Efficacy and Safety of EGT0001442 in Patients With Type 2 Diabetes Mellitus

• Sponsor: Theracos (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01377844
• Collaborator: (none)
• Enrollment: 288
• Locations: 11
• Arms: 2
• Duration (Months): 24
• Patients Per Site: 26.2
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the efficacy of EGT0001442 in lowering glycosylated Hemoglobin (HbA1c, A laboratory test to diagnose three months average of blood sugar)levels at 24th week from baseline, when compared to placebo group(no diabetic medication given). The secondary aim of the study is to evaluate the efficacy of EGT0001442 in lowering fasting blood glucose at the weeks 2 and 24 and comparing the results with placebo group. This study assess the efficacy of EGT0001442 based on the proportion of subjects who reach the American Diabetes Association (ADA) target of HbA1c of < 7% in EGT0001442 group and comparison with placebo. The study also evaluates the effect of EGT0001442 on systolic, diastolic pressures, body weight and compare with the respective placebo groups.This study also assess the change from baseline in HbA1c overtime, from week 1 to week 96. Finally, to assess the safety of EGT0001442 in the Type 2 Diabetic patients (adult/maturity onset).

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus	Drug: EGT0001442; Drug: Placebo	Phase 2

Detailed Description

EGT0001442 is a compound that may inhibit the effect of other compounds in the body known as sugar transporters. The use of EGT0001442 may enhance the elimination of glucose from the blood by increasing the amount of urine produced. Hence the blood glucose levels are significantly decreased and the efficacy of EGT001442 can be established by assessing the three months average blood glucose levels (HbA1c). Due to the increased urinary output, the effect of EGT001442 on blood pressure levels are also assessed.

Study Design

• Study Type: Interventional
• Actual Enrollment: 288 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official 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 Start Date: Dec 1, 2011
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: EGT0001442 EGT0001442 capsule, 20 mg, daily, 96 weeks	Drug: EGT0001442; Other Names: Bexagliflozin
Placebo Comparator: Placebo Placebo	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Hemoglobin A1c at 24 Weeks [Baseline and Week 24]

   Changes from baseline in HbA1c in placebo and treatment group at end of 24 weeks treatment

Secondary Outcome Measures

1. Changes in Systolic and Diastolic Blood Pressure at Week 24 [Baseline and Week 24]

   Changes from baseline in systolic and diastolic blood pressure in placebo and treatment group after 24 weeks of treatment

2. Changes in Body Weight at Week 24 [Baseline and week 24]

   Changes from baseline in body weight in placebo and treatment group after 24 weeks of treatment

3. Change From Baseline in HbA1c Over 96 Weeks Time [Baseline and up to 96 weeks]

   Change from baseline in HbA1c level over 96 weeks in placebo and treatment group. The treatment group was treated with EGT0001442 for 24 weeks.

4. Change From Baseline Over Time in Fasting Plasma Glucose (FPG) [24 weeks]

   Changes from baseline in FPG in placebo and treatment group over 24 weeks of treatment

5. Percentage of Subjects Achieving HbA1c <7% [Baseline and up to 96 weeks]

   The number and percentage of subjects achieving HbA1c response levels <7% for the FAS using LOCF is reported

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female subjects ≥18 years old

• Diagnosed with type 2 diabetes

• Body mass index (BMI) ≤ 45 kg/m2

• HbA1c between 7 and 10% (inclusive) at screening

• 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

• Diabetes currently treated with diet and exercise only or diet and exercise along with one approved oral anti-diabetic agent

• If taking anti-diabetic medication, dose and regimen must be stable for past 3 months

• If taking anti-hypertensive medication, dose and regimen must be stable for past 3 months

• If taking lipid modifying therapy, dose and regimen must be stable for past 3 months

• Blood glucose <250 mg/dL based on finger stick blood glucose for all subjects at randomization

Exclusion Criteria:

• Hemoglobinopathy that affects HbA1c measurement

• Current use of injected therapy for treatment of diabetes (insulin or GLP-1 receptor based therapy)

• Genitourinary tract infection within 6 weeks of screening

• Greater than 2 episodes of genitourinary tract infection in the past year

• History of kidney stones, bladder malfunction or other significant risk factor for urinary tract infections

• eGFR, as calculated by the modification of diet in renal disease study equation (MDRD), < 50 mL/min/1.73 m2

