A Placebo Controlled Safety and Efficacy Study of INT131 Besylate in Type 2 Diabetes, With an Active Comparator

Condition(s) targeted: Type 2 Diabetes Mellitus

Intervention: INT131 besylate (Drug); Pioglitazone HCl (Drug); Placebo (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: InteKrin Therapeutics, Inc.

Official(s) and/or principal investigator(s):
David Orloff, MD, Study Director, Affiliation: Medpace, Inc.

Overall contact:
Jennifer Kelch, Phone: 513-579-9911, Ext: 2275, Email: j.kelch@medpace.com

This is a 24 week study comparing the efficacy of four dose levels of INT131 besylate with pioglitazone HCl in patients with type 2 diabetes. Eligible patients will be men and women (of non-childbearing potential or using dual barrier methods of contraception) between 30 and 75 years of age who are minimally responsive to treatment with sulfonylurea monotherapy or sulfonylurea plus metformin combination therapy.

Official title: A Randomized, Double-Blind, Placebo-Controlled, 24-Week Study to Evaluate the Efficacy and Safety of INT131 Besylate Compared to Pioglitazone in Subjects With Type 2 Diabetes

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Dose Comparison, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Change in HbA1c

Secondary outcome:

Change in fasting plasma glucose (FPG), insulin, C-peptide, serum lipids, C-reactive protein (CRP), and body weight

Efficacy and Safety of INT131 besylate compared with pioglitazone

Safety and tolerability of INT131 besylate as assessed by biochemical, physical and subjective clinical measures

Minimum age: 30 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Diagnosis of Type 2 diabetes and on either sulfonylurea monotherapy or sulfonylurea

plus metformin combination therapy for at least 3 months at stable dose

- Males and Females (of non-childbearing potential or who are using dual barrier methods

of contraception) between 30 and 75 years of age

- HbA1c must be ≥7. 5% and ≤10% at screening

- Fasting Plasma Glucose must be <240 mg/dL at screening

Exclusion Criteria:

- History of type 1 diabetes

- History of diabetic ketoacidosis

- NYHA Class III or IV cardiac status or hospitalization for congestive heart failure

within 6 weeks prior to Visit 1

- Treatment with any non-peroxisome proliferator-activated receptor (non-PPAR)

antidiabetic agent, investigational or approved, other than metformin or permitted sulfonylureas within 3 months prior to screening

- Treatment with rosiglitazone, pioglitazone, or any PPAR investigational antidiabetic

agent within 6 month prior to screening

- Body mass index >45 kg/m2

- Fasting triglycerides >500 mg/dL

- Uncontrolled hypertension (sitting systolic blood pressure >160 mmHg and/or sitting

diastolic blood pressure >100 mmHg

- Presence of diabetic complications, which in the opinion of the investigator, would

complicate the subject's participation in the study (i. e., require initiation of new medication)

Jennifer Kelch, Phone: 513-579-9911, Ext: 2275, Email: j.kelch@medpace.com

Mexico City 1400, Mexico; Not yet recruiting
Carlos A Salinas, MD, Principal Investigator
Melchor A Salazar, MD, Principal Investigator

Instituto Mexicano de Investigacion, Mexico City CP06700, Mexico; Not yet recruiting
Hermann Enkerlin, MD, Principal Investigator

Mexico City CP06100, Mexico; Not yet recruiting
Israel Olvera, MD, Principal Investigator

Nuevo Leon CP66220, Mexico; Not yet recruiting
Hector Tamez, MD, Principal Investigator

National Research Institute, Los Angeles, California 90057, United States; Recruiting
Andrew Lewin, MD, Principal Investigator

Northern California Research, Carmichael, California 95608, United States; Recruiting
Douglas Young, MD, Principal Investigator

Apex Research Institute, Santa Ana, California 92705, United States; Recruiting
Eric Ross, MD, Principal Investigator

VA San Diego Healthcare System, San Diego, California 92161, United States; Recruiting
Sunder (Henry) Mudaliar, MD, Principal Investigator

Munni Selagamsetty, MD, PC, Colorado Springs, Colorado 80910, United States; Recruiting
Munni Selagamsetty, MD, Principal Investigator

Creekside Endocrine Associates, PC, Denver, Colorado 80209, United States; Recruiting
Leonard Zemel, MD, Principal Investigator

Clinical Research Consulting, LLC, Milford, Connecticut 06460, United States; Recruiting
Selwyn Cohen, MD, Principal Investigator

MedStar Research Institute, Washington, District of Columbia 20003, United States; Recruiting
Phone: 202-787-5383, Email: Vanita.R.Aroda@medstar.net
Vanita R Aroda, MD, Principal Investigator

Clinical Research of South Florida, Coral Gables, Florida 33134, United States; Recruiting
Jeff Rosen, MD, Principal Investigator

