Efficacy and Safety of EGT0001442 Compared With Placebo in Patients With Type 2 Diabetes Mellitus Inadequately Controlled by Diet and Exercise and up to One Oral Anti-diabetes Agent
Phase: PHASE2
Conditions: Diabetes Mellitus
Sponsor: Theracos

 
 
Clinical Trial Protocol: THR-1442-C-418 
Study Title: 
Efficacy and safety of EGT0001442 compared with placebo in patients 
with type 2 diabetes mellitus inadequately controlled by diet and 
exercise and up to one oral anti-diabetes agent. 
Study Number: 
THR-1442-C-418 
Study Phase: 
3 
Product Name: 
EGT0001442 tablet 
IND Number: 
103822 
Indication: 
Type 2 diabetes mellitus 
Investigators: 
Multiple center 
Sponsor: 
Theracos, Inc. 
Sponsor Contact: 
Albert Collinson, Ph.D. 
Theracos, inc. 
550 Del Rey Avenue 
Sunnyvale, CA 94085 
Phone: 408-992-1100 
Sponsor protocol 
representative 
Monica Tettamanti 
185 Cambridge Street 
Boston, MA 02114 
Telephone number:  617-643-5696 
Fax number:  617-726-2879 
E-mail: mtettamanti@ccib.mgh.harvard.edu 
 
 
Date 
Original Protocol: 
02 February 2011 
 
Confidentiality Statement 
The following confidential information is the property of Theracos, Inc.  As long as the 
information contained in this protocol has not been published, it may only be used when 
permission has been obtained from Theracos 

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SYNOPSIS 
Sponsor: 
Theracos, Inc. 
Name of Finished Product: 
EGT0001442 tablet 
Name of Active Ingredient: 
EGT0001442 
Study Title:  
Efficacy and safety of EGT0001442 compared with placebo in patients with type 2 diabetes 
mellitus inadequately controlled by diet and exercise and up to one oral anti-diabetes agent.  
Study Number: 
THR-1442-C-418 
Study Phase: 3 
Primary Objective(s):  
To assess the efficacy of EGT0001442 in lowering HbA1c at week 24 compared with 
placebo 
Secondary Objective(s): 
 To assess the efficacy of EGT0001442 in lowering FPG at weeks 2 and 24 compared 
with placebo 
 To assess the efficacy of EGT0001442 based on the proportion of subjects in the 
EGT0001442 group reaches the American Diabetes Association (ADA) target HbA1c 
of <7% compared with placebo 
 To assess the effect of EGT0001442 on systolic and diastolic blood pressure 
compared with placebo 
 To assess the effect of EGT0001442 on body weight compared with placebo 
 To assess the change in HbA1c change over time, week 1 to week 96 
 To assess the safety of EGT0001442 in patients with T2DM 
 
Study Design: 
A multinational, 2 arm parallel groups, randomized, double-blind placebo-controlled study to 
compare the treatment of once daily EGT0001442 at 30 mg with matching placebo in 
treatment-naïve type 2 diabetic patients (i.e. not taking an antihyperglycaemic agent for ≥16 
weeks prior to study entry) or with diet and exercise in combination with one oral 
antidiabetes drug and an HbA1c of 7-10%.  Approximately 300 eligible subjects will start a 
2-week placebo run-in period prior to being randomly assigned to either once daily 
EGT0001442 or placebo in a 1:1 ratio for 24 weeks.  Subjects with hyperglycemia may 
receive approved anti-diabetic medication.  At week 24, subjects who have completed the 
main treatment period will continue to receive study drug until week 96.  In the treatment 

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extension period, subjects who have elevated HbA1c will have additional antidiabetic 
therapy added to the study drug consistent with treatment recommendations for type 2 
diabetes.   
 
Study Population and main eligibility criteria:  
Approximately 300 patients that are inadequately controlled by diet and exercise or by 
treatment with a single oral anti-diabetes agent, randomized 1:1 to placebo and EGT0001442 
 Type 2 diabetes per the American Diabetes Association criteria  
 Male or female 
 Age ≥ 18 years 
 Receiving one or no oral anti-diabetic agent and diet and exercise instruction 
 HbA1c between 7 and 10% at screening 
 Body mass index (BMI) ≤ 37 kg/m2 
 Fasting plasma glucose <250 mg/dL at screening for subjects not treated with oral 
anti-diabetic therapies 
 Fasting plasma glucose <240 mg/dL at screening for subjects treated with anti-
diabetic therapies 
 Fasting plasma glucose <250 mg/dL for all subjects at randomization 
Test Product, Dose, and Mode of Administration:  
EGT0001442 tablets 30 mg once daily by mouth 
Reference Therapy; Dose; and Mode of Administration: 
 Placebo – once daily by mouth 
Duration of Treatment:  
 98 week (2wk run-in, 24 week primary evaluation, 72 week extension) 
Statistical Methods:  
The primary objective of this trial is to assess the efficacy of EGT0001442 in treatment-naïve 
type-2 diabetic patients or patients on a single oral anti-diabetic drug in combination with 
diet and exercise with an HbA1c between 7 and 10%.  Efficacy is defined as a significant 
reduction in HbA1c at week 24 when compared to placebo.  The effect of EGT0001442 on 
fasting glucose, blood pressure, body weight and the general safety of EGT0001442 in 
patients with T2DM will also be explored. 
Statistical analyses and summaries of safety and tolerability will be performed using SAS® 
software (SAS Institute, Cary, NC).  In all cases, significance will be judged at the =0.05 
level.  No multiplicity adjustment will be required for the single primary endpoint. 
 
Date of Original Approved Protocol: 02 February 2011 

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TABLE OF CONTENTS 
SYNOPSIS .................................................................................................................................2 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ............................................8 
NO OBSERVABLE ADVERSE EFFECT LEVEL ..................................................................9 
1 
INTRODUCTION ...........................................................................................................11 
1.1 
EGT0001442 for the treatment of type 2 diabetes mellitus ...................................11 
1.1.1 
Summary of non-clinical data with EGT0001442 .......................................12 
1.1.2 
Summary of Clinical data with EGT0001442 .............................................12 
2 
STUDY OBJECTIVES ....................................................................................................14 
2.1 
Primary Objective(s) ..............................................................................................14 
2.2 
Secondary Objective(s) ..........................................................................................14 
3 
INVESTIGATIONAL PLAN ..........................................................................................15 
3.1 
Overall Study Design and Plan ..............................................................................15 
3.2 
Rationale for Study Design and Control Group .....................................................17 
3.3 
Study Duration and Dates ......................................................................................18 
4 
STUDY POPULATION SELECTION ...........................................................................19 
4.1 
Study Population ....................................................................................................19 
4.2 
Inclusion Criteria ...................................................................................................19 
4.3 
Exclusion criteria ...................................................................................................19 
5 
STUDY TREATMENT(S) ..............................................................................................21 
5.1 
Description of Treatment(s) ...................................................................................21 
5.1.1 
Study Drug ...................................................................................................21 
5.1.2 
Placebo .........................................................................................................21 
5.1.3 
Rescue medications ......................................................................................21 
5.2 
Treatments Administered .......................................................................................22 
5.3 
Selection and Timing of Dose for Each Patient .....................................................22 
5.4 
Method of Assigning Patients to Treatment Groups ..............................................22 
5.5 
Blinding..................................................................................................................22 
5.6 
Concomitant Therapy.............................................................................................23 
5.7 
Restrictions ............................................................................................................24 
5.7.1 
Prior Therapy ...............................................................................................24 
5.7.2 
Fluid and Food Intake ..................................................................................24 
5.7.3 
Patient Activity Restrictions ........................................................................24 
5.8 
Treatment Compliance ...........................................................................................24 
5.9 
Packaging and Labeling .........................................................................................25 
5.9.1 
Study drug for main treatment period ..........................................................25 

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5.9.2 
Study drug for the treatment extension period .............................................25 
5.10 
Storage and Accountability ....................................................................................25 
5.11 
Investigational Product Retention at Study Site ....................................................25 
6 
STUDY PROCEDURES .................................................................................................26 
6.1 
Informed Consent...................................................................................................26 
6.2 
Medical History .....................................................................................................26 
6.3 
Physical Examination.............................................................................................27 
6.4 
Vital Signs ..............................................................................................................27 
6.5 
Electrocardiography ...............................................................................................27 
6.6 
Diet and exercise counseling .................................................................................27 
6.7 
Clinical Laboratory Tests .......................................................................................27 
6.7.1 
Laboratory Parameters .................................................................................27 
6.7.2 
Sample Collection, Storage, and Shipping ..................................................28 
6.7.2.1 
HEMATOLOGY AND BLOOD CHEMISTRY ...............................28 
6.7.2.2 
URINALYSIS ....................................................................................29 
6.8 
Dispensing Study Drug ..........................................................................................29 
6.9 
Adverse Events Assessments .................................................................................29 
6.9.1 
Definitions....................................................................................................29 
6.9.2 
Eliciting and Reporting Adverse Events ......................................................31 
6.9.3 
Immediately Reportable Adverse Events (IRAE) ........................................31 
6.9.4 
Pregnancy .....................................................................................................31 
6.9.5 
Procedure for Breaking the Blind ................................................................33 
6.9.6 
Follow-up of Adverse Events ......................................................................33 
6.9.6.1 
FOLLOW-UP OF NON-SERIOUS ADVERSE EVENTS ...............33 
6.9.6.2 
FOLLOW-UP OF POST STUDY SERIOUS ADVERSE 
EVENTS ............................................................................................33 
6.9.7 
Adverse event of special interest .................................................................34 
6.9.7.1 
GENITOURINARY INFECTIONS ..................................................34 
6.9.7.2 
RENAL AND URINARY DISORDERS ..........................................34 
6.9.7.3 
MAJOR ADVERSE CARDIOVASCULAR EVENT (MACE) .......34 
6.9.7.4 
HYPOGLYCEMIA............................................................................34 
6.10 
Concomitant Medication Assessments ..................................................................34 
6.11 
Removal of Patients from the Trial or Study Drug ................................................35 
6.12 
Other Study Procedures .........................................................................................35 
7 
STUDY ACTIVITIES .....................................................................................................36 
7.1.1 
Visit 1 - Screening (weeks –5 to -2) ............................................................36 
7.1.2 
Visit 2 – run-in period (day -14±3) ..............................................................36 

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7.2 
Primary Efficacy Phase ..........................................................................................37 
7.2.1 
Visit 3 – procedures (Day 1 in Week 0) ......................................................37 
7.2.2 
Visit 4 – Procedures (week 2) ......................................................................37 
7.2.3 
Visit 5 – Procedures (week 6) ......................................................................38 
7.2.4 
Visit 6 – Procedures (week 12) ....................................................................38 
7.2.5 
Visit 7 – Procedures (week 18) ....................................................................39 
7.2.6 
Visit 8 – Procedures (week 24) ....................................................................39 
7.3 
Extension Phase .....................................................................................................40 
7.3.1 
Visit 9 – Procedures (week 36) ....................................................................40 
7.3.2 
Visit 10 – Procedures (week 48) ..................................................................40 
7.3.3 
Visit 11 – Procedures (week 60) ..................................................................41 
7.3.4 
Visit 12 – Procedures (week 72) ..................................................................41 
7.3.5 
Visit 13 – Procedures (week 84) ..................................................................42 
7.3.6 
Visit 14 – Procedures (week 96) ..................................................................42 
7.3.7 
Visit 15 – Exit Visit (week 97) ....................................................................43 
7.4 
Early Termination Procedures ...............................................................................43 
8 
QUALITY CONTROL AND ASSURANCE .................................................................45 
9 
PLANNED STATISTICAL METHODS ........................................................................46 
9.1 
General Considerations ..........................................................................................46 
9.1.1 
Handling Dropouts, Multiples, Missing Data, and Outliers ........................46 
9.1.2 
Multiple Comparisons / Multiplicity ...........................................................46 
9.2 
Determination of Sample Size ...............................................................................46 
9.3 
Analysis Populations ..............................................................................................47 
9.4 
Demographics and Baseline Characteristics ..........................................................47 
9.5 
Analysis of Efficacy ...............................................................................................47 
9.5.1 
Primary Efficacy Endpoint ..........................................................................47 
9.5.2 
Secondary Efficacy Endpoints .....................................................................48 
9.5.3 
Additional Efficacy Endpoints .....................................................................48 
9.6 
Analysis of Safety ..................................................................................................49 
9.6.1 
Adverse Events ............................................................................................49 
9.6.2 
Adverse event of special interest .................................................................49 
9.6.2.1 
GENITOURINARY INFECTIONS ..................................................49 
9.6.2.2 
MAJOR ADVERSE CARDIOVASCULAR EVENT (MACE) .......49 
9.6.2.3 
HYPOGLYCEMIA............................................................................50 
9.6.2.4 
RENAL AND URINARY DISORDERS ..........................................50 
9.6.3 
Clinical and Laboratory Events and Analyses .............................................50 
9.6.4 
Concomitant Medications ............................................................................50 

