A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Pharmacodynamic Effects of GLY-200 in Type 2 Diabetic Patients
Phase: PHASE2
Conditions: Type 2 Diabetes
Sponsor: Glyscend, Inc.

A Phase 2 Randomized, Double-Blind, Placebo-Controlled
Study to Evaluate the Safety, Tolerability, and
Pharmacodynamic Effects of GLY-200 in Type 2 Diabetic
Patients
Study Number: GLY-200-02 
Sponsor: Glyscend, Inc.
Version Number: Amendment 02 Version 01 
Date: 06 October 2022 
Supersedes:
The information contained in this document is the property of Glyscend, Inc. and may not be 
reproduced, published or disclosed to others without written authorization from Glyscend, Inc. 
The information in this document contains trade secrets and commercial information that are 
privileged or confidential and may not be disclosed unless such disclosure is required by 
applicable law or regulations. In any event, persons to whom the information is disclosed must 
be informed that the information is privileged or confidential and may not be further disclosed by 
them. These restrictions on disclosure will apply equally to all future information supplied to 
you, which is indicated as privileged or confidential.
Amendment 01 Version 01
Dated: 19 July 2022 
Version 1.0
Dated: 02 June 2022

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6.3
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING.................................29
6.4
STUDY INTERVENTION COMPLIANCE...........................................................................29
6.5
DOSE MODIFICATION/ADJUSTMENTS/DELAYS.............................................................29
6.6
CONTINUED ACCESS TO STUDY INTERVENTION AFTER THE END OF THE STUDY ...........29
6.7
TREATMENT OF OVERDOSE.........................................................................................29
6.8
CONCOMITANT THERAPY............................................................................................30
Prohibited Medications, Treatments, and Procedures .............................................30
Rescue Medicine....................................................................................................31
7.
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...............................................................................31
7.1
DISCONTINUATION OF STUDY INTERVENTION..............................................................31
7.2
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY..............................31
Reasons for Discontinuation/Withdrawal ...............................................................31
Handling of Participant Discontinuation/Withdrawal .............................................31
7.3
LOST TO FOLLOW-UP..................................................................................................32
8.
STUDY ASSESSMENTS AND PROCEDURES............................................................32
8.1
EFFICACY ASSESSMENTS ............................................................................................32
8.2
SAFETY ASSESSMENTS................................................................................................32
Medical History .....................................................................................................33
Height and Weight.................................................................................................33
Physical Examination.............................................................................................33
Abdominal Examination ........................................................................................33
Vital Signs.............................................................................................................33
Electrocardiograms................................................................................................33
Clinical Laboratory Evaluations.............................................................................34
Pregnancy Test ......................................................................................................35
Other Laboratory Tests ..........................................................................................35
Fluid Balance.........................................................................................................35
Documentation of Food Intake...............................................................................35
Food Intake and Appetite Assessments ..................................................................35
Mixed Meal Tolerance Test ...................................................................................35
8.3
ADVERSE EVENTS, SERIOUS ADVERSE EVENTS, AND OTHER SAFETY REPORTING ........36
Time Period and Frequency for Collecting AE and SAE Information.....................36
Method of Detecting AEs and SAEs ......................................................................36
Follow-up of AEs and SAEs ..................................................................................36
Regulatory Reporting Requirements for SAEs .......................................................37
Pregnancy..............................................................................................................37
Disease-related Events and/or Disease-related Outcomes not Qualifying as AEs or 
SAEs
..............................................................................................................................37
Adverse Events of Special Interest.........................................................................37
8.4
EXPLORATORY PHARMACODYNAMICS AND PHARMACOKINETICS.................................37
Continuous Glucose Monitoring ............................................................................38
9.
STATISTICAL CONSIDERATIONS............................................................................38

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9.1
STATISTICAL HYPOTHESES..........................................................................................38
9.2
SAMPLE SIZE DETERMINATION ...................................................................................38
9.3
ANALYSIS SETS...........................................................................................................38
9.4
STATISTICAL ANALYSES.............................................................................................39
General Considerations..........................................................................................39
Analysis of Primary Safety and Tolerability Endpoints ..........................................39
Analysis of Secondary and Exploratory Pharmacodynamic Endpoints ...................39
Baseline Descriptive Statistics ...............................................................................39
9.5
INTERIM ANALYSES....................................................................................................40
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .41
10.1
APPENDIX 1: REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS........41
Regulatory and Ethical Considerations...................................................................41
Informed Consent Process......................................................................................41
Data Protection ......................................................................................................42
Committees Structure.............................................................................................42
Safety Oversight ....................................................................................................42
Dissemination of Clinical Study Data.....................................................................42
Data Quality Assurance .........................................................................................42
Source Documents.................................................................................................43
Study Records Retention........................................................................................43
Quality Assurance and Quality Control..................................................................44
Protocol Deviations................................................................................................44
Premature Termination or Study Suspension..........................................................44
Publication Policy..................................................................................................44
Future Use of Stored Specimens and Data..............................................................45
10.2
APPENDIX 2: AES AND SAES: DEFINITIONS AND PROCEDURES FOR RECORDING,
EVALUATING, FOLLOW-UP, AND REPORTING...........................................................................46
Definition of AE....................................................................................................46
Definition of SAE..................................................................................................47
Definition of Unanticipated Problems (UP)............................................................48
Recording and Follow-Up of AE and/or SAE.........................................................48
Reporting of SAEs.................................................................................................49
Reporting of UPs ...................................................................................................50
10.3
APPENDIX 3: CONTRACEPTIVE AND BARRIER GUIDANCE .............................................51
10.4
APPENDIX 4: CLINICAL LABORATORY ASSESSMENTS...................................................52
10.5
APPENDIX 5: ABBREVIATIONS.....................................................................................54
11. LITERATURE REFERENCES......................................................................................57
12. AMENDMENTS..............................................................................................................58

 
 
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Inclusion/ 
Exclusion  
Criteria:  
  