• Abnormal tests of liver function ALT, AST or bilirubin ≥ 3x ULN

• Diagnosis of retinopathy or significant nephropathy (eGFR < 50 mL/min/1.73 m2

• Uncontrolled hypertension (systolic blood pressure >160 or diastolic blood pressure

• Not willing to use effective birth control, if female with child-bearing potential

• Life expectancy < 2 years

• New York Heart Association (NYHA) Class 4 heart failure

• Sera positive of HCV, HIV, or positive on drug screen

• Currently participating in another interventional trial

• Previous treatment with EGT0001442 or EGT0001474

• Not able to comply with the study scheduled visits

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 5	Buena Park	California	United States
2	Site 4	Los Angeles	California	United States
3	Site 3	Santa Ana	California	United States
4	Site 1	Hialeah	Florida	United States
5	Site 9	Berlin	New Jersey	United States
6	Site 7	Cary	North Carolina	United States
7	Site 6	Marion	Ohio	United States
8	Site 8	Munroe Falls	Ohio	United States
9	Site 2	Portland	Oregon	United States
10	Site 11	North Richland Hills	Texas	United States
11	Site 7	San Antonio	Texas	United States

Sponsors and Collaborators

• Theracos

Investigators

• Study Director: Mason W Freeman, M.D., Massachusetts General Hospital

Study Documents (Full-Text)

• Study Protocol - Feb 2, 2011
• Statistical Analysis Plan - Nov 22, 2011

More Information

Publications

• American Diabetes Association. Standards of medical care in diabetes--2011. Diabetes Care. 2011 Jan;34 Suppl 1:S11-61. doi: 10.2337/dc11-S011.
• Ehrenkranz JR, Lewis NG, Kahn CR, Roth J. Phlorizin: a review. Diabetes Metab Res Rev. 2005 Jan-Feb;21(1):31-8. Review.
• Ferrannini E, Ramos SJ, Salsali A, Tang W, List JF. 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. 2010 Oct;33(10):2217-24. doi: 10.2337/dc10-0612. Epub 2010 Jun 21.
• Han S, Hagan DL, Taylor JR, Xin L, Meng W, Biller SA, Wetterau JR, Washburn WN, Whaley JM. Dapagliflozin, a selective SGLT2 inhibitor, improves glucose homeostasis in normal and diabetic rats. Diabetes. 2008 Jun;57(6):1723-9. doi: 10.2337/db07-1472. Epub 2008 Mar 20.
• Komoroski B, Vachharajani N, Boulton D, Kornhauser D, Geraldes M, Li L, Pfister M. Dapagliflozin, a novel SGLT2 inhibitor, induces dose-dependent glucosuria in healthy subjects. Clin Pharmacol Ther. 2009 May;85(5):520-6. doi: 10.1038/clpt.2008.251. Epub 2009 Jan 7.
• Komoroski B, Vachharajani N, Feng Y, Li L, Kornhauser D, Pfister M. Dapagliflozin, a novel, selective SGLT2 inhibitor, improved glycemic control over 2 weeks in patients with type 2 diabetes mellitus. Clin Pharmacol Ther. 2009 May;85(5):513-9. doi: 10.1038/clpt.2008.250. Epub 2009 Jan 7. Erratum in: Clin Pharmacol Ther. 2009 May;85(5):558.
• Neumiller JJ, White JR Jr, Campbell RK. Sodium-glucose co-transport inhibitors: progress and therapeutic potential in type 2 diabetes mellitus. Drugs. 2010 Mar 5;70(4):377-85. doi: 10.2165/11318680-000000000-00000. Review.
• Santer R, Kinner M, Lassen CL, Schneppenheim R, Eggert P, Bald M, Brodehl J, Daschner M, Ehrich JH, Kemper M, Li Volti S, Neuhaus T, Skovby F, Swift PG, Schaub J, Klaerke D. Molecular analysis of the SGLT2 gene in patients with renal glucosuria. J Am Soc Nephrol. 2003 Nov;14(11):2873-82.
• 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 LP, Assink K, Willemsen M, Monnens L. Autosomal recessive renal glucosuria attributable to a mutation in the sodium glucose cotransporter (SGLT2). Hum Genet. 2002 Dec;111(6):544-7. Epub 2002 Sep 27.

