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

Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01377844
• Other study ID #: THR-1442-C-418
• Status: Completed
• Phase: Phase 2
• Start date: December 2011
• Est. completion date: December 2013

Study information

• Verified date: June 2021
• Source: Theracos
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 288
• Est. completion date: December 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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 >95)

• 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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• EGT0001442

• Placebo

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Theracos

Country where clinical trial is conducted

United States, 

References & Publications (10)

American Diabetes Association. Standards of medical care in diabetes--2011. Diabetes Care. 2011 Jan;34 Suppl 1:S11-61. doi: 10.2337/dc11-S011. — View Citation

Ehrenkranz JR, Lewis NG, Kahn CR, Roth J. Phlorizin: a review. Diabetes Metab Res Rev. 2005 Jan-Feb;21(1):31-8. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Hemoglobin A1c at 24 Weeks	Changes from baseline in HbA1c in placebo and treatment group at end of 24 weeks treatment	Baseline and Week 24
Secondary	Changes in Systolic and Diastolic Blood Pressure at Week 24	Changes from baseline in systolic and diastolic blood pressure in placebo and treatment group after 24 weeks of treatment	Baseline and Week 24
Secondary	Changes in Body Weight at Week 24	Changes from baseline in body weight in placebo and treatment group after 24 weeks of treatment	Baseline and week 24
Secondary	Change From Baseline in HbA1c Over 96 Weeks Time	Change from baseline in HbA1c level over 96 weeks in placebo and treatment group. The treatment group was treated with EGT0001442 for 24 weeks.	Baseline and up to 96 weeks
Secondary	Change From Baseline Over Time in Fasting Plasma Glucose (FPG)	Changes from baseline in FPG in placebo and treatment group over 24 weeks of treatment	24 weeks
Secondary	Percentage of Subjects Achieving HbA1c <7%	The number and percentage of subjects achieving HbA1c response levels <7% for the FAS using LOCF is reported	Baseline and up to 96 weeks