery during the 3 months before the Screening Visit. 
4. Participant has evidence of unexplained recurrent dizziness or syncope within 6 months 
prior to the Screening Visit. 
5. Participant has a history of intolerance to phlebotomy, (eg, experiences dizziness or 
syncope). 
6. Female participants with a history of galactorrhea, or unexplained amenorrhea. 
7. Participant has history of or current clinically significant cardiac arrhythmia, including 
ventricular tachycardia, ventricular fibrillation, Torsade des Pointes, bradycardia, sinus 
node dysfunction, heart block, or family history prolonged QT syndrome. Participants 
with minor forms of ectopy (eg, premature atrial contractions) are not necessarily 
excluded. 
8. Significant CV events (eg, myocardial infarction, unstable angina, hospitalization for 
congestive heart failure, cardiac surgery, ischemic or hemorrhagic stroke, or transient 
ischemic attack) within 6 months before the Screening visit. 
9. Participant has a history of cancer, including prolactinoma (resected basal cell or 
squamous cell carcinoma of the skin is acceptable). Note: Participants with a history of 
cancer are eligible provided that the malignancy has been in complete remission 


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(disappearance of all signs of cancer in response to treatment) for at least 5 years before 
the Screening Visit. 
10. Participant has a history of active alcoholism or drug addiction within 12 months prior to 
the Screening Visit.  
11. Participant engages in daily recreational use of marijuana. Note: If participants are 
currently using marijuana or other cannabinoids, concomitant use is allowed if it is 
considered stable over the 4 weeks before Screening. Use must not increase during the 
study. Up to approximately 140 participants can be cannabinoid users (see Section 9.1), 
and of these up to approximately 56 can be marijuana users. 
12. Urine drug screen positive for non-prescribed drugs, except cannabinoids if use is 
reported by the participant. 
13. Participant engages in vaping. 
14. Participant has been hospitalized for a psychiatric condition or has made a suicide 
attempt within 12 months prior to the Screening Visit. 
15. Participant has a history of clinically significant hypersensitivity or allergies to any of the 
excipients contained in the study medication (NG101 or placebo). 
16. Participant has an acute or chronic condition that, in the investigator’s opinion or 
sponsor’s opinion, would limit the participant’s ability to complete or participate in this 
clinical study. 
17. Participant has a body mass index < 18 kg/m2 or > 39 kg/m2. 
Prior / Concomitant Therapy 
18. Participant has had endoscopic pyloric injections of botulinum toxin within the 6 months 
prior to the Screening Visit. 
19. Participant has received and tolerated an adequate course (at least 10 mg administered at 
least 3 times a day for at least 1 month) of treatment with domperidone and showed no 
notable symptomatic improvement in gastroparesis symptoms. 
20. Use prior to Screening (within the previous 14 days or 7 half-lives, whichever is longer) 
or intended use during the study of any prohibited medications (see Appendix 10.2). 
21. Initiation of treatment or change in dose or dose regimen within 3 months prior to the 
Screening Visit for any drug that prolongs QT interval. Note: Concomitant use of drugs 
that prolong QT interval is permitted provided that the participant has been receiving the 
drug for at least 3 months, has a normal QT interval at the Screening Visit, and remains 
on same dose and regimen during the clinical study (see Appendix 10.2). 
22. Use of ondansetron or promethazine as an anti-emetic more than 2 times/day (total daily 
doses should not exceed 16 mg ondansetron or 50 mg promethazine). 
23. Use of anti-emetics (ie, ondansetron or promethazine) within 24 hours prior to the Day 1 
visit. 
24. Participant is receiving parenteral nutrition or using a feeding tube. 
25. Change in use of any alternative treatment (eg, acupuncture, hypnosis) from 2 weeks 
prior to the Screening Visit until the EoS. 


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26. Changes in dose or dose regimen from 30 days prior to the Screening Visit until the EoS 
visit for any chronically administered concomitant medications listed in the permitted 
medications section (see Appendix 10.2). 
Prior / Concurrent Clinical Study Experience 
27. Current enrollment or past participation within the last 30 days before signing of consent 
in any other clinical study involving an investigational study treatment or device or is 
planning to receive another investigational intervention at any time during the study (see 
Appendix 10.2). 
Diagnostic Assessments 
28. Participant has uncontrolled diabetes defined as HgbA1c > 10% at the Screening Visit. 
29. Participant has thyroid stimulating hormone (TSH) below the lower limit of normal, or 
above the upper limit of normal (ULN) if free T4 is below the lower limit of normal. 
30. Male participants with serum testosterone below the lower limit of normal at Screening. 
31. Participant has prolactin levels > 2 x ULN 
32. Participant has QTcF > 450 msec for male participants or QTcF > 470 msec for female 
participants, or QTcF > 480 msec in participants with right bundle branch block 
(participants with left bundle branch block are excluded). 
33. Participant experiences any clinically significant finding on a physical exam, 12-lead 
ECG, or clinical laboratory test after signing the ICF but prior to randomization. The 
investigator will determine if a particular finding is clinically significant. In making this 
determination, the investigator will consider whether the particular finding could prevent 
the participant from performing any of the protocol-specified assessments, could 
represent a condition that would exclude the participant from the study, could represent a 
safety concern if the participant continues in the study, or could confound the 
study-specified assessments of safety or efficacy.  
Note: By definition, a positive drug screen is clinically significant (with the exception of 
marijuana). 
34. Participant has severe postural symptoms and/or absolute systolic BP < 90 mm Hg upon 
standing. Note: these severe symptoms include presyncope, syncope, and other severe 
AEs that are considered of substantial clinical relevance by the investigator (see Table 3 
for additional details and definitions). 
35. Estimated glomerular filtration rate ≤ 45 mL/minute/1.73 m2 (based on the Chronic 
Kidney Disease Epidemiology Collaboration [CKD-EPI] equation; see Appendix 10.7). 
36. Aspartate aminotransferase or alanine aminotransferase > 2 x ULN; alkaline phosphatase 
or bilirubin >1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is 
fractionated and direct bilirubin < 35%). 
Other Exclusions 
37. Donation of blood or blood loss > 400 mL within 90 days prior to the Screening Visit.  


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5.3. 
Lifestyle Considerations 
No restrictions to lifestyle considerations are required for this study. However, as indicated in 
Section 5.1 (inclusion criterion 6), participants must agree to refrain from making any major 
changes in diet, weight, exercise, or other major lifestyle patterns after signing the ICF and 
through the EoS Visit. 
5.3.1. 
Meals and Dietary Restrictions 
Refrain from consumption of Seville oranges, grapefruit or grapefruit juice for a minimum of 
7 days prior to starting study drug until after the final dose. 
The study drug should be taken by participants approximately 30 minutes before a meal 3 times a 
day and 30 minutes before bedtime, with a minimum interval of 4 hours between doses. 
Day 1 and Week 2 Visits: 
For the Day 1 and Week 2 PK assessments, participants who are not in the Intensive PK Subset 
should arrive at the clinic in the morning after fasting (water is allowed) for at least 4 hours, and 
either prior to taking any study drug or within 4 to 6 hours after the first dose of study drug of the 
day. (See also Section 8.7.1.)  
For the Day 1 and Week 2 PK assessments in the Intensive PK Subset, participants should arrive 
at the clinic in the morning after fasting (water is allowed) for at least 8 hours and prior to the 
first dose of study drug of the day. (See also Section 8.7.1.) 
At the Day 1 and Week 2 visits, study drug should be administered in the clinic approximately 
30 minutes before eating. The first dose should be administered with 240 mL of water. No 
additional water is permitted until 30 minutes after dosing, after which time, water is allowed ad 
libitum. 
5.3.2. 
Caffeine, Alcohol, and Tobacco 
The intake of alcohol, caffeine and tobacco should not be increased during the study. 
5.3.3. 
Activity 
No study-specific activity restrictions apply, except to refrain from making any major changes in 
diet, weight, exercise, or other major lifestyle patterns after signing the ICF and through the EoS 
Visit. 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently entered in the study. A minimal set of screen failure information is required to 
ensure transparent reporting of screen failure participants to meet the Consolidated Standards of 
Reporting Trials publishing requirements and to respond to queries from regulatory authorities. 
Minimal information includes demography, reason for screen failure, and any serious adverse 
event (SAE). 


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Participants who do not initially meet study Screening criteria (ie, are screen failures) may be re-
screened (no more than 1 additional Screening) after consultation with and approval by the 
sponsor Medical Monitor or designee. 
5.5. 
Pretreatment Period Failures 
Pretreatment failures are defined as participants who do not meet the prespecified criteria for 
eligibility regarding the Pretreatment Period assessments (see Section 5.1, inclusion criterion 4). 
Participants who are pretreatment failures may be re-screened upon approval from the sponsor 
and/or Medical Monitor or designee. 


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6. 
Study Drug 
Study drug is defined as any investigational intervention(s), marketed product(s), placebo, or 
medical device(s) intended to be administered to a study participant according to the study 
protocol. 
6.1. 
Study Drug(s) Administered 
The study drugs planned for use are described in Table 1 below: 
Table 1: 
Study Drugs 
Arm Name 
NG101 5 mg Arm 
NG101 10 mg Arm 
NG101 20 mg Arm 
Placebo Arm 
Intervention 
Name 
Metopimazine 
mesylate 
Metopimazine 
mesylate 
Metopimazine 
mesylate 
Placebo 
Type  
Drug 
Drug 
Drug 
Placebo 
Dose 
Formulation 
Capsule 
Capsule 
Capsule 
Capsule 
Dosage Level(s) 
NG101 5 mg, QID 
NG101 10 mg, QID NG101 20 mg, QID 
Placebo, QID 
Route of 
Administration 
Oral 
Oral 
Oral 
Oral 
Use 
Experimental 
Experimental 
Experimental 
Placebo 
comparator 
IMP and NIMP IMP  
IMP  
IMP  
NIMP 
Sourcing 
Provided by the 
sponsor  
Provided by the 
sponsor  
Provided by the 
sponsor  
Provided by the 
sponsor  
Packaging and 
Labeling 
NG101 5 mg 
capsules will be 
provided in a 
blister pack 
labeled as required 
per country 
requirement 
NG101 10 mg 
capsules will be 
provided in a 
blister pack labeled 
as required per 
country 
requirement 
NG101 20 mg 
capsules will be 
provided in a blister 
pack labeled as 
required per country 
requirement 
Placebo capsules 
will be provided 
in a blister pack 
labeled as 
required per 
country 
requirement 