• Responsible Party: Theracos
• ClinicalTrials.gov Identifier: NCT01377844
• Other Study ID Numbers: THR-1442-C-418
• First Posted: Jun 21, 2011
• Last Update Posted: Jul 1, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Theracos: Diabetes mellitus
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Bexagliflozin

Study Results

Participant Flow

Arm/Group Title	EGT0001442	Placebo
Arm/Group Description	EGT0001442 capsule, 20 mg, orally once daily	Placebo capsule, orally once daily
Period Title: Overall Study
STARTED	145	143
Safety Population	145	141
COMPLETED	109	108
NOT COMPLETED	36	35

Baseline Characteristics

Arm/Group Title	EGT0001442	Placebo	Total
Arm/Group Description	EGT0001442 capsule, 20 mg, orally once daily	Placebo capsule, 20 mg, orally once daily	Total of all reporting groups
Overall Participants	145	141	286
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.2 (10.94)	54.7 (10.30)	55.4 (10.64)
Sex: Female, Male (Count of Participants)
Female	78 53.8%	91 64.5%	169 59.1%
Male	67 46.2%	50 35.5%	117 40.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	129 89%	125 88.7%	254 88.8%
Not Hispanic or Latino	16 11%	16 11.3%	32 11.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.7%	1 0.7%	2 0.7%
Asian	0 0%	1 0.7%	1 0.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 2.1%	2 1.4%	5 1.7%
White	110 75.9%	112 79.4%	222 77.6%
More than one race	31 21.4%	25 17.7%	56 19.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Body Mass Index (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	29.7 (5.35)	30.6 (5.41)	30.1 (5.39)
Baseline HbA1c Category (Count of Participants)
< 8.5%	87 60%	100 70.9%	187 65.4%
> 8.5%	58 40%	41 29.1%	99 34.6%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Hemoglobin A1c at 24 Weeks
Description	Changes from baseline in HbA1c in placebo and treatment group at end of 24 weeks treatment
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

Number of subjects with a value at baseline and at the specified visit

Arm/Group Title	EGT0001442	Placebo
Arm/Group Description	EGT0001442 capsule, 20 mg, orally once daily	Placebo capsule, orally once daily
Measure Participants	140	131
Least Squares Mean (Standard Error) [percentage of glycated hemoglobin]	-0.28 (0.194)	0.51 (0.200)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EGT0001442, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	The p-value is from a 2-sided t-test for the difference in means of change from baseline. Statistical significant is set at 0.05 level.
	Method	ANCOVA
	Comments	Based on analysis of covariance, including treatment group, baseline HbA1c, site, age category, gender and race
Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.79
	Confidence Interval	(2-Sided) 95%; -1.06 to -0.53
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Changes in Systolic and Diastolic Blood Pressure at Week 24
Description	Changes from baseline in systolic and diastolic blood pressure in placebo and treatment group after 24 weeks of treatment
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

Number of subjects with a value at baseline and a the specified visit

Arm/Group Title	EGT0001442	Placebo
Arm/Group Description	EGT0001442 capsule, 20 mg, orally once daily	Placebo capsule, orally once daily
Measure Participants	140	131
Systolic blood pressure	-8.62 (1.903)	-3.08 (1.964)
Diastolic blood pressure	-3.07 (1.223)	-0.40 (1.275)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EGT0001442, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	The p-value is from a 2-sided t-test for the difference in means of change from baseline. Statistical significant is set at 0.05 level.
	Method	ANCOVA
	Comments	Based on analysis of covariance, including treatment group, baseline systolic BP, baseline HbA1c category, site, age category, gender and race
Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-5.53
	Confidence Interval	(2-Sided) 95%; -8.02 to -3.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	EGT0001442, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0015
	Comments	The p-value is from a 2-sided t-test for the difference in means of change from baseline. Statistical significant is set at 0.05 level.
	Method	ANCOVA
	Comments	Based on analysis of covariance, including treatment group, baseline diastolic BP, baseline HbA1c category, site, age category, gender and race
Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-2.67
	Confidence Interval	(2-Sided) 95%; -4.30 to -1.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Changes in Body Weight at Week 24
Description	Changes from baseline in body weight in placebo and treatment group after 24 weeks of treatment
Time Frame	Baseline and week 24

