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

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

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).

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Drug: Placebo; Drug: EGT0001442

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 Type: Interventional
• Enrollment (Actual): 288
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo
EXPERIMENTAL: EGT0001442; EGT0001442 capsule, 20 mg, daily, 96 weeks	Drug: EGT0001442; Other Names: Bexagliflozin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.
• American Diabetes Association. Standards of medical care in diabetes--2011. Diabetes Care. 2011 Jan;34 Suppl 1(Suppl 1):S11-61. doi: 10.2337/dc11-S011. No abstract available.
• Ehrenkranz JR, Lewis NG, Kahn CR, Roth J. Phlorizin: a review. Diabetes Metab Res Rev. 2005 Jan-Feb;21(1):31-8. doi: 10.1002/dmrr.532.
• 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.
• 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. doi: 10.1097/01.asn.0000092790.89332.d2.
• 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. doi: 10.1007/s00439-002-0820-5. Epub 2002 Sep 27.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (ACTUAL): November 1, 2013
• Study Completion (ACTUAL): December 1, 2013

Study Registration Dates

• First Submitted: June 13, 2011
• First Submitted That Met QC Criteria: June 19, 2011
• First Posted (ESTIMATE): June 21, 2011

Study Record Updates

• Last Update Posted (ACTUAL): July 1, 2021
• Last Update Submitted That Met QC Criteria: June 29, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Diabetes mellitus
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Bexagliflozin
• Other Study ID Numbers: THR-1442-C-418

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO