Clinical trial NCT01377844: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus
Keywords: Diabetes mellitus
Lead sponsor: Theracos
Sponsor class: INDUSTRY
First posted: 2011-06-21
Enrollment: 288
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change From Baseline in Hemoglobin A1c at 24 Weeks
timeFrame: Baseline and Week 24
Secondary outcomes:
measure: Changes in Systolic and Diastolic Blood Pressure at Week 24
timeFrame: Baseline and Week 24
measure: Changes in Body Weight at Week 24
timeFrame: Baseline and week 24
measure: Change From Baseline in HbA1c Over 96 Weeks Time
timeFrame: Baseline and up to 96 weeks
measure: Change From Baseline Over Time in Fasting Plasma Glucose (FPG)
timeFrame: 24 weeks
measure: Percentage of Subjects Achieving HbA1c <7%
timeFrame: Baseline and up to 96 weeks
Other outcomes:
Locations:
city: Buena Park
country: United States
facility: Site 5
state: California
city: Los Angeles
country: United States
facility: Site 4
state: California
city: Santa Ana
country: United States
facility: Site 3
state: California
city: Hialeah
country: United States
facility: Site 1
state: Florida
city: Berlin
country: United States
facility: Site 9
state: New Jersey
city: Cary
country: United States
facility: Site 7
state: North Carolina
city: Marion
country: United States
facility: Site 6
state: Ohio
city: Munroe Falls
country: United States
facility: Site 8
state: Ohio
city: Portland
country: United States
facility: Site 2
state: Oregon
city: North Richland Hills
country: United States
facility: Site 11
state: Texas
city: San Antonio
country: United States
facility: Site 7
state: Texas
Study officials:
affiliation: Massachusetts General Hospital
name: Mason W Freeman, M.D.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
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.
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.
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.
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.
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.
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. doi: 10.1097/01.asn.0000092790.89332.d2.
citation: Sicree, R., Shaw, J., and Zimmet, P. (2010). The Global Burden - Diabetes and Impaired Glucose Tolerance (Baker IDI Heart and Diabetes Institute).
citation: 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.