Safety, Tolerability and Pharmacokinetics Study of EGT0001474 in Subjects With Type 2 Diabetes

Diabetes Mellitus Type 2 Clinical Trial

Official title:

A Phase I, Randomized, Placebo-Controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of EGT0001474 in Subjects With Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00924053
• Other study ID #: THR-1474-C-396
• Status: Completed
• Phase: Phase 1
• Start date: June 2009
• Est. completion date: July 2009

Study information

• Verified date: June 2019
• Source: Theracos
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: July 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus Type 2
• Diabetes Mellitus, Type 2

Intervention

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.
• Placebo
Placebo capsules to match EGT0001474

Locations

Country	Name	City	State
United States	dgd Research Inc., a Cetero Research Company	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Theracos

Country where clinical trial is conducted

United States, 

References & Publications (14)

American Diabetes Association. Economic costs of diabetes in the U.S. In 2007. Diabetes Care. 2008 Mar;31(3):596-615. doi: 10.2337/dc08-9017. Review. Erratum in: Diabetes Care. 2008 Jun;31(6):1271. — View Citation

American Diabetes Association. Standards of medical care in diabetes--2008. Diabetes Care. 2008 Jan;31 Suppl 1:S12-54. doi: 10.2337/dc08-S012. — View Citation

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. — View Citation

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. — View Citation

Ehrenkranz JR, Lewis NG, Kahn CR, Roth J. Phlorizin: a review. Diabetes Metab Res Rev. 2005 Jan-Feb;21(1):31-8. Review. — View 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. — View Citation

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. doi: 10.1111/j.1742-1241.2008.01829.x. Review. — View 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. Erratum in: Clin Pharmacol Ther. 2009 May;85(5):558. — View Citation

Krook A, Kawano Y, Song XM, Efendic 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. — View Citation

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. — View Citation

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. — View 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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

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