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Study drug will be dispensed at each visit during the Treatment Period. Each participant will also 
be dispensed an extra blister pack in case dispensed study drug becomes depleted. Participants 
will be required to return for clinic visits with all dispensed medication (ie, study drug and rescue 
medication) to ensure use is recorded properly. Note that during the following visits, study drug 
will be administered in the clinic: 
• 
Day 1: first dose in the clinic, and second dose of the day in the clinic for those 
participants in the Intense PK subset 
• 
Week 1: a dose in the clinic (ie, not necessarily the first dose of the day) 
• 
Week 2: first dose of the day in the clinic 
• 
Week 12: a dose in the clinic (ie, not necessarily the first dose of the day) 
All study drug capsules will be identical in appearance in order to maintain the blind. 
Participants in the 20 mg treatment arm will be titrated up to the target dose in a blinded fashion. 
Specifically, the 20 mg arm initiation blister pack will contain a 4-day supply of 5 mg QID, and a 
3-day supply of 10 mg QID, after which the blister packs will contain a 7-day supply of 20 mg 
QID. (Note: For participants in the placebo, 5 mg, or 10 mg arms, the blister pack will contain 
only the assigned treatment doses.)  
If a dose is missed, (eg, not taken by at least 1 hour after a meal), then participants should skip 
the missed dose and resume dosing with the next planned dose (30 minutes before the next meal 
or before bedtime).   
6.2. 
Preparation / Handling / Storage / Accountability 
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study drug received and any discrepancies are reported and 
resolved before use of the study drug. 
Only participants enrolled in the study may receive study drug and only authorized site staff may 
supply or administer study drug. All study drug must be stored in a secure, environmentally 
controlled, and monitored (manual or automated) area in accordance with the labeled storage 
conditions with access limited to the investigator and authorized site staff. 
The study drug will be shipped with a temperature monitor and under ambient storage 
conditions. 
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study drug accountability, reconciliation, and record maintenance (ie, receipt, 
reconciliation, and final disposition records). 
Further guidance and information for the final disposition of unused study drug s are provided in 
the Pharmacy Manual. 


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6.3. 
Measures to Minimize Bias: Randomization and Blinding 
Participants eligible to participate in the clinical study will be randomized in a 1:1:1:1 ratio to 
receive either NG101 treatment arms of 5 mg, 10 mg, or 20 mg, or matching placebo. 
Randomization will be stratified on the following factors: gastroparesis etiology (diabetes vs 
idiopathic), sex (male vs female), and cannabinoid use (yes vs no). Determination of diabetes 
etiology will be done according to the medical history data at Screening. 
All participants will be centrally assigned to randomized study drug using interactive response 
technologies (IRT). Before the study is initiated, the log in information and directions for the 
IRT will be provided to each site.  
Study drug will be dispensed at the study visits summarized in the SoA.  
Returned study drug should not be re-dispensed to the participants. 
Blind Break: 
The IRT will be programmed with blind-breaking instructions. In case of an emergency, the 
investigator has the sole responsibility for determining if unblinding of a participants’ 
intervention assignment is warranted. Participant safety must always be the first consideration in 
making such a determination. If the investigator decides that unblinding is warranted, the 
investigator should make every effort to contact the sponsor’s medical monitor or designee prior 
to unblinding a participant’s intervention assignment unless this could delay emergency 
treatment of the participant. If a participant’s intervention assignment is unblinded, the sponsor 
must be notified within 24 hours after breaking the blind. The date and reason that the blind was 
broken must be recorded in the source documentation and case report form (CRF), as applicable. 
6.4. 
Study Compliance 
Compliance with completing study visits and assessments per protocol will be assessed 
throughout the study.  
Compliance with completing daily diaries during the Pretreatment Period and the Treatment 
Period will also be assessed. 
When participants are dosed at the site (Day 1, Week 1 and Week 2), they will receive study 
drug under medical supervision. The date and time of each dose administered in the clinic will be 
recorded in the source documents and recorded in the CRF.  
Compliance with study drug will be assessed at each visit. Compliance will be assessed by 
counting returned capsules during the site visits and documented in the source documents and 
CRF. Deviation(s) from the prescribed dosage regimen should be recorded in the eCRF. A record 
of the number of capsules dispensed to and taken by each participant must be maintained and 
reconciled with study drug and compliance records. Intervention start and stop dates, including 
dates for intervention delays and/or dose reductions will also be recorded in the CRF. 


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6.5. 
Concomitant Therapy 
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins, 
and/or herbal supplements) that the participant is receiving at the time of enrollment or receives 
during the study must be recorded along with: 
• 
Reason for use 
• 
Dates of administration including start and end dates 
• 
Dosage information including dose and frequency 
The Medical Monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
The prohibited medications indicated in Appendix 10.2 are excluded within the previous 14 days 
or 7 half-lives (whichever is longer) before the Screening Visit. 
Participants should be on a stable dose of permitted concomitant medications, as indicated in 
Appendix 10.2, including herbal treatments, for at least 30 days prior to the Screening Visit. 
Participants should intend to maintain their usual medication regimen throughout the study. 
6.5.1. 
Rescue Medicine 
The study site will supply anti-emetic rescue medication that will be provided by the sponsor. 
The following rescue medications may be used: 
• 
Ondansetron (4 mg tablet)  
• 
Promethazine (25 mg tablet)  
The use of rescue medications is allowed up to 2 times daily during the Pretreatment Period and 
the Treatment Period, except on the day prior to (within 24 hours) and the day of clinic visits.  
Participants will be instructed to use rescue medication only during a day when nausea or 
vomiting is intolerable. For participants taking ondansetron, a second 4 mg tablet may be taken 
1 hour after the first dose if there has been insufficient relief of nausea; thus, participants are 
allowed up to 4 tablets (16 mg) per day.  
Participants are required to use only the study-provided rescue medications. Use of rescue 
medication will be captured in the daily diary; compliance with regard to rescue medication will 
be assessed at each study visit and captured in the source documents. As described in 
Section 9.3.4, weekly use of rescue medication will also be assessed as an additional secondary 
endpoint. 


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6.6. 
Dose Modification 
Participants will receive either NG101 5, 10 or 20 mg QID or matching placebo QID for 
12 weeks. Participants in the 20 mg treatment arm will be titrated up to the target dose in a 
blinded fashion. 
Dose modification is not permitted; however, if deemed medically necessary, study medication 
may be temporarily interrupted and restarted after consultation with the Medical Monitor or 
designee. See Section 7.1.1. 
6.7. 
Intervention after the End of the Study 
No extension study is planned. 
Upon completing the Treatment Period or End of Treatment / Early Termination Visit, 
participants should be treated according to the local standard of care. 


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7. 
Discontinuation of Study Drug and Participant 
Discontinuation / Withdrawal 
7.1. 
Discontinuation of Study Drug 
In rare instances, it may be necessary for a participant to permanently discontinue (definitive 
discontinuation) study drug. If study drug is definitively discontinued, the participant will remain 
in the study to be evaluated for follow-up.  
If a clinically significant finding in clinical laboratory or ECG parameters is identified 
(including, but not limited to changes from baseline in QT interval corrected using Fridericia’s 
formula [QTcF] after enrollment), the investigator or qualified designee will determine if the 
participant can continue in the study and if any changes in participant management are needed. 
This review of the ECG printed at the time of collection must be documented. Any new 
clinically relevant finding should be reported as an AE. 
For any female participants, or partners of male participants, who become pregnant during the 
study, see guidance in Appendix 10.6. 
See the SoA for data to be collected at the time of discontinuation of study drug and follow-up, 
and for any further evaluations that need to be completed (Section 1.3). 
Criteria for Withdrawal from Treatment: 
• 
AE(s) which, in the opinion of the investigator or sponsor, make continued treatment in 
the study inappropriate  
• 
AEs consistent with EPS, such as acute dyskinesias and dystonic reactions, tardive 
dyskinesia, Parkinsonism, akinesia, or akathisia. 
• 
Neuroleptic malignant syndrome.  
• 
Worsening of gastroparesis signs and/or symptoms that cannot be adequately controlled 
by the participant’s current treatment regimen (including the protocol-allowed rescue 
treatment), and thus make continued treatment in the study inappropriate.  
• 
Significant non-compliance  
• 
Withdrawal of consent to receive the study treatment  
• 
Orthostatic hypotension (decrease in systolic BP of at least 20 mm Hg) with associated 
severe postural symptoms (including presyncope, syncope, and other severe AEs that 
are considered of substantial clinical relevance by the investigator). See Table 3 for 
additional details and definitions. 
o Participants meeting this discontinuation criterion while under observation during 
clinical visits must be monitored in the clinic until postural symptoms are no longer 
severe, and will be withdrawn from the study. Participants who develop severe 
postural symptoms at home will hold any further dosing and return to the study site 
as soon as possible for further evaluation. 


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7.1.1. 
Temporary Interruption 
Temporary interruption of study drug may occur in cases where necessary. If the study drug must 
be interrupted for longer than 3 days, consult the Medical Monitor about the participant’s 
continuation in the study. If this temporary interruption is due to an AE, this should be indicated 
as an outcome of the AE in the CRF. 
7.1.2. 
Reinitiation 
Reinitiation of study drug after interruptions of at least 3 days should be discussed with the 
Medical Monitor.  
In order to maintain the blind, all participants who have treatment interrupted for at least 3 days 
will reinitiate dosing using a blinded initiation blister pack.  
Since participants in the 20 mg treatment arm will initially titrate up to the targeted dose of 
20 mg, all participants in this arm who temporarily interrupt study drug will reinitiate dosing via 
titration beginning with 5 mg QID. Specifically, the 20 mg arm reinitiation blister pack will 
contain a 4-day supply of 5 mg QID, and a 3-day supply of 10 mg QID. (Note: For participants 
in the placebo, 5 mg, or 10 mg arms, the blister pack will contain only the assigned treatment 
doses.) 
7.2. 
Participant Discontinuation / Withdrawal from the Study 
A participant may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons. This is expected to be uncommon. 
At the time of discontinuing from the study, if possible, an early discontinuation visit should be 
conducted, as shown in the SoA (Section 1.3). The participant will be permanently discontinued 
both from the study drug and from the study at that time. 
If the participant withdraws consent for disclosure of future information, the sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. If a participant 
withdraws from the study, he/she may request destruction of any samples taken and not tested, 
the investigator must document this in the site study records, and the sponsor representative 
should be notified. 
Participants who either complete the Treatment Period or have an Early Discontinuation visit 
should be treated according to the local standard of care. However, if possible, prohibited 
medications should be avoided during the 2-week Follow up Period. 
Criteria for Withdrawal from Study 
• 
Withdrawal of consent to participate in the study 
• 
Lost to follow up (despite attempts to contact the participant) 
• 
Death 


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7.3. 
Lost to Follow up 
A participant will be considered lost to follow-up if he/she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• 
The site must attempt to contact the participant and reschedule the missed visit as soon 
as possible and counsel the participant on the importance of maintaining the assigned 
visit schedule and ascertain whether or not the participant wishes to and/or should 
continue in the study. 
• 
Before a participant is deemed lost to follow up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, 
if necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the participant’s 
medical record. 
• 
Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study.  
Discontinuation of specific sites or of the study as a whole are handled as part of 
Appendix 10.1.9. 