Criteria for inclusion:   
1. Patients diagnosed with type 2 diabetes: 
a. treated with a stable dose of metformin 750 mg/day for at least 3 
months prior to screening 
b. willing to come off current metformin treatment during washout 
and treatment period 
c. HbA1c  6.0 and  8.5% at screening 
d. completed at least 12 days of metformin washout without meeting 
rescue criteria prior to dosing  
2. 0DOH RU IHPDOH  30 DQG   \HDUV ROG DW WKH WLPH RI VFUHHQLQJ 
3. BMI  18 and  40 at screening 
4. Capable of consent, and written informed consent signed prior to entry 
into the study 
5. Willing to consume standard meals provided by the study center 
6. Able and willing to attend the necessary visits to the study center 
7. Willing to stop antacid use at screening 
8. Male subjects with female partners of childbearing potential must comply 
with the contraception requirements as described in Appendix 3 from the 
time of first dose of study medication until 90 days after the last dose of 
study medication (i.e., one sperm cycle) 
9. Female subjects must comply with contraception requirements as 
described in Appendix 3 from the screening period through the end of 
study or be of non-childbearing potential, defined as meeting at least one 
of the following criteria: 
a. Achieved postmenopausal status, defined as: cessation of regular 
menses for at least 12 consecutive months with no alternative 
pathological or physiological cause; and have a serum follicular 
stimulating hormone (FSH) level within the laboratory’s reference 
range for postmenopausal women 
b. Have undergone a documented hysterectomy and/or bilateral 
oophorectomy 
c. Have medically confirmed ovarian failure 
All other female subjects (including women with tubal ligations and 
women who do NOT have a documented hysterectomy, bilateral 
oophorectomy and/or ovarian failure) will be considered to be of 
childbearing potential.  
PLEASE NOTE: ORAL CONTRACEPTION IS NOT ALLOWED (and is 
exclusionary) IN THIS STUDY AS THE STUDY DRUG (GLY-200) MAY 
REDUCE THE EFFECTIVENESS OF ORAL CONTRACEPTION DUE TO 
POTENTIAL DISRUPTION ON GI ABSORPTION. 
10. Fully vaccinated against COVID-19 based on the recommendations of the 

 
 
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region at least 14 days prior to dosing 
 
Criteria for exclusion:   
1. Women who are pregnant (as confirmed by a serum or urine human 
chorionic gonadotrophin [hCG] test) or lactating 
2. Women of childbearing potential who are using oral contraception  
3. Vegetarian or vegan 
4. Treated with any prescription medication for the treatment of type 2 
diabetes or weight loss other than metformin in the last 3 months prior to 
screening 
5. Use of any drug treatment that affects gastric pH (prescription or over-the 
counter), such as H2-receptor antagonists and proton pump inhibitors for 
3 months prior to screening (e.g., famotidine, ranitidine, esomeprazole, 
dexlansoprazole, omeprazole, pantoprazole)  
6. Use of any drug treatment that affects gastrointestinal motility including 
but not limited to cholinergic agonists and antagonists, prokinetic agents, 
opioid antagonists, antidiarrheals, and antibiotics in the last 3 months 
prior to screening (e.g., cevimeline, pilocarpine, loperamide, 
erythromycin, metoclopramide, domperidone, cisapride, mosapride, 
sincalide) 
7. Any chronic condition that requires oral drug treatment that would violate 
concomitant medication use restrictions described in Section 6.8 (i.e., all 
orally administered concomitant medications must be administered at 
least 2 hours before and 4 hours after GLY-200 dosing), TID (three times 
a day) drugs, or drugs with very narrow therapeutic windows (e.g., 
warfarin) 
8. Fasting blood glucose > 190 mg/dL at screening 
9. Diagnosis or treatment of any clinically symptomatic biochemical or 
structural abnormality of the GI tract or active disease within 12 months 
prior to screening; including but not limited to inflammatory bowel 
disease (IBD), irritable bowel syndrome (IBS), gastroesophageal reflux 
disease (GERD), GI cancer, diverticulitis, duodenal ulcer, erosive 
esophagitis, gastric ulcer, pancreatitis, symptomatic gallbladder disease, 
ileus, intestinal/pyloric stenosis/obstruction, fistula, malabsorption, 
esophageal anatomic abnormalities, or other severe GI disease, 
particularly those that may impact digestion, nutrient absorption, 
intestinal motility, and/or gastric emptying 
10. History of any previous abdominal or intestinal surgery including 
endoscopic, open or laparoscopic thoracic or abdominal surgery, surgical 
resection of the stomach, small or large intestine (excluding 
appendectomy, cholecystectomy, or resection of benign polyps), or of any 

 
 
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other risk of abdominal adhesions or obstruction. Appendectomy  
months prior to screening is allowed. 
11. Clinically significant symptoms (as determined by the Investigator) of 
nausea, vomiting, bloating, diarrhea, flatulence, constipation, or 
abdominal pain in the last 30 days prior to screening 
12. Use of systemic corticosteroids by oral, intravenous, or intramuscular 
route; or potent, inhaled, or intrapulmonary steroids known to have a high 
rate of systemic absorption within 3 months of screening 
13. Clinically significant medical condition as judged by the Investigator that 
could potentially affect study participation and/or personal well-being, 
including but not limited to the following conditions: 
a. Uncontrolled hypertension 
b. Uncontrolled hyperlipidaemia 
c. Hepatic disease 
d. Renal disease (eGFR value of <60 mL/min/1.73 m2) based on the 
Modification of Diet in Renal Disease equation. 
e. Endocrine disorder other than diabetes 
f. Cardiovascular event in the last 12 months 
g. Central nervous system diseases 
h. Organ transplantation 
i. Chronic or acute infection 
j. Orthostatic hypotension, fainting spells, or blackouts 
14. Any evidence of or treatment of malignancy (other than localized basal 
cell, squamous cell skin cancer, non-aggressive prostate cancer, or cancer 
in situ that has been resected) within the previous year 
15. Clinically significant electrocardiogram (ECG) abnormalities or vital sign 
abnormalities as determined by the Investigator 
16. Clinical laboratory test (clinical chemistry, hematology, coagulation 
parameters, or urinalysis) abnormality, other than that related to T2D, 
judged by the Investigator to be clinically significant 
17. Alanine aminotransferase or aspartate aminotransferase result >2.5 × 
upper limit of normal (ULN) or a total bilirubin result >1.5 × ULN 
18. Physical, psychological, or historical finding that, in the Investigator’s 
opinion, would make the subject unsuitable for the study 
19. Severe infections, injuries, or major surgeries (as determined by the 
Investigator) within 4 weeks prior to screening or intend to undergo any 
surgery during the trial 
20. Use of a live vaccine within 30 days prior to screening or anticipated need 
for a live vaccine during the study or for 30 days following the last dose 
of study drug 

 
 