Outcome Measure Data

Analysis Population Description

Number of subjects with a value at baseline and at the specified visit

Arm/Group Title	EGT0001442	Placebo
Arm/Group Description	EGT0001442 capsule, 20 mg, orally once daily	Placebo capsule, orally once daily
Measure Participants	128	104
Least Squares Mean (Standard Error) [kg]	-2.95 (0.555)	-1.22 (0.592)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EGT0001442, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	The p-value is from a 2-sided t-test for the difference in means of change from baseline. Statistical significant is set at 0.05 level.
	Method	ANCOVA
	Comments	Based on analysis of covariance, including treatment group, baseline weight, baseline HbA1c category, site, age category, gender and race
Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-1.72
	Confidence Interval	(2-Sided) 95%; -2.52 to -0.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in HbA1c Over 96 Weeks Time
Description	Change from baseline in HbA1c level over 96 weeks in placebo and treatment group. The treatment group was treated with EGT0001442 for 24 weeks.
Time Frame	Baseline and up to 96 weeks

Outcome Measure Data

Analysis Population Description

Number of subjects with a value at baseline and at the specified visit

Arm/Group Title	EGT0001442	Placebo
Arm/Group Description	EGT0001442 capsule, 20 mg, orally once daily	Placebo capsule, orally once daily
Measure Participants	136	128
Week 2	-0.10 (0.083)	0.22 (0.084)
Week 6	-0.11 (0.137)	0.49 (0.141)
Week 12	-0.19 (0.180)	0.53 (0.186)
Week 18	-0.28 (0.195)	0.43 (0.201)
Week 24	-0.28 (0.194)	0.51 (0.200)
Week 36	-0.52 (0.202)	0.42 (0.209)
Week 48	-0.45 (0.215)	0.54 (0.222)
Week 60	-0.57 (0.219)	0.41 (0.226)
Week 72	-0.43 (0.213)	0.50 (0.220)
Week 84	-0.60 (0.218)	0.38 (0.225)
Week 96	-0.48 (0.215)	0.54 (0.222)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EGT0001442, Placebo
	Comments	Change from baseline in HbA1c (%) at Week 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	The p-value is from a 2-sided t-test for the difference in means of change from baseline. Statistical significant is set at 0.05 level.
	Method	ANCOVA
	Comments	Based on analysis of covariance, including treatment group, baseline HbA1c, site, age category, gender and race
Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.32
	Confidence Interval	(2-Sided) 95%; -0.42 to -0.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	EGT0001442, Placebo
	Comments	Change from baseline in HbA1c (%) at Week 6
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	The p-value is from a 2-sided t-test for the difference in means of change from baseline. Statistical significant is set at 0.05 level.
	Method	ANCOVA
	Comments	Based on analysis of covariance, including treatment group, baseline HbA1c, site, age category, gender and race
Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.59
	Confidence Interval	(2-Sided) 95%; -0.78 to -0.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	EGT0001442, Placebo
	Comments	Change from baseline in HbA1c (%) at Week 12
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	The p-value is from a 2-sided t-test for the difference in means of change from baseline. Statistical significant is set at 0.05 level.
	Method	ANCOVA
	Comments	Based on analysis of covariance, including treatment group, baseline HbA1c, site, age category, gender and race
Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.72
	Confidence Interval	(2-Sided) 95%; -0.96 to -0.48
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	EGT0001442, Placebo
	Comments	Change from baseline in HbA1c (%) at Week 18
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	The p-value is from a 2-sided t-test for the difference in means of change from baseline. Statistical significant is set at 0.05 level.
	Method	ANCOVA
	Comments	Based on analysis of covariance, including treatment group, baseline HbA1c, site, age category, gender and race
Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.71
	Confidence Interval	(2-Sided) 95%; -0.97 to -0.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	EGT0001442, Placebo
	Comments	Change from baseline in HbA1c (%) at Week 24
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	The p-value is from a 2-sided t-test for the difference in means of change from baseline. Statistical significant is set at 0.05 level.
	Method	ANCOVA
	Comments	Based on analysis of covariance, including treatment group, baseline HbA1c, site, age category, gender and race
Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.79
	Confidence Interval	(2-Sided) 95%; -1.06 to -0.53
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	EGT0001442, Placebo
	Comments	Change from baseline in HbA1c (%) at Week 36
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	The p-value is from a 2-sided t-test for the difference in means of change from baseline. Statistical significant is set at 0.05 level.
	Method	ANCOVA
	Comments	Based on analysis of covariance, including treatment group, baseline HbA1c, site, age category, gender and race
Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.93
	Confidence Interval	(2-Sided) 95%; -1.21 to -0.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	EGT0001442, Placebo
	Comments	Change from baseline in HbA1c (%) at Week 48
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	The p-value is from a 2-sided t-test for the difference in means of change from baseline. Statistical significant is set at 0.05 level
	Method	ANCOVA
	Comments	Based on analysis of covariance, including treatment group, baseline HbA1c, site, age category, gender and race
Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.99
	Confidence Interval	(2-Sided) 95%; -1.28 to -0.70
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	EGT0001442, Placebo
	Comments	Change from baseline in HbA1c (%) at Week 60
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	The p-value is from a 2-sided t-test for the difference in means of change from baseline. Statistical significant is set at 0.05 level
	Method	ANCOVA
	Comments	Based on analysis of covariance, including treatment group, baseline HbA1c, site, age category, gender and race
Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.98
	Confidence Interval	(2-Sided) 95%; -1.27 to -0.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	EGT0001442, Placebo
	Comments	Change from baseline in HbA1c (%) at Week 72
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	The p-value is from a 2-sided t-test for the difference in means of change from baseline. Statistical significant is set at 0.05 level
	Method	ANCOVA
	Comments	Based on analysis of covariance, including treatment group, baseline HbA1c, site, age category, gender and race
Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.93
	Confidence Interval	(2-Sided) 95%; -1.22 to -0.64
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	EGT0001442, Placebo
	Comments	Change from baseline in HbA1c (%) at Week 84
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	The p-value is from a 2-sided t-test for the difference in means of change from baseline. Statistical significant is set at 0.05 level.
	Method	ANCOVA
	Comments	Based on analysis of covariance, including treatment group, baseline HbA1c, site, age category, gender and race
Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.98
	Confidence Interval	(2-Sided) 95%; -1.27 to -0.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	EGT0001442, Placebo
	Comments	Change from baseline in HbA1c (%) at Week 96
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	The p-value is from a 2-sided t-test for the difference in means of change from baseline. Statistical significant is set at 0.05 level.
	Method	ANCOVA
	Comments	Based on analysis of covariance, including treatment group, baseline HbA1c, site, age category, gender and race
Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-1.02
	Confidence Interval	(2-Sided) 95%; -1.31 to -0.73
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline Over Time in Fasting Plasma Glucose (FPG)
Description	Changes from baseline in FPG in placebo and treatment group over 24 weeks of treatment
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Only included number of subjects with a value at baseline and at the specified visit