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8. 
Study Assessments and Procedures 
Study procedures and their timing are summarized in the SoA (Section 1.3). Protocol waivers or 
exemptions are not allowed. Adherence to the study design requirements, including those 
specified in the SoA, is essential and required for study conduct. 
All Screening evaluations must be completed and reviewed to confirm that potential participants 
meet all eligibility criteria. The investigator will maintain a screening log to record details of all 
participants screened and to confirm eligibility or record reasons for screening failure, as 
applicable. Procedures conducted as part of the participant’s routine clinical management (eg, 
blood count) and obtained before signing of the ICF may be utilized for screening or baseline 
purposes provided the procedures met the protocol-specified criteria and were performed within 
the time frame defined in the SoA. 
Immediate safety concerns should be discussed with the sponsor immediately upon occurrence or 
awareness to determine if the participant should continue or discontinue study drug. 
When several procedures are scheduled at the same theoretical time and/or visit, in general the 
study assessments should be performed in the following order: 
• 
PRO assessments 
• 
12-lead ECG  
• 
Vital signs 
• 
Blood samples 
8.1. 
Total Volume of Blood 
The maximum amount of blood collected from each participant over the duration of the study, 
including any extra assessments that may be required, will not exceed 224 mL (Table 2). Repeat 
or unscheduled samples may be taken for safety reasons, or for technical issues with the samples. 


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Table 2: 
Total Volume of Blood Required for Each Assay 
Assay 
Number of samples 
Volume per sample 
(mL) 
Total  
volume (mL) 
Males 
Females 
Optional genetic testing 
sample 
1 
5 
5 
5 
Serum pregnancy test 
(females only) 
1 
2 
-- 
2 
HgbA1c 
4 
1 
4 
4 
Thyroid stimulating 
hormone (TSH) 
1 
3 
3 
3 
Serum testosterone  
(males only) 
1 
0.5 
0.5 
-- 
Serum prolactin 
 
 
 
 
All participants 
8 
2 
16 
16 
Intensive PK subset 
14 
2 
28 
28 
Serology 
1 
8 
8 
8 
Hepatitis B surface antigen 
Hepatitis C antibody 
Hepatitis C viral load RNA 
HIV 1 and 2 antibody 
Geenius HIV 1/2 
differentiation 
Hematology 
9 
2 
18 
18 
Serum chemistry 
9 
4 
36 
36 
PK blood sample collection 
Sparse PK  
(all participants) 
8 
6 
48 
48 
Intensive PK Subset 
20 
6 
120 
120 
 
Total Volume - Sparse PK (all participants) 
138.5 
140 
 
Total Volume - Intensive PK Subset 
222.5 
224 


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8.2. 
Gastric Emptying Test 
The Gastric Emptying Breath Test (GEBT), to be used with the GEBT test meal, is intended for 
use in the measurement of the rate of gastric emptying of solids and as an aid in the diagnosis of 
delayed gastric emptying (gastroparesis) in adult humans who are symptomatic for gastroparesis 
(GEBT Summary of Safety and Effectiveness, 2015). The GEBT is a non-radioactive, non-
invasive, orally administered test for measurement of the rate of solid phase gastric emptying in 
adults. The GEBT has been validated against the reference method of gastric scintigraphy. The 
GEBT utilizes the stable isotope carbon-13 (13C). The GEBT measures how fast the stomach 
empties solids after ingestion of a cooked egg test meal, labeled with 13C-Spirulina particles. The 
GEBT may be administered in a primary care facility, clinic or tertiary care setting. 
The GEBT procedure is conducted over a 4-hour period. Following an overnight (or ≥ 8 hour) 
fast, duplicate pre-meal breath samples are collected from the participant (used to establish a 
participant’s baseline 13CO2 level). Following pre-meal breath sample collection, the participant 
is administered the test meal. Single post-meal breath samples are subsequently collected at 45, 
90, 120, 150, 180, and 240 minutes from the end of test meal consumption. Breath samples, 
collected in capped glass tubes before and after test meal administration and are analyzed by gas 
isotope ratio mass spectrometry to determine the ratio of 13CO2/12CO2 in each sample. By 
measuring the change in this ratio over time as compared to the pre-meal value, the rate of 13CO2 
excretion can be calculated and the individual’s gastric emptying rate determined. 
Contraindications 
Individuals with known hypersensitivity to Spirulina, egg, milk or wheat allergens should avoid 
the GEBT (GEBT Summary of Safety and Effectiveness, 2015).  
Because the GEBT is an indirect multi-compartmental method of measuring gastric emptying, 
GEBT results may be inaccurate in individuals compromised with significant small bowel, 
pancreatic, liver and/or lung disease. Consequently, the GEBT should not be administered to 
patients with pulmonary dysfunction (eg, COPD) and/or small bowel malabsorption. 
8.3. 
Efficacy Assessments 
Planned time points for all efficacy assessments are provided in the SoA (Section 1.3). 
8.3.1. 
Diabetic and Idiopathic Gastroparesis Symptoms Daily Diary (DIGS-DD) 
Participants will be required to complete the Diabetic and Idiopathic Gastroparesis Symptoms 
daily diary (DIGS-DD) to record daily symptoms of gastroparesis. The DIGS-DD consists of 
4 questions asking participants to rate their nausea, early satiety, post-prandial fullness, and 
abdominal pain at its worst in the past 24 hours using a 0 to 10-point numeric rating scale. A 
score of 0 indicates no symptoms and a score of 10 indicates the worst possible symptoms. There 
are also questions asking participants to record the number of times they vomited/threw up in the 
past 24-hours, and rate their vomiting severity.  
A summary of the questions included in the DIGS-DD is provided in Appendix 10.4. 


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8.3.1.1. 
Gastroparesis - Additional Daily Assessments 
Additional assessments related to the DIGS-DD will be conducted to fully assess the symptoms 
of gastroparesis. These questions will assess the previous 24 hours in terms of the number of 
hours of nausea, the impact of nausea on the participant’s life, and the number of hours of 
abdominal pain, feeling of fullness, and abdominal bloating. 
8.3.2. 
Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD) 
The American Neurogastroenterology and Motility Society’s Gastroparesis Cardinal Symptom 
Index Daily Diary (GCSI-DD) is designed to assess gastrointestinal symptoms associated with 
idiopathic or diabetic gastroparesis (Revicki et al. 2018; Parkman et al. 2018). The instrument 
asks participants to rate the severity of 4 symptoms: nausea, inability to finish a normal-sized 
meal (ie, early satiety), feeling excessively full after meals (ie, post-prandial fullness), and upper 
abdominal pain. The severity response is rated by the participant as the worst severity of the 
symptom over the previous 24 hours, using a 5-point scale (none, mild, moderate, severe, very 
severe). For vomiting, the number of vomiting episodes (emesis) over the last 24 hours is 
recorded by the participant. In addition, overall severity of gastroparesis is assessed. The overall 
severity of gastroparesis takes into account that other symptoms might impact a participant’s 
condition. 
8.3.3. 
Patient Assessment of Upper Gastrointestinal Disorders -Symptoms 
Questionnaire 
The Patient Assessment of Upper Gastrointestinal Disorders (PAGI)- Symptoms (SYM) 
questionnaire will be assessed during the Treatment Period (with the exception of Week 1) and at 
the Early Discontinuation and End of Study visits. The PAGI-SYM is intended to cover the main 
symptom groupings for the following upper GI disorders: gastroesophageal reflux disease, 
dyspepsia, and gastroparesis, for application in clinical trials and other studies 
(Rentz et al. 2004). 
The PAGI-SYM contains 20 items and 6 subscales covering heartburn/regurgitation (7 items), 
nausea/vomiting (3 items), post-prandial fullness/early satiety (4 items), bloating (2 items), upper 
abdominal pain (2 items), and lower abdominal pain (2 items). A 6-point Likert response scale, 
ranging from 0 (none) to 5 (very severe), is used for rating the severity of each symptom item 
over a 2-week recall period. 
8.3.4. 
Patient Assessment of Upper Gastrointestinal Disorders -Quality of Life 
Questionnaire 
The PAGI- quality of life (QOL) questionnaire will be assessed during the Treatment Period 
(with the exception of Week 1) and at the Early Discontinuation and End of Study visits. The 
PAGI-QOL was designed to comprehensively measure QOL outcomes for patients with upper 
GI disorders (de la Loge et al. 2004). 
The PAGI-QOL consists of 30 items each having a 6-point Likert-type scale and five 
dimensions: Daily Activities (DAC; 10 items related to avoiding or having difficulties in 
performing DAC), Clothing (CLO; 2 items, one related to feeling constricted and 1 to the 
frustration felt about not being able to dress as wanted), Diet and Food Habits (DIE; 7 items 


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related to restrictions made and induced frustration), Relationship (REL; 3 items, describing 
impact of the disease on relationships with partner, relatives and friends), and Psychological 
Well-Being and Distress (PSY; 8 items describing impact of the disease on feelings or emotional 
state). 
8.3.5. 
Nausea Profile  
The nausea profile (NP) will be assessed during the Treatment Period (with the exception of 
Week 1) and at the Early Discontinuation and End of Study visits. The NP is a subjective 
symptom checklist with the goal of obtaining a more in-depth description of what patients are 
experiencing when they report the feeling of nausea (Muth 1996). 
The NP self-reported instrument will be administered to evaluate participants’ nausea over time. 
The NP evaluates 17 descriptors of nausea across 3 subscales (somatic distress, gastrointestinal 
distress, and emotional distress) and overall. Scores for each descriptor range from 0-9, where 
0 indicates that the participants felt the nausea descriptor (eg, shaky) ‘not at all’ and 9 indicates 
that the participants felt the nausea descriptor (eg, shaky) ‘severely’. The NP was validated 
against a Visual Analog Scale measure of nausea (Muth 1996) and has been adapted for use in 
patients with gastroparesis (Jaffe 2011). 
8.3.6. 
Patient Global Impression of Severity Questionnaire 
The Patient Global Impression of Severity (PGI-S) questionnaire will be assessed weekly using a 
5-point Likert rating scale as an anchor-based approach to estimate the severity of the 
participants’ condition. The responses to this participants-completed scale range from 0 = no 
signs and symptoms; to 4 = very severe. 
8.3.7. 
Patient Global Impression of Change Questionnaire 
The Patient Global Impression of Change (PGI-C) questionnaire will be assessed weekly using a 
5-point Likert rating scale as an anchor-based approach to estimate meaningful change in a 
participant’s condition. The responses to this participant-completed scale range from 0 = no signs 
and symptoms; to 4 = very severe. 
8.3.8. 
Treatment Satisfaction Assessment 
Treatment satisfaction will be assessed weekly using a 5-point Likert rating scale to determine 
how satisfied the participant is with the study medication’s ability to relieve symptoms 
(Chey et al. 2014). The responses to this participant-completed scale range from 1 = not at all 
satisfied, to 5 = very satisfied.  
8.3.9. 
Nausea Improvement 
The Nausea Improvement assessment is a 5-category response scale asking whether the 
participant experienced any improvement in nausea symptoms over the course of the study and, 
if so, the level of importance.  
This assessment will be conducted as an End of Study assessment. 