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9.7 
Interim Analysis .....................................................................................................50 
10 ADMINISTRATIVE CONSIDERATIONS ....................................................................51 
10.1 
Investigators and Study Administrative Structure .................................................51 
10.2 
Institutional Review Board (IRB) or Independent Ethics Committee (IEC) 
Approval ................................................................................................................51 
10.3 
Ethical Conduct of the Study .................................................................................51 
10.4 
Patient Information and Consent ...........................................................................52 
10.5 
Patient Confidentiality ...........................................................................................52 
10.6 
Study Monitoring ...................................................................................................52 
10.7 
Case Report Forms and Study Records .................................................................53 
10.8 
Protocol Violations/Deviations ..............................................................................53 
10.9 
Access to Source Documentation ..........................................................................53 
10.10 Data Generation and Analysis ...............................................................................54 
10.11 Retention of Data ...................................................................................................54 
10.12 Publication and Disclosure Policy .........................................................................54 
11 REFERENCE LIST .........................................................................................................56 
 
LIST OF IN-TEXT TABLES 
Table 1. 
List of Laboratory Tests .............................................................................27 
 
LIST OF APPENDICES 
Appendix 1 
Schedule of Events .....................................................................................57 
Appendix 2 
Estimating glomerular filtration rate ..........................................................59 
Appendix 3 
Sponsor Signatures.....................................................................................60 
Appendix 4 
Investigator’s Signature .............................................................................61 
 
 

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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
ADA 
American Diabetes Association 
AE 
adverse event 
ALB 
albumin 
ALT 
alanine aminotransferase 
AP 
alkaline phosphatase 
AST 
aspartate aminotransferase  
AUC0-24 
area under the curve from 0 to 24 hours 
BMI 
body mass index 
BUN 
blood urea nitrogen 
Ca 
calcium 
CBC 
complete blood count 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
Cl 
chloride 
Cmax 
observed maximum concentration 
CRF 
case report form 
CRO 
Contract Research Organization 
CV 
coefficient of variation 
CVA 
cerebral vascular accident 
DSMB 
Data and safety monitoring board 
EC 
ethics committee 
ECG 
electrocardiogram 
eGFR 
estimating glomerular filtration rate 
FDA 
Food and Drug Administration 
FPG 
fasting plasma glucose 
GCP 
Good Clinical Practice 
GLP-1 
glucagon-like peptide-1 

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GGT 
gamma glutamyl transferase 
HbA1c 
glycosylated hemoglobin A1c 
Hct 
hematocrit 
HDL-C 
high density lipoprotein cholesterol 
Hgb 
hemoglobin 
HIPAA 
Health Information Portability and Accountability Act 
HIV 
Human immunodeficiency virus 
ICH 
International Conference on Harmonisation  
IND 
Investigational New Drug  
IRAE 
Immediately Reportable Adverse Event 
IRB 
Institutional Review Board 
ITT 
intent-to-treat 
IVRS 
Interactive voice response system 
LDH 
lactic dehydrogenase 
LDL-C 
Low density lipoprotein cholesterol 
MACE 
Major Adverse Cardiovascular Event 
MAD 
multiple ascending dose 
MedDRA 
Medical Dictionary for Regulatory Activities 
MDRD 
Modification of Diet in Renal Disease 
NOAEL 
No observable adverse effect level 
NYHA 
New York Heart Association 
OAM 
oral anti-diabetic medications 
PD 
pharmacodynamics 
PK 
pharmacokinetics 
PP 
per protocol 
PT 
prothrombin  
RBC 
red blood cell (count) 
SAD 
single ascending dose 

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SAE 
serious adverse event 
SD 
standard deviation 
SMBG 
self monitored blood glucose 
T2DM 
type 2 diabetes mellitus 
TEAEs 
Treatment emergent adverse events 
tmax 
time to maximum concentration 
UGE0-24 
urinary glucose excretion from 0 to 24 h post dose 
ULRR 
Upper Limit of the Reference Range 
USP/NF 
The United States Pharmacopeia–National Formulary 
UTI 
urinary tract infections 
WBC 
white blood cell (count) 
WHODRUG 
World Health Organization Drug Dictionary 
WOCBP 
Women of childbearing potential 
 

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1 
INTRODUCTION 
Diabetes mellitus, characterized by hyperglycemia, is caused by defective insulin secretion, 
resistance to insulin action, or a combination of both.  Approximately 285 million people 
worldwide, or 6.6%, in the age group 20-79 have diabetes in 2010.  The prevalence of 
diabetes is projected to be 438 million or 7.8% of the adult population by 2030 (Sicree et al., 
2010). Over 90% of diabetic patients have type 2 diabetes mellitus (T2DM) and over 80% of 
the type 2 diabetic patients are overweight or obese.  Several classes of agents for type 2 
diabetes are available for treating hyperglycemic conditions including insulin secretagogues, 
PPAR agonists, metformin, alpha glucosidase inhibitors, glucagon-like peptide 1 (GLP-1) 
analogues, and dipeptidyl peptidase 4 (DPP4) inhibitors.  Insulin and its analogues also are 
prescribed for the treatment of type 2 diabetes as the disease progresses.  However, a rapid 
rise in the number of adult type 2 diabetics has led to an increasing recognition that 
additional therapeutic modalities are needed to provide safe and effective reductions of 
elevated plasma glucose levels. 
The renal Na+/glucose transporter SGLT2 (gene name SLC5A2) is a member of a sugar 
transporter family that actively transports extracellular hexoses into cells using the driving 
energy of the transmembrane electrochemical potential for sodium ions.  Individuals with 
disruptions in the gene encoding SGLT2 exhibit prominent glucosuria in the absence of 
significant comorbidities (Santer et al., 2003; van den Heuvel et al., 2002).  Significantly, 
neither hypoglycemia nor an increased incidence of urinary tract infections have been 
reported in these individuals. The elimination of glucose from the blood via urinary excretion 
has the potential to improve both fasting and postprandial hyperglycemia without increasing 
insulin secretion, causing weight gain, or inducing hypoglycemia.   
Phlorizin, a natural product inhibitor of SGLT1 and 2, has been shown to produce urinary 
glucose excretion (UGE) and lower plasma glucose levels in several animal models 
(Ehrenkranz et al., 2005).  Development of phlorizin was discontinued due to its rapid 
degradation by lactase-phlorizin hydrolase and poor absorption from the gastrointestinal 
tract.  Several SGLT2 inhibitors are in development (Han et al., 2008; Neumiller et al., 
2010).  Dapagliflozin is the SGLT2 inhibitor with the most extensive clinical data.  Early 
phase studies demonstrated sustained, dose-dependent glucosuria over 24 hours with once 
daily oral dosing (Komoroski et al., 2009a; Komoroski et al., 2009b).  A double blind, 
placebo controlled study showed that treatment with dapagliflozin for 6 months resulted in  
0.58% – 0.89% reduction of glycosylated hemoglobin A1c (HbA1c) from baseline compared 
with -0.23% in the placebo group with a placebo-subtracted changes in weight up to 1.1 kg 
(Ferrannini et al., 2010).  Increased numbers of urinary tract and genital infections were 
observed in the treated groups. 
1.1 
EGT0001442 for the treatment of type 2 diabetes mellitus 
EGT0001442, a candidate oral antidiabetic agent, is a potent, highly specific inhibitor of the 
renal Na+/glucose transporter SGLT2. It is a benzylbenzene C-glycoside of the same 

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chemical structural class as dapagliflozin.  EGT00001442 elicits a prominent and predictable 
glucosuria in laboratory animals and in healthy and diabetic subjects in clinical studies. 
Several previous non-clinical and clinical studies were conducted with EGT0001474, a now-
discontinued crystalline formulation of EGT0001442 and L-proline in 1:2 stoichiometry.  
The mass ratio of EGT0001474 to EGT0001442 is 1.5:1. In this protocol, all studies 
performed with EGT0001474 are described in terms of the EGT0001442 content. For 
example if a study used 50 mg of EGT0001474 it is described as 33 mg of EGT0001442 
(delivered as proline cocrystal).  EGT0001474 and EGT0001442 have similar solubility in 
water, similar dissolution rates when formulated as capsules, and show similar exposure in 
rat, monkey, and human studies. 
1.1.1 
Summary of non-clinical data with EGT0001442 
The potential adverse effects of EGT0001442 have been evaluated through safety 
pharmacology, genotoxicity, acute, chronic, and reproductive toxicity studies. Repeat dose 
toxicity studies performed in rats, dogs and monkeys found diarrhea and gastric irritation 
including sporadic ulceration, at the lowest observable effect level.  The NOAELs based on 
these studies are 6.7 and 20 mg/kg/day in rats and monkeys, respectively, representing safety 
multiples of 8.1 and 19.6 relative to anticipated exposures in diabetic patients at the planned 
clinical dose of 20 mg/day.  Chronic exposures produced similar toxicity profiles, with the 
additional finding of microvacuolization of renal cortical cells in monkeys after 39 weeks 
dosing.  This microscopic pathology occurred without clinical chemistry correlates, and the 
renal effects generally reversed during the recovery phase.  EGT0001442 does not affect 
fertility or in utero development up to the maximum tolerated doses in rats and rabbits.  
Details of the toxicology findings are described in the Investigator’s Brochure. 
1.1.2 
Summary of Clinical data with EGT0001442 
Clinical studies have been conducted to evaluate safety, tolerability, pharmacokinetics (PK), 
pharmacodynamics (PD), metabolism, and efficacy of EGT0001442.  No deaths or study 
drug related serious adverse events (AEs) have been reported in the clinical trials.  
EGT0001442 up to 100 mg for up to 14 days was safe and tolerated in healthy volunteers.  In 
a phase 2, double-blind, placebo-controlled study, subjects with type 2 diabetes mellitus were 
treated with EGT0001442 in doses of 5 to 50 mg or a placebo for 28 days.  The most 
frequently occurring AEs were headache (4% in the placebo and 11% in the treatment 
groups), pollakiuria (none in the placebo and 4% in the treatment groups), fatigue (7% in the 
placebo and 2% in the treated group), and nausea (4% in the placebo and 3% in the treated 
group).  No hypoglycemia was reported.  Genital and urinary tract infections were observed 
in some subjects in the EGT0001442 treated groups, including balanitis candida, urinary tract 
infection, bacterial vaginitis, vulvovaginal candidiasis, and vulvovaginal mycotic infection. 
Urinary glucose excretion (UGE) was measured in healthy and diabetic subjects.  
EGT0001442 increased UGE in a dose-dependent and saturable manner.  The plateau in 
UGE corresponded to dosages of EGT0001442 above 20 mg/day.  EGT0001442 treatment in 
subjects with T2DM for 4 weeks was effective in reducing FPG by 24 to 41.6 mg/dL in the 

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groups dosed with 5 to 50 mg/day EGT0001442.  Subjects receiving EGT0001442 also had a 
reduction in body weight, blood pressure, and postprandial glucose compared to the changes 
in the placebo group.  Details of the safety and efficacy information are described in the 
Investigator’s Brochure 

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2 
STUDY OBJECTIVES 
2.1 
Primary Objective(s)  
The primary objective of this study is to assess the efficacy of EGT0001442 in lowering 
HbA1c at week 24 compared with placebo. 
2.2 
Secondary Objective(s)  
The secondary objective(s) of this study is (are): 
 To assess the efficacy of EGT0001442 in lowering FPG at weeks 2 and 24 compared 
with placebo 
 To assess the efficacy of EGT0001442 based on the proportion of subjects in the 
EGT0001442 group reaches the American Diabetes Association (ADA) target HbA1c 
of <7% compared with placebo 
 To assess the effect of EGT0001442 on systolic and diastolic blood pressure 
compared with placebo 
 To assess the effect of EGT0001442 on body weight compared with placebo 
 To assess the change in HbA1c change over time, week 1 to week 96 
 To assess the safety of EGT0001442 in patients with T2DM 
 

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3 
INVESTIGATIONAL PLAN 
3.1 
Overall Study Design and Plan 
STUDY DESIGN 
THR-1442-C-418 is a multinational, 2 arm parallel groups, randomized, double-blind 
placebo-controlled study to compare the treatment of once daily EGT0001442 at 30 mg with 
matching placebo in treatment-naïve type 2 diabetic patients (i.e. not taking an 
antihyperglycaemic agent for ≥16 weeks prior to study entry) or with diet and exercise in 
combination with one oral antidiabetes drug and an HbA1c of 7-10%.  Approximately 300 
eligible subjects will start a 2-week placebo run-in period prior to being randomly assigned to 
either once daily EGT0001442 or placebo, using a computer-generated allocation schedule, 
in a 1:1 ratio for 24 weeks.  Subjects with hyperglycemia may receive approved anti-diabetic 
medication.  At the end of week 24, subjects who have completed the main treatment period 
will continue to receive study drug until week 96.  In the treatment extension period, subjects 
who have elevated HbA1c will have additional antidiabetic therapy added to the study drug 
consistent with treatment recommendations for type 2 diabetes.  The primary analysis is to 
assess whether EGT0001442 is superior to placebo based on HbA1c change from baseline to 
week 24.   
RESEARCH METHODS AND PROCEDURES 
At screening visit, subjects who meet all the inclusion criteria, none of the exclusion criteria, 
and who consent to participate in the study will receive counseling for appropriate diet and 
exercise.  Those who are on an oral antidiabetic medication (OAM) will discontinue the 
medication and receive placebo in this run-in prior for 14 ± 3 days.  Eligible diabetic subjects 
who are treatment naïve and who control their hyperglycemia through diet and exercise will 
also receive placebo and the hyperglycemia will be monitored to ensure that their fasting 
blood glucose levels remain below 250 mg/dL during this interval of 14 ± 3 days.   
After the run-in period, approximately 300 subjects will complete the baseline assessment on 
day 1 after overnight fasting to confirm their eligibility.  The subjects that remain eligible 
will be randomly assigned to one of the 2 treatment groups on day 1.  Randomization will be 
stratified by study center and based on screening HbA1c (≥7 to <8.5% or ≥8.5 to 10%). The 
planned doses are 30 mg/day of EGT0001442 or placebo.  Each subject will be provided with 
study drug for 6 weeks, dosing instructions and log, diet and exercise counseling, and a diary 
card for recording food and fasting glucose information on the days prior to each clinic visit. 
Each subject will be instructed to return to the clinic on weeks 2, 6, 12, 18, and 24 for safety 
monitoring and efficacy assessment including review of adverse events, concomitant 
medication, ECG, vital signs, physical examinations, testing of blood chemistry and 
hematology laboratory parameters, and a urinalysis. 
Subjects who complete the 24-week treatment period will continue receiving the study drug 
for an additional 72 weeks.  Subjects who receive rescue medication due to poor glycemic 