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21. History of bleeding associated with procedures (e.g., endoscopy or 
phlebotomy) or with use of medications (e.g., nonsteroidal anti-
inflammatory drugs [NSAIDs] or aspirin) within 28 days prior to 
screening or planned use during the study 
22. Positive test for human immunodeficiency virus (HIV), hepatitis B 
surface antigen (HBsAg), or hepatitis C antibodies (HCV) 
23. History of severe allergy to any drug, food, toxin, or other exposure  
24. History of heavy alcohol use within 1 year prior to screening, as defined 
by:  
a. Exceeding 4 standard drinks on any day or more than 14 standard 
drinks per week for men, or more than 3 standard drinks on any 
day or more than 7 standard drinks per week for women; one 
standard drink=10 grams of alcohol (equivalent to 12.5 mL of 
pure alcohol, 285 mL of full-strength beer, 375 mL of mid-
strength beer, 425 mL of low-strength beer, 100 mL of wine, or 30 
mL of 40% alcohol spirits). 
25. History of illicit or prescription drug abuse or addiction within 1 year of 
screening, or positive urine drug screen at screening and Day -1. The 
urine drug screen may be repeated at the discretion of the Investigator and 
the reason for repeat needs to be documented clearly (e.g., suspicion of 
false positive due to diet). 
26. Participation in a clinical trial involving the administration of an 
investigational or marketed drug or device within 90 days of screening   
27. Donation of plasma within 7 days prior to the first administration or 
donation or loss of blood (excluding volume drawn at screening) of 50 
mL to 499 mL of blood within 30 days, or more than 499 mL within 56 
days prior to the first administration. 
28. Subjects who are unlikely to comply with the study protocol OR those 
who would not be suitable candidates for participation in the opinion of 
the Investigator including any reason which, in the opinion of the 
Investigator, would prevent the subject from completing all study 
procedures and complying with study restrictions.  
29. Any other conditions (e.g., not suitable for venous access) or laboratory 
abnormality that may increase the risk associated with study participation 
or study drug administration or interfere with the interpretation of study 
results and, at the discretion of the investigator, makes the subject 
inappropriate for entry into this study 
Study 
Assessments: 
Safety and Tolerability: 
• 
Medical history, including evaluation of any on-study AEs and 
concomitant medication use 
• 
Height and weight 
• 
Physical examination 

 
 
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• 
Vital signs (supine systolic and diastolic blood pressure, heart rate, 
respiratory rate, body temperature)  
• 
12-lead ECGs 
• 
Analysis of laboratory safety markers (including hematology, chemistry, 
coagulation, and urinalysis) 
Exploratory Pharmacodynamics: 
Blood (serum and plasma), stool/fecal samples, and urine samples will be 
collected for analysis and identification of GLY-200-induced PD marker 
changes. 
Statistical 
Considerations:  
Overview: 
In general, clinical data will be summarized for each dose group using 
descriptive statistics. 
Safety and Tolerability: 
The primary analysis will assess the safety and tolerability of GLY-200 in 
patients. The sample size chosen for this study was selected without statistical 
considerations.  
Safety Analysis 
All subjects that are randomised and receive at least one dose of study drug 
will be included in the Safety population. The safety endpoint includes 
evaluation of AEs, clinical laboratory assessments, vital signs, 12-lead ECGs, 
and the use of concomitant medications. 
Safety data will be aggregated and tabulated based on the safety dataset for 
each treatment including but not limited to: 
• 
Analysis of withdrawal or suspension of medication due to AEs 
• 
Incidence and severity of AEs 
• 
Analysis of the correlation between AEs and study drug 
• 
Analysis of AE outcome 
• 
Analysis of SAEs 
• 
Descriptive statistical summary of laboratory tests, vital signs, and ECG 
data 
• 
Incidence of abnormal laboratory results. 
Exploratory Pharmacodynamics: 
PD marker parameters will be summarized using descriptive statistics and 
graphs (mean ± SEM) for each treatment at each timepoint.   

 
 
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Abbreviations: BP = blood pressure; CGM = continuous glucose monitor; ECG = electrocardiogram; EOS = End of Study; ET = Early Termination; FSH = 
follicular stimulating hormone; HR = heart rate; MMTT = mixed meal tolerance test; PD = pharmacodynamic(s); PK = pharmacokinetic(s); RR = respiratory 
rate; Temp = body temperature; VAS = visual analog scale. 
Note: Prescreening laboratory values can be used to determine subject eligibility if they were collected within the screening window. 
Footnotes:  
1. 
Subjects are required to fast for at least 8 hours prior to every morning assessment. “Pre-dose” and “post-dose” refer to the first dose of the day. 
2. 
At the Day -14 phone visit, site staff are to instruct subjects to begin the metformin washout.  
3. 
Eligibility to be confirmed prior to dose administration on Day 1. 
4. 
BMI to be calculated using the height value recorded at screening. 
5. 
Full physical examination to include, at a minimum, assessment of the following: assessment of the following systems: HEENT, Mouth/Dental (if required), 
Neck (incl Thyroid & Nodes), Cardiovascular, Respiratory, Gastrointestinal, Renal, Neurological, Musculoskeletal, Skin, Other 
6. 
Abdominal physical examination to include palpation, auscultation (noting presence and frequency of bowel sounds), percussion (looking for signs of 
peritonitis or localized tenderness). Abdominal examinations are to be conducted at indicated study visits prior to dosing, if applicable. 
7. 
Symptom directed physical examination will include volunteer elicited examinations only.  
8. 
Patients should be resting in a supine position for at least 5 minutes prior to and during vital signs measurements. Vital signs will be assessed at indicated 
study visits prior to dosing, if applicable.  
9. 
At Screening and prior to first dose, triplicate 12-lead ECGs each separated by at least 1 minute will be taken to establish eligibility and baseline. The 
average value for the triplicate will be utilized for assessing QTcF exclusion criteria. Post-first dose ECGs will be single readings. In case of evident bad 
quality (e.g., muscle tremor) of the tracing, the ECG will be repeated. ECGs will be taken after at least 5 minutes resting quietly in a supine position. ECGs 
will be assessed at indicated study visits prior to dosing, if applicable. 
10. Hematology, chemistry, coagulation tests, and urinalysis will be performed. Refer to Section 8.2.7. Subjects will be required to fast for at least 8 hours prior 
to clinical laboratory blood sampling. Specific vitamin and mineral panels will only be assessed on Day 1 pre-dose and Day 14.  
11. Human immunodeficiency virus, hepatitis B surface antigen, hepatitis C virus antibody testing. Subjects to be counselled if tests return positive result. 
12. If the urine pregnancy test is positive, pregnancy will be confirmed by a serum pregnancy test. 
13. Adverse events to be monitored at all times. 
14. Subjects must refrain from food for a minimum of 2 hours prior to and a minimum of 1 hour following each administration of GLY-200 or placebo. At study 
visits where MMTT will be performed, dosing should occur 1 hour prior to the meal challenge (refer to MMTT Test Schedule in Section 1.3.1). 
15. Subjects will be provided collection containers and will be instructed to collect all bowel movements, if possible, within 24 hours of their Day -1 and Day 21 
(EOS) or ET visits. All bowel movements should also be collected at the site, if possible, anytime between check-in on Day -2 and Day 1 pre-dose. During 
the inpatient period starting on Day 10 until check-out on Day 14, all bowel movements should be collected. Additional samples are to be collected at the 
Day 21 (EOS) or ET visits if possible. Approximate weights of fecal collections should be recorded by site staff. Refer to the Laboratory Manual for 
additional details.  
16. Refer to the MMTT Test Schedule in Section 1.3.1 for blood sample collection timepoints on MMTT days.  