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8.4. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
8.4.1. 
Physical Examinations 
A complete physical exam, including neurologic, cardiovascular, pulmonary, abdominal and 
breast exams, will be performed at Screening, Day 1, and Weeks 4, 8, and 12 as well as at the 
Follow-up Visit. Weight will be measured at all visits. Height (without shoes) will also be 
measured and recorded on Day 1. Investigators should pay special attention to clinical signs 
related to previous serious illnesses. For female participants, menstrual cycle will be recorded 
during the study. 
Only clinically significant changes in physical examination findings will be recorded at 
subsequent visits, as indicated in the SoA (Section 1.3). 
8.4.2. 
Vital Signs 
Vital signs, including oral temperature, pulse rate, respiratory rate, and BP will be measured at 
each study visit while the participant is in the sitting position. A standardized oscillometric 
automated BP device will be used; manual auscultatory assessment will be used only if the BP 
reading cannot be captured by the standardized automated device (eg, based on specific 
physiologic condition, or if the automated device is not functional). Blood pressure and pulse 
measurements should be preceded by at least 5 minutes of rest for the participant in a quiet 
setting without distractions (eg, television, cell phones). Additional information regarding the 
standardized automated office BP assessment will be outlined in the training manual provided by 
the cardiac safety laboratory. 
Orthostatic vital signs will be assessed as follows (and as clinically indicated; see also the SoA in 
Section 1.3).  
• 
At Screening, BP and heart rate will be measured while sitting and after 1 minute in the 
standing position. 
• 
At the Day 1 Visit, BP and heart rate will be measured before dosing and at 1, 2, and 
3 hours after dosing. Measurements will be done while the participant is sitting, as well 
as after 1 minute in the standing position.    
• 
At the Week 1 Visit, BP and heart rate should be measured before dosing and at 1 hour 
after dosing. Measurements will be done while the participant is sitting, as well as after 
1 minute in the standing position. 
• 
At the Week 2 visit, BP and heart rate will be measured before dosing, and at 1, 2, and 
3 hours after dosing. Measurements will be done while the participant is sitting, as well 
as after 1 minute in the standing position.  
For participants in the Intensive PK subset, in addition to the assessments described above, 
orthostatic vital signs will also be assessed at the Day 1 and Week 2 visits at hours 4, 5, and 6, as 
well as 1 and 2 hours after the second dose in the clinic on Day 1. 


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8.4.3. 
Electrocardiograms 
Triplicate 12-lead ECGs will be obtained as outlined in the SoA (see Section 1.3) using an ECG 
machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTcF 
intervals.  
At each time point at which triplicate ECG are required, 3 individual ECG tracings should be 
obtained as closely as possible in succession, but no more than 2 minutes apart. The full set of 
triplicates should be completed in less than 4 minutes. 
Participants must rest in the recumbent position for at least 10 minutes before the ECG recording 
is started. A qualified physician will review the ECGs promptly and any clinically important 
finding will be recorded on the appropriate CRF. The investigator is responsible for reviewing all 
ECGs. All ECGs will also be centrally read. 
8.4.4. 
Clinical Safety Laboratory Assessments 
See Appendix 10.3 for the list of clinical laboratory tests to be performed and the SoA for the 
timing and frequency. 
All clinical laboratory assessments will be conducted by a central laboratory. The use of local 
laboratories is allowed in cases where safety assessment is time sensitive and the central 
laboratory results will not be available before potential actions need to be taken for safety 
reasons. 
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF. The 
laboratory reports must be filed with the source documents. Clinically significant abnormal 
laboratory findings are those which are not associated with the underlying disease, unless judged 
by the investigator to be more severe than expected for the participants condition.  
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study should be repeated until the values return to normal or baseline or are no longer 
considered clinically significant by the investigator or medical monitor 
• 
If such values do not return to normal/baseline within a period of time judged 
reasonable by the investigator, the etiology should be identified, and the sponsor 
notified. 
• 
All protocol-required laboratory assessments, as defined in Appendix 10.3, must be 
conducted in accordance with the laboratory manual and the SoA. 
• 
If laboratory values from non-protocol specified laboratory assessments performed at 
the institution’s local laboratory require a change in participant management or are 
considered clinically significant by the investigator (eg, SAE or AE or dose 
modification), then the results must be recorded in the CRF. 


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8.5. 
Adverse Events and Serious Adverse Events 
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or the 
participant's legally authorized representative). 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up AEs that are serious, considered related to the study drug or study procedures, or that caused 
the participant to discontinue the study drug (see Section 7). 
8.5.1. 
Time Period and Frequency for Collecting AE and SAE Information 
All AEs and SAEs will be collected starting after the ICF is signed until the End of Study / 
Follow-up Visit as specified in the SoA (Section 1.3). 
All SAEs will be recorded and reported to the sponsor or designee immediately and under no 
circumstance should this exceed 24 hours, as indicated in Appendix 10.5.4. The investigator will 
submit any updated SAE data to the sponsor within 24 hours of it being available. 
Investigators are not obligated to actively seek AE or SAE after conclusion of the study 
participation. However, if the investigator learns of any SAE, including a death, at any time after 
a participant has been discharged from the study, and he/she considers the event to be reasonably 
related to the study drug or study participation, the investigator must promptly notify the 
sponsor. 
8.5.2. 
Method of Detecting AEs and SAEs 
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Appendix 10.5. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences. 
8.5.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits / contacts. All AEs considered related to study drug, SAEs, (and AEs of 
special interest, as defined in Section 8.5.7), will be followed until resolution, stabilization, the 
event is otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). 
Further information on follow-up procedures is provided in Appendix 10.5.3. 
8.5.4. 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the investigator to the sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a study 
drug under clinical investigation are met. 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study drug under clinical investigation. The sponsor 
will comply with country-specific regulatory requirements relating to safety reporting to the 


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regulatory authority, Institutional Review Boards (IRB)/Independent Ethics Committees (IEC), 
and investigators. 
For all studies except those utilizing medical devices investigator safety reports must be prepared 
for suspected unexpected serious adverse reactions (SUSAR) according to local regulatory 
requirements and sponsor policy and forwarded by the sponsor (or designee) to investigators as 
necessary. 
An investigator who receives an investigator safety report describing a SAE or other specific 
safety information (eg, summary or listing of SAEs) from the sponsor will review and then file it 
along with the IB and will notify the IRB/IEC, if appropriate according to local requirements. 
8.5.5. 
Pregnancy 
Details of all pregnancies in female participants and female partners of male participants will be 
collected after the start of study drug and the participant will be followed until the outcome of 
the pregnancy is known. 
If a pregnancy is reported, the investigator should inform the sponsor within 24 hours of learning 
of the pregnancy and should follow the procedures outlined in Appendix 10.6. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs. 
8.5.6. 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs 
Worsening of gastroparesis will not be considered an AE since it is captured by PRO efficacy 
assessments. However, the signs, symptoms, and / or clinical sequelae resulting from worsening 
of disease will be reported as an SAE if the definition of an SAE is fulfilled, or if they are 
considered by the investigator not to be adequately captured by the protocol-specified 
disease-related assessments (see Appendix 10.5.1 and Appendix 10.5.2, respectively). 


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8.5.7. Adverse Events of Special Interest  
Treatment-emergent AESIs are based on the known effects of D2 and alpha-1 antagonists, as 
well as observations in the nonclinical and phase 1 studies. The rationale for inclusion of each 
TEAESI is provided in Table 3 below: 
Table 3: 
Adverse Events of Special Interest: Rationale for Inclusion and Criteria for 
Diagnosis 
AESI 
Rationale and Criteria for Diagnosis 
Gynecomastia 
Rationale: Effects of treatment with NG101 in animals were consistent with 
the non-CNS effects seen with other D2 antagonists. These are considered 
secondary to increased prolactin levels resulting from D2 receptor antagonism. 
Criteria for diagnosis: Per the opinion of the treating investigator. 
Galactorrhea 
Menstrual 
irregularity 
Decreased libido 
Impotence 
Extrapyramidal 
symptoms (EPS) 
Rationale: Although metopimazine is not expected to penetrate the CNS, 
AEs from central D2 blockade may include events of EPS. 
Criteria for diagnosis: Extrapyramidal symptoms can include events 
categorized as acute (dystonia, akathisia and parkinsonism) or tardive (tardive 
dyskinesia and tardive dystonia; Pierre 2005). 
Neuroleptic malignant 
syndrome (NMS) 
Rationale: Although metopimazine is not expected to penetrate the CNS, 
AEs from central D2 blockade may include events of NMS. 
Criteria for diagnosis: Neuroleptic malignant syndrome is considered in 
cases with recent dopamine antagonist exposure, or dopamine agonist 
withdrawal. Clinical features include hyperthermia; rigidity; mental status 
alteration; creatine kinase elevation; sympathetic nervous system lability; 
tachycardia plus tachypnea; and a negative work-up for other causes.  
The following are critical values for quantitative criteria (Gurrera et al. 2011): 
hyperthermia, > 100.4°F or > 38.0°C on at least 2 occasions; creatine kinase 
elevation, at least 4 x ULN; blood pressure elevation ≥ 25% above baseline; 
blood pressure fluctuation, ≥ 20 mm Hg (diastolic) or ≥ 25 mm Hg (systolic) 
change within 24 hours; tachycardia, ≥ 25% above baseline; and tachypnea, 
≥ 50% above baseline. 