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control will continue to receive approved anti-diabetic medications and standard of care per 
investigator decision according to current treatment guidelines for 72 weeks.  In the treatment 
extension period, subjects must return to the clinic on weeks 36, 48, 60, 72, 84, and 96 for 
continuous safety monitoring and efficacy assessment, including review of HbA1c values, 
adverse events, concomitant medication, ECG, vital signs, and physical examinations.  A 
follow up exit visit will be conducted at 1 week after the last dose.  Subjects will be advised 
to see their primary physician and resume standard of treatment to control diabetes. 
GLYCEMIC CONTROL 
During the run-in period, subjects will be instructed to determine daily self-monitored blood 
glucose (SMBG) after an overnight fast.  The SMBG record will be reviewed by the 
investigator at each clinic visit.  If the fasting blood glucose is > 216 mg/dL (12 mmol/L) in 
two consecutive days, the subject should contact the clinical staff.  In addition, subjects will 
be instructed that they must contact the clinic within 24 h if SMBG is ≥ 270 mg/dL (15 
mmol/L).  If the fasting SMBG is ≥ 270 mg/dL (15 mmol/L) without explanations for the 
elevation, the investigator will review the SMBG record and determine if the subject should 
attempt to improve diet and exercise to maintain glycemic control or if the subject must 
discontinue from the study and resume diabetic medications.  Subjects with symptomatic 
hyperglycemia or hypoglycemia should be withdrawn if the symptoms are severe.   
During the 24-week main treatment period, study subjects will be advised to continue daily 
SMBG measurements and contact the clinic if the SMBG is ≥270 mg/dL (15 mmole/L) from 
week 1 (week of randomization) to week 6, ≥240 mg/dL (13.3 mmole/L) from week 6 to 
week 12, or ≥200 mg/dL (11.1 mmole/L) from week 12 to week 24.  During the 72-week 
extension period (weeks 25 to 96), subjects will continue to monitor the SMBG and contact 
the clinic if SMBG is ≥200 mg/dL (11.1 mmole/L).  Values of HbA1c will be evaluated in 
the extension period by the investigator and approved standard of oral therapy will be 
prescribed if HbA1c is elevated. 
The investigator must review the SMBG record and FPG values in every clinic visit and 
assess whether any subject should receive rescue medications to treat the hyperglycemic 
condition during the 24-week main treatment period.  The subject must be queried to assess 
compliance with a minimum of a 10 h fast prior to blood draw to ensure the FPG values can 
be accurately determined.  If a subject has not fasted for 10 h, the subject must return within 
a week after proper fasting. The investigator will provide diet and exercise counseling and 
determine if the subject should receive additional rescue medication as a result of the 
glucose.  A serum sample must be drawn prior to the rescue medication so that the last 
HbA1c value while the subject is on study drug only can be carried forward to 24 weeks for 
the primary end point analysis.   
OTHER SAFETY MONITORING ACTIVITIES 
The safety monitoring activities will include vital signs, physical examinations, urinalysis, 
adverse events, and concomitant medication use.  The occurrence of blood, liver, or skin 
disorders will be monitored through laboratory testing and adverse event documentation.  

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Adverse event of special interests will include any clinical signs and symptoms indicating 
either upper or non-upper urinary tract infections (UTIs) and genital infections.  Any adverse 
events that mapped to UTIs or genital infections must be documented. 
DATA AND SAFETY MONITORING BOARD (DSMB) 
An independent Data and Safety Monitoring Board (DSMB) will monitor the overall safety 
information during the EGT0001442 development.  The safety review activity and potential 
risk benefit assessment will be defined in the charter. 
MAJOR ADVERSE CARDIOVASCULAR EVENT ADJUDICATION 
An independent cardiovascular adjudication committee is established to review the 
cardiovascular events during the study in a blinded fashion.  These events include 
cardiovascular mortality, myocardial infarction, stroke, and hospitalization for acute coronary 
syndromes, urgent revascularization procedures, and, other possible serious cardiovascular 
events.  The adjudicated events will be documented and archived to allow a meta-analysis to 
be performed to assess if there is any increase of cardiovascular risk to an unacceptable 
extent at the time of completion of all phase 3 clinical studies.   
3.2 
Rationale for Study Design and Control Group 
THR-1442-C-418 is designed to evaluate the efficacy of EGT0001442 in the treatment of 
patients with T2DM.  A randomized, double-blind study is the most suitable design and 
placebo is the appropriate control to evaluate a new agent in diabetic subjects.  Diet and 
exercise counseling during the entire study will be provided to all participating subjects to 
reduce risks of worsening diabetic conditions.  Monitoring plan based on SMBG, FPG, and 
HbA1c measurements as well as criteria to initiate rescue medications are included in the 
protocol to prevent prolonged hyperglycemia. 
Results from published data in individuals with genetic mutations in the gene encoding 
SGLT2, subjects that have been treated with other SGLT2 inhibitors, and from previous 
clinical studies in healthy or diabetic subjects treated with EGT0001442 indicate that the risk 
of induced hypoglycemia as a consequence of the loss of SGLT2 activity should be minimal. 
Reduction in HbA1c directly reflects improvement in glycemic control and is considered a 
well validated surrogate for the long-term microvascular complications of diabetes mellitus.  
Results from study THR-1442-C-402 demonstrated that 4 weeks of treatment resulted with a 
dose dependent reduction of 24 – 42 mg/dL FPG in subjects receiving EGT0001442 5 – 50 
mg per day.  Thirty (30) mg/ day of EGT0001442 dosage was chosen in the proposed study 
based on the near saturation of UGE and FPG decrease in previous clinical studies in healthy 
or diabetic subjects.  Clinical data in the previous studies indicated that 30 mg/day 
EGT0001442 is well tolerated. 

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3.3 
Study Duration and Dates 
In the proposed study, diabetic subjects will be screened within 3 weeks of washout start.  
Eligible subjects who sign the written consent will receive placebo and start a 2 week run-in 
period prior to study drug administration.  Subjects will receive 24 weeks of treatment for the 
main efficacy study and will continue for an additional 72 weeks for additional safety and 
efficacy study.  All subjects will be followed for 1 week after the last dose.  The overall study 
duration from screening until follow-up could last a maximum of 102 weeks for the study 
subjects.  The duration of the overall study depends on the rate of patient accrual.  For details 
of the schedule and nature of the investigations, see the Trial Activities Charts in Appendix 1 

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4 
STUDY POPULATION SELECTION 
4.1 
Study Population 
The study population will include approximately 300 subjects diagnosed with T2DM that are 
inadequately controlled by diet and exercise or by treatment with a single oral anti-diabetes 
agent and have the HbA1c between 7% and 10%.  The study will recruit subjects from 
approximately 50 trial centers in 3 countries. 
4.2 
Inclusion Criteria 
1. Male or female subjects ≥18 years old  
2. Diagnosed with type 2 diabetes 
3. Body mass index (BMI) ≤ 37 kg/m2 
4. HbA1c between 7 and 10% (inclusive) at screening based on an upper limit of normal 
for the HbA1c assay being 6.5±0.2 % 
5. FPG <250 mg/dL at screening for subjects not treated with oral anti-diabetic therapies 
or FPG <240 mg/dL at screening for subjects treated with anti-diabetic therapies 
6. Diabetes currently treated with diet and exercise only or diet and exercise along with 
one approved oral anti-diabetic agent 
7. If taking anti-diabetic medication, dose and regimen must be stable for past 3 months 
8. If taking antihypertensive medication, dose and regimen must be stable for past 3 
months 
9. If taking lipid modifying therapy, dose and regimen must be stable for past 3 months 
10. Blood glucose <250 mg/dL based on finger stick blood glucose for all subjects at 
randomization 
11. Subjects willing and able to comply with the investigational nature of the study and 
able to communicate well with investigators.  
12. Able to comprehend and willing to provide written informed consent in accordance 
with institutional and regulatory guidelines.  
 
4.3 
Exclusion criteria 
Subjects meet any of the criteria will be excluded: 
1. Hemoglobinopathy that affects HbA1c measurement 
2. Current use of injected therapy for treatment of diabetes (insulin or GLP-1 receptor 
based therapy) 
3. Genitourinary tract infection within 6 weeks of screening 
4. Greater than 2 episodes of genitourinary tract infection in the past year 
5. History of kidney stones, bladder malfunction or other significant risk factor for 
urinary tract infections 

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6. eGFR, as calculated by the modification of diet in renal disease study equation 
(MDRD), < 50 mL/min/1.73 m2 (Appendix 2) 
7. Abnormal tests of liver function ALT, AST or bilirubin ≥ 3x ULRR 
8. Diagnosed with proliferative retinopathy 
9. Uncontrolled hypertension (blood pressure >150/95) 
10. Not willing to use effective birth control if female with child-bearing potential 
11. Female subjects who are pregnant or nursing 
12. Life expectancy < 2 years 
13. New York Heart Association (NYHA) Class 4 heart failure 
14. Sera positive of HCV, HIV, or positive on drug screen 
15. Currently participating another interventional trial 
16. Not able to comply the study scheduled visits 
 

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5 
STUDY TREATMENT(S) 
5.1 
Description of Treatment(s) 
5.1.1 
Study Drug 
Theracos, Inc. will provide EGT0001442 tablets in one of the four different strengths as 
follows: 
10 mg SR formulation (EGT0001442 SR Tablet, 10 mg) 
15 mg SR formulation (EGT0001442 SR Tablet, 15 mg) 
20 mg SR formulation (EGT0001442 SR Tablet, 20 mg) 
20 mg IR formulation (EGT0001442 IR Tablet, 20 mg) 
 
The SR tablet formulations consist of EGT0001442 (active pharmaceutical ingredient) and 
excipients including HPMC, lactose monohydrate, sodium bicarbonate, colloidal silicon 
dioxide and magnesium stearate in the 10, 15, and 20 mg dosages.  The IR tablet formulation 
consists of 20 mg EGT0001442 (active pharmaceutical ingredient) and excipients including 
microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, colloidal silicon 
dioxide, and magnesium stearate. 
All study drug supplies will be prepared and labeled according to the requirements of local 
law and legislation and will be kept in a secure storage facility at controlled room 
temperature, 15 – 30°C (59 – 86°F).  The pharmacist or designated CRO personnel will 
dispense the study drugs for each subject according to randomization assignment made in the 
IVRS. 
5.1.2 
Placebo  
Theracos, Inc. will provide placebo tablets.  The placebo control tablets consist of HPMC, 
lactose monohydrate, sodium bicarbonate, colloidal silicon dioxide and magnesium stearate. 
Placebo will be prepared in white opaque tablets of the same size and appearance as the 
active drug tablets.  All placebo supplies will be prepared and labeled according to the 
requirements of local law and legislation and will be kept in a secure storage facility at 
controlled room temperature, 15 – 30°C (59 – 86°F).  The placebo control is packaged in a 
manner identical to the active drug product.  The placebo tablets will be administered 
identically to the EGT0001442 tablets. 
5.1.3 
Rescue medications 
Approved anti-diabetic medications will be provided to subjects who met the criteria to 
receive rescue medication due to poor glycemic control. 

