Efficacy and Safety of EGT0001442 in Patients With Type 2 Diabetes Mellitus - Full Text View

Purpose

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	Intervention	Phase
Diabetes Mellitus	Drug: EGT0001442	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Diabetes Type 2

U.S. FDA Resources

Further study details as provided by Theracos:

Primary Outcome Measures:

Changes in Hemoglobin A1c levels at 24 weeks [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Changes from basline in HbA1c levels in placebo and treatment group at end of 24 weeks treatment

Secondary Outcome Measures:

Changes in systolic and diastolic blood pressure at 24 weeks [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: Yes ]
Number of participants with adverse events in placebo and treatment group during 96 weeks time

Estimated Enrollment:	300
Study Start Date:	December 2011
Estimated Study Completion Date:	December 2013
Estimated Primary Completion Date:	November 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Drug: EGT0001442	Drug: EGT0001442 Placebo capsules to match EGT0001442 Other Name: Inhibitor of SGLT2
Placebo Comparator: Placebo	Drug: EGT0001442 Placebo capsules to match EGT0001442 Other Name: Inhibitor of SGLT2

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.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01377844

Locations

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

Sponsors and Collaborators

Theracos

Investigators

Study Director:

Mason W Freeman, M.D.

Massachusetts General Hospital

More Information

Publications:

ADA (2011). Standards of medical care in diabetes--2011. Diabetes Care 34 Suppl 1, S11-61.

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 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. 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. 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. Epub 2009 Jan 7. Erratum in: Clin Pharmacol Ther. 2009 May;85(5):558.

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.

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 History of Changes
Other Study ID Numbers:	THR-1442-C-418
Study First Received:	June 13, 2011
Last Updated:	April 17, 2013
Health Authority:	United States: Food and Drug Administration Mexico: Ministry of Health Mexico: Ethics Committee Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos

Keywords provided by Theracos:

Diabetes mellitus

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on June 17, 2013