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Orthostatic 
hypotension (OH) 
Rationale: OH was observed in phase 1 studies, and likely occurs due to 
partial inhibition of α-1 receptors. 
Criteria for diagnosis: OH is defined by a decrease in systolic BP of at least 
20 mm Hg, and/or decrease in diastolic BP of at least 10 mm Hg, with 
associated severe postural symptoms. 
Postural AEs can include feelings of lightheadedness, general weakness, 
warmth, diaphoresis, nausea, palpitations or blurry vision 
(Whitledge et al. 2019). Severe postural symptoms include presyncope, 
syncope, and other severe AEs that are considered of substantial clinical 
relevance by the investigator. Presyncope is defined as “feeling like one was 
going to pass out but without actual loss of consciousness” 
(Whitledge et al. 2019). Syncope is “the sudden loss of consciousness, 
associated with inability to maintain postural tone, with immediate and 
spontaneous recovery without requiring electrical or chemical cardioversion” 
(da Silva 2014). 
Abbreviations: AE = adverse event; AESI = adverse event of special interest; BP = blood pressure; CNS = central 
nervous system; D2 = dopamine receptor; EPS = extrapyramidal symptoms; NMS = neuroleptic malignant 
syndrome; OH = orthostatic hypotension; ULN = upper limit of normal. 
8.6. 
Treatment of Overdose 
For this study, participants are expected to take no more than 4 capsules in 1 day. 
In the event of an overdose, participants should notify the investigator and the investigator 
should: 
1. Contact the Medical Monitor immediately. 
2. Continue to monitor the participant for any AE / SAE and laboratory abnormalities  
3. Document the quantity of the excess dose. 
4. Consider skipping the next dose of NG101. NG101 can be reinitiated, with the timing 
depending on the amount of overdose and considering the half-life of metopimazine 
(approximately 2 hours). Reinitiation should be discussed with the medical monitor. 
Participants should be treated according to the symptoms they are experiencing. If a participant 
has symptoms suggestive of orthostasis, then the participant should sit down or lie down, 
depending on the severity of symptoms. Participants will be trained to recognize the signs and 
symptoms of OH. 
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the participant. 


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8.7. 
Pharmacokinetics 
Pharmacokinetic data collected in this study will be analyzed according to a separate PK 
Analysis Plan and reported separately from the primary study results. 
As noted in Section 8, when several procedures are scheduled at the same theoretical time and/or 
visit, study assessments should be performed in the following order: PRO assessments; 12-lead 
ECG; vital signs; blood samples. 
8.7.1. 
Pharmacokinetic Assessment Methods and Timing  
All participants will participate in PK assessment. A subset of participants who consent will 
participate in intensive PK sampling. The timing of blood sample collections is provided in 
Table 4 below. 
At the Day 1 and Week 2 visits, participants should arrive at the clinic after fasting (see 
Section 5.3.1 for further details). Participants may have water during the fasting period, but no 
food should be consumed. Study drug should be taken 30 minutes before eating, at which point 
240 mL of water should be provided with the dose. No additional water is permitted until 
30 minutes after dosing, after which time, water is allowed ad libitum and a meal will be 
consumed. 


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Table 4: 
Pharmacokinetic Sampling Times 
Study Day 
Sparse PK  
Intensive PK Subset 
PK Sample Timepoint  
(Hours after dose) 
(± Time window) 
PK Sample Timepoint  
(Hours after dose) 
(± Time window) 
Day 1 
Predosea 
Predosea 
 
-- 
0.5 hours (± 5 minutes) 
 
1 hour (± 5 minutes) 
1 hour (± 5 minutes) 
 
-- 
1.5 hours (± 5 minutes) 
 
2 hours (± 10 minutes) 
2 hours (± 10 minutes) 
 
3 hours (± 10 minutes) 
3 hours (± 10 minutes) 
 
-- 
4 hours (± 10 minutes) 
 
-- 
5 hours (± 10 minutes) 
 
-- 
6 hours (± 10 minutes) 
 
-- 
Administer second dose 
 
-- 
1 hour (± 5 minutes) 
 
-- 
2 hours (± 10 minutes) 
Week 2 
Predosea 
Predosea 
 
-- 
0.5 hour (± 5 minutes) 
 
1 hour (± 5 minutes) 
1 hour (± 5 minutes) 
 
-- 
1.5 hours (± 5 minutes) 
 
2 hours (± 10 minutes) 
2 hours (± 10 minutes) 
 
3 hours (± 10 minutes) 
3 hours (± 10 minutes) 
 
-- 
4 hours (± 10 minutes) 
 
-- 
5 hours (± 10 minutes) 
 
-- 
6 hours (± 10 minutes) 
Abbreviations: PK = pharmacokinetic 
a Within 15 to 20 minutes before dosing. 
Note: For the Week 2 assessment in the Sparse PK group, participants should arrive at the clinic in the morning after 
fasting for at least 4 hours, and either prior to taking any study drug or within 4 to 6 hours after the first dose of 
study drug of the day.  
Note: For the Week 2 assessment in the Intensive PK group, participants should arrive at the clinic in the morning 
after fasting for at least 8 hours and prior to the first dose of study drug of the day. 
8.7.1.1. 
Blood Sample Assessment 
Venous blood samples (6 mL) for the determination of plasma concentrations of metopimazine 
and metabolite (metopimazine acid) will be drawn by direct venipuncture or via an IV catheter 
into K2 EDTA Vacutainer® tubes at the times indicated in Table 4. Additional information 
regarding blood collection and sample preparation are provided in the Laboratory Manual.  
Drug concentration information will be masked prior to database lock since these parameters 
have the potential to unblind a participant’s dose group. 


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Sample handling and labelling  
Each aliquot of plasma will be identified as follows:  
• 
Line 1: Study NG101-201  
• 
Line 2: randomization number,  
• 
Line 3: Study Day (ie, Day 1 or Week 2) and time since the first dose administered in 
clinic on that day. 
• 
Line 4: Plasma PK assay, Aliquot number  
Sample Shipment and Storage  
The samples will be shipped in a container filled with enough dry ice to ensure that the samples 
are kept frozen.  
The study samples will be shipped to the Sample Custodian as defined in the Lab Manual.  
Bioanalytical Method  
Plasma concentrations of metopimazine and metopimazine acid will be measured by 
 
. using a fully validated method.  
8.7.1.2. 
Pharmacokinetic Parameters  
Pharmacokinetic data collected in this study may be analyzed according to a separate PK 
Analysis Plan and reported separately from the primary study results. 
8.8. 
Pharmacodynamics 
Inhibition of dopamine receptors is associated with an increase in serum prolactin levels. This is 
because dopamine has an inhibitory effect on the anterior pituitary lactotrophs which secrete 
prolactin. Thus, prolactin levels will be measured in this study (as indicated in Table 5) to 
characterize the pharmacodynamic effects of NG101. Blood samples for serum prolactin 
assessment will be sent to the central laboratory 
. Results of prolactin level measurements 
after the pre-dose assessment on Day 1 will remain blinded until database lock. 
Note that during the following visits, study drug will be administered in the clinic: 
• 
Day 1: first dose in the clinic, and second dose of the day in the clinic for those 
participants in the Intense PK subset 
• 
Week 1: a dose in the clinic (ie, not necessarily the first dose of the day) 
• 
Week 2: first dose of the day in the clinic 
• 
Week 12: a dose in the clinic (ie, not necessarily the first dose of the day) 
 


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Table 5: 
Serum Prolactin Sampling Times 
Study Day 
All Participants  
(± Time window) 
Intensive PK Subset 
(± Time window) 
Screening Visit 
Screening Visit 
Screening Visit 
Day 1 
Predosea 
Predosea 
 
1 hour (± 5 minutes) 
1 hour (± 5 minutes) 
 
-- 
2 hours (± 5 minutes) 
 
-- 
3 hours (± 10 minutes) 
 
-- 
6 hours (± 10 minutes) 
Week 2 Visit 
Predosea 
Predosea 
 
1 hour (± 5 minutes) 
1 hour (± 5 minutes) 
 
-- 
2 hours (± 10 minutes) 
 
-- 
3 hours (± 10 minutes) 
 
-- 
6 hours (± 10 minutes) 
Week 12 or E/D Visit 
Predosea 
Predosea 
 
1 hour (± 5 minutes) 
1 hour (± 5 minutes) 
EoS / Follow-up Visit 
EoS / Follow-up Visit 
EoS / Follow-up Visit 
Abbreviations: E/D = Early discontinuation; EoS = End of study; PK = pharmacokinetic 
a Within 15 to 20 minutes before dosing. 
8.9. 
Genetics 
Genetic research will be conducted in this study. A 5 mL blood sample will be collected for the 
analysis of one or more genes or genetic markers throughout the genome. Genetic analysis is 
noted as optional on the consent form, and participants will have the opportunity to consent or 
opt out without impacting their participation in the study. 
In the event of DNA extraction failure, a replacement genetic blood sample may be requested 
from the participant. 
See Appendix 10.8 for information regarding genetic research. Details on processes for 
collection and shipment and destruction of these samples can be found in the Laboratory Manual. 
8.10. 
Biomarkers 
No additional biomarkers are planned to be evaluated in this study. 
8.11. 
Immunogenicity Assessments 
Immunogenicity will not be evaluated in this study. 


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8.12. 
Healthcare Resource Utilization 
Health economics data associated with medical encounters will be collected in the CRF by the 
investigator and study-site personnel for all participants throughout the study. Protocol-mandated 
procedures, tests, and encounters are excluded. 
The data collected may be used to conduct exploratory economic analyses and will include: 
• 
Number and duration of medical care encounters, including surgeries, and other 
selected procedures (inpatient and outpatient) 
• 
Duration of hospitalization (total days or length of stay, including duration by wards 
[eg, intensive care unit]) 
• 
Number and type of diagnostic and therapeutic tests and procedures 
• 
Outpatient medical encounters and interventions (including physician urgent care clinic 
or emergency room visits, tests and procedures, and medications). 