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5.2 
Treatments Administered 
Study drug will be provided to the pharmacist in bottles of 45 tablets per bottle.  Individual 
bottles of placebo will be provided for the run-in portion of the study.  For the first 24 weeks 
of the study, subject kits will be provided and each kit will contain 4 bottles containing 45 
tablets per bottle.  For study weeks 25 – 96, subject kits will contain 2 bottles of 45 tablets.  
Study drug, EGT0001442 10, 15, or 20 mg tablets or matching placebo, will be dispensed by 
the pharmacy or designated study staff every 6 - 12 weeks.  There will be no intra-subject 
dose escalation or back-titration. 
Subjects who require rescue medication due to hyperglycemia will receive standard care for 
treating type 2 diabetes in addition to the study drug.  The pharmacist will dispense the 
medications per investigator’s prescription.   
5.3 
Selection and Timing of Dose for Each Patient 
Dosing with either active drug or placebo will be based on randomized assignment.  All 
study subjects will be instructed to self-administer one capsule prior to breakfast once daily 
and complete the dosing log.  Subjects will be advised to take the study medication with a 
glass of water.  The tablets will be swallowed without chewing.  
On the day of scheduled clinic visits, subjects must fast for a minimum of 10 h prior to the 
visits at which blood samples will be drawn.  During fasting, only water will be permitted.  
Subjects will be asked to record the meals they consume and the time that they last ate prior 
to blood draw for FPG and other laboratory testing. 
5.4 
Method of Assigning Patients to Treatment Groups 
Eligible subjects who complete the 14 ± 3 day washout period to verify eligibility for the 
study and stability of their diabetes will be randomized to receive EGT0001442 or placebo 
according to a randomization code.  Subjects are assigned to placebo or EGT0001442 at 30 
mg/day in a 1:1 ratio.  The random assignment of study subjects to treatment groups will be 
centrally located and managed utilizing an Interactive Voice Response Systems (IVRS).  
Randomization will be stratified by study center and based on screening HbA1c (≥7 to 
<8.5% or ≥8.5 to 10%). This randomization protocol is designed to balance experimental 
treatments within each center and the baseline HbA1c. 
The study will be conducted at multiple investigative sites and will likely involve variable 
numbers of subjects at each site.  Enrollment will be on a competitive basis but will be 
capped at 30% of the total randomized subjects (90 subjects) from one center. 
5.5 
Blinding 
The study drug will be blinded to the sponsor, investigators, study coordinators, pharmacists, 
study subjects, and the cardiovascular adjudication committee members.  Upon 
randomization, each subject will receive a subject randomization number and a drug kit 

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assigned to the subject.  To maintain blinding of the treatment, the values of the HbA1c after 
dosing starts will remain blinded to all study personnel and patients until all subjects have 
completed the 24 week treatment period. 
If knowledge of the test substance is needed to manage the subject’s condition, the 
investigator will contact the IVRS to obtain the treatment assignment.  If unblinding occurs, 
the time and reason for unblinding will be recorded on the CRF and the sponsor must be 
notified within 24 h. 
A designated statistician who is not involved with the study operation will hold the treatment 
code.  The unblinded treatment information can be provided to the DSMB to facilitate the 
evaluation of any clinically important increase in the rate of a serious suspected adverse 
reaction or to the designated safety contact when the treatment information is required to 
determine if an expedited safety report must be submitted to regulatory agencies.  The 
treatment code will be unblinded when the clinical database is locked and data are to be 
analyzed. 
The treatment assignment will continue to be withheld from the cardiovascular adjudication 
committee members at the conclusion of the study until all phase 2 and phase 3 
investigational studies are completed and a meta-analysis to assess cardiovascular risk is 
conducted. 
5.6 
Concomitant Therapy 
Medications to control blood pressure, specified lipid lowering drugs, and aspirin are allowed 
during the study period.  Allowed anti-hypertensive medications include ACE inhibitors, 
angiotensin receptor blockers, calcium channel blockers, beta blockers and diuretics.  The 
antihypertensive medications should continue for 24 weeks without changing unless 
clinically indicated.  In the extension period, the investigators should evaluate the blood 
pressure of each subject and determine if adjustment of the anti-hypertension drug should be 
adjusted per guideline. 
Subjects may receive any medications for adverse events that are necessary in the 
investigators’ judgment.  Subjects are permitted to take their prescription medications or 
medicinal supplements. 
Concomitant medications administered at the time of randomization and during the study are 
to be recorded on the CRF.  The medication name, dose, frequency, route of administration, 
date(s) of administration and reason for administration must be recorded.  Glucose for the 
treatment of hypoglycemia will be considered concomitant medication and must be recorded 
on the CRF.  This documentation should continue through the treatment period and the 
follow up period.  Medications that a subject receives after enrollment to the study and prior 
to randomization must be recorded in the CRF. 

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5.7 
Restrictions 
5.7.1 
Prior Therapy 
Medications for controlling diabetes, hypertension, hyperlipidemia, and aspirin as specified 
in the eligibility criteria are allowed as prior therapy.  No subject shall have been treated with 
an investigational drug within 30 days or 7 half lives, nor have used steroids within 14 days 
prior to the first dose of study medication.  Use of acetaminophen or multivitamins in this 
interval is permitted.   
5.7.2 
Fluid and Food Intake  
Enrolled diabetic subjects will receive counseling regarding an appropriate diet to achieve 
glycemic control based on standards of medical care in diabetes (ADA, 2008).  The diet 
should be low in saturated fat, high in fiber, and low in simple carbohydrates and contain 
appropriate caloric intake to maintain weight. 
Subjects will fast for a minimum of 10 h prior to any of the visits at which blood samples 
will be drawn.  During fasting, only water will be permitted.  Subjects will be asked to record 
the meals they consume and the time that they last ate prior to blood draw for FPG and other 
laboratory testing.  
5.7.3 
Patient Activity Restrictions 
Throughout the study period, subjects are advised to perform at least 150 min/week of 
physical activity that is appropriate for their physical condition. 
5.8 
Treatment Compliance 
To ensure the treatment compliance, subjects will be provided with dosing instruction and a 
dosing record.  The dosing record will be reviewed with the study staff during each visit and 
drug accountability will be performed and recorded at the end of the treatment period for 
each subject. 
Approximately 0.5 mL plasma sample will be collected and stored at -20oC at each clinic 
visit during the treatment period.  The samples will be shipped to the analytical laboratory in 
batches.  EGT0001442 plasma concentration may be determined from all or a portion of the 
samples to verify the drug exposure.  The results of the analysis will not be disclosed to the 
study team during the 24 week main treatment period until the clinical data for the primary 
analysis are locked. 

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5.9 
Packaging and Labeling 
5.9.1 
Study drug for main treatment period 
EGT0001442 tablets and placebo are packaged in high density polyethylene (HDPE) bottles 
sealed with a child resistant closure.   Each kit will include 4 bottles of study drug.  The 
product is packaged with 45 tablets per bottle including a 3 tablet overage in each bottle for 
accidental loss of study drug during the treatment period between visits. 
Study drug bottles will be labeled with the protocol number, product identification, lot 
number, kit number, Sponsor’s name and address, and the investigational drug caution 
statement. 
5.9.2 
Study drug for the treatment extension period 
The study drug EGT0001442 tablets and placebo are packaged in HDPE bottles sealed with a 
child resistant closure.   Study drug bottles will be labeled with the protocol number, product 
identification lot number, the sponsor’s name and address, and the investigational drug 
caution statement. 
5.10 Storage and Accountability 
EGT0001442 tablets and matching placebo will be stored at controlled room temperature, 15 
– 30°C (59 – 86°F).  The rescue medications will be stored in conditions specified in the 
manufacturers’ labeling information. 
5.11 Investigational Product Retention at Study Site 
The investigational products should be stored in a secure area with limited access.  The drug 
storage facility must comply with the medication storage instructions. EGT0001442 or 
placebo should be stored at controlled room temperature until ready for dispensing to study 
subjects.  The trial staff must record the amount of investigational product dispensed to each 
subject on the dosing record.  To ensure adequate record keeping, subjects must return all 
trial products at the end of the treatment period and the remaining tablets will be accounted 
for in the CRF and drug accountability forms provided. The procedures for obtaining drug 
resupply will be provided by the sponsor.  At the completion of the trial, all used and unused 
bottles must be destroyed after drug accountability is verified by Theracos or its designee. 

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6 
STUDY PROCEDURES 
6.1 
Informed Consent 
All subjects will be informed of the nature and purpose of the study and their written 
informed consent will be obtained during the pre-study screening procedures conducted 
within three weeks prior to the start of the run-in period. A copy of the Informed Consent 
form, including subject information, will be provided to each subject in his native language. 
6.2 
Medical History 
The following information will be collected at the screening period: 
• Demographic information including age, sex, race, and whether a female subject is of 
childbearing potential or not 
• Significant medical, surgical history with dates. 
• History of kidney stones, bladder malfunction, or frequent urinary tract infections 
• Incident of genitourinary tract infections in the previous 6 weeks  
• History of smoking, alcohol or drug dependence or abuse 
• History of diagnosis with HIV sero-positive acquired immunodeficiency syndrome 
(AIDS) or Hepatitis B/C 
• Use of any investigational drug in the previous 30 days or seven half-lives, whichever is 
longer 
• Prior treatment with EGT0001474 or EGT0001442.  Currently participating another 
interventional trial or not. 
• Use of aspirin, and use of cholesterol-lowering drugs and any other medications 
including over the counter drugs, vitamins, or dietary supplements within 14 days 
• Type of diabetes and time of first diagnosis 
• Anti- diabetic or hypertension medication history 
• History of cardiovascular events including angina, hypertension, congestive heart failure, 
atherosclerotic cardiovascular disease, myocardial infarction and diagnosis based on the 
New York Heart Association class, peripheral edema, and cerebrovascular ischemia (TIA 
or CVA). 
• History of cardiac procedures including any re-vascularization procedures or 
hospitalization for chest pain.  
 

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6.3 
Physical Examination 
A complete physical examination will be performed by the investigator at screening and at 
the termination visit.  A complete physical examination will include measurement of body 
weight and height (height will be measured only at screening), general assessment of all body 
systems including the skin, head, eyes, ears, nose, throat, neck, thyroid, lungs, heart, 
abdomen, lymph nodes, and extremities. 
An abbreviated physical examination will include body weight and general assessment of the 
skin, heart, lungs and abdomen.  Abbreviated physical examinations will be performed by the 
investigator at all other time points, unless clinically indicated. 
The body weight must be determined using a scale that is calibrated regularly and no less 
than annually. 
6.4 
Vital Signs 
Vitals signs include pulse, systolic and diastolic blood pressure at sitting position after a 
subject has been sitting for 5 minutes, respiration rate, and temperature.  Vital signs must be 
taken twice with at least 3 minutes apart. 
6.5 
Electrocardiography 
A 12-lead electrocardiogram (ECG) will be conducted as listed in study activity chart in 
Appendix 1 and whenever clinically indicated. 
6.6 
Diet and exercise counseling 
Enrolled diabetic subjects will receive counseling regarding an appropriate diet to aid in  
glycemic control based on standards of medical care in diabetes throughout the study (ADA, 
2008). 
6.7 
Clinical Laboratory Tests 
6.7.1 
Laboratory Parameters 
Subjects will be in a seated or supine position during blood collection.  Schedule of each 
laboratory test is outlined in Appendix 1.  Clinical laboratory tests will include the following: 
Table 1. 
List of Laboratory Tests 
Hematology: 
- 
Hematocrit (Hct) 
- 
Hemoglobin (Hgb) 
- 
Platelet count 
Serum Chemistry: 
- 
Albumin (ALB) 
- 
Alanine aminotransferase (ALT;  
- 
Aspartate aminotransferase (AST;  

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- 
Red blood cell (RBC) count  
- 
White blood cell (WBC) count with 
differential  
 
Urinalysis:  
- 
Appearance 
- 
Bilirubin 
- 
Color 
- 
Glucose 
- 
Ketones 
- 
Microscopic examination of 
sediment  
- 
Nitrite  
- 
Occult blood 
- 
pH 
- 
Protein 
- 
Specific gravity 
- 
Urobilinogen 
 
Hepatitis screening HBsAg, HBcAg, and 
HCV 
 
Urine drug screen 
 
Urine human chorionic gonadotropin 
(hCG) (only for females who are not 
diagnosed as postmenopausal)  
 
- 
Blood urea nitrogen (BUN) 
- 
Calcium (Ca) 
- 
Carbon dioxide (CO2) 
- 
Chloride (Cl) 
- 
Creatinine 
- 
Glucose 
- 
Phosphorus 
- 
Potassium (K) 
- 
Sodium (Na) 
- 
Magnesium 
- 
Total bilirubin 
- 
Direct bilirubin 
- 
Total cholesterol 
- 
High density lipoprotein 
cholesterol (HDL-C) 
- 
Low density lipoprotein 
cholesterol (LDL-C, calculated) 
- 
ApoB  
- 
Total protein 
- 
Triglycerides 
- 
Uric acid 
- 
Fasting plasma glucose  
- 
HbA1c  
 
Coagulation:  
- 
Prothrombin time (PT) 
 
6.7.2 
Sample Collection, Storage, and Shipping 
6.7.2.1 
Hematology and blood chemistry 
Blood samples for hematology, coagulation, and chemistry will be collected.  Timing of 
collection is described in the Schedule of Events (see Appendix 1). 
The study staff will contact each subject prior to a scheduled clinic visit to confirm the time 
of the visit and to remind the subject of appropriate diet and exercise control, proper fasting, 
and to record the diary card with meals of the day and time that the subject ate prior to the 

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clinic visit.  A subject must be queried to assess compliance with a minimum of a 10 hour 
fast prior to blood draw to ensure the FPG and triglycerides values can be accurately 
determined.  If a subject has not fasted for 10 hours, the subject must return as soon as can be 
arranged (within 7 days) after proper fasting.  If the 10 h fast is not collected within 7 days of 
the visit, the fasting plasma glucose will be considered missing. 
6.7.2.2 
Urinalysis 
Clean-catch, midstream urine samples will be collected per schedule outlined in Section 7. 
Dipstick urinalysis will be conducted.  Microscopy will be conducted if the subject has a 
positive result on any of the dipstick tests that require microscopic follow-up to clarify their 
significance. 
6.8 
Dispensing Study Drug 
Study drug will be dispensed by the pharmacist or designated personnel on day 1 with self 
administered dosing instructions and a dosing log. 
6.9 
Adverse Events Assessments 
6.9.1 
Definitions 
An adverse event (AE) is defined as any new medical problem, or exacerbation of an 
existing problem, experienced by a subject while enrolled in the study, whether or not it is 
considered drug-related by the investigator. 
A serious adverse event (SAE) includes any event that results in any of the following 
outcomes: 
- 
death 
- 
life-threatening, i.e., the subject was, in the opinion of the investigator, at immediate 
risk of death from the event as it occurred.  It does not include an event that, had it 
occurred in a more severe form, might have caused death. 
- 
persistent or significant disability/incapacity 
- 
requires in-patient hospitalization or prolongs hospitalization 
- 
congenital anomaly/birth defect 
- 
other medically significant events that, based upon appropriate medical judgment, 
may jeopardize the subject and may require medical or surgical intervention to 
prevent one of the outcomes listed above, e.g., allergic bronchospasm requiring 
intensive treatment in an emergency room or home, blood dyscrasias or convulsions 
that do not result in hospitalization, or the development of drug dependency or drug 
abuse. 
 