Arm/Group Title	EGT0001442	Placebo
Arm/Group Description	EGT0001442 capsule, 20 mg, orally once daily	Placebo capsule, 20 mg, orally once daily
Measure Participants	145	138
Week 2	-1.39 (0.407)	0.85 (0.422)
Week 6	-1.23 (0.482)	1.22 (0.499)
Week 12	-1.75 (0.489)	0.67 (0.507)
Week 18	-1.87 (0.451)	0.83 (0.467)
Week 24	-1.74 (0.462)	0.89 (0.478)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EGT0001442, Placebo
	Comments	Difference of mean-adjusted change from baseline in FPG (mmol/L) at Week 2, between EGT0001442 and Placebo group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	The p-value is from a two-sided t-test for the difference in means of change from baseline
	Method	ANCOVA
	Comments	Based on analysis of covariance, including treatment group, baseline FPG, baseline HbA1c category, site, age category, gender and race
Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-2.24
	Confidence Interval	(2-Sided) 95%; -2.79 to -1.70
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	EGT0001442, Placebo
	Comments	Difference of mean-adjusted change from baseline in FPG (mmol/L) at Week 6, between EGT0001442 and Placebo group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	The p-value is from a two-sided t-test for the difference in means of change from baseline
	Method	ANCOVA
	Comments	Based on analysis of covariance, including treatment group, baseline FPG, baseline HbA1c category, site, age category, gender and race
Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-2.45
	Confidence Interval	(2-Sided) 95%; -3.09 to -1.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	EGT0001442, Placebo
	Comments	Difference of mean-adjusted change from baseline in FPG (mmol/L) at Week 12, between EGT0001442 and Placebo group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	The p-value is from a two-sided t-test for the difference in means of change from baseline
	Method	ANCOVA
	Comments	Based on analysis of covariance, including treatment group, baseline FPG, baseline HbA1c category, site, age category, gender and race
Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-2.42
	Confidence Interval	(2-Sided) 95%; -3.06 to -1.77
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	EGT0001442, Placebo
	Comments	Difference of mean-adjusted change from baseline in FPG (mmol/L) at Week 18, between EGT0001442 and Placebo group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	The p-value is from a two-sided t-test for the difference in means of change from baseline.
	Method	ANCOVA
	Comments	Based on analysis of covariance, including treatment group, baseline FPG, baseline HbA1c category, site, age category, gender and race
Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-2.71
	Confidence Interval	(2-Sided) 95%; -3.30 to -2.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	EGT0001442, Placebo
	Comments	Difference of mean-adjusted change from baseline in FPG (mmol/L) at Week 24, between EGT0001442 and Placebo group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	The p-value is from a two-sided t-test for the difference in means of change from baseline.
	Method	ANCOVA
	Comments	Based on analysis of covariance, including treatment group, baseline FPG, baseline HbA1c category, site, age category, gender and race
Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-2.63
	Confidence Interval	(2-Sided) 95%; -3.24 to -2.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Subjects Achieving HbA1c <7%
Description	The number and percentage of subjects achieving HbA1c response levels <7% for the FAS using LOCF is reported
Time Frame	Baseline and up to 96 weeks