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9. 
Statistical Considerations 
9.1. 
Sample Size Determination 
A total of approximately 280 participants will be randomized to achieve an estimated 
224 participants completing the 12-week treatment period (and approximately 56 participants per 
treatment arm). At least 120 randomized participants will have diabetic gastroparesis and at least 
120 randomized patients will have idiopathic gastroparesis. Up to approximately 140 participants 
can be cannabinoid users, and of these, approximately 56 can be marijuana users. 
A sample size of 280 participants provides approximately 83% power to detect a mean treatment 
difference in the nausea severity score of 1.0 (on an 11-point scale) between an active dose group 
versus placebo at the 2-sided 0.05 significance level. This is based on a standard deviation of 1.8, 
a 20% drop-out rate, and a 2-sample t-test. 
9.2. 
Populations for Analyses 
The following populations are defined: 
Population 
Description 
Enrolled  
All participants who sign the ICF. 
Intensive PK 
All Enrolled participants who consented to the intensive PK 
sampling. Participants will be analyzed according to the study 
medication they actually received. 
Intent-to-Treat (ITT)  
All Enrolled participants who are randomized. Participants will be 
analyzed according to the study medication to which they were 
randomized. 
Per Protocol (PP) 
All participants in the ITT population who do not have any major 
protocol violations. Participants will be analyzed according to the 
study medication they actually received. 
Safety 
All participants who take at least 1 dose of study drug. Participants 
will be analyzed according to the study drug they actually received. 
9.3. 
Statistical Analyses 
The statistical analysis plan (SAP) will be finalized prior to unblinding and will include a more 
technical and detailed description of the statistical analyses described in this section. This section 
is a summary of the planned statistical analyses of the most important endpoints, including 
primary and key secondary endpoints. 
9.3.1. General considerations 
Continuous variables will be summarized using the number of observations, mean, standard 
deviation (SD) median, minimum, and maximum. Categorical variables will be summarized 
using frequency counts and percentages. 


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9.3.2. 
Efficacy Endpoints 
The following algorithm will be applied to the daily GI assessments in the DIGS-DD and other 
GI assessments to create the baseline and weekly treatment period scores: 
• 
A participant’s baseline score will be the mean of the scores during the 2-week 
Pretreatment Period (ie, each weekly score is the mean of the daily scores)  
• 
For each week in the 12-week Treatment Period, a participant’s score for that week will 
be the mean of the daily scores for that week. 
• 
Change from baseline for a particular week in the Treatment Period is that week’s score 
minus the baseline score. 
• 
If a participant has < 4 non-missing values for a week, the weekly score will be set to 
missing. 
9.3.2.1. 
Primary Efficacy Endpoint 
The primary efficacy endpoint is the change from baseline at Weeks 7 through 12 for the nausea 
severity score on the DIGS-DD (described in Section 8.3.1). 
The primary efficacy endpoint will be analyzed using a mixed-effect model for repeated 
measures (MMRM) on the weekly mean change from baseline scores in the Treatment Period 
(ie, Weeks 1 through 12). The model will have treatment group, baseline nausea score, sex, 
gastroparesis etiology, cannabinoid use, study week, treatment group × study week (interaction 
effect), baseline nausea score × study week (interaction effect), sex × study week (interaction 
effect), and gastroparesis etiology × study week (interaction effect), and cannabinoid use × study 
week (interaction effect) as fixed effects and participant as a random effect. The average value 
across Weeks 7 through 12 will be calculated for each treatment group using the MMRM along 
with the difference between each NG101 group versus the placebo group. 
The primary analysis will be performed on the PP population using an observed-case analysis for 
handling missing data. For each NG101 group versus the placebo group, the average value across 
Weeks 7 through 12 will be tested at the 2-sided 0.05 level.   
Subgroup analyses on the primary endpoint will be performed on the randomization stratification 
factors (sex, gastroparesis etiology, and cannabinoid use) to assess the consistency of treatment 
effect. Additional sensitivity and supportive analyses for the primary endpoint analysis will be 
provided in the SAP. 
The primary analysis will not exclude or censor observations due to rescue medication use. 
Supplemental analyses which exclude observations due to rescue medication use will be detailed 
in the SAP. 


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9.3.3. 
Key Secondary Efficacy Endpoints 
The following are the set of key secondary endpoints. These endpoints are derived from the 
PROs in the DIGS-DD assessment (described in Section 8.3.1). 
• 
Change from baseline at Weeks 7 through 12 in the number of discrete episodes of 
vomiting  
• 
Change from baseline at Weeks 7 through 12 in the early satiety severity score 
• 
Change from baseline at Weeks 7 through 12 in the post-prandial fullness severity score 
• 
Change from baseline at Weeks 7 through 12 in the abdominal pain severity score 
• 
Change from baseline at Weeks 7 through 12 in the total severity score (nausea, early 
satiety, post-prandial fullness, and abdominal pain) 
These endpoints will be analyzed in a manner similar to the primary endpoint (Section 9.3.2.1), 
the difference being that the baseline nausea severity score covariate will be replaced with the 
corresponding baseline value for the endpoint being analyzed. 
9.3.4. 
Additional Secondary Efficacy Endpoints 
Below are the set of additional secondary endpoints. The analysis methods for the additional 
secondary endpoints will be provided in the SAP. 
• 
Change from baseline at Weeks 7 through 12 in the number of hours of nausea per 
24-hour period. This endpoint is derived from the Gastroparesis – Additional Daily 
Assessments described in Section 8.3.1.1. 
• 
Change from baseline at Weeks 7 through 12 in the number of hours of abdominal pain 
per 24-hour period reported. This endpoint is derived from the Gastroparesis – 
Additional Daily Assessments described in Section 8.3.1.1.  
• 
Change from baseline at Weeks 7 through 12 in the vomiting severity score. This 
endpoint is derived from the vomiting PROs in the DIGS-DD assessment (described in 
Section 8.3.1). 
• 
Percent of nausea-free days. The percent of nausea-free days is derived from a score of 
zero on the nausea component of DIGS-DD. 
• 
Change from baseline to Week 12 in PGI-S score. The PGI-S endpoint is derived from 
the PGI-S questionnaire described in Section 8.3.6. 
• 
Change from baseline to Week 12 in PGI-C score. The PGI-C endpoint is derived from 
the PGI-C questionnaire described in Section 8.3.7. 
• 
Change from baseline to Week 12 in the PAGI-SYM. The PAGI-SYM is composed of 
20 items and 6 subscales (see Section 8.3.3). Subscale scores are calculated by 
averaging across items comprising the subscale; scores vary from 0 (none or absent) to 
5 (very severe) (Revicki et al. 2004). The overall PAGI-SYM score is the average of the 
6 subscale scores (Rentz et al. 2004).   
• 
Change from baseline to Week 12 in the PAGI-QOL total score. The PAGI-QOL 
assessments are presented in Section 8.3.4. Each of the 5 PAGI-QOL dimensions are 


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calculated by taking the mean of the items in each subscale after reversing item scores. 
The PAGI-QOL total score is calculated by taking the mean of the corresponding 
subscales (de la Loge et al. 2004). 
• 
Change from baseline to Week 12 in total and subscale scores on the NP. The NP 
assessments are described in Section 8.3.5. The Total NP score is calculated as the 
percent of total points scored. Similarly, the 3 dimensions scores are calculated as the 
percent of total points scored of the assessments associated with that dimension. 
• 
Change from baseline at Week 4 in each of the 5 symptom scores on the DIGS-DD: 
nausea, vomiting, early satiety, post-prandial fullness, and abdominal pain. These 
endpoints are derived from the DIGS-DD assessment (described in Section 8.3.1). 
• 
Change from baseline in gastroparesis symptoms as measured by the Gastroparesis 
Cardinal Symptom Index daily diary (GCSI-DD). The GCSI-DD is described in 
Section 8.3.2. 
• 
Change from baseline to Week 12 in Treatment Satisfaction score. The Treatment 
Satisfaction endpoint is derived from the Treatment Satisfaction questionnaire described 
in Section 8.3.8. 
• 
Weekly use of rescue medication: As described in Section 6.5.1, rescue medication use 
will be captured in the daily diary. 
• 
PK parameters 
• 
Change from baseline in prolactin levels at indicated timepoints. 
9.3.5. 
Exploratory Endpoint(s) 
The following are exploratory endpoints: 
• 
Change from baseline at Weeks 7 through 12 in the feeling of abdominal fullness 
severity score. This endpoint is derived from the Gastroparesis – Additional Daily 
Assessments described in Section 8.3.1.1.  
• 
Change from baseline at Weeks 7 through 12 in the abdominal bloating severity score. 
This endpoint is derived from the Gastroparesis – Additional Daily Assessments 
described in Section 8.3.1.1. 
• 
Level of improvement reported on the Nausea Improvement assessment (see 
Section 8.3.9). 
• 
Association of PK parameters and changes in gastroparesis symptom PRO scores. 
• 
Association of PK parameters and safety assessments. 
• 
Achievement of threshold levels of improvement or worsening in each of the 4 numeric 
rating scale symptom assessments on the DIGS-DD (nausea, vomiting, early satiety, 
post-prandial fullness, and abdominal pain).   
• 
Composite symptom severity scores 
• 
Number of visits to healthcare providers (see Section 8.12). 


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• 
Association of serum glucose levels and HgbA1c with gastroparesis symptom PRO 
scores. 
The analysis methods for the exploratory endpoints will be provided in the SAP. Additional 
exploratory endpoints may also be defined in the SAP and / or the PK Analysis Plan. 
9.3.6. 
Safety Endpoints 
The safety endpoints are the incidence of TEAEs, TEAESIs (eg, dopamine-receptor antagonist 
effects and alpha-1 antagonist effects), and TESAEs; evaluation of clinical safety laboratory 
assessments, vital signs, ECG results, and physical exam findings. 
AEs will be coded using the Medical Dictionary for Regulatory Activities. Incidence rates for 
TEAEs will be summarized overall, by maximum severity, and by relationship to study drug for 
each treatment group. Treatment-emergent AESIs and SAEs will also be summarized by 
treatment group.  
Summary descriptive statistics will be provided for other safety parameters (laboratory tests, 
ECG parameters, and vital signs). 
9.4. 
Interim Analyses  
To assist with designing future studies, an interim analysis of this study may be performed. 
Selected sponsor members will be unblinded at the treatment group level, remaining blinded to 
subject-level treatment assignments. The results of this interim analysis will not be used to 
modify the study design or stop the study early due to positive efficacy results. 
9.5. 
Data Monitoring Committee (DMC) and Data Safety Monitoring 
Board (DSMB) 
A Data Monitoring Committee (DMC) comprised of representatives from the sponsor and CRO 
will review blinded data on an ongoing basis.  
An unblinded independent safety review conducted by a Data Safety Monitoring Board (DSMB) 
will be triggered if any of the following conditions are met: 3 or more participants in the study 
exhibit extrapyramidal symptoms (EPS); 1 or more participants have neuroleptic malignant 
syndrome (NMS); 3 or more participants are discontinued due to orthostatic hypotension-related 
adverse events (AEs); other events considered of high clinical significance by the sponsor are 
observed. The DSMB will then make any recommendations to the sponsor regarding conduct of 
the study. 