International Research Associates, LLC, Miami, Florida 33156, United States; Recruiting
Christian Breton, MD, Principal Investigator

Elite Research Institute, Miami, Florida 33169, United States; Recruiting
Ernesto Fuentes, MD, Principal Investigator

Suncoast Clinical Research, Inc., New Port Richey, Florida 34652, United States; Recruiting
Lisa Cohen, MD, Principal Investigator

Suncoast Clinical Research, Inc., Palm Harbor, Florida 34652, United States; Recruiting
Sanford Plevin, MD, Principal Investigator

Baptist Diabetes Associates, PA, Miami, Florida 33156, United States; Recruiting
Peter Weissman, MD, Principal Investigator

Meridien Research, Tampa, Florida 33606, United States; Recruiting
Cynthia L Huffman, MD, Principal Investigator

Meridien Research, Tampa, Florida 34203, United States; Recruiting
Louis B Chaykin, MD, Principal Investigator

The Center for Diabetes and Endocrine Care, Hollywood, Florida 33021, United States; Recruiting
Sam Lerman, MD CM, Principal Investigator

ICCT Reseach International, Chicago, Illinois 60611, United States; Recruiting
Jeannine Turner, MD, Principal Investigator

American Health Network, Indianapolis, Indiana 46254, United States; Recruiting
Thomas Moretto, MD, Principal Investigator

Hospital "Dr. Angel Leano", Zapopan, Jalisco, Mexico; Not yet recruiting
Fernando F Lozano, MD, Principal Investigator

Nucleo Medico Vallarta, Guadalajara, Jalisco, Mexico; Not yet recruiting
Guillermo Gonzalez-Galvez, MD, Principal Investigator

New Orleans Center for Clinical Research, New Orleans, Louisiana 70119, United States; Recruiting
Arnold Alper, MD, Principal Investigator

Baltimore, Maryland 21234, United States; Recruiting
Stephen Smith, MD, Principal Investigator

Olive Branch Family Medical Center, Olive Branch, Mississippi 38654, United States; Recruiting
Randall Huling, MD, Principal Investigator

Diabetes and Endocrinology Specialists, Inc., Chesterfield, Missouri 63017, United States; Recruiting
Norman Fishman, MD, Principal Investigator

Saint Luke's Lipid and Diabetes Reseach Center, Kansas City, Missouri 64111, United States; Recruiting
Alan Forker, MD, Principal Investigator

Bozeman Deaconess Internal Medicine Associates, Bozeman, Montana 59715, United States; Recruiting
Michael Vlases, MD, Principal Investigator

Kaleida Health Diabetes Center, Buffalo, New York 14209, United States; Recruiting
Paresh Dandona, MD, Principal Investigator

Fairbrook Medical Clinic, Hickory, North Carolina 28602, United States; Recruiting
Jonathan Wilson, DO, Principal Investigator

UNC Diabetes Care Center/Highgate Specialty Center, Durham, North Carolina 27713, United States; Recruiting
John Buse, MD, Principal Investigator

Delaware Smith Clinic, Delaware, Ohio 43015, United States; Recruiting
Bruce Barker, MD, Principal Investigator

The Lindner Clinical Trial Center, Cincinnati, Ohio 45219, United States; Recruiting
Dean Kereiakes, MD, Principal Investigator

Your Diabetes Endocrine Nutrition Group, LLC, Mentor, Ohio 44060, United States; Recruiting
Daniel Weiss, MD, Principal Investigator

Opitmed Research, LTD, Columbus, Ohio 43235, United States; Recruiting
Donald L McNeil, MD, Principal Investigator

Tri-State Medical Group, Inc., Beaver, Pennsylvania 15009, United States; Recruiting
Peter Manolukas, DO, Principal Investigator

New England Center for Clinical Research, Cranston, Rhode Island 02920, United States; Recruiting
Frank Maggiacomo, DO, Principal Investigator

Medical Research South, Charleston, South Carolina 29407, United States; Recruiting
Timothy Jones, MD, Principal Investigator

Diabetes Center of the Southwest, Midland, Texas 79705, United States; Recruiting
Murthy Gollapudi, MD, Principal Investigator

DGD Research, San Antonio, Texas 78229, United States; Recruiting
Mark Kipnes, MD, Principal Investigator

Quality Research, Inc., San Antonio, Texas 78209, United States; Recruiting
Curtis Horn, MD, Principal Investigator

Research Institute of Dallas, Dallas, Texas 75231, United States; Recruiting
Stephen Aronoff, MD, Principal Investigator

Baylor University Endocrine Center, Dallas, Texas 75246, United States; Recruiting
Priscilla Hollander, MD, Principal Investigator

Dallas Diabetes and Endocrine Research Center, Dallas, Texas 75230, United States; Recruiting
Julio Rosenstock, MD, Principal Investigator

Salem VA Medical Center R&D Office, Salem, Virginia 24153, United States; Recruiting
Ali Iranmanesh, MD, Principal Investigator

Related publications:

Rosen ED, Spiegelman BM. PPARgamma : a nuclear regulator of metabolism, differentiation, and cell growth. J Biol Chem. 2001 Oct 12;276(41):37731-4. Epub 2001 Jul 17. Review. No abstract available.