 
 
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17. Urine is to be collected over 24 hours for exploratory PK/PD analysis (boron, etc.) from Day -1 to pre-dose on Day 1, post-dose on Day 1 to Day 2, Day 2 to 
Day 3, Day 3 to Day 4, and from Day 10 to 14. Urine samples for PD analysis are also to be collected by the subject from Day 14 to Day 17 and for the 24 
hours prior to their Day 21 (EOS) or ET visit. All samples collected by the subject can be returned to the site at the Day 21 (EOS) or ET visit.      
18. Recording of water and fluids in and output (urine volume out) over 24 hours daily.   
19. The Appetite VAS Questionnaire will be completed by the subject pre-dose (or ~60 minutes before the meals on Day -1), pre-meal, immediately post-meal, 
and 30, 60, 90, 120, 150, 180, 210, and 240 minutes post-meal on the study days indicated. VAS assessments may be performed within a ± 10-minute 
window. 
20. CGM automatic applicator will placed/replaced at indicated study visits for continuous measuring throughout the study; for the Day -1 visit, the CGM can be 
placed on Day -2 (check-in). The CGM is to be removed on Day 14 prior to check-out.  
21. Refer to the MMTT Test Schedule in Section 1.3.1 for further details. 

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Findings in animal toxicity studies demonstrated the lack of systemic toxicity and no clearly 
adverse local effects in the GI tract. The potential adverse effects from GLY-200 in humans are 
therefore anticipated to be based on local tolerance effects to the GI tract and decreased 
nutritional uptake. In the Phase 1 MAD study where subjects were dosed for up to 5 days, the 
most common reported AEs were: 
•
Nausea
•
Decreased appetite
•
Vomiting
•
Abdominal distension
•
Flatulence
•
Diarrhea
•
Constipation
•
Headache
•
Abdominal discomfort
•
Eructation
•
Dry mouth
•
Abdominal pain upper
•
Dyspepsia
Allergic Reactions
As with any drug, there is the chance of an allergic reaction that may include difficulty breathing, 
rash, flushing, weakness, lightheadedness, dizziness, and swelling. 
Blood Sampling
There is some risk of pain or local bruising and infection at the site where blood is drawn for 
laboratory tests. There is also a small risk of a fainting episode, which can occur as a reaction to 
giving blood.
The total amount of blood that will be collected over the course of screening and the 21-day 
study is  600 mL. The total amount of blood that will be collected is less than 1.5 standard 
blood donations. There is a risk that subjects may experience anemia.
Electrocardiograms
Up to 12 self-adhesive electrodes will be attached to the subject’s skin on their arms, legs, and 
chest. The areas where the electrodes will be placed will be cleaned; some areas may need to be 
shaved. Some skin irritation can occur where the electrodes are placed.
KNOWN POTENTIAL BENEFITS 
Information from this study may help Investigators and the Sponsor learn more about GLY-200
and its ability to improve the management of uncontrolled glycemia and increased weight in 
patients with T2D. This information may help other subjects in future studies.
OVERALL BENEFIT: RISK CONCLUSION
The results of Glyscend’s preclinical study program strongly supports the conclusion that GLY-

 
 
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11. Clinically significant symptoms (as determined by the Investigator) of nausea, vomiting, 
bloating, diarrhea, flatulence, constipation, or abdominal pain in the last 30 days prior to 
screening 
12. Use of systemic corticosteroids by oral, intravenous, or intramuscular route; or potent, 
inhaled, or intrapulmonary steroids known to have a high rate of systemic absorption within 
3 months of screening 
13. Clinically significant medical condition as judged by the Investigator that could potentially 
affect study participation and/or personal well-being, including but not limited to the 
following conditions: 
a. Uncontrolled hypertension 
b. Uncontrolled hyperlipidaemia 
c. Hepatic disease 
d. Renal disease (eGFR value of <60 mL/min/1.73 m2) based on the Modification of 
Diet in Renal Disease equation. 
e. Endocrine disorder other than diabetes 
f. Cardiovascular event in the last 12 months 
g. Central nervous system diseases 
h. Organ transplantation 
i. Chronic or acute infection 
j. Orthostatic hypotension, fainting spells, or blackouts 
14. Any evidence of or treatment of malignancy (other than localized basal cell, squamous cell 
skin cancer, non-aggressive prostate cancer, or cancer in situ that has been resected) within 
the previous year 
15. Clinically significant electrocardiogram (ECG) abnormalities or vital sign abnormalities as 
determined by the Investigator 
16. Clinical laboratory test (clinical chemistry, hematology, coagulation parameters, or 
urinalysis) abnormality, other than that related to T2D, judged by the Investigator to be 
clinically significant 
17. Alanine aminotransferase or aspartate aminotransferase result >2.5 × upper limit of normal 
(ULN) or a total bilirubin result >1.5 × ULN 
18. Physical, psychological, or historical finding that, in the Investigator’s opinion, would make 
the subject unsuitable for the study 
19. Severe infections, injuries, or major surgeries (as determined by the Investigator) within 4 
weeks prior to screening or intend to undergo any surgery during the trial 
20. Use of a live vaccine within 30 days prior to screening or anticipated need for a live vaccine 
during the study or for 30 days following the last dose of study drug 
21. History of bleeding associated with procedures (e.g., endoscopy or phlebotomy) or with use 
of medications (e.g., nonsteroidal anti-inflammatory drugs [NSAIDs] or aspirin) within 28 
days prior to screening or planned use during the study 
22. Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), 
or hepatitis C antibodies (HCV) 

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MEDICAL HISTORY
A medical history will be obtained and will include demographic data (e.g., age, race/ethnicity). 
In addition, medical information will also be recorded, including a detailed oncologic history 
with specifics of previous cancer treatments, other medical and surgical history, medication 
history and drug allergies and any other medical conditions and disease states that, in the opinion 
of the Investigator, are relevant to the subject’s study participation.
HEIGHT AND WEIGHT
Body height and weight will be measured, and body mass index (BMI) will be calculated using 
the height recorded at screening. Height should be measured on a wall-mounted stadiometer. 
Weight should be measured in light-weight clothing, without shoes.
PHYSICAL EXAMINATION 
A complete physical examination will be performed at Screening and at the EOS or ET visit. The 
complete physical examination will include, at a minimum, assessment of the following systems: 
HEENT, Mouth/Dental (if required), Neck (including Thyroid & Nodes), Cardiovascular, 
Respiratory, Gastrointestinal, Renal, Neurological, Musculoskeletal, Skin, Other. All other 
scheduled examinations will be symptom-directed.
All physical examinations are to be conducted by a medically qualified Investigator.
ABDOMINAL EXAMINATION
Abdominal examinations are to include at a minimum palpation, auscultation (noting presence 
and frequency of bowel sounds), and percussion (looking for signs of peritonitis or localized 
tenderness). Abdominal examinations are to be conducted at the study visits indicated in the SoA 
prior to dosing.
Besides local gastrointestinal tolerability effects, such as nausea, vomiting, diarrhea, and 
constipation, there is a theoretical risk of small or large bowel obstruction. To mitigate this risk, 
particular attention will be applied for abdominal examination, with particular interest in signs of 
obstruction (reduced bowel sounds, decreased stool, bilious vomiting, and abdominal discomfort 
and distension). If an obstruction is suspected, the subject will be transferred to a medical facility 
and an abdominal X-ray obtained as well as other imaging that may be appropriate.
VITAL SIGNS
Vital signs will be measured by a qualified staff member. Vital signs assessments will include 
systolic and diastolic blood pressure, heart rate, respiratory rate, and body temperature. Patients 
should be resting in a supine position for at least 5 minutes prior to and during vital signs 
measurements. 
ELECTROCARDIOGRAMS
Twelve-lead ECGs will be assessed (including but not limited to the measurements of ventricular 