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10. 
Supporting Documentation and Operational Considerations 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
• 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
• 
Applicable ICH Good Clinical Practice (GCP) Guidelines 
• 
Applicable laws and regulations 
The protocol, protocol amendments, ICF, Investigator Brochure, and other relevant documents 
(eg, advertisements) must be submitted to an IRB/IEC by the investigator and reviewed and 
approved by the IRB/IEC before the study is initiated. 
Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants. 
The investigator will be responsible for the following: 
• 
Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/IEC 
• 
Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
• 
Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 536/2014 
for clinical studies (if applicable), and all other applicable local regulations 
10.1.2. 
Financial Disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study. 


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10.1.3. 
Informed Consent Process 
The investigator or his/her representative will explain the nature of the study to the participant or 
his/her legally authorized representative and answer all questions regarding the study. 
Participants must be informed that their participation is voluntary. Participants or their legally 
authorized representative will be required to sign a statement of informed consent that meets the 
requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance Portability and 
Accountability Act (HIPAA) requirements, where applicable, and the IRB/IEC or study center. 
The medical record must include a statement that written informed consent was obtained before 
the participant was enrolled in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF. 
Participants must be re-consented to the most current version of the ICF(s) during their 
participation in the study. 
A copy of the ICF(s) must be provided to the participant or the participant’s legally authorized 
representative. 
A participant who is rescreened is not required to sign another ICF if the rescreening occurs 
within 28 days from the previous ICF signature date. 
Participants willing to provide a sample for genetic analysis will sign consent via the ICF. 
10.1.4. 
Data Protection 
Participants will be assigned a unique identifier by the sponsor. Any participant records or 
datasets that are transferred to the sponsor will contain the identifier only; participant names or 
any information which would make the participant identifiable will not be transferred. 
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant who will be required to give consent for their data to be used as 
described in the informed consent  
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
10.1.5. 
Committees Structure 
Data Safety Monitoring Board 
If an independent safety review committee is needed, a Data Safety Monitoring Board (DSMB) 
will be available on an ad hoc basis. The committee will include members who each have 
expertise in at least 1 of the following: neurology, cardiovascular disease, endocrinology, 
gastroenterology and statistics. Additional details are available in the DSMB Charter. 
10.1.6. 
Dissemination of Clinical Study Data 
The sponsor is committed to making study-related data available in accordance with standard 
industry procedures. 


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10.1.7. 
Data Quality Assurance 
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or electronically 
signing the CRF. 
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
The investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents. 
Monitoring details describing strategy, methods, responsibilities and requirements, including 
handling of noncompliance issues and monitoring techniques (central, remote, or on-site 
monitoring) are provided in the Data Monitoring Plan. 
The sponsor or designee is responsible for the data management of this study including quality 
checking of the data. 
The sponsor assumes accountability for actions delegated to other individuals (eg, Contract 
Research Organizations). 
Study monitors / CRAs will perform ongoing source data verification to confirm that data 
entered into the CRF by authorized site personnel are accurate, complete, and verifiable from 
source documents; that the safety and rights of participants are being protected; and that the 
study is being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements. 
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the investigator for 2 years after shipment and delivery of the drug for investigational 
use is discontinued, or as long as required by local regulations, whichever is longer. No records 
may be destroyed during the retention period without the written approval of the sponsor. No 
records may be transferred to another location or party without written notification to the 
sponsor. 
10.1.8. 
Source Documents 
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site. 
Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on the 
study. Also, current medical records must be available. 
The definition of what constitutes source data can be found in the Data Management Plan. 


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10.1.9. 
Study and Site Start and Closure 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
The sponsor designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time upon discussion with the sponsor or 
designee, provided there is reasonable cause and sufficient notice is given in advance of the 
intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to: 
• 
Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the sponsor's procedures, or GCP guidelines 
• 
Inadequate recruitment of participants by the investigator 
• 
Discontinuation of further study drug development 
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up 
10.1.10. 
Publication Policy 
The results of this study may be published or presented at scientific meetings. If this is foreseen, 
the investigator agrees to submit all manuscripts or abstracts to the sponsor before submission. 
This allows the sponsor to protect proprietary information and to provide comments. 
The sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a 
coordinating investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International Committee of 
Medical Journal Editors authorship requirements. 
 
 


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10.2. 
Appendix 2: Prohibited and Permitted Medications 
Prohibited Medications: 
Unless otherwise stated, the following medications are excluded within the previous 14 days or 
7 half-lives (whichever is longer) before the Screening Visit. Note that many of these 
medications have more than one reason for exclusion; in those cases, they are only listed once. 
Chronic use of systemic 
glucocorticoids 
Systemic short course (≤ 7 days), inhaled, and topical administration is 
permitted 
D2 agonists / partial 
agonists/ antagonists 
Agonists: 
• 
Apomorphine, bromocriptine, cabergoline, pramipexole, 
ropinirole. 
Partial Agonists: 
• 
Brexpiprazole, cariprazine. 
Antagonists: 
• 
Metoclopramide, domperidone. 
• 
1st generation antipsychotics (typical antipsychotics also known 
as neuroleptics): 
Phenothiazine drugs: 
Chlorpromazine, fluphenazine, levomepromazine, pericyazine, 
perphenazine, pipotiazine, prochlorperazine, promazine, 
promethazine (except as rescue medication), thiethylperazine, 
thioridazine, trifluoperazine, triflupromazine.  
Non-phenothiazine drugs: 
Benperidol, clopenthixol, clotiapine, droperidol, flupenthixol, 
fluspirilene, haloperidol, loxapine, pimozide, thiothixene, 
zuclopenthixol. 
• 
2nd generation antipsychotics (atypical antipsychotics also 
known as serotonin-dopamine antagonists): aripiprazole, 
asenapine, clozapine, iloperidone, lurasidone, olanzapine, 
olanzapine / fluoxetine, paliperidone, quetiapine, risperidone, 
ziprasidone. 
Drugs associated with 
NMS 
Carbamazepine, mibefradil 
Drugs associated with 
orthostatic hypotension 
• 
Antihypertensive agents with alpha-1 adrenergic antagonist 
activity (eg, terazosin prazosin, doxazosin); agents with 
preferential selectivity for alpha-1a receptors in the prostate are 
allowed if blood pressure change upon standing at the Screening 
Visit is ≤ 10 mm Hg.) 
• 
Others: bretylium, dronabinol, tizanidine. 
Acetylcholinesterase 
inhibitors 
Donepezil, galantamine, neostigmine, pyridostigmine, rivastigmine. 


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Drugs affecting gastric 
motility 
• 
Drugs with known pharmacological activity at 5-
hydroxytryptophan (HT)1, 5-HT3, or 5 HT4 receptors (eg, 
ondansetron [except as rescue medication] cisapride, mosapride, 
prucalopride, tegaserod, tropisetron, granisetron, dolasetron, 
naratriptan, sumatriptan, and zolmitriptan). Note: buspirone and 
mirtazapine are permitted provided that the participant has been 
on a stable dose for at least 3 months prior to the Screening 
Period and can remain on the same stable dose for the duration of 
the study. 
• 
Anti-cholinergic and anti-muscarinic agents (eg, benztropine 
mesylate, biperiden, clomipramine, darifenacin, dicyclomine, 
flavoxate, hyoscyamine, oxybutynin, propantheline, scopolamine, 
solifenacin, tolterodine, trihexyphenidyl, and trospium). Note: 
inhaled ipratropium and tiotropium are permitted. 
• 
GLP-1 receptor agonists (eg Dulaglutide, Lixisenatide) 
• 
Pramlintide 
• 
Acarbose 
• 
All narcotics either alone or in combination (eg, codeine, 
diphenoxylate, morphine, paregoric, and propoxyphene). Notes: 
narcotics used as anesthesia for an esophagogastroduodenoscopy 
require a 5-calendar-day wash-out prior to the participant 
entering the Pretreatment Period. Loperamide may be used as 
needed (prn) for diarrhea. Occasional use (up to 2 times per 
week) of tramadol is permitted for pain.  
• 
Macrolide antibiotics (eg, azithromycin, clarithromycin, 
erythromycin, spiramycin, telithromycin, troleandomycin). 
• 
Any fundic-relaxing agents not otherwise excluded such as, but 
not limited to, clonidine, nitrates, and triptan containing 
medications. Note: intermittent use (no more than once a week) 
of triptan-containing medications is permitted to treat migraine 
headache.  
• 
Other medicines which may affect gastric emptying (eg, 
colchicine and misoprostol). Note: linaclotide and lubiprostone 
may be used to treat concurrent constipation. 
Clinical P-glycoprotein 
inhibitors 
Amiodarone, carvedilol, dronedarone, itraconazole, lapatinib, lopinavir, 
propafenone, quinidine, ranolazine, ritonavir, saquinavir, tamoxifen, 
telaprevir, tipranavir, verapamil. 
Any investigational or 
imported drugs that have 
not been approved for 
human use by the FDA 
 
 


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Permitted Medications 
Participants should be on a stable dose of allowed concomitant medications, including herbal 
treatments and probiotics, for at least 30 days prior to the Screening Visit and should intend to 
maintain their usual medication regimen throughout the study. Insulin and other medications for 
glucose control can be adjusted as needed. 
The following concomitant medications are permitted during the study: 
Cannabinoids 
Cannabinoid (eg, marijuana, CBD) use provided that use is stable over the 
previous 4 weeks. Recreational use of marijuana and other THC containing 
cannabinoids must not be daily. Use must not be expected to increase during the 
study. 
D2 antagonists / H1 
antagonists 
Promethazine (25 mg) up to 2 times / day as an anti-emetic rescue medication 
5HT3 receptor 
antagonist 
Ondansetron (4 mg) up to 2 times / day as an anti-emetic rescue medication.  
A 4 mg dose of ondansetron may be repeated after 60 minutes if relief is 
insufficient. 
Alpha1 receptor 
antagonists 
Prostate specific inhibitors of alpha - receptors (eg, tamsulosin) if at Screening 
the systolic BP decreases ≤ 10 mm Hg upon standing for 1 minute. 
Glucocorticoids 
Systemic short course (≤ 7 days), inhaled, and topical administration of 
glucocorticoids. 
Drugs affecting 
gastric motility 
• 
Buspirone and mirtazapine (provided that the participant has been on a 
stable dose for at least 3 months prior to the Screening Period and can 
remain on the same stable dose for the duration of the study). 
• 
Inhaled ipratropium and tiotropium. 
• 
Loperamide, as needed (prn), for diarrhea. 
• 
Tramadol (up to 2 times per week) for pain. 
• 
Triptan-containing medications (no more than once a week) for 
migraine headache. 
• 
Linaclotide, plenacatide, Miralax, Magnesium based laxatives, 
bisacodyl and senna for concurrent constipation. 