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Non-serious adverse events are all events that do not meet the criteria for a "serious" adverse 
event. 
Immediately Reportable Adverse Event (IRAE):  Any serious adverse event or any 
adverse event that necessitates discontinuation of study drug, including pregnancy. 
Clinical Laboratory Changes:  It is the investigator’s responsibility to review the results of 
all laboratory tests as they become available.  For each abnormal laboratory test result, the 
investigator needs to ascertain if this is an abnormal (i.e., clinically significant) change from 
baseline for that individual subject. (This determination, however, does not necessarily need 
to be made the first time an abnormal value is observed.  The investigator may repeat the 
laboratory test or request additional tests to verify the results of the original laboratory tests).  
If this laboratory value is determined to be an abnormal change from baseline for that 
subject, this is considered an AE.  
High serum or plasma glucose (hyperglycemia) and high HbA1c, the disease related 
morbidity, are being followed as the study endpoints and will not be documented as adverse 
events.  If, however, the event fulfills any of the criteria for a “serious” adverse event, it must 
be recorded and reported as such. 
Hypoglycemia will be defined as any FPG or SMBG value < 70 mg/dL. 
Any increase in liver function tests (AST, ALT, or bilirubin) greater than 3X the ULN for the 
laboratory utilized will be considered a clinical laboratory adverse event. 
Increase in creatinine from baseline by 0.5 mg/dL or more will be reported as a laboratory 
adverse event. 
Severity:  Adverse events will be graded on a 3-point scale and reported as indicated on the 
CRF.  The intensity of an adverse experience is defined as follows: 
1 = Mild: Discomfort noticed, but no disruption to daily activity. 
2 = Moderate: Discomfort sufficient to reduce or affect normal daily activity. 
3 = Severe: 
Inability to work or perform normal daily activity. 
 
Study Drug Causality: Relationship of an adverse event to treatment will be assessed as 
follows: 
- 
Definite: There is a reasonable causal relationship between the study drug and the 
AE, when the event responds to withdrawal of the study drug (dechallenge), and 
recurs with rechallenge by administration of the study drug. 
- 
Probable: There is a reasonable causal relationship between the study drug and the 
AE.  The event responds to dechallenge.  Rechallenge not required. 
- 
Possible: There is a reasonable causal relationship between the study drug and the 
AE.  Dechallenge is lacking or unclear. 

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- 
Not Likely: There is a temporal relationship to study drug administration, but there is 
not a reasonable causal relationship between the study drug and the event. 
- 
Unrelated: There is not a temporal or causal relationship to the study drug 
administration. 
 
6.9.2 
Eliciting and Reporting Adverse Events 
The investigator will periodically assess subjects for the occurrence of adverse events.  In 
order to avoid bias in eliciting adverse events, subjects should be asked the following non-
leading question: "How have you felt since your last visit?"  All adverse events (serious and 
non-serious) reported by the subject must be recorded on the source documents and CRFs 
provided by the sponsor.   
In addition, Theracos or its designated personnel must be notified immediately by telephone 
or fax of any immediately reportable adverse events according to the procedure outlined 
below.  Special attention should be paid to recording hospitalization and concomitant 
medications. 
6.9.3 
Immediately Reportable Adverse Events (IRAE) 
The investigator must report any serious adverse event or pregnancy, by telephone or by fax 
to Theracos immediately after the investigator becomes aware of the event.  An Immediately 
Reportable Adverse Event (IRAE) form should be completed and sent by fax or overnight 
courier to the sponsor within 24 hours of knowledge of the event by the site. 
Non-serious events that require discontinuation of study drug (including laboratory 
abnormalities) should be reported to Theracos within 3 working days.  The IRAE form 
should be completed and sent by fax or overnight courier to the sponsor.   
Subjects experiencing serious adverse events should be followed clinically until their health 
has returned to baseline status or until all parameters have returned to normal, or have 
otherwise been explained.  It is expected that the investigator will provide or arrange 
appropriate supportive care for the subject.  
6.9.4 
Pregnancy 
Women of childbearing potential (WOCBP) who are sexually active must use an effective 
method of birth control during the course of the study, in a manner such that risk of failure is 
minimized.  Unless the subject and his/her partner(s) are sterile (i.e., women who have had a 
hysterectomy or have been postmenopausal for at least 12 consecutive months) or remain 
abstinent, two of the following precautions must be used: vasectomy, tubal ligation, vaginal 
diaphragm, intrauterine device (IUD), birth control pills, birth control implant, condom or 
sponge with spermicide.  Any single method of birth control, including vasectomy and tubal 
ligation, may fail, leading to pregnancy. 

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Before enrolling WOCBP in this clinical trial, investigators must review guidelines about 
study participation for WOCBP.  The topics should generally include: 
- 
General information 
- 
Informed consent form 
- 
Pregnancy prevention information 
- 
Drug interactions with hormonal contraceptives. 
- 
Contraceptives in current use. 
- 
Guidelines for the follow-up of a reported pregnancy. 
 
Prior to study enrollment, WOCBP must be advised of the importance of avoiding pregnancy 
during trial participation and the potential risk factors for an unintentional pregnancy.  The 
subject must sign an informed consent form stating that the above-mentioned risk factors and 
the consequences were discussed with her. 
During the study, all WOCBP should be instructed to contact the investigator immediately if 
they suspect they might be pregnant (e.g., missed or late menstrual cycle). 
If a subject or investigator suspects that the subject may be pregnant prior to study drug 
administration, the study drug administration must be withheld until the results of blood and 
urine pregnancy tests are available.  If the pregnancy is confirmed, the subject must not 
receive the study drug and must not be enrolled in the study.  If pregnancy is suspected while 
the subject is receiving study treatment, the study drug must be withheld immediately (if 
reasonable, taking into consideration any potential withdrawal risks) until the result of the 
pregnancy is known.  If pregnancy is confirmed, the study drug will be permanently 
discontinued in an appropriate manner (e.g., dose tapering if necessary for subject safety) and 
the subject withdrawn from the trial.  [Exceptions to study discontinuation may be considered 
for life-threatening conditions only after consultations with a Theracos Medical Monitor (see 
Appendix III).] 
The investigator must immediately notify the Medical Monitor of any female subject who 
becomes pregnant within 30 days after study drug exposure.  The investigator must record 
the event on the Pregnancy Surveillance form and forward it to Theracos Clinical Drug 
Safety. 
Protocol required procedures for study discontinuation and follow-up must be performed on 
the subject unless contraindicated by pregnancy (e.g., x-ray studies).  Other appropriate 
pregnancy follow-up procedures should be considered if indicated.  In addition, the 
investigator must report to Theracos, on appropriate Pregnancy Surveillance form(s), follow-
up information regarding the course of the pregnancy, including perinatal and neonatal 
outcome.  Infants will be followed for a minimum of six months. 

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6.9.5 
Procedure for Breaking the Blind  
The investigator should remain blinded of the subject treatment during the entire study 
UNLESS knowledge of the subject’s treatment is required for the clinical care and safety.  
Emergency Code Break module in the IVRS is used for such emergency situations.  The 
investigator must confirm the intention to unblind the subject’s treatment to obtain the dose 
information.  Upon completion of the unblinding, the system will send an alert to designated 
study team members that an unblinding event occurred.  Documentation of breaking the blind 
should be recorded in the subject’s medical record with the date and time the blind was 
broken, and the names of the personnel involved. 
6.9.6 
Follow-up of Adverse Events  
6.9.6.1 
Follow-up of Non-serious Adverse Events 
Non-serious adverse events that are identified on the last scheduled contact must be recorded 
on the AE CRF with the current status noted.  All non-serious events that are ongoing at this 
time will be recorded as ongoing on the CRF. 
6.9.6.2 
Follow-up of Post Study Serious Adverse Events 
Serious adverse events that are identified on the last scheduled contact must be recorded on 
the AE CRF page and reported to Theracos according to the reporting procedures outlined in 
Section 6.9.3.   This may include unresolved previously reported serious adverse events, or 
new serious adverse events.  The investigator should follow these serious adverse events until 
the events are resolved, or the subject is lost to follow-up.  Resolution means the subject has 
returned to the baseline state of health, or the investigator does not expect any further 
improvement or worsening of the subject’s condition.  The investigator should continue to 
report any significant follow-up information to Theracos up to the point the event has been 
resolved.   
Any new serious adverse events reported by the subject to the investigator that occur after the 
last scheduled contact, and are determined by the investigator to be reasonably associated 
with the use of the study drug, should be reported to Sponsor.  This may include serious 
adverse events that are captured on follow-up telephone contact or at any other time point 
after the defined study period (i.e., up to last scheduled contact). The investigator should 
follow serious related adverse events identified after the last scheduled contact until the 
events are resolved, or the subject is lost to follow-up.  The investigator should continue to 
report any significant follow-up information to Sponsor up to the point the event has been 
resolved.   
Any serious adverse events reported by the subject to the investigator that occur after the last 
scheduled visit, and are determined by the investigator to be reasonably associated with the 
use of the study drug, should be reported to Sponsor.  This study requires that subjects be 
actively monitored for serious adverse events at least 14 days after discharge from the study. 

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6.9.7 
Adverse event of special interest 
6.9.7.1 
Genitourinary infections  
Events representing genitourinary infection (e.g. cystitis, urethritis, pyelonephritis, balanitis, 
vulvovaginitis should be carefully evaluated and documentation of signs, symptoms, 
infectious agent (bacterial or fungal), and treatment should be undertaken. 
6.9.7.2 
Renal and urinary disorders 
Events that may be related to the diuretic effect of an SGLT2 inhibitor (e.g. nocturia, 
pollakiuria, polyuria, and dysuria) should be carefully evaluated and documented. 
6.9.7.3 
Major Adverse Cardiovascular Event (MACE) 
Evaluation of major adverse cardiovascular events will be undertaken across the 
development program for EGT0001442.  All events that potentially represent myocardial 
infarction, cerebrovascular accident (stroke), acute coronary syndrome, or cardiovascular 
death are to be evaluated by an adjudication committee. 
6.9.7.4 
Hypoglycemia 
Severe hypoglycemia is defined as hypoglycemia with documented blood glucose 2.8 
mmol/L (50 mg/dL) or symptoms that promptly resolve with oral carbohydrate, intravenous 
glucose, or glucagon that require the assistance of medical or paramedical personnel. 
6.10 Concomitant Medication Assessments 
A concomitant medication is any medication the patient enters the trial using and is expected 
to continue using for some portion of the trial as well as any medication the patient uses 
during the course of the trial.  All concomitant medications recorded at trial entry must have 
a related concomitant illness listed under the medical history as ongoing at the time of patient 
entry into the trial unless the medication is an allowed treatment for the disease under study.   
EGT0001442 or placebo are the study drugs and are not considered concomitant 
medications.  The rescue medications for controlling hyperglycemia must be recorded as 
concomitant medications. 
All prescription and over-the-counter medications patients receive pre-study and continue 
during the trial as well as any new medications started during the trial must be documented 
on the CRF.  This documentation should continue until one week from the end of the last 
treatment.  
Concomitant medications will be coded using the World Health Organization dictionary 
(WHODRUG). A table of concomitant medications based on the anatomic therapeutic 
chemical classification (ATC) and preferred name will be produced.  A listing of 
concomitant medications will include all medications taken during the course of the study.  

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Any medications taken prior to the start of the study medication will be listed and 
summarized. 
6.11 Removal of Patients from the Trial or Study Drug 
The investigator may withdraw a patient from any of the following reasons: 
• A protocol violation occurs, 
• A serious or intolerable adverse event occurs, 
• A clinically significant change in a laboratory parameter occurs,  
• The sponsor or investigator terminates the study, or 
• The patient requests to be discontinued from the study. 
 
6.12 Other Study Procedures 
Approximately 0.5 mL plasma sample will be collected and stored at -20oC at each clinic 
visit during the treatment period.  The samples will be shipped to the analytical laboratory in 
batches.  EGT0001442 plasma concentration may be determined from all or a portion of the 
samples to verify the drug exposure. 

