Saxagliptin in Combination With Dapagliflozin - Effects on Islet Cell Function

NCT02304081 | Completed Phase 4

• 1 other identifier: 95/8010-DASA-001
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate alpha- and beta-cell function during combination treatment with saxagliptin in addition to dapagliflozin and metformin compared to placebo in addition to dapagliflozin and metformin in subjects with T2DM on stable metformin background therapy.

Conditions

Type2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Glucagon / insulin ratio during hyperglycaemic clamp phase (AUCGluc270-390min / AUCIns270-390min)

  at baseline (Day 0) as well as after Treatment Phase 1 (after 30 days) and after Treatment Phase 2 (after 60 days)

Secondary Outcomes (18)

• Glucagon release during hyperglycaemic clamp phase (AUCGluc270-390min; pg/ml*min)

  at baseline (Day 0) as well as after Treatment Phase 1 (after 30 days) and after Treatment Phase 2 (after 60 days)

• First phase glucagon release during hyperglycaemic clamp phase (AUCGluc270-290min; pg/ml*min)

  at baseline (Day 0) as well as after Treatment Phase 1 (after 30 days) and after Treatment Phase 2 (after 60 days)

• First phase insulin release during hyperglycaemic clamp phase (AUCIns270-290min; pmol/l*min)

  at baseline (Day 0) as well as after Treatment Phase 1 (after 30 days) and after Treatment Phase 2 (after 60 days)

• Second phase insulin release during hyperglycaemic clamp phase (AUCIns290-390min; pmol/l*min)

  at baseline (Day 0) as well as after Treatment Phase 1 (after 30 days) and after Treatment Phase 2 (after 60 days)

• First Phase glucagon / insulin ratio during hyperglycaemic clamp phase (AUCGluc270-290min / AUCIns270-290min)

  at baseline (Day 0) as well as after Treatment Phase 1 (after 30 days) and after Treatment Phase 2 (after 60 days)

Study Arms (2)

Saxagliptin

ACTIVE COMPARATOR

Metformin and Dapagliflozin background therapy

Drug: Saxagliptin

Placebo

PLACEBO COMPARATOR

Metformin and Dapagliflozin background therapy

Drug: Placebo for Saxagliptin

Interventions

Saxagliptin DRUG

competitive inhibitor of human dipepitdylpeptidase (DPP)-IV

Also known as: Onglyza®

Saxagliptin

Placebo for Saxagliptin DRUG

Placebo

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diabetes mellitus type 2 for at least three months prior to Screening
• HbA1c 7.0%-9.9%, both inclusive
• Treatment with metformin (daily dose 1500 - 3000 mg)
• Age 30-75 years, both inclusive
• BMI 25-35 kg/m\^2, both inclusive

You may not qualify if:

• Use of any oral antidiabetic treatment except for metformin (i.e., sulphonylureas, DPP-IV inhibitors, thiazolidinediones, SGLT-2 inhibitors) within the last three months prior to Screening
• Use of insulin or GLP-1 analogues within three months prior to Screening
• Treatment with any other investigational drug within three months before screening
• History of diabetes mellitus type 1
• Acute infections within the last two weeks prior to Screening
• Anamnestic history of hypersensitivity to the study drugs or to drugs with similar chemical structures
• History of severe or multiple allergies
• GFR (as calculated by the Cockroft-Gault equation) \< 60 ml/min at Screening
• State after kidney transplantation
• Laboratory safety value(s) outside the reference range and deemed clinically relevant by the Investigator
• Sexually active woman of childbearing age not practicing a highly effective method of birth control as defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, hormonal IUDs, sexual abstinence or vasectomised partner
• Pregnancy or breast feeding
• Systolic blood pressure outside the range of 100-160 mmHg or diastolic blood pressure above 90 mmHg at Screening
• Acute myocardial infarction or cerebral event (stroke/TIA) within six months prior to Screening
• Uncontrolled unstable angina pectoris or history of pericarditis, myocarditis, endocarditis

Sponsors & Collaborators

• Prof. Dr. Thomas Forst: lead

Study Sites (1)

Profil Mainz GmbH & Co. KG

Mainz, 55116, Germany

Location

Related Publications (13)

• List JF, Woo V, Morales E, Tang W, Fiedorek FT. Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes. Diabetes Care. 2009 Apr;32(4):650-7. doi: 10.2337/dc08-1863. Epub 2008 Dec 29.

  PMID: 19114612 RESULT

• Rosenstock J, Vico M, Wei L, Salsali A, List JF. Effects of dapagliflozin, an SGLT2 inhibitor, on HbA(1c), body weight, and hypoglycemia risk in patients with type 2 diabetes inadequately controlled on pioglitazone monotherapy. Diabetes Care. 2012 Jul;35(7):1473-8. doi: 10.2337/dc11-1693. Epub 2012 Mar 23.