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Other Screening 
Tests 
• 
Highly sensitive serum and urine human chorionic gonadotropin (hCG) 
pregnancy test (as needed for women of childbearing potential)b 
• 
Serum testosterone test (for male participants only) 
• 
Serology (HIV antibody, hepatitis B surface antigen [HBsAg], and hepatitis C 
virus antibody)  
• 
Urine drug test (eg, amphetamines, barbiturates, benzodiazepines, cannabinoids, 
cocaine, methadone, opiates, phencyclidine). The results of each test must be 
entered into the CRF. 
NOTES: 
a If TSH is above ULN at Screening then free T4 will be checked. 
b  Local urine testing will be standard for the protocol unless serum testing is required by local regulation or 
IRB/IEC. 
All events of ALT ≥ 3 × upper limit of normal (ULN) and bilirubin ≥ 2 × ULN (> 35% direct bilirubin) or ALT 
≥ 3 × ULN which may indicate severe liver injury (possible Hy’s Law), must be reported as an SAE (excluding 
studies of hepatic impairment or cirrhosis). 
Investigators must document their review of each laboratory safety report, with designation for 
clinically significant (CS) / not clinically significant (NCS) for out of range results. 
Laboratory / analyte results that could unblind the study (eg, prolactin test results) will not be 
reported to investigative sites or other blinded personnel until the study has been unblinded or for 
safety issues. 
 
 
















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10.6. 
Appendix 6: Contraceptive Guidance and Collection of Pregnancy 
Information 
Definitions: 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile (see below). 
 
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study drug, additional evaluation should be considered. 
Women in the following categories are not considered WOCBP: 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
• Documented hysterectomy 
• Documented bilateral salpingectomy 
• Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (eg, mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study entry. 
Note: Documentation can come from the site personnel’s: review of the participant’s medical 
records, medical examination, or medical history interview. 
3. Postmenopausal female 
• A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
o A high follicle stimulating hormone (FSH) level in the postmenopausal range may be 
used to confirm a postmenopausal state in women not using hormonal contraception 
or hormonal replacement therapy (HRT). However, in the absence of 12 months of 
amenorrhea, confirmation with more than one FSH measurement is required.  
• Females on HRT and whose menopausal status is in doubt will be required to use one of 
the non-estrogen hormonal highly effective contraception methods if they wish to 
continue their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 


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Contraception Guidance: 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
Highly Effective Methodsb That Have Low User Dependency  
• 
Implantable progestogen-only hormone contraception associated with inhibition of ovulationc 
• 
Intrauterine device  
• 
Intrauterine hormone-releasing system (IUS)c 
• 
Bilateral tubal occlusion 
• 
Vasectomized partner 
• 
(Vasectomized partner is a highly effective contraceptive method provided that the partner is the sole sexual 
partner of the woman of childbearing potential and the absence of sperm has been confirmed. If not, an 
additional highly effective method of contraception should be used. Spermatogenesis cycle is approximately 
90 days.) 
Highly Effective Methodsb That Are User Dependent  
• 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of 
ovulationc 
o 
oral 
o 
intravaginal 
o 
transdermal 
o 
injectable 
• 
Progestogen-only hormone contraception associated with inhibition of ovulationc 
o 
oral 
o 
injectable 
• 
Sexual abstinence 
(Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of risk associated with the study drug. The reliability of sexual abstinence 
needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the 
participant.) 
a) Contraceptive use by men or women should be consistent with local regulations regarding the use of 
contraceptive methods for those participating in clinical studies. 
b) Failure rate of <1% per year when used consistently and correctly. Typical use failure rates differ from those 
when used consistently and correctly. 
c.) If locally required, in accordance with Clinical Trial Facilitation Group (CTFG) guidelines, acceptable 
contraceptive methods are limited to those which inhibit ovulation as the primary mode of action. 
Note: Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhoea method (LAM) are not acceptable methods of contraception 
for this study. Male condom and female condom should not be used together (due to risk of failure with 
friction) 
 


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Collection of Pregnancy Information 
Male participants with partners who become pregnant 
• The investigator will attempt to collect pregnancy information on any male participant’s 
female partner who becomes pregnant while the male participant is in this study. This 
applies only to male participants who receive NG101. 
• After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the investigator will record pregnancy information on the appropriate form and 
submit it to the sponsor within 24 hours of learning of the partner’s pregnancy. The 
female partner will also be followed to determine the outcome of the pregnancy. 
Information on the status of the mother and child will be forwarded to the sponsor. 
Generally, the follow-up will be no longer than 6 to 8 weeks following the estimated 
delivery date. Any termination of the pregnancy will be reported regardless of fetal status 
(presence or absence of anomalies) or indication for the procedure.  
Female Participants who become pregnant 
• 
The investigator will collect pregnancy information on any female participant who 
becomes pregnant while participating in this study. The initial information will be 
recorded on the appropriate form and submitted to the sponsor within 24 hours of 
learning of a participant's pregnancy.  
• 
The participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on the participant and the neonate and the 
information will be forwarded to the sponsor. Generally, follow-up will not be required 
for longer than 6 to 8 weeks beyond the estimated delivery date. Any termination of 
pregnancy will be reported, regardless of fetal status (presence or absence of anomalies) 
or indication for the procedure. 
• 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be reported 
as an AE or SAE.  
• 
A spontaneous abortion (occurring at < 22 weeks gestational age) or still birth (occurring 
at > 22 weeks gestational age) is always considered to be an SAE and will be reported as 
such.  
• 
Any post-study pregnancy related SAE considered reasonably related to the study drug 
by the investigator will be reported to the sponsor as described in Section 8.5.4. While the 
investigator is not obligated to actively seek this information in former study participants, 
he or she may learn of an SAE through spontaneous reporting. 
• 
Any female participant who becomes pregnant while participating in the study will 
discontinue study drug or be withdrawn from the study. 
 
 


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10.7. 
Appendix 7: Estimated Glomerular Filtration Rate 
The Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation should be used 
to calculate estimated glomerular filtration rate (eGFR). The CKD-EPI equation is: 
eGFR = 141 × min(Scr/κ, 1)α × max(Scr/κ, 1)-1.209 × 0.993Age × 1.018 [if 
female] × 1.159 [if black] 
Where: 
Scr = serum creatinine in mg/dL 
κ = 0.7 if female 
κ = 0.9 if male 
α = -0.329 if female 
α = -0.411 if male 
min indicates the minimum of Scr/κ or 1 
max indicates the maximum of Scr/κ or 1 
 
 


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10.8. 
Appendix 8: Genetics 
Use/Analysis of DNA 
• 
Genetic variation may impact a participant’s response to study drug, susceptibility to, 
and severity and progression of disease. Variable response to study drug may be due to 
genetic determinants that impact drug absorption, distribution, metabolism, and 
excretion; mechanism of action of the drug; disease etiology; and/or molecular subtype 
of the disease being treated. Therefore, where local regulations and IRB/IEC allow, a 
blood sample will be collected for DNA analysis from consenting participants. 
• 
DNA samples will be used for research related to NG101 or gastroparesis and related 
diseases. They may also be used to develop tests/assays including diagnostic tests 
related to NG101 and gastroparesis. Genetic research may consist of the analysis of one 
or more candidate genes or the analysis of genetic markers throughout the genome (as 
appropriate). 
• 
DNA samples will be analyzed genetic variations associated with clinical responses. 
Additional analyses may be conducted if it is hypothesized that this may help further 
understand the clinical data. 
• 
The results of genetic analyses may be reported in the clinical study report (CSR) or in a 
separate study summary. 
• 
The sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality. 
• 
The samples will be retained while research on NG101 or gastroparesis continues but 
no longer than 10 years or other period as per local requirements. 
 
 
 


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10.9. 
Appendix 9: Abbreviations 
Abbreviation 
Definition 
AE 
Adverse event 
AUC 
Area under the plasma concentration-time curve 
AUC0-inf 
Area under the plasma concentration-time curve from time 0 extrapolated to infinity 
BP 
Blood pressure 
CI 
Confidence interval 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration 
Cl/F 
Total clearance 
Cmax 
Maximum plasma concentration 
CNS 
Central nervous system 
CRF 
Case report form 
CV 
Cardiovascular 
DIGS-DD 
Diabetic and Idiopathic Gastroparesis Symptoms Daily Diary 
DMC 
Data Monitoring Committee 
DSMB 
Data Safety Monitoring Board 
ECG 
Electrocardiogram 
E/D 
Early discontinuation 
eGFR 
Estimated glomerular filtration rate 
EoS 
End of study 
EPS 
Extrapyramidal symptoms 
FDA 
Food and Drug Administration 
GEBT 
Gastric emptying breath test 
GCSI-DD 
Gastroparesis Cardinal Symptom Index Daily Diary 
GI 
Gastrointestinal 
hERG 
human Ether-à-go-go-related gene 
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonisation 
ICF 
Informed consent form 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
IRT 
Interactive response technologies 
ITT 
Intent-to-treat 


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IV 
Intravenous 
MAD 
Multiple ascending dose 
MMRM 
Mixed-effect model for repeated measures 
NMS 
Neuroleptic malignant syndrome 
NP 
Nausea Profile 
OH 
Orthostatic hypotension 
PAGI-QOL 
Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life  
PAGI-SYM 
Patient Assessment of Upper Gastrointestinal Disorders-Symptoms 
PD 
Pharmacodynamic 
PK 
Pharmacokinetic 
PGI-C 
Patient Global Impression of Change 
PGI-S 
Patient Global Impression of Severity 
PO 
Orally 
PRO 
Patient reported outcomes 
QID 
4 times daily 
Q6H 
Every 6 hours 
QOL 
Quality of life 
QTcF 
QT interval corrected using Fridericia’s formula 
SAD 
Single ascending dose 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SoA 
Schedule of Activities 
Study drug 
NG101 
t1/2 
Terminal half-life 
Tlast 
Time of the last measurable concentration 
Tmax 
Time of maximum plasma concentration 
TEAE 
Treatment-emergent adverse event 
TEAESI 
Treatment-emergent adverse event of special interest 
TESAE 
Treatment-emergent serious adverse event 
THC 
Tetrahydrocannabinol 
TSH 
Thyroid stimulating hormone 
WOCBP 
Women of child bearing potential 
ULN 
Upper limit of normal 
US 
United States  


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11. 
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INVESTIGATOR’S STATEMENT 
 
 
I agree to conduct the trial in accordance with the protocol and with all applicable government 
regulations and good clinical practice guidance. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Investigator’s Signature  
 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
Investigator’s Name