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7 
STUDY ACTIVITIES 
The study activities in each clinic visit are listed below and are presented in Appendix A.  
Screening period may last up to 21 days (Visit 1 to Visit 2), Run-in period is to be 14±3 days 
(Visit 2 to Visit 3), Visit 3 to Visit 4 window is 14±3 days.  All other visit windows are the 
nominal duration from randomization ± 7 days. 
7.1.1 
Visit 1 - Screening (weeks –5 to -2) 
The screening can be performed up to 3 weeks from the start of study activities.  During the 
screening period, the following information will be gathered or the indicated procedure will 
be performed: 
• Informed Consent and medical history obtained, and Inclusion/Exclusion criteria 
evaluated 
• Complete physical examination including height and weight 
• Vital Signs: blood pressure, pulse, temperature, respiratory rate taken in the sitting 
position after at least 5 minutes of rest.  Blood pressure must be measured twice with at 
least 3 min apart 
• 12 lead ECG taken in the supine position after at least 5 minutes of rest 
• Blood draw for hematology (CBC with platelets, WBC with differential), serum 
chemistry including FPG, and coagulation as detailed in section 6.7.1 
• Urinalysis 
• Urine screen for drugs of abuse.  Drug screening includes amphetamines, barbiturates, 
cocaine metabolites, opiates, benzodiazepines, and cannabinoids.  
• Urine pregnancy test (only for females who are not postmenopausal) 
• The subject must be queried to assess compliance with a minimum of a 10 h fast prior to 
blood draw to ensure the FPG values can be accurately determined.  If a subject has not 
fasted for 10 h, the subject should return within a week after proper fasting. 
 
7.1.2 
Visit 2 – run-in period (day -14±3) 
• Confirm eligibility  
• Diet and exercise counseling 
• Glucometer dispensing and training for SMBG determination 
• Discontinue anti-diabetic medication 
• Vital Signs: blood pressure, pulse, temperature, respiratory rate taken in the sitting 
position after at least 5 minutes of rest.  Blood pressure must be measured twice with at 
least 3 min apart 

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• Dispense study medication for the run-in period 
 
7.2 
Primary Efficacy Phase 
7.2.1 
Visit 3 – procedures (Day 1 in Week 0) 
 The subject must be queried to assess compliance with a minimum of a 10 h fast prior to 
blood draw to ensure the FPG values can be accurately determined.  Only water is 
permitted.  If a subject has not fasted for 10 h, the subject should return within a week 
after proper fasting. 
• Confirm eligibility  
• Diary and SMBG review 
• Adverse events and pre-treatment medications assessment 
• Randomization 
• Vital Signs: blood pressure, pulse, temperature, respiratory rate taken in the sitting 
position after at least 5 minutes of rest.  Blood pressure must be measured twice with at 
least 3 min apart 
• 12 lead ECG taken in the supine position after at least 5 minutes of rest 
• Dispense study medication based on randomization assignment 
• Blood draw for hematology (CBC with platelets, WBC with differential), serum 
chemistry including FPG, and coagulation as detailed in section 6.7.1 
• Urinalysis 
 
7.2.2 
Visit 4 – Procedures (week 2) 
 The subject must be queried to assess compliance with a minimum of a 10 h fast prior to 
blood draw to ensure the FPG values can be accurately determined.  Only water is 
permitted.  If a subject has not fasted for 10 h, the subject should return within a week 
after proper fasting. 
• Diary and SMBG review 
• Vital Signs: blood pressure, pulse, temperature, respiratory rate taken in the sitting 
position after at least 5 minutes of rest.  Blood pressure must be measured twice with at 
least 3 min apart 
• Blood draw for hematology (CBC with platelets, WBC with differential), serum 
chemistry including FPG, and coagulation as detailed in section 6.7.1 
• Urinalysis 

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• Collect plasma sample for drug exposure verification 
• Assess adverse events and record concomitant medications 
 
7.2.3 
Visit 5 – Procedures (week 6) 
 The subject must be queried to assess compliance with a minimum of a 10 h fast prior to 
blood draw to ensure the FPG values can be accurately determined.  Only water is 
permitted.  If a subject has not fasted for 10 h, the subject should return within a week 
after proper fasting. 
• Diary and SMBG review 
• Vital Signs: blood pressure, pulse, temperature, respiratory rate taken in the sitting 
position after at least 5 minutes of rest.  Blood pressure must be measured twice with at 
least 3 min apart 
• Dispense study medication 
• Blood draw for hematology (CBC with platelets, WBC with differential), serum 
chemistry including FPG, and coagulation as detailed in section 6.7.1 
• Urinalysis 
• Collect plasma sample for drug exposure verification 
• Assess adverse events and record concomitant medications 
 
7.2.4 
Visit 6 – Procedures (week 12) 
 The subject must be queried to assess compliance with a minimum of a 10 h fast prior to 
blood draw to ensure the FPG values can be accurately determined.  Only water is 
permitted.  If a subject has not fasted for 10 h, the subject should return within a week 
after proper fasting. 
• Diary and SMBG review 
• Diet and exercise counseling 
• Physical examination 
• Vital Signs: blood pressure, pulse, temperature, respiratory rate taken in the sitting 
position after at least 5 minutes of rest.  Blood pressure must be measured twice with at 
least 3 min apart 
• Dispense study medication 
• Blood draw for hematology (CBC with platelets, WBC with differential), serum 
chemistry including FPG, and coagulation as detailed in section 6.7.1 

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• Urinalysis 
• Collect plasma sample for drug exposure verification 
• Assess adverse events and record concomitant medications 
 
7.2.5 
Visit 7 – Procedures (week 18) 
 The subject must be queried to assess compliance with a minimum of a 10 h fast prior to 
blood draw to ensure the FPG values can be accurately determined.  Only water is 
permitted.  If a subject has not fasted for 10 h, the subject should return within a week 
after proper fasting. 
• Diary and SMBG review 
• Vital Signs: blood pressure, pulse, temperature, respiratory rate taken in the sitting 
position after at least 5 minutes of rest.  Blood pressure must be measured twice with at 
least 3 min apart 
• Dispense study medication 
• Blood draw for hematology (CBC with platelets, WBC with differential), serum 
chemistry including FPG, and coagulation as detailed in section 6.7.1 
• Urinalysis 
• Collect plasma sample for drug exposure verification 
• Assess adverse events and record concomitant medications 
 
7.2.6 
Visit 8 – Procedures (week 24) 
 The subject must be queried to assess compliance with a minimum of a 10 h fast prior to 
blood draw to ensure the FPG values can be accurately determined.  Only water is 
permitted.  If a subject has not fasted for 10 h, the subject should return within a week 
after proper fasting. 
• Diary and SMBG review 
• Diet and exercise counseling 
• Physical examination 
• Vital Signs: blood pressure, pulse, temperature, respiratory rate taken in the sitting 
position after at least 5 minutes of rest.  Blood pressure must be measured twice with at 
least 3 min apart 
• 12 lead ECG taken in the supine position after at least 5 minutes of rest 
• Dispense study medication 

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• Blood draw for hematology (CBC with platelets, WBC with differential), serum 
chemistry including FPG, and coagulation as detailed in section 6.7.1 
• Urinalysis 
• Collect plasma sample for drug exposure verification 
• Assess adverse events and record concomitant medications 
 
7.3 
Extension Phase 
7.3.1 
Visit 9 – Procedures (week 36) 
 The subject must be queried to assess compliance with a minimum of a 10 h fast prior to 
blood draw to ensure the FPG values can be accurately determined.  Only water is 
permitted.  If a subject has not fasted for 10 h, the subject should return within a week 
after proper fasting. 
• Diary and SMBG review 
• Vital Signs: blood pressure, pulse, temperature, respiratory rate taken in the sitting 
position after at least 5 minutes of rest.  Blood pressure must be measured twice with at 
least 3 min apart 
• Dispense study medication 
• Blood draw for hematology (CBC with platelets, WBC with differential), serum 
chemistry including FPG, and coagulation as detailed in section 6.7.1 
• Urinalysis 
• Collect plasma sample for drug exposure verification 
• Assess adverse events and record concomitant medications 
 
7.3.2 
Visit 10 – Procedures (week 48) 
 The subject must be queried to assess compliance with a minimum of a 10 h fast prior to 
blood draw to ensure the FPG values can be accurately determined.  Only water is 
permitted.  If a subject has not fasted for 10 h, the subject should return within a week 
after proper fasting. 
• Diary and SMBG review 
• Diet and exercise counseling 
• Physical examination 

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• Vital Signs: blood pressure, pulse, temperature, respiratory rate taken in the sitting 
position after at least 5 minutes of rest.  Blood pressure must be measured twice with at 
least 3 min apart 
• Dispense study medication 
• Blood draw for hematology (CBC with platelets, WBC with differential), serum 
chemistry including FPG, and coagulation as detailed in section 6.7.1 
• Urinalysis 
• Collect plasma sample for drug exposure verification 
• Assess adverse events and record concomitant medications 
 
7.3.3 
Visit 11 – Procedures (week 60) 
 The subject must be queried to assess compliance with a minimum of a 10 h fast prior to 
blood draw to ensure the FPG values can be accurately determined.  Only water is 
permitted.  If a subject has not fasted for 10 h, the subject should return within a week 
after proper fasting. 
• Diary and SMBG review 
• Vital Signs: blood pressure, pulse, temperature, respiratory rate taken in the sitting 
position after at least 5 minutes of rest.  Blood pressure must be measured twice with at 
least 3 min apart 
• 12 lead ECG taken in the supine position after at least 5 minutes of rest 
• Dispense study medication 
• Blood draw for hematology (CBC with platelets, WBC with differential), serum 
chemistry including FPG, and coagulation as detailed in section 6.7.1 
• Urinalysis 
• Collect plasma sample for drug exposure verification 
• Assess adverse events and record concomitant medications 
 
7.3.4 
Visit 12 – Procedures (week 72) 
 The subject must be queried to assess compliance with a minimum of a 10 h fast prior to 
blood draw to ensure the FPG values can be accurately determined.  Only water is 
permitted.  If a subject has not fasted for 10 h, the subject should return within a week 
after proper fasting. 

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• Diary and SMBG review 
• Diet and exercise counseling 
• Physical examination 
• Vital Signs: blood pressure, pulse, temperature, respiratory rate taken in the sitting 
position after at least 5 minutes of rest.  Blood pressure must be measured twice with at 
least 3 min apart 
• Dispense study medication 
• Blood draw for hematology (CBC with platelets, WBC with differential), serum 
chemistry including FPG, and coagulation as detailed in section 6.7.1 
• Urinalysis 
• Collect plasma sample for drug exposure verification 
• Assess adverse events and record concomitant medications 
 
7.3.5 
Visit 13 – Procedures (week 84) 
 The subject must be queried to assess compliance with a minimum of a 10 h fast prior to 
blood draw to ensure the FPG values can be accurately determined.  Only water is 
permitted.  If a subject has not fasted for 10 h, the subject should return within a week 
after proper fasting. 
• Diary and SMBG review 
• Vital Signs: blood pressure, pulse, temperature, respiratory rate taken in the sitting 
position after at least 5 minutes of rest.  Blood pressure must be measured twice with at 
least 3 min apart 
• Dispense study medication 
• Blood draw for hematology (CBC with platelets, WBC with differential), serum 
chemistry including FPG, and coagulation as detailed in section 6.7.1 
• Urinalysis 
• Collect plasma sample for drug exposure verification 
• Assess adverse events and record concomitant medications 
 
7.3.6 
Visit 14 – Procedures (week 96) 
 The subject must be queried to assess compliance with a minimum of a 10 h fast prior to 
blood draw to ensure the FPG values can be accurately determined.  Only water is 

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permitted.  If a subject has not fasted for 10 h, the subject should return within a week 
after proper fasting. 
• Diary and SMBG review 
• Physical examination 
• Vital Signs: blood pressure, pulse, temperature, respiratory rate taken in the sitting 
position after at least 5 minutes of rest.  Blood pressure must be measured twice with at 
least 3 min apart 
• 12 lead ECG taken in the supine position after at least 5 minutes of rest 
• Blood draw for hematology (CBC with platelets, WBC with differential), serum 
chemistry including FPG, and coagulation as detailed in section 6.7.1 
• Urinalysis 
• Collect plasma sample for drug exposure verification 
• Assess adverse events and record concomitant medications 
 
7.3.7 
Visit 15 – Exit Visit (week 97) 
Follow-up is planned at approximately one week after the last dose is administered.  If 
subjects have an ongoing adverse event, the subject will be followed until the adverse event 
is resolved or returns to baseline. All possible attempts will be made to document resolution 
of acute and chronic toxicities. Diary and SMBG review 
• Physical examination 
• Vital Signs: blood pressure, pulse, temperature, respiratory rate taken in the sitting 
position after at least 5 minutes of rest.  Blood pressure must be measured twice with at 
least 3 min apart 
• 12 lead ECG taken in the supine position after at least 5 minutes of rest 
• Blood draw for hematology (CBC with platelets, WBC with differential), serum 
chemistry including FPG, and coagulation as detailed in section 6.7.1 
• Urinalysis 
• Assess adverse events and record concomitant medications 
 
7.4 
Early Termination Procedures 
Subjects removed from study due to drug related toxicity will be followed until resolution or 
stabilization of the adverse event.  Sponsor must be notified in the event that a subject 
withdraws or is withdrawn from the study. 

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Subjects who withdraw consent and have received study drug will have a follow-up 
examination, including a complete physical examination, vital signs, ECG, CBC, urinalysis, 
and serum chemistry tests. 
 

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8 
QUALITY CONTROL AND ASSURANCE 
The clinical research facility will be monitored by the study monitor to ensure correct 
performance of the study procedures and assure that the study will be conducted according to 
the protocol and relevant regulatory requirements.  CRF entries will be verified with the 
source documentation. 
Quality control principles will be applied throughout the performance of this study by 
following the SOPs of the CRO and the sponsor. Review procedures will be implemented at 
the CRO for all documents that are generated in relation to the study. 