  PMID: 22446170 RESULT

• Tahara A, Kurosaki E, Yokono M, Yamajuku D, Kihara R, Hayashizaki Y, Takasu T, Imamura M, Li Q, Tomiyama H, Kobayashi Y, Noda A, Sasamata M, Shibasaki M. Effects of SGLT2 selective inhibitor ipragliflozin on hyperglycemia, hyperlipidemia, hepatic steatosis, oxidative stress, inflammation, and obesity in type 2 diabetic mice. Eur J Pharmacol. 2013 Sep 5;715(1-3):246-55. doi: 10.1016/j.ejphar.2013.05.014. Epub 2013 May 23.

  PMID: 23707905 RESULT

• Chen L, Klein T, Leung PS. Effects of combining linagliptin treatment with BI-38335, a novel SGLT2 inhibitor, on pancreatic islet function and inflammation in db/db mice. Curr Mol Med. 2012 Sep;12(8):995-1004. doi: 10.2174/156652412802480970.

  PMID: 22804249 RESULT

• Kurosaki E, Ogasawara H. Ipragliflozin and other sodium-glucose cotransporter-2 (SGLT2) inhibitors in the treatment of type 2 diabetes: preclinical and clinical data. Pharmacol Ther. 2013 Jul;139(1):51-9. doi: 10.1016/j.pharmthera.2013.04.003. Epub 2013 Apr 4.

  PMID: 23563279 RESULT

• Forst T, Dworak M, Berndt-Zipfel C, Loffler A, Klamp I, Mitry M, Pfutzner A. Effect of vildagliptin compared to glimepiride on postprandial proinsulin processing in the beta cell of patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2013 Jun;15(6):576-9. doi: 10.1111/dom.12063. Epub 2013 Feb 6.

  PMID: 23384119 RESULT

• Forst T, Anastassiadis E, Diessel S, Loffler A, Pfutzner A. Effect of linagliptin compared with glimepiride on postprandial glucose metabolism, islet cell function and vascular function parameters in patients with type 2 diabetes mellitus receiving ongoing metformin treatment. Diabetes Metab Res Rev. 2014 Oct;30(7):582-9. doi: 10.1002/dmrr.2525.

  PMID: 24459063 RESULT

• Ferrannini E, Muscelli E, Frascerra S, Baldi S, Mari A, Heise T, Broedl UC, Woerle HJ. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest. 2014 Feb;124(2):499-508. doi: 10.1172/JCI72227. Epub 2014 Jan 27.

  PMID: 24463454 RESULT

• Merovci A, Solis-Herrera C, Daniele G, Eldor R, Fiorentino TV, Tripathy D, Xiong J, Perez Z, Norton L, Abdul-Ghani MA, DeFronzo RA. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production. J Clin Invest. 2014 Feb;124(2):509-14. doi: 10.1172/JCI70704. Epub 2014 Jan 27.

  PMID: 24463448 RESULT

• Zhang Y, Chi J, Wang W, Hong J, Gu W, Wang B, Ning G. Different effects of two dipeptidyl peptidase-4 inhibitors and glimepiride on beta-cell function in a newly designed two-step hyperglycemic clamp. J Diabetes. 2015 Mar;7(2):213-21. doi: 10.1111/1753-0407.12175. Epub 2014 Jul 29.

  PMID: 24889731 RESULT

• McGuire EA, Helderman JH, Tobin JD, Andres R, Berman M. Effects of arterial versus venous sampling on analysis of glucose kinetics in man. J Appl Physiol. 1976 Oct;41(4):565-73. doi: 10.1152/jappl.1976.41.4.565.

  PMID: 985402 RESULT

• Liu D, Moberg E, Kollind M, Lins PE, Adamson U, Macdonald IA. Arterial, arterialized venous, venous and capillary blood glucose measurements in normal man during hyperinsulinaemic euglycaemia and hypoglycaemia. Diabetologia. 1992 Mar;35(3):287-90. doi: 10.1007/BF00400932.

  PMID: 1563586 RESULT

• Cobb J, Gall W, Adam KP, Nakhle P, Button E, Hathorn J, Lawton K, Milburn M, Perichon R, Mitchell M, Natali A, Ferrannini E. A novel fasting blood test for insulin resistance and prediabetes. J Diabetes Sci Technol. 2013 Jan 1;7(1):100-10. doi: 10.1177/193229681300700112.

  PMID: 23439165 RESULT

Related Links

• Publication of study results

MeSH Terms

Interventions

saxagliptin

Study Officials

• Thomas Forst, Prof. Dr.

  Profil Mainz GmbH & Co KG, Rheinstraße 4c, 55116 Mainz

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Executive Officer (Prof. Dr.)

Study Record Dates

• First Submitted: November 11, 2014
• First Posted: December 1, 2014
• Study Start: January 1, 2015
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: June 20, 2018

Record last verified: 2018-06

Locations

DE (1)