Outcome Measure Data

Analysis Population Description

Only included number of subjects with a value at baseline and at the specified visit

Arm/Group Title	EGT0001442	Placebo
Arm/Group Description	EGT0001442 capsule, 20 mg, orally once daily	Placebo capsule, orally once daily
Measure Participants	145	138
Week 2	14 9.7%	13 9.2%
Week 6	22 15.2%	15 10.6%
Week 12	27 18.6%	17 12.1%
Week 18	29 20%	14 9.9%
Week 24	33 22.8%	14 9.9%
Week 36	35 24.1%	14 9.9%
Week 48	41 28.3%	20 14.2%
Week 60	39 26.9%	18 12.8%
Week 72	39 26.9%	17 12.1%
Week 84	43 29.7%	16 11.3%
Week 96	44 30.3%	14 9.9%

Adverse Events

Time Frame	The adverse event data were collected from Week 0 (Visit 3) up to Week 97 (Visit 15, 1 week follow-up after completion of study).
Arm/Group Title	EGT0001442		Placebo
Arm/Group Description	EGT0001442 capsule, 20 mg, orally once daily		Placebo capsule, 20 mg, orally once daily
All Cause Mortality
	EGT0001442		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/145 (0.7%)		0/141 (0%)
Serious Adverse Events
	EGT0001442		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/145 (2.1%)		12/141 (8.5%)
Cardiac disorders
Cardiac arrest	1/145 (0.7%)		0/141 (0%)
Tachycardia	0/145 (0%)		1/141 (0.7%)
Hypertensive crisis	0/145 (0%)		1/141 (0.7%)
Gastrointestinal disorders
Diverticulitis	1/145 (0.7%)		0/141 (0%)
Infections and infestations
Pneumonia	0/145 (0%)		1/141 (0.7%)
Urinary tract infection	0/145 (0%)		1/141 (0.7%)
Cellulitis	2/145 (1.4%)		0/141 (0%)
Herpes zoster	0/145 (0%)		1/141 (0.7%)
Injury, poisoning and procedural complications
Wrist fracture	1/145 (0.7%)		0/141 (0%)
Patella fracture	0/145 (0%)		1/141 (0.7%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	0/145 (0%)		1/141 (0.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-Hodgkin's lymphoma	1/145 (0.7%)		0/141 (0%)
Tonsil cancer	0/145 (0%)		1/141 (0.7%)
Nervous system disorders
Spinal column stenosis	0/145 (0%)		1/141 (0.7%)
Peripheral nerve lesion	0/145 (0%)		1/141 (0.7%)
Acute polyneuropathy	0/145 (0%)		1/141 (0.7%)
Lumbar spinal stenosis	0/145 (0%)		1/141 (0.7%)
Respiratory, thoracic and mediastinal disorders
Respiratory disorder	0/145 (0%)		1/141 (0.7%)
Other (Not Including Serious) Adverse Events
	EGT0001442		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	50/145 (34.5%)		62/141 (44%)
Infections and infestations
Urinary Tract Infection	17/145 (11.7%)		28/141 (19.9%)
Metabolism and nutrition disorders
Hypoglycemia	24/145 (16.6%)		24/141 (17%)
Dyslipidaemia	5/145 (3.4%)		8/141 (5.7%)
Hypertriglyceridaemia	5/145 (3.4%)		8/141 (5.7%)
Nervous system disorders
Headache	7/145 (4.8%)		9/141 (6.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The PI is not allowed to publish trial results.