Maegawa H, Ide R, Hasegawa M, Ugi S, Egawa K, Iwanishi M, Kikkawa R, Shigeta Y, Kashiwagi A. Thiazolidine derivatives ameliorate high glucose-induced insulin resistance via the normalization of protein-tyrosine phosphatase activities. J Biol Chem. 1995 Mar 31;270(13):7724-30.

Koshida H, Shibata K, Kametani T. Pleuropulmonary disease in a man with diabetes who was treated with troglitazone. N Engl J Med. 1998 Nov 5;339(19):1400-1. No abstract available.

Niemeyer NV, Janney LM. Thiazolidinedione-induced edema. Pharmacotherapy. 2002 Jul;22(7):924-9. Review.

Thomas ML, Lloyd SJ. Pulmonary edema associated with rosiglitazone and troglitazone. Ann Pharmacother. 2001 Jan;35(1):123-4. No abstract available.

Spiegelman BM. PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. Diabetes. 1998 Apr;47(4):507-14. Review.

Willson TM, Brown PJ, Sternbach DD, Henke BR. The PPARs: from orphan receptors to drug discovery. J Med Chem. 2000 Feb 24;43(4):527-50. Review. No abstract available.

Hulin B, Newton LS, Lewis DM, Genereux PE, Gibbs EM, Clark DA. Hypoglycemic activity of a series of alpha-alkylthio and alpha-alkoxy carboxylic acids related to ciglitazone. J Med Chem. 1996 Sep 27;39(20):3897-907.

Mudaliar S, Henry RR. New oral therapies for type 2 diabetes mellitus: The glitazones or insulin sensitizers. Annu Rev Med. 2001;52:239-57. Review.

Lehmann JM, Moore LB, Smith-Oliver TA, Wilkison WO, Willson TM, Kliewer SA. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J Biol Chem. 1995 Jun 2;270(22):12953-6.

Berger J, Bailey P, Biswas C, Cullinan CA, Doebber TW, Hayes NS, Saperstein R, Smith RG, Leibowitz MD. Thiazolidinediones produce a conformational change in peroxisomal proliferator-activated receptor-gamma: binding and activation correlate with antidiabetic actions in db/db mice. Endocrinology. 1996 Oct;137(10):4189-95.

[No authors listed] Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):837-53. Erratum in: Lancet 1999 Aug 14;354(9178):602.

American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 2003 Jan;26 Suppl 1:S33-50. No abstract available. Erratum in: Diabetes Care. 2003 Mar;26(3):972.

Adams TD, Gress RE, Smith SC, Halverson RC, Simper SC, Rosamond WD, Lamonte MJ, Stroup AM, Hunt SC. Long-term mortality after gastric bypass surgery. N Engl J Med. 2007 Aug 23;357(8):753-61.

Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002 Feb 7;346(6):393-403.

Hirsch IB, Kelly J, Cooper S. Pulmonary edema associated with troglitazone therapy. Arch Intern Med. 1999 Aug 9-23;159(15):1811. No abstract available.

Ghazzi MN, Perez JE, Antonucci TK, Driscoll JH, Huang SM, Faja BW, Whitcomb RW. Cardiac and glycemic benefits of troglitazone treatment in NIDDM. The Troglitazone Study Group. Diabetes. 1997 Mar;46(3):433-9.

Shibuya A, Watanabe M, Fujita Y, Saigenji K, Kuwao S, Takahashi H, Takeuchi H. An autopsy case of troglitazone-induced fulminant hepatitis. Diabetes Care. 1998 Dec;21(12):2140-3.

Watkins PB, Whitcomb RW. Hepatic dysfunction associated with troglitazone. N Engl J Med. 1998 Mar 26;338(13):916-7. No abstract available.

Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007 Jun 14;356(24):2457-71. Epub 2007 May 21. Erratum in: N Engl J Med. 2007 Jul 5;357(1):100.

Lincoff AM, Wolski K, Nicholls SJ, Nissen SE. Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA. 2007 Sep 12;298(10):1180-8.

Rosen CJ. The rosiglitazone story--lessons from an FDA Advisory Committee meeting. N Engl J Med. 2007 Aug 30;357(9):844-6. Epub 2007 Aug 8. No abstract available.

Starting date: February 2008
Last updated: October 31, 2008