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heart rate (HR), PR interval, respiratory rate (RR), QRS duration, QT interval and QT interval 
corrected by the Fridericia’s formula [QTcF]). Screening and prior to first dose, triplicate 12-lead 
ECGs each separated by at least 1 minute will be taken to establish eligibility at baseline. The 
average value for the triplicate will be utilized for assessing QT interval corrected using 
Fridericia’s formula (QTcF) exclusion criteria. All other post-first dose ECGs will be single 
readings. However, if any of the ECG measurements is out of normal range, it will be repeated in 
triplicate (separated by at least 1 minute).
ECG normal ranges are as follows:
•
PR interval: 120 msec – 220 msec (inclusive);
•
QRS duration: < 120 msec;
•
47F)  PVHF PDOHV 47F)  PVHF Iemales);
•
HR 45-100 beats/min (inclusive)
If the “re-check” triplicate’s average is still above these parameters, the PI shall be notified for a 
determination on further action. The same model of ECG machine should be used for Screening, 
pre-dose and post-dose readings for all patients. ECGs will be taken after at least 5 minutes in a 
supine quiet rest. ECGs will be interpreted, signed and dated by the PI, or medically qualified 
designee. The ECGs will be classified as normal, not having a clinically significant abnormality 
or having a clinically significant abnormality. In addition, ECG parameters of HR, PR interval, 
QT interval, PR interval, RR interval, QRS duration, and QTcF will be noted on the eCRF. All 
clinically significant findings will be recorded as AEs. Clinical staff are required to perform 
ECG assessments at the nominated time-points within the time windows indicated in the SoA.  
CLINICAL LABORATORY EVALUATIONS
Subjects will be required to fast for at least 8 hours prior to clinical laboratory blood sample 
collection. Samples for local clinical laboratory analysis will be collected by a qualified staff 
member. All safety laboratory assessments will be assessed by a certified local laboratory, using 
the relevant laboratory’s internal and standard normal range values.
At a minimum, the following tests will be conducted:
•
Hematology: hemoglobin, hematocrit, red blood cell indices, thrombocyte count 
(platelets), reticulocyte count, white blood cell count with differential (including 
neutrophils, eosinophils, basophils, lymphocytes and monocytes). 
•
Coagulation: international normalized ratio, prothrombin time and activated partial 
thromboplastin time. 
•
Chemistry: sodium, potassium, magnesium, chloride, bicarbonate, phosphate, calcium, 
amylase, lipase, uric acid, albumin, globulins, protein, lactate dehydrogenase, creatine 
kinase, creatinine (estimated glomerular filtration rate), blood urea nitrogen, alkaline 
phosphatase, ALT, AST, GGT, total bilirubin, conjugated and unconjugated bilirubin, 
total cholesterol, high-density lipoproteins, low-density lipoproteins, triglycerides, 
glucose. Vitamin and mineral panels will be evaluated per the SoA.
•
Urinalysis: pH, specific gravity, protein, glucose, ketones, bilirubin, blood, nitrites, 
urobilinogen, leukocyte esterase. Urine sediment microscopy will be conducted in the 

Protocol GLY-200-02 AM02V01
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       35
instance of abnormal urinalysis findings.
Refer to Appendix 4 for a table of clinical laboratory assessments.
The Investigator or designee must review the results of each subject’s screening clinical 
laboratory test results prior to first dose. The subject must not be treated on Day 1 if the subject 
has any clinically significant laboratory abnormalities as defined in the eligibility criteria. 
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 eCRF.
PREGNANCY TEST
Blood samples for serum pregnancy analysis will be collected from all female subjects by a 
qualified staff member.
Serum and urine human chorionic gonadotropin pregnancy testing will be performed.
Any positive urine pregnancy test will be confirmed with a serum pregnancy test.
OTHER LABORATORY TESTS
•
Serology: HIV, HBsAg, HCV antibodies 
•
Follicle-stimulating hormone (FSH) and estradiol levels (for post-menopausal females only)
•
Drugs of abuse screen: The urine screen will include methamphetamines, opiates, cocaine, 
phencyclidine, benzodiazepines, barbiturates, methadone, amphetamines. 
FLUID BALANCE
Urine samples will be taken for volume over a 24-hour period and compared with intake of fluids 
to provide the fluid balance. 
DOCUMENTATION OF FOOD INTAKE
During the inpatient period, food intake (date, time, and quantity [% consumed based on visual 
estimation]) will be documented daily.
FOOD INTAKE AND APPETITE ASSESSMENTS
Food intake and appetite assessments will be performed at breakfast and dinner on Days -1, 1, 
and 13 to assess changes in food intake, kcals, and macronutrients based on food weight 
consumed and nutrient analysis.
For appetite assessments on these days, subjects will complete appetite visual analog scale 
(VAS) questionnaires.
MIXED MEAL TOLERANCE TEST
The MMTT is performed in the morning. Subjects should fast at least 8 hours prior to the 
MMTT. The mixed meal used in this protocol is Ensure Plus (100 g carb, 700 kcal in 16 fl 

Protocol GLY-200-02 AM02V01
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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. 
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.
COMMITTEES STRUCTURE 
Not applicable.
SAFETY OVERSIGHT
Clinical safety oversight will be performed by centralized review conducted by Medical 
Monitors per the Medical Monitoring Plan. In addition, on-site review of all data including safety
data will be conducted routinely by clinical monitors /clinical research associates.
DISSEMINATION OF CLINICAL STUDY DATA
This study will be posted on the US National Institutes of Health’s website 
www.clinicaltrials.gov.
DATA QUALITY ASSURANCE
As defined by ICH guidelines, the CRF is a printed, optical, or electronic document designed to 
record all protocol-required information to be reported to the Sponsor on each study subject.
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the Sponsor or designee electronically (e.g., laboratory data). The Investigator is 
responsible for verifying that data entries are accurate and correct by physically or electronically 
signing the CRF.

