Safety, Tolerability and Pharmacokinetics Study of EGT0001474 in Subjects With Type 2 Diabetes - Full Text View

Sponsor:	Theracos
Information provided by:	Theracos
ClinicalTrials.gov Identifier:	NCT00924053

Purpose

The purpose of this study is to determine the safety, tolerability and pharmacokinetics (how much of the drug gets into the blood and how long it takes the body to get rid of it) of single doses of EGT0001474 given to patients with Type 2 diabetes. The study will also evaluate how EGT0001474 affects the amount of glucose produced by the body in the urine.

Condition	Intervention	Phase
Diabetes Mellitus Type 2	Drug: EGT0001474 Drug: Placebo	Phase I

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Phase I, Randomized, Placebo-Controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of EGT0001474 in Subjects With Type 2 Diabetes

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetes Diabetes Type 2

U.S. FDA Resources

Further study details as provided by Theracos:

Primary Outcome Measures:

Safety and Tolerability of EGT0001474 [ Time Frame: 25 days ] [ Designated as safety issue: Yes ]
Safety and tolerability were measured in terms of the number of mild, moderate and severe adverse events experienced by any participants.
AUC 0-t [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]
Area under the plasma concentration-time curve from time 0 to time t
AUC0-24 [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]
Area under the plasma concentration-time curve from time 0 to hour 24
AUC Inf [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]
Area under the plasma concentration-time curve from time 0 to infinity
Cmax [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]
Maximum plasma concentration
Tmax [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]
Time of maximum plasma concentration
λz [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]
Terminal phase rate constant
t1/2 [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]
Apparent terminal half life
CL/F [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]
The apparent rate of oral clearance of EGT0001474.Oral clearance was defined as rate of drug removal from the body after oral administration.
Vz/F [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]
Apparent volume of distribution

Enrollment:	24
Study Start Date:	June 2009
Study Completion Date:	July 2009
Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: EGT0001474	Drug: EGT0001474 Cohort 1: single dose of 25 mg EGT0001474 given as an oral capsule; Cohort 2: single dose of 75 mg EGT0001474 given as 3 oral capsules; Cohort 3: single dose of 150 mg EGT0001474 given as 6 oral capsules. Other Name: Human SGLT2 inhibitor
Placebo Comparator: Placebo	Drug: Placebo Placebo capsules to match EGT0001474 Other Name: Human SGLT2 inhibitor

Detailed Description:

EGT0001474 is a compound that may inhibit the effect of other compounds in the body known as sugar transporters. The use of EGT0001474 may enhance the elimination of glucose from the blood by increasing the amount of urine produced. This would help prevent an abnormal decrease in blood sugar (hypoglycemia) both during fasting and after meals without increasing insulin secretion (which may result in weight gain or an abnormal increase in blood sugar known as Type 2 diabetes).

Eligibility

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

Criteria

Inclusion Criteria:

Male or females between the ages of 18 to 70 diagnosed with Type 2 diabetes.
Body mass Index (BMI) between 18 kg/m2 and 37 kg/m2.
HbA1c levels between 6.5 and 9.0 (inclusive) where the upper limit of normal for the HbA1c assay is 6.4% or 6.2-9.0% (inclusive) where the upper limit of normal for the HbA1c assay is 6.1% and fasting plasma glucose between 110 and 240 mg/dL (inclusive) while on diabetic medications.
If taking drugs for diabetes, must be medically able and willing to discontinue diabetes medications for the duration of the study.
Female subjects must be surgically sterilized or postmenopausal.
Non-smoker for at least 3 months.
Negative alcohol screen.

Exclusion Criteria:

Type 1 diabetes.
Use of insulin therapy or oral antidiabetic medication other than metformin, sitagliptin or a sulfonylurea.
Sitting blood pressure above 150/95 mmHg on 2 evaluations at least 10 minutes apart at screening.
Treatment with an investigational drug within 30 days or 7 half-lives, whichever is longer.
Previous treatment with EGT0001474.
Vaccination within 30 days prior to the first dose of study medication.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00924053

Locations

United States, Texas
dgd Research Inc., a Cetero Research Company
San Antonio, Texas, United States, 78229

Sponsors and Collaborators

Theracos

Investigators

Study Chair:

Mason W. Freeman, M.D.

Massachusetts General Hospital

More Information

Publications:

Blondel O, Bailbe D, Portha B. Insulin resistance in rats with non-insulin-dependent diabetes induced by neonatal (5 days) streptozotocin: evidence for reversal following phlorizin treatment. Metabolism. 1990 Aug;39(8):787-93.

Cowie CC, Rust KF, Byrd-Holt DD, Eberhardt MS, Flegal KM, Engelgau MM, Saydah SH, Williams DE, Geiss LS, Gregg EW. Prevalence of diabetes and impaired fasting glucose in adults in the U.S. population: National Health And Nutrition Examination Survey 1999-2002. Diabetes Care. 2006 Jun;29(6):1263-8.

American Diabetes Association. Standards of medical care in diabetes--2008. Diabetes Care. 2008 Jan;31 Suppl 1:S12-54. No abstract available.

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.

Jabbour SA, Goldstein BJ. Sodium glucose co-transporter 2 inhibitors: blocking renal tubular reabsorption of glucose to improve glycaemic control in patients with diabetes. Int J Clin Pract. 2008 Aug;62(8):1279-84. Review.

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.

Krook A, Kawano Y, Song XM, Efendi? S, Roth RA, Wallberg-Henriksson H, Zierath JR. Improved glucose tolerance restores insulin-stimulated Akt kinase activity and glucose transport in skeletal muscle from diabetic Goto-Kakizaki rats. Diabetes. 1997 Dec;46(12):2110-4.

Oku A, Ueta K, Arakawa K, Ishihara T, Nawano M, Kuronuma Y, Matsumoto M, Saito A, Tsujihara K, Anai M, Asano T, Kanai Y, Endou H. T-1095, an inhibitor of renal Na+-glucose cotransporters, may provide a novel approach to treating diabetes. Diabetes. 1999 Sep;48(9):1794-800.

Pajor AM, Wright EM. Cloning and functional expression of a mammalian Na+/nucleoside cotransporter. A member of the SGLT family. J Biol Chem. 1992 Feb 25;267(6):3557-60.

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.

Toggenburger G, Kessler M, Semenza G. Phlorizin as a probe of the small-intestinal Na+,D-glucose cotransporter. A model. Biochim Biophys Acta. 1982 Jun 14;688(2):557-71.

Tsujihara K, Hongu M, Saito K, Inamasu M, Arakawa K, Oku A, Matsumoto M. Na(+)-glucose cotransporter inhibitors as antidiabetics. I. Synthesis and pharmacological properties of 4'-dehydroxyphlorizin derivatives based on a new concept. Chem Pharm Bull (Tokyo). 1996 Jun;44(6):1174-80.

Responsible Party:	Albert R. Collinson., President and CEO, Theracos
ClinicalTrials.gov Identifier:	NCT00924053 History of Changes
Other Study ID Numbers:	THR-1474-C-396
Study First Received:	June 16, 2009
Results First Received:	October 25, 2010
Last Updated:	July 21, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Theracos:

Diabetes Mellitus Type 2

Additional relevant MeSH terms:

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

ClinicalTrials.gov processed this record on February 09, 2012