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9 
PLANNED STATISTICAL METHODS 
9.1 
General Considerations 
The primary objective of this trial is to assess the efficacy of EGT0001442 in treatment-naïve 
type-2 diabetic patients or patients on a single oral anti-diabetic drug in combination with 
diet and exercise with an HbA1c between 7 and 10%.  Efficacy, in this case, is defined as a 
significant reduction in HbA1c at week 24 when compared to placebo.  The effect of 
EGT0001442 on fasting glucose, blood pressure, body weight and the general safety of 
EGT0001442 in patients with T2DM will also be explored. 
Statistical analyses and summaries of safety and tolerability will be performed using SAS® 
software (SAS Institute, Cary, NC).  In all cases, significance will be judged at the =0.05 
level.  No multiplicity adjustment will be required for the single primary endpoint. 
9.1.1 
Handling Dropouts, Multiples, Missing Data, and Outliers 
Discontinuation criteria are explained in Section 6.11.  Patients who discontinue will not be 
replaced.  Data will be evaluated for any bias in the pattern of missing data prior to inference 
testing.  Absence of a discernable pattern will be taken as a reliable indication that the 
incidences of missing data are random occurrences and will not be addressed further.  
Clinically relevant patterns of missing data will be summarized in the Clinical Trial Report 
and summarized as notes to any affected tables and listings.  Missing data will not be 
imputed and the observation for that subject will be effectively deleted for that subject.   
9.1.2 
Multiple Comparisons / Multiplicity 
There is a single primary endpoint in this study and no correction for multiple comparisons is 
needed.  Important secondary endpoints are considered exploratory and will not be corrected. 
9.2 
Determination of Sample Size 
Approximately 300 patients will be enrolled and equitably allocated to receive either 20 
mg/day EGT0001442 or placebo.   
The sample size of 150 subjects per group was calculated based on the following 
assumptions:  
1.  This effect size is the mean difference between baseline and week 24.  The active 
doses will decrease the HbA1c by 0.4%. 
2. The placebo will not experience a substantive average decrease in mean HbA1c from 
baseline to week 24 
3. The standard deviation of this difference is the same for both groups and is 1.0%.   
4. The study design is balanced and the two-sided significance level for the hypothesis 
is 0.05.  
 

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Under the above assumptions, an evaluable sample size of 131 evaluable patients per 
treatment arm yields approximately 90% power that EGT0001442 treatment will be found to 
be significantly different from placebo.  A sample size of 150 subjects per treatment arm will 
be enrolled to account for any subject lost-to-follow-up. 
9.3 
Analysis Populations  
This study will be conducted at multiple investigative sites and will likely involve variable 
numbers of subjects at each site.  Enrollment will be on a competitive basis but will be 
capped at 90 subjects in one center. 
All patients in the Intent-to-Treatment (ITT) sample will be analyzed according to the 
treatment they were randomized to receive, and not according to what they actually received, 
if different.  All efficacy analyses will be performed on the ITT sample. All patients in the 
Per Protocol (PP) sample will be analyzed according to the treatment actually received, and 
not according to the treatment they were randomized to receive, in the event there is a 
discrepancy.  The analyses of primary efficacy endpoint and selected secondary efficacy 
endpoints will be performed on the PP sample.  The Safety sample will include all 
randomized patients who have received study drug.  The safety sample will be used for safety 
analysis. 
9.4 
Demographics and Baseline Characteristics 
Patients must meet all inclusion criteria and none of the exclusion criteria in order to 
participate in the study.  Demographic characteristics include age, gender, race, ethnicity, and 
study center.  Baseline characteristics include baseline HbA1c values, blood pressure, Body 
Mass Index (BMI in kg/m2), whether treatment naïve or not.  Summary descriptive statistics 
will include counts and percentages for discrete variables and estimation of means, standard 
deviations, medians, inter-quartile range, minimum and maximum for continuous metrics. 
9.5 
Analysis of Efficacy 
Efficacy data includes HbA1c, FPG, body weight, systolic and diastolic blood pressure, and 
% of subject who achieve HbA1c <7% at week 24.  Observed data will be summarized as 
counts and percentages for discrete variables and estimation of means, standard deviations, 
medians, inter-quartile range, minimum and maximum for continuous metrics.  All data will 
be presented in by-subject listings and included in the clinical trial report. 
9.5.1 
Primary Efficacy Endpoint 
The primary hypothesis is that EGT0001442 reduces HbA1c after 24 weeks of treatment 
when compared to placebo controls.  Change in HbA1c will be estimated as HbA1c at 24 
weeks minus HbA1c at baseline.  The two groups will be compared with a t-test at a 
significance level of 0.05.  For subjects that receive rescue medication due to hyperglycemia, 
the last HbA1c prior to receiving rescue medication will be carried forward to week 24.   

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9.5.2 
Secondary Efficacy Endpoints 
The secondary endpoints are considered exploratory and will not be corrected for 
multiplicity.  The first secondary hypothesis is that EGT0001442 reduces FPG at weeks 2 
and 24 when compared to controls.  Change in FPG for each follow up visit will be estimated 
as follow-up minus baseline and the two treatment groups will be compared with two paired 
t-tests. 
The second hypothesis is that EGT0001442 reduces the HbA1c to less that 7% of more 
patients when compared to placebo.  HbA1c categories will be assessed for each patient as 
<7% or ≥7% of each subject.  The 2x2 contingency table of treatment by HbA1c category 
will be analyzed with a test.  
The third hypothesis is that EGT0001442 reduces blood pressure compared to placebo.  
Systolic and Diastolic blood pressure will be measured at baseline and at weeks 2 and weeks 
24.  Change in each blood pressure metric for both follow up visits will be estimated as 
follow-up minus baseline and the two treatment groups will be compared with four paired t-
tests. 
The fourth hypothesis is that EGT0001442 reduces body weight compared to placebo.  Body 
weight will be measured at baseline and at weeks 2 and weeks 24.  Change in body weight 
for both follow up visits will be estimated as follow-up minus baseline and the two treatment 
groups will be compared with two paired t-tests. 
The final secondary hypothesis is that EGT0001442 induced change in HbA1c is evident 
over time, present at week 24 and maintained over the 96 weeks of the study.  HbA1c is 
collected at baseline and weeks 2, 6, 12, 24, 36, 48, 60, 72, 84 and 96.  Repeated measures of 
HbA1c will be analyzed with a linear mixed effect model to assess the overall treatment 
effect.  Subsequently the change in each time point will be estimated as described for the 
primary endpoint and evaluated with 10 t-tests. 
9.5.3 
Additional Efficacy Endpoints 
As with HbA1c, repeated measures are available for body weight, systolic and diastolic 
blood pressure, and fasting plasma glucose. Repeated measures of these variables will be 
analyzed individually with a linear mixed effect model to assess the overall treatment effect.  
Subsequently the change in each time point will be estimated as described for the primary 
endpoint and evaluated with t-tests.   
The effect of demographic covariates such as gender, race, age, treatment center, will be 
evaluated on the primary endpoint and selected secondary endpoints (FPG, blood pressure, 
and body weight) using Analysis of Covariance.  Demographic variables will be included in 
the model of change in the dependent variable with treatment. 

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9.6 
Analysis of Safety  
Safety data includes adverse events (AEs), physical exam results, vital signs, ECG results, 
and clinical lab results including serum chemistry, hematology, and urinalysis. Observed data 
will be described as counts and percentages for discrete variables and estimation of means, 
standard deviations, medians, inter-quartile range, minimum and maximum for continuous 
metrics.  All patients will be included in the safety analysis.  All safety data will be presented 
in by-subject listings and included in the clinical trial report. 
9.6.1 
Adverse Events 
Adverse events will be mapped to preferred term and body system using the Medical 
Dictionary for Regulatory Activities (MedDRA) dictionary. The number and percentage of 
patients reporting adverse events will be determined by relationship to treatment and by 
severity of the event. Drug-related adverse events will be considered those to be at least 
possibly related to EGT0001442 administration. 
Adverse event listings will be provided for the following subsets: 
• All treatment emergent AEs (TEAEs) 
• All TEAEs at least possibly related to EGT0001442 
• Serious TEAEs (if any) 
• TEAEs leading to study discontinuation (if any) 
 
AEs are treatment emergent if occurring on or after EGT0001442 administration. TEAEs 
will be considered at least possibly related to EGT0001442 based on the investigators 
assessment. Only TEAEs will be tabulated in summary tables. 
Tabulations will display TEAEs by severity, and relationship to EGT0001442. 
9.6.2 
Adverse event of special interest  
9.6.2.1 
Genitourinary infections  
Genitourinary infections as defined in Section 6.9.7.1 will be summarized.  Event terms, 
signs, symptoms, infectious agent (bacterial or fungal), and treatment undertaken will be 
documented in the listing. 
9.6.2.2 
Major Adverse Cardiovascular Event (MACE) 
All events that potentially represent myocardial infarction, cerebrovascular accident (stroke), 
acute coronary syndrome, or cardiovascular death are to be evaluated by an independent 
adjudication committee.  There will not be any analysis performed. 

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9.6.2.3 
Hypoglycemia 
Severe hypoglycemia as defined in Section 6.9.7.3 will be presented in a listing and 
summarized. 
9.6.2.4 
Renal and Urinary disorders 
Events as defined in Section 6.9.7.1 will be summarized.  Event terms, signs, and symptoms 
will be documented in the listing. 
9.6.3 
Clinical and Laboratory Events and Analyses 
Clinical and laboratory metrics are measured at baseline and weeks 2, 6, 12 and 24 during the 
study.  During the treatment extension they are measured every 12 weeks up to a total of 96 
weeks.  These variables include vital signs (blood pressure, respiration, and temperature), 
Clinical laboratory (see section 6.7 for a complete list) and ECGs. 
Laboratory data will be summarized using Low-Normal-High shift tables.  ECG results will 
be summarized as changes from baseline in intervals.  Abnormalities as well as changes from 
previous assessment will be listed. 
9.6.4 
Concomitant Medications 
Concomitant medications will be coded using the World Health Organization Drug 
Dictionary (WHODRUG).  A by-subject listing of concomitant medications will include all 
medications taken during the study.  All medications started prior to the administration of the 
study drug will be included in the data but will be flagged as prior.  Only the concomitant 
medication use will be summarized. 
9.7 
Interim Analysis 
An independent Data and Safety Monitoring Board (DSMB) will monitor the safety of this 
study.  The objectives of the DSMB are to assess drug safety and allow for protocol 
modification or early stopping due to safety concerns.  The DSMB members will include at 
least one statistician, one clinician of relevant specialty, and one endocrinologist that is 
familiar with the care of patients with type 2 diabetes.  No interim efficacy assessment will 
be performed. 

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10 ADMINISTRATIVE CONSIDERATIONS 
10.1 Investigators and Study Administrative Structure 
Information regarding key personnel involved in the conduct of the study, including names 
and contact details of participating investigators, monitors, clinical laboratories, technical 
departments and/or institutions, as well as information on members of additional study 
committees, will be found in the study files of the study sites. 
10.2 Institutional Review Board (IRB) or Independent Ethics Committee 
(IEC) Approval 
This protocol, informed consent document, relevant supporting information, and all types of 
subject recruitment or advertisement information must be submitted to the IEC or IRB for 
review and must be approved by The Sponsor and the IEC/IRB before the study is initiated.  
Any amendments or addenda to the protocol must also be approved by the IEC/IRB prior to 
implementing changes in the study.  The Investigator is responsible for keeping the IEC/IRB 
apprised of the progress of the study and of any changes made to the protocol as deemed 
appropriate, but in any case at least once a year.  The Investigator must also keep the 
IEC/IRB informed of any SAEs occurring to subjects under their supervision. 
10.3 Ethical Conduct of the Study 
The procedures set out in this protocol, pertaining to the conduct, evaluation, and 
documentation of this study, are designed to ensure that the sponsor and investigator abide by 
Good Clinical Practice Guidelines and under the guiding principles detailed in the 
Declaration of Helsinki. The study will also be carried out in keeping with applicable local 
law(s) and regulation(s). This may include an inspection by the sponsor representatives 
and/or their designee and/or FDA representatives at any time. The investigator must agree to 
the inspection of study-related records by the FDA/sponsor representatives, and must allow 
direct access to source documents to the FDA/sponsor representatives. 
The investigator is responsible for complying with the protocol and all appropriate 
regulations and guidelines governing global clinical research. Additionally, he/she is 
responsible for ensuring that all participating staff members are adequately trained and 
competent to perform his/her assigned tasks. 
Modifications to the study protocol will not be implemented by either the sponsor or the 
investigator without agreement by both parties. However, the investigator may implement a 
deviation form, or a change of, the protocol to eliminate an immediate hazard(s) to the trial 
subjects without prior IRB/sponsor approval/favorable opinion. As soon as possible, the 
implemented deviation or change, the reasons for it and if appropriate the proposed protocol 
amendment should be submitted to the IRB/sponsor. 
Any deviations from the protocol must be fully explained and documented by the 
investigator. The circumstances, action taken and impact of the deviation on the trial must be 

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communicated by the Principal Investigator to the designated Medical Monitor. Any 
subsequent actions will be assessed by the designated Medical Monitor and documented. 
10.4 Patient Information and Consent 
Prior to the beginning of the study, the investigator must have the EC/IRB written approval/ 
favorable opinion of the written Informed Consent Form and any other written information to 
be provided to subjects. The written approval of the EC/IRB together with the approved 
subject information/Informed Consent Forms must be filed in the study files. The Informed 
Consent Form must contain all elements required by the FDA under 21 CFR Part 50 and the 
International Conference on Harmonisation (ICH) Good Clinical Practices (GCP) Guidelines 
(E6) in addition to any other elements required by state, local or institutional policy.  
Written informed consent must be obtained before any study specific procedure takes place. 
Participation in the study and date of informed consent given by the subject should be 
documented appropriately in the subject’s files. A copy of the signed informed consent form 
must be provided to the subject.  If applicable, it will be provided in a certified translation in 
the language understood by the subject if not English.  Signed consent forms must remain in 
each subject’s study file and must be available for verification by study monitors at any time. 
10.5 Patient Confidentiality 
The information obtained during the conduct of this clinical study is confidential, and 
disclosure to third parties other than those noted below is prohibited.  Information obtained 
during the conduct of this study will be used by The Sponsor in connection with the 
development of the study drug.  The study Investigator is obliged to provide the Sponsor with 
complete test results and all data developed in this study.  Subject-specific information may 
be provided to other appropriate medical personnel only with the subject’s permission.  To 
ensure compliance with current ICH guidelines, data generated by this study must be 
available for inspection upon request by representatives of national and local health 
authorities, the Sponsor and the IRB for each study site. 
Subject names and other identifiers, such as photographs, audio or videotapes, may not be 
disclosed in any publication without prior written authorization from the subject. 
10.6 Study Monitoring 
An authorized Sponsor representative will conduct site visits to inspect study data, subjects’ 
medical records and CRFs in accordance with ICH guidelines, GCPs and the respective local 
and national government regulations and guidelines. 
The Investigator will permit authorized representatives of the Sponsor and the respective 
national or local health authorities to inspect facilities and records relevant to this study. 