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Data collection on the CRF will follow the instructions described in the CRF Completion 
Guidelines. Copies of the completed eCRFs will be retained by the investigational center as well 
as the Sponsor.
The Sponsor or designee is responsible for the data management of this study including quality 
checking of the data.
SOURCE DOCUMENTS
The Investigator must maintain required records for all study subjects. Source data are all 
information, original records of clinical findings, observations, or other activities in a clinical 
trial necessary for the reconstruction and evaluation of the trial. Source data for this study will be 
recorded in the subject’s source documents and on the eCRFs, unless otherwise noted. All data 
on these eCRFs should be recorded completely and promptly. A copy of the completed eCRFs 
for each subject will be retained by the investigational center.
The Investigator must maintain adequate and accurate source documents upon which eCRFs for 
each subject are based. They are to be separate and distinct from eCRFs, except for cases in 
which the Sponsor has predetermined that direct data entry into specified pages of the subject’s 
eCRF is appropriate.
Study monitors will perform ongoing source data verification to confirm that data entered into 
the eCRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of 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.
STUDY RECORDS RETENTION 
During this study, the Investigator is required to prepare and maintain adequate and accurate case 
histories designed to record all observations and other data pertinent to the investigation on each 
individual treated with the IP or entered as a control in the investigation.
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the Investigator for the maximum period required by (1) applicable regulations and 
guidelines or institution procedures or (2) for the period specified by the Sponsor, whichever is 
longer. The Investigator must contact the Sponsor before destroying any records associated with 
the study. No records may be destroyed during the retention period without the written approval 
of the Sponsor.
The Sponsor will notify the Investigator when the study records are no longer needed.
In the event the Investigator withdraws from the study (e.g., relocation, retirement), the records 
shall be transferred to a mutually agreed-upon designee (e.g., another Investigator). Notice of 
such transfer will be given in writing to the Sponsor.
The Sponsor will maintain correspondence with the Investigator after study closeout to ensure 
that study documentation is retained for the appropriate amount of time. 

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QUALITY ASSURANCE AND QUALITY CONTROL
This study will be organized, performed, and reported in compliance with the protocol, SOPs, 
site/Investigator training, and applicable regulations and guidelines. Clinical Investigator sites
will be trained at the Investigator Meeting(s) and/or at on-site visits. All aspects of the study will 
be monitored carefully by the Sponsor’s designees with respect to current GCP and SOPs for 
compliance with applicable government regulations. It is the responsibility of the Investigator to 
provide all study records, including CRFs and source documents, among other records, for 
review and inspection by the clinical monitor, representatives of the Sponsor, and regulatory 
authorities, as needed.
Clinical monitoring will be performed per the Clinical Monitoring Plan. Clinical 
monitors/clinical research associates will periodically evaluate the progress of the study, 
including the verification of appropriate consent form procedures and the verification of the 
accuracy and completeness of eCRFs. Clinical monitors/clinical research associates will also 
ensure that all protocol requirements, applicable US FDA regulations, other regulatory 
requirements, and the Investigator’s obligations are being fulfilled.
PROTOCOL DEVIATIONS
A protocol deviation is any noncompliance with the clinical trial protocol or ICH GCP. The 
noncompliance may be either on the part of the participant, the Investigator, or the study site 
staff. 
The Investigator and study staff will apply due diligence to avoid protocol deviations. If protocol 
deviations do occur, the Investigator or study staff must report them to the local IRB/IEC per 
their policies.
PREMATURE TERMINATION OR STUDY SUSPENSION
The Sponsor reserves the right to prematurely terminate the study or specific groups within the 
study at any time for administrative, safety, or treatment-related benefit-risk reasons. Written 
notification documenting the reason for study suspension or termination will be provided to the 
Investigator and regulatory authorities as appropriate. If the study is prematurely terminated or 
suspended, the Investigator will promptly inform the IRB and will provide the reason(s) for the 
termination or suspension.
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 

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Medical Journal Editors authorship requirements.  
FUTURE USE OF STORED SPECIMENS AND DATA
Data and biospecimens collected in this study may be useful for other research studies. 
Samples (blood, urine, and fecal) will be stored for future metabolite analysis and may be used to 
assess additional PK and PD markers of GLY-200.

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AEs of Special Interest 
The following are considered AEs of special interest in this study:
x
Hyperglycemia with evidence of diabetic ketoacidosis (DKA) or impending DKA: A blood glucose 
value > 300 mg/dL with symptoms of DKA (e.g., nausea, dizziness, abdominal pain, lethargy) and 
capillary ketones > 1.5 mmol/L or urine ketone positivity
x
Clinically significant hypoglycemia: A blood glucose measurement of <54 mg/dL (<3.0 mmol/L) that 
may or may not have immediate symptoms depending on the level of hypoglycemia unawareness
DEFINITION OF SAE
An SAE is defined as any serious adverse event that, at any dose:
1.
Results in death
2.
Is life-threatening
x
The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in which the subject was at 
risk of death at the time of the event. It does not refer to an event, which hypothetically might have 
caused death, if it were more severe.
3.
Requires inpatient hospitalization or prolongation of existing hospitalization
x
In general, hospitalization signifies that the participant has been admitted (usually involving at least an 
overnight stay) at the hospital or emergency ward for observation and/or treatment that would not have 
been appropriate in the physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfills any other serious criteria, 
the event is serious. When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious.
x
Hospitalization for elective treatment of a pre-existing condition that did not worsen from baseline is not 
considered an AE.
4.
Results in persistent or significant disability/incapacity
x
The term disability means a substantial disruption of a person’s ability to conduct normal life functions.
x
This definition is not intended to include experiences of relatively minor medical significance such as 
uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma (e.g., sprained 
ankle) which may interfere with or prevent everyday life functions but do not constitute a substantial 
disruption.
5.
Is a congenital anomaly/birth defect
6.
Is an important medical event, defined as an event that does not fit one of the other outcomes, but may 
jeopardize the subject and may require medical or surgical intervention (treatment) to prevent one of 
the other outcomes
x
Examples of such events include intensive treatment for allergic bronchospasm (a serious problem with 
breathing) requiring treatment in an emergency room, serious blood dyscrasias (blood disorders), 
seizure/convulsion that does not result in hospitalization or development of intervention dependency or 
intervention abuse.

