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

• ClinicalTrials.gov Identifier: NCT01377844
• Recruitment Status: Completed
• First Posted: June 21, 2011
• Results First Posted: June 16, 2021
• Last Update Posted: July 1, 2021
• Sponsor: Theracos
• Information provided by (Responsible Party): Theracos

Tracking Information

• First Submitted Date: June 13, 2011
• First Posted Date: June 21, 2011
• Results First Submitted Date: May 21, 2021
• Results First Posted Date: June 16, 2021
• Last Update Posted Date: July 1, 2021
• Study Start Date: December 2011
• Actual Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 29, 2021)

Change From Baseline in Hemoglobin A1c at 24 Weeks [ Time Frame: Baseline and Week 24 ]

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

Original Primary Outcome Measures (submitted: June 19, 2011)

Changes from basline in Hemoglobin A1c (HbA1c) levels at 24 weeks [ Time Frame: 24 weeks ]

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

Current Secondary Outcome Measures (submitted: June 29, 2021)

• Changes in Systolic and Diastolic Blood Pressure at Week 24 [ Time Frame: Baseline and Week 24 ]
  Changes from baseline in systolic and diastolic blood pressure in placebo and treatment group after 24 weeks of treatment
• Changes in Body Weight at Week 24 [ Time Frame: Baseline and week 24 ]
  Changes from baseline in body weight in placebo and treatment group after 24 weeks of treatment
• Change From Baseline in HbA1c Over 96 Weeks Time [ Time Frame: 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.
• Change From Baseline Over Time in Fasting Plasma Glucose (FPG) [ Time Frame: 24 weeks ]
  Changes from baseline in FPG in placebo and treatment group over 24 weeks of treatment
• Percentage of Subjects Achieving HbA1c <7% [ Time Frame: Baseline and up to 96 weeks ]
  The number and percentage of subjects achieving HbA1c response levels <7% for the FAS using LOCF is reported

Original Secondary Outcome Measures (submitted: June 19, 2011)

• Changes from baseline in systolic and diastolic blood pressure at 24 weeks [ Time Frame: 24 weeks ]
  Changes from basline in systolic and diastolic blood pressure in placebo and treatment group at 24 weeks treatment
• Changes in body weight at 24 weeks treatment [ Time Frame: 24 weeks ]
  Changes from baseline in body weight in placebo and treatment group at 24 weeks treatment
• Changes in Hemoglobin A1c level over 96 weeks time [ Time Frame: 96 weeks ]
  Change in HbA1c level over 96 weeks time in plaebo and treatment group. The treatment group received 24 weeks treatment with EGT0001442.
• Number of participants with adverse events during 96 weeks time [ Time Frame: 96 weeks ]
  Number of participants with adverse events in placebo and treatment group during 96 weeks time

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Safety of EGT0001442 in Patients With Type 2 Diabetes Mellitus
• 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
• 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).
• 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
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Diabetes Mellitus

Intervention

• Drug: EGT0001442
  Other Name: Bexagliflozin
• Drug: Placebo

Study Arms

• Experimental: EGT0001442
  EGT0001442 capsule, 20 mg, daily, 96 weeks
  Intervention: Drug: EGT0001442
• Placebo Comparator: Placebo
  Placebo
  Intervention: Drug: Placebo

Publications *

• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 27, 2014): 288
• Original Estimated Enrollment (submitted: June 19, 2011): 300
• Actual Study Completion Date: December 2013
• Actual Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01377844
• Other Study ID Numbers: THR-1442-C-418
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Theracos
• Original Responsible Party: Albert R. Collison, Ph.D., President and CEO, Theracos
• Current Study Sponsor: Theracos
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Theracos
• Verification Date: June 2021