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10.7 Case Report Forms and Study Records 
For each subject consented, a case report form (CRF) will be supplied and maintained by the 
CRO staff and signed by the investigator or authorized designee to indicate that he/she has 
reviewed and agrees with the entered data. This also applies to those subjects who fail to 
complete the trial. The reason a subject is withdrawn must be recorded in the case report 
form. 
Entries made in the CRF must be verifiable against source documents. Source documents are 
defined as all medical records, medical notes, laboratory results, ECG traces and any 
additional document other than the CRF that has original subject information contained 
within it.  The diary card that subjects will complete with meal information will be archived 
but meal information will not be entered in the database.  Whether the subject was fasting for 
10 hr or not prior to sample collection will be captured in the CRF. 
All CRFs and source documents should be completed following GCPs and the CRO’s 
standard operating procedures. 
10.8 Protocol Violations/Deviations 
Protocol “violations” include deviations from the inclusion and exclusion criteria, 
concomitant medication restrictions, and any other protocol requirement that results in a 
significant added risk to the patient or has an impact on the quality of the data collected or 
the outcome of the study.  Protocol violations must be reported to the Ethics Committee or 
Institutional Review Board in a timely manner. Protocol violations must be reported in the 
final study report. 
A protocol deviation occurs when there is non-adherence to study procedures or schedules, as 
specified by the protocol, which does not involve inclusion/exclusion criteria or the primary 
endpoint and which does not place the patient at any added risk or affect the data quality or 
study outcome.  If deviations occur, such as a missed visit or missed sampling window, the 
investigator must decide whether to proceed, for example, whether or not to complete the 
visit or sample collection outside of the protocol-defined window.  The sponsor’s medical 
monitor must be notified immediately when protocol deviations are discovered so that a 
decision can be made about the continued participation of the subject in the study. 
A departure from the protocol for an individual subject can only be made without the 
Sponsor approval in the event of an emergency.  The nature and reasons for the protocol 
deviation will be recorded in the CRF and the Principal Investigator must notify the Sponsor. 
10.9 Access to Source Documentation 
Authorized Sponsor representatives will conduct site visits to inspect study data, subject 
medical records and CRFs in accordance with ICH guidelines, GCP and the respective local 
and national government regulations and guidelines. 

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The Investigator will permit authorized representatives of the Sponsor and the respective 
national or local health authorities to inspect facilities and records relevant to this study. 
Each center will be visited at regular intervals by a monitor to ensure compliance with the 
study protocol, GCP and legal aspects. This will include on-site checking of the case report 
forms (CRF) for completeness and clarity, cross-checking with source documents, and 
clarification of administrative matters. 
All CRF data will be entered into a clinical database.  Following the correction of any errors, 
the clinical database will be locked. 
10.10 Data Generation and Analysis 
For each subject who is randomized to receive study drug, a case report form (CRF) must be 
maintained by a trial coordinator and signed by the investigator or authorized designee to 
indicate that he/she has reviewed and agrees with the entered data.  This also applies to those 
subjects who fail to complete the trial.  The reason a subject is withdrawn must be recorded 
in the CRF.  Subjects whose eligibility is not confirmed on day 1 are considered screen 
failure and no CRF will be maintained for those subjects. 
Entries made in the CRF must be either verifiable against source documents, or have been 
directly entered into the CRF, in which case the entry in the CRF will be considered as the 
source data.  Source documents are defined as all medical records, medical notes, laboratory 
results, ECG traces and any additional document other than the CRF that has original patient 
information contained within it. 
All source documents must be legible.  Errors must be lined out and the correction must be 
made, initialed and dated by the person making the correction. 
The Sponsor or designated CRO is responsible for data processing and data query.  The 
investigator or designated staff is responsible for query resolution and data clarification. 
10.11 Retention of Data 
The study file and all source data should be retained until notification given by the sponsor 
for destruction.  If the investigator withdraws from the trial and relinquishes his/her 
responsibility for the maintenance and retention of records, he/she must notify the Sponsor in 
writing so arrangements can be made to properly store the trial materials. 
10.12 Publication and Disclosure Policy 
All data and results and all intellectual property rights in the data and results derived from the 
study will be the property of the Sponsor, who may utilize the data in various ways, such as 
for submission to government regulatory authorities or disclosure to other investigators. 

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No publication or disclosure of study results will be permitted except as specified in a 
separate, written agreement between Theracos, Inc. and the investigator.  If results of this 
study are reported in medical journals or at meetings, all subjects’ identities will remain 
confidential. 

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11 REFERENCE LIST 
ADA (2008). Standards of medical care in diabetes--2008. Diabetes Care 31 Suppl 1, S12-54. 
Ehrenkranz, J.R., Lewis, N.G., Kahn, C.R., and Roth, J. (2005). Phlorizin: a review. Diabetes 
Metab Res Rev 21, 31-38. 
Ferrannini, E., Ramos, S.J., Salsali, A., Tang, W., and List, J.F. (2010). Dapagliflozin 
monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and 
exercise: a randomized, double-blind, placebo-controlled, phase 3 trial. Diabetes Care 33, 
2217-2224. 
Han, S., Hagan, D.L., Taylor, J.R., Xin, L., Meng, W., Biller, S.A., Wetterau, J.R., 
Washburn, W.N., and Whaley, J.M. (2008). Dapagliflozin, a selective SGLT2 inhibitor, 
improves glucose homeostasis in normal and diabetic rats. Diabetes 57, 1723-1729. 
Komoroski, B., Vachharajani, N., Boulton, D., Kornhauser, D., Geraldes, M., Li, L., and 
Pfister, M. (2009a). Dapagliflozin, a novel SGLT2 inhibitor, induces dose-dependent 
glucosuria in healthy subjects. Clin Pharmacol Ther 85, 520-526. 
Komoroski, B., Vachharajani, N., Feng, Y., Li, L., Kornhauser, D., and Pfister, M. (2009b). 
Dapagliflozin, a novel, selective SGLT2 inhibitor, improved glycemic control over 2 weeks 
in patients with type 2 diabetes mellitus. Clin Pharmacol Ther 85, 513-519. 
Neumiller, J.J., White, J.R., Jr., and Campbell, R.K. (2010). Sodium-glucose co-transport 
inhibitors: progress and therapeutic potential in type 2 diabetes mellitus. Drugs 70, 377-385. 
Santer, R., Kinner, M., Lassen, C.L., Schneppenheim, R., Eggert, P., Bald, M., Brodehl, J., 
Daschner, M., Ehrich, J.H., Kemper, M., et al. (2003). Molecular analysis of the SGLT2 gene 
in patients with renal glucosuria. J Am Soc Nephrol 14, 2873-2882. 
Sicree, R., Shaw, J., and Zimmet, P. (2010). The Global Burden - Diabetes and Impaired 
Glucose Tolerance (Baker IDI Heart and Diabetes Institute). 
van den Heuvel, L.P., Assink, K., Willemsen, M., and Monnens, L. (2002). Autosomal 
recessive renal glucosuria attributable to a mutation in the sodium glucose cotransporter 
(SGLT2). Hum Genet 111, 544-547. 
 
 

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Appendix 1 
Schedule of Events 
 
Screening 
& Run-in 
Primary Efficacy Phase 
Extension Phase 
Visit Number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
ET 
Time Relative to Randomization Visit 
(weeks)1 
-5 
-2 
0 
2 
6 
12 
18 
24 
36 
48 
60 
72 
84 
96 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening for I/E criteria 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Diet & exercise counseling 
 
X 
 
 
 
X 
 
X 
 
X 
 
X 
 
 
 
Diary Review 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Discontinue anti-diabetic medication 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Physical exam 
X 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECG 
X 
 
X 
 
 
 
 
X 
 
 
X 
 
 
X 
X 
Dispense study medication 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Blood draw for clinical lab test2 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PK sample 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urinalysis3 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AE4 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Con Med 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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1 
Screening period may last up to 21 days (V1 to V2), Run-in period is to be 14±3 days (V2 to V3), V3 to V4 window is 14±3 days, all other visit windows 
are the nominal duration from randomization ± 7 days. 
2 
Blood sample for these lab tests at the designated visit: 
V1: CBC, electrolytes, BUN, creatinine, Lipids (TG, TC, HDL-C), ALT, AST, bilirubin (total and direct), PT, HbA1c, FPG, TSH, aPTT, Hepatitis Screen 
(HBsAg, HBcAg, HCV) 
V3: CBC, electrolytes, BUN, creatinine, Lipids (TG, TC, HDL-c), ALT, AST, bilirubin (total and direct), HbA1c, FPG 
V4: CBC, electrolytes, BUN, creatinine, HbA1c, FPG 
V5: CBC, electrolytes, BUN, creatinine, HbA1c, FPG 
V6: CBC, electrolytes, BUN, creatinine, Lipids (TG, TC, HDL-c), ALT, AST, bilirubin (total and direct), HbA1c, FPG 
V7: CBC, electrolytes, BUN, creatinine, HbA1c, FPG 
V8-V14 and ET: CBC, electrolytes, BUN, creatinine, Lipids (TG, TC, HDL-c), ALT, AST, bilirubin (total and direct), HbA1c, FPG 
3 
Clean catch sample to be collected at each visit. If urine is dipstick positive for WBC or blood sample is to be sent for microscopic evaluation and culture.  
Urine pregnancy test and drug screen on screening (visit 1) 
4 
Adverse events of special interest are specified to be: 
 
Cardio- and cerebro- vascular events,  
 
Genitourinary infections  
 
Increase in creatinine from baseline by 0.5 mg/dL or more  
 
Increase in ALT, AST or bilirubin to >3x ULRR 
 
 

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Appendix 2 
Estimating glomerular filtration rate 
Estimating the glomerular filtration rate (eGFR), as calculated by the modification of diet in 
renal disease study equation (MDRD), should be calculated based on following equation: 
GFR (mL/min/1.73 m2) = 175 x (Scr)-1.154 x (Age)-0.203 x (0.742 if female) x (1.212 if African 
American) (conventional units) 
 

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Appendix 3 
Sponsor Signatures 
Study Title: 
Efficacy and safety of EGT0001442 compared with placebo in 
patients with type 2 diabetes mellitus inadequately controlled by diet 
and exercise and up to one oral anti-diabetes agent. 
Study Number: 
THR-1442-C-418 
Final Date: 
02 February 2011 
 
This clinical study protocol was subject to critical review and has been approved by the 
sponsor. The following personnel contributed to writing and/or approving this protocol: 
 
 
Signed: 
 
 
Date:  
 
Yuan-Di Halvorsen, Ph.D.  
Protocol Originator 
Consultant for Theracos, Inc. 
 
 
Signed: 
 
 
Date:  
 
R. Paul Aftring, M.D., Ph.D.  
Medical Director 
Consultant for Theracos, Inc. 
 
 
Signed: 
 
 
Date:  
 
Ulrich Granzer, Ph.D.  
Regulatory Affairs 
Consultant for Theracos Inc. 

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Appendix 4 
Investigator’s Signature 
Study Title: 
Efficacy and safety of EGT0001442 compared with placebo in 
patients with type 2 diabetes mellitus inadequately controlled by diet 
and exercise and up to one oral anti-diabetes agent. 
Study Number: 
THR-1442-C-418 
Final Date: 
02 February 2011 
I have read the protocol described above. I agree to comply with all applicable regulations 
and to conduct the study as described in the protocol.  
 
 
 
Signed: 
 
 
Date:  
 
Principal Investigator