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DEFINITION OF UNANTICIPATED PROBLEMS (UP) 
UP Definition
x
An unanticipated problem is defined as, in general, any incident, experience, or outcome that meets all of 
the following criteria: 
o
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that are 
described in the protocol-related documents, such as the IRB-approved research protocol and informed 
consent document; and (b) the characteristics of the subject population being studied; 
o
Related or possibly related to participation in the research (“possibly related” means there is a
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research); and 
o
Suggests that the research places subjects or others at a greater risk of harm (including physical, 
psychological, economic, or social harm) than was previously known or recognized.  
RECORDING AND FOLLOW-UP OF AE AND/OR SAE
AE and SAE Recording
x
Serious Adverse Events (SAEs) should be reported to the Sponsor and/or CRO within 24 hours from 
the discovery of the event. 
x
When an AE/SAE occurs, it is the responsibility of the investigator to review all documentation (e.g., 
hospital progress notes, laboratory reports, and diagnostics reports) related to the event.
x
The Investigator will then record all relevant AE/SAE information.
x
The Investigator will attempt to establish a diagnosis of the event based on signs, symptoms, and/or other 
clinical information. Whenever possible, the diagnosis (not the individual signs/symptoms) will be 
documented as the AE/SAE.
Assessment of Severity
The investigator will make an assessment of severity for each AE and SAE reported during the study and assign it 
to 1 of the following categories: 
x
Mild: An event that is easily tolerated by the participant, causing minimal discomfort and not interfering 
with everyday activities.
x
Moderate: An event that causes sufficient discomfort to interfere with normal everyday activities.
x
Severe: An event that prevents normal everyday activities. An AE that is assessed as severe should not be 
confused with an SAE. Severe is a category utilized for rating the intensity of an event; and both AEs and 
SAEs can be assessed as severe.
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as described in the definition 
of an SAE, NOT when it is rated as severe.
Assessment of Relationship to Study Agent
The relationship of the study treatment to an AE will be determined by the Investigator based on the following 
definitions:  
1. Not Related 
The AE is not related if (1) administration of the study medication has not occurred or (2) the occurrence of 
the AE is not reasonably related in time or (3) the AE is considered related to another event, medical 

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Assessment of Relationship to Study Agent
condition or product not associated with the study medication (such as disease progression, environmental 
factors, unrelated trauma, etc.) 
2.  Unlikely Related
The AE is unlikely related if (1) the AE is unlikely related in time or (2) the AE is considered unlikely to be 
related to use of the study medication (i.e., there are no facts [evidence] or arguments to suggest a causal 
relationship), or the AE is considered possibly related to another event, medical condition or product not 
associated with the study medication. 
3.  Possibly Related
The AE is possibly related if (1) the study medication and AE are considered reasonably related in time and
(2) the AE could equally be explained by causes other than exposure to the study medication. 
4.  Probably Related
The AE is probably related if (1) the study medication and AE are considered reasonably related in time and 
(2) the study medication is more likely than other causes to be responsible for the AE or is the most likely 
cause of the AE.
x
The Investigator will use clinical judgment to determine the relationship.
x
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as well as the 
temporal relationship of the event to study intervention administration will be considered and investigated.
x
There may be situations in which an SAE has occurred and the Investigator has minimal information to 
include in the initial report (refer to Section 10.2.5). However, it is very important that the Investigator 
always make an assessment of causality for every event before the initial transmission of the SAE data (refer 
to Section 10.2.5). 
x
The Investigator may change his/her opinion of causality in light of follow-up information and send an SAE 
follow-up report with the updated causality assessment.
x
The causality assessment is one of the criteria used when determining regulatory reporting requirements.
Assessment of Expectedness
x
The Sponsor will be responsible for determining whether an AE/SAE is expected or unexpected.
x
An AE/SAE will be considered unexpected if the nature, severity, or frequency of the event is not 
consistent with the risk information previously described for the study agent in the IB or is not listed in the 
IB at the specificity or severity that has been observed. 
REPORTING OF SAES
SAE Reporting to Sponsor and IRB
x
Any AE that meets any criterion for an SAE requires the completion of an SAE Report Form in addition to 
being recorded on the AE page/screen of the eCRF. 
x
All SAEs must be reported by email to Sponsor Drug Safety or its designee within 24 hours of the 
Investigator’s knowledge of the event. 
o Sponsor Drug Safety Contact Information: SAE@glyscend.com  
o ProSciento Safety Team Email: pvsafety@prosciento.com
x
The Investigator is required to ensure that the data on these forms is accurate and consistent. This 
requirement applies to all SAEs (regardless of relationship to IP) that occur during the study (from the time 
the participant signs informed consent until post-treatment follow up visit, or any SAE made known to the 

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SAE Reporting to Sponsor and IRB
Investigator at any time thereafter that are suspected of being related to IP). Serious adverse events 
occurring prior to treatment (after signing the ICF) will be captured.
x
The SAE report should provide a detailed description of the SAE and include a concise summary of 
hospital records and other relevant documents. If a participant died and an autopsy has been performed, 
copies of the autopsy report and death certificate are to be sent to Sponsor Drug Safety or its designee as 
soon as these become available. Any follow-up data should be detailed in a subsequent SAE Report Form, 
or approved equivalent form, and sent to Sponsor Drug Safety or its designee. 
x
Where required by local legislation, the Investigator is responsible for informing the IRB/EC of the SAE 
and providing them with all relevant initial and follow-up information about the event. The Investigator 
must keep copies of all SAE information on file including correspondence with Sponsor and the IRB/EC.
x
Details will be provided in the Safety Management Plan (SMP).
x
There may be instances when copies of medical records for certain cases are requested by the Sponsor. In 
this case, all subject identifiers, with the exception of the subject number, will be redacted on the copies of 
the medical records before submission to Sponsor.
REPORTING OF UPS
Unanticipated Problem Reporting
x
Incidents or events that meet the criteria for unanticipated problem require the creation and completion of 
an UP report. It is the site Investigator’s responsibility to report UPs to their IRB and to the Sponsor. The 
UP report will include the following information: 
o
Protocol identifying information: protocol title and number, PI’s name, and the IRB project 
number; 
o
A detailed description of the event, incident, experience, or outcome; 
o
An explanation of the basis for determining that the event, incident, experience, or outcome 
represents an UP; and 
o
A description of any changes to the protocol or other corrective actions that have been taken or 
are proposed in response to the UP. 
x
To satisfy the requirement for prompt reporting, UPs will be reported using the following timeline: 
o
UPs that are SAEs will be reported to the IRB and to the Sponsor within 24 hours of the 
Investigator becoming aware of the event. 
o
Any other UP will be reported to the IRB and to the Sponsor within the IRB-required reporting 
timeframe. 
o
All UPs should be reported to appropriate institutional officials (as required by an institution’s 
written reporting procedures) and IRB within the timeframe specified by the institution 
procedures and IRB.

 
 
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Abbreviations: RBC = red blood cell; WBC = white blood cell; PT = prothrombin time; INR = international 
normalized ratio; aPTT = activated partial prothrombin time; HIV = Human Immunodeficiency Virus; HBsAg = 
Hepatitis B surface antigen; LDH = lactate dehydrogenase; ALP = alkaline phosphatase; ALT = alanine 
aminotransferase; AST = aspartate aminotransferase; GGT = gamma-glutamyl transferase; HDL = high-density 
lipoprotein; LDL = low-density lipoprotein; TIBC = total iron binding capacity; HCV = hepatitis C virus; hCG = 
human chorionic gonadotropin; CRP = C-reactive protein. 
 
 
 

 
 
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Abbreviation 
Term 
HDL 
high-density lipoprotein 
HIPAA 
Health Insurance Portability and Accountability Act  
HR 
heart rate 
IB 
Investigator's Brochure 
IBD 
inflammatory bowel disease 
IBS 
irritable bowel syndrome 
ICF 
informed consent form 
ICH 
International Council for Harmonisation  
IP 
investigational product 
IRB 
Institutional Review Board 
IV 
intravenous 
LDL 
low-density lipoprotein  
MAD 
multiple ascending dose 
MedDRA 
Medical Dictionary for Regulatory Activities  
MMTT 
mixed meal tolerance test 
NSAIDs 
nonsteroidal anti-inflammatory drugs 
PD 
pharmacodynamic(s) 
PK 
pharmacokinetic(s) 
PT 
preferred term 
PYY 
peptide YY 
RR 
respiratory rate 
RYGB 
Roux-en-Y gastric bypass 
SAD 
single ascending dose 
SAE(s) 
serious adverse event(s) 
SAP 
statistical analysis plan 
SD 
standard deviation  
SEM 
standard error of the mean 
SoA 
Schedule of Activities  
SOC 
system organ class 
SOP 
standard operating procedure 
T2D 
type 2 diabetes 

 
 
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Abbreviation 
Term 
TEAE(s) 
treatment-emergent adverse event(s) 
TID 
three times a day 
ULN 
upper limit of normal 
UP 
Unanticipated Problem 
VAS 
visual analog scale 
wt. 
weight 
 
 
 
 

 
 
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Change 
Section(s) Affected 
Rationale 
Day 14.” 
Section 6.1.2 was updated: “Each 
subject will be randomly assigned to a 
group at Day -1 or Day 1.” 
Section 6.1.2 
Update was made to allow for 
randomization on Day -1.  
Tetrahydrocannabinol was removed 
from the “Drugs of abuse” screen. 
Section 8.2.9 
THC was deleted from the drug screen 
list as it is not an exclusionary drug.  
“Clinically significant hyperglycemia” 
and “clinically significant 
hypoglycemia” (and definitions) were 
added to as AEs of special interest.  
Section 8.3.7 and 
Section 10.2.1 
Additions were made per FDA 
recommendation. 
“Fasting Lipids” was removed from 
the “Day 1 predose and Day 14 only” 
clinical laboratory assessments. 
Section 10.4 
Deletion was made because the lipid 
panel done as part of the standard 
chemistry lab is sufficient.  
 
Amendment 01 Version 01 Summary of Changes 
Purpose:  The primary purpose of this amendment is to address FDA comments received in 
response to the protocol submission as part of the original IND. Additional edits are 
also made to refine and clarify the study procedures. 
Summary of Changes 
Change 
Section(s) Affected 
Rationale 
Added amendment version/date and 
Summary of Changes 
Throughout and 
Section 12 
To reflect protocol Amendment 01 
Sponsor Signature Pages were 
combined into one page. 
Sponsor Signature 
Page 
Administrative edit 
Glucagon was added to 
pharmacodynamic measures in the 
exploratory objectives 
Synopsis, Section 
1.3.1, Section 3, and 
Section 8.4 
To refine exploratory PD tests 
Inclusion criterion 1c was revised: 
“HbA1c  7 6.5 DQG  9.6 8.5% at 
screening” 
Synopsis, Section 5.1 
Per FDA recommendation 
Inclusion criterion 1d was added:     
“d. completed at least 12 days of 
metformin washout without meeting 
Synopsis, Section 5.1 
To clarify that subjects meeting criteria 
for rescue during the washout period 

 
 
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Change 
Section(s) Affected 
Rationale 
rescue criteria prior to dosing” 
will not be randomized 
Inclusion criterion 3 was revised: BMI 
  DQG   at screening 
Synopsis, Section 5.1 
To clarify timing of 
inclusion/exclusion criteria assessment 
Exclusion criterion 8 was revised: 
Fasting blood glucose > 210 190 
mg/dL at screening; can be reassessed 
once during the screening period 
Synopsis, Section 5.2 
Per FDA recommendation 
“Urine Dipstick (ketones)” row was 
removed from the SoA. 
Section 1.3 
Ketones are assessed as part of clinical 
laboratory urinalysis. 
“FSH Test” row was added to the SoA.  
Section 1.3 
To reflect FSH testing performed on 
postmenopausal women at screening 
The following was added to the SoA: 
“Note: Prescreening laboratory values 
can be used to determine subject 
eligibility if they were collected within 
the screening window.” 
Section 1.3 
To clarify screening procedures 
Footnote 9 was updated in the SoA: 
“ECGs will be taken after at least 10 5 
minutes resting quietly…” 
Section 1.3 
For consistency with Section 8.2.6 
Electrocardiograms 
The following was added to SoA 
footnote 15: “Approximate weights of 
fecal collections should be recorded by 
site staff.” 
Section 1.3 
To refine study procedures 
Footnote 18 was updated in the SoA: 
“Recording of water and fluids in and 
output (urine volume out) over 24 
hours daily during confinement.”   
Section 1.3 
To clarify that fluid balance is only 
being performed on a subset of 
inpatient days as noted in the SoA 
The following was added to the 
protocol: “Fractionated bile acids will 
be analyzed in a subset of 
subjects/doses based on initial total 
bile acid data.”  
Section 1.3.1 and 
Section 8.4 
To refine exploratory PD analysis 
testing strategy 
The following was added to Section 
6.8.2 Rescue Medicine: “Fasting blood 
glucose will be measured by the 
subject using a home glucose meter 
Section 6.8.2 
To clarify that subjects meeting criteria 
for rescue during the washout period 
will not be randomized 

 
 
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Change 
Section(s) Affected 
Rationale 
daily from Day -7 to inpatient check-
in. If a subject meets criteria for rescue 
during the washout period, the subject 
will not be randomized.” 
Section 8.2.6 Electrocardiograms was 
edited: “Day 1 pre dose and all other 
post-first dose ECGs will be single 
readings.” 
Section 8.2.6 
To enhance accuracy; Day 1 pre-dose 
ECG will be in triplicate. 
Alcohol breath test was removed from 
Section 8.2.9 Other Laboratory Tests. 
Section 8.2.9 
Alcohol breath test is part of the site’s 
prescreening process.  
Section 8.4 was reorganized, and 
calprotectin (fecal analysis) and 
calcium (urine analysis) were deleted.  
Section 8.4 
To clarify exploratory PD vs PK 
markers and to delete assays that were 
included in error 
Corrected section references in Section 
10.2.4 Recording and Follow-up of AE 
and/or SAE 
Section 10.2.4 
Administrative edit; section references 
in Assessment of Relationship to Study 
Agent were incorrect 
Added sponsor drug safety contact 
information. 
Section 10.2.5 
Previously omitted in error 
Appendix 4: Clinical Laboratory 
Assessments was edited: 
x Clarification was made to refer to 
the SoA for timepoints 
x Full iron panel was defined 
x Timing of “Other Serum & Plasma 
tests” was clarified 
x Abbreviations were updated for 
completeness. 
Section 10.4 
Edits were made to clarify clinical 
laboratory assessments