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Saxagliptin in Combination With Dapagliflozin - Effects on Islet Cell Function

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ClinicalTrials.gov Identifier: NCT02304081
Recruitment Status : Completed
First Posted : December 1, 2014
Last Update Posted : June 20, 2018
Sponsor:
Information provided by (Responsible Party):
Prof. Dr. Thomas Forst, Profil Mainz GmbH & Co KG

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.

Condition or disease Intervention/treatment Phase
Type2 Diabetes Mellitus Drug: Saxagliptin Drug: Placebo for Saxagliptin Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Saxagliptin in Addition to Dapagliflozin and Metformin on Insulin Resistance, Islet Cell Dysfunction, and Metabolic Control in Subjects With Type 2 Diabetes Mellitus on Previous Metformin Treatment
Study Start Date : January 2015
Actual Primary Completion Date : August 2016
Actual Study Completion Date : August 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Saxagliptin
Metformin and Dapagliflozin background therapy
Drug: Saxagliptin
competitive inhibitor of human dipepitdylpeptidase (DPP)-IV
Other Name: Onglyza®

Placebo Comparator: Placebo
Metformin and Dapagliflozin background therapy
Drug: Placebo for Saxagliptin



Primary Outcome Measures :
  1. Glucagon / insulin ratio during hyperglycaemic clamp phase (AUCGluc270-390min / AUCIns270-390min) [ Time Frame: at baseline (Day 0) as well as after Treatment Phase 1 (after 30 days) and after Treatment Phase 2 (after 60 days) ]

Secondary Outcome Measures :
  1. Glucagon release during hyperglycaemic clamp phase (AUCGluc270-390min; pg/ml*min) [ Time Frame: at baseline (Day 0) as well as after Treatment Phase 1 (after 30 days) and after Treatment Phase 2 (after 60 days) ]
    Pharmacodynamic endpoints

  2. First phase glucagon release during hyperglycaemic clamp phase (AUCGluc270-290min; pg/ml*min) [ Time Frame: at baseline (Day 0) as well as after Treatment Phase 1 (after 30 days) and after Treatment Phase 2 (after 60 days) ]
    Pharmacodynamic endpoints

  3. First phase insulin release during hyperglycaemic clamp phase (AUCIns270-290min; pmol/l*min) [ Time Frame: at baseline (Day 0) as well as after Treatment Phase 1 (after 30 days) and after Treatment Phase 2 (after 60 days) ]
    Pharmacodynamic endpoints

  4. Second phase insulin release during hyperglycaemic clamp phase (AUCIns290-390min; pmol/l*min) [ Time Frame: at baseline (Day 0) as well as after Treatment Phase 1 (after 30 days) and after Treatment Phase 2 (after 60 days) ]
    Pharmacodynamic endpoints

  5. First Phase glucagon / insulin ratio during hyperglycaemic clamp phase (AUCGluc270-290min / AUCIns270-290min) [ Time Frame: at baseline (Day 0) as well as after Treatment Phase 1 (after 30 days) and after Treatment Phase 2 (after 60 days) ]
    Pharmacodynamic endpoints

  6. Second Phase glucagon / insulin ratio during hyperglycaemic clamp phase (AUCGluc290-390min / AUCIns290-390min) [ Time Frame: at baseline (Day 0) as well as after Treatment Phase 1 (after 30 days) and after Treatment Phase 2 (after 60 days) ]
    Pharmacodynamic endpoints

  7. Intact proinsulin release during hyperglycaemic clamp (AUCIP270-390min ; pmol/l*min) [ Time Frame: at baseline (Day 0) as well as after Treatment Phase 1 (after 30 days) and after Treatment Phase 2 (after 60 days) ]
    Pharmacodynamic endpoints

  8. Insulin / proinsulin ratio during hyperglycaemic clamp (AUCIns270-390min / AUCIP270-390min) [ Time Frame: at baseline (Day 0) as well as after Treatment Phase 1 (after 30 days) and after Treatment Phase 2 (after 60 days) ]
    Pharmacodynamic endpoints

  9. C-Peptide release during hyperglycaemic clamp (AUCC-Pep270-390min ; pmol/l*min) [ Time Frame: at baseline (Day 0) as well as after Treatment Phase 1 (after 30 days) and after Treatment Phase 2 (after 60 days) ]
    Pharmacodynamic endpoints

  10. C-Peptide/Insulin ratio during hyperglycaemic clamp (AUCC-Pep270-390min / AUCIP270-390min) [ Time Frame: at baseline (Day 0) as well as after Treatment Phase 1 (after 30 days) and after Treatment Phase 2 (after 60 days) ]
    Pharmacodynamic endpoints

  11. M-Value during euglycaemic-hyperinsulinaemic clamp phase (mg/kg*min) [ Time Frame: at baseline (Day 0) as well as after Treatment Phase 1 (after 30 days) and after Treatment Phase 2 (after 60 days) ]
    Pharmacodynamic endpoints

  12. HOMAIR Index [ Time Frame: at baseline (Day 0) as well as after Treatment Phase 1 (after 30 days) and after Treatment Phase 2 (after 60 days) ]
    Pharmacodynamic endpoints

  13. Body Weight (kg) [ Time Frame: at baseline (Day 0) as well as after Treatment Phase 1 (after 30 days) and after Treatment Phase 2 (after 60 days) ]
    Pharmacodynamic endpoints

  14. Fasting Adiponectin (µg/ml) [ Time Frame: at baseline (Day 0) as well as after Treatment Phase 1 (after 30 days) and after Treatment Phase 2 (after 60 days) ]
    Pharmacodynamic endpoints

  15. Fasting Plasma Glucose (mg/dl) [ Time Frame: at baseline (Day 0) as well as after Treatment Phase 1 (after 30 days) and after Treatment Phase 2 (after 60 days) ]
    Pharmacodynamic endpoints

  16. HbA1C (mmol/mol; %) [ Time Frame: at baseline (Day 0) as well as after Treatment Phase 1 (after 30 days) and after Treatment Phase 2 (after 60 days) ]
    Pharmacodynamic endpoints

  17. QuantoseTM Score [ Time Frame: at baseline (Day 0) as well as after Treatment Phase 1 (after 30 days) and after Treatment Phase 2 (after 60 days) ]
    Pharmacodynamic endpoints

  18. Blood Lipids (Triglycerides [mg/dl]; total, HDL, LDL cholesterol [mg/dl]) [ Time Frame: at baseline (Day 0) as well as after Treatment Phase 1 (after 30 days) and after Treatment Phase 2 (after 60 days) ]
    Pharmacodynamic endpoints



Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  1. 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
  2. Use of insulin or GLP-1 analogues within three months prior to Screening
  3. Treatment with any other investigational drug within three months before screening
  4. History of diabetes mellitus type 1
  5. Acute infections within the last two weeks prior to Screening
  6. Anamnestic history of hypersensitivity to the study drugs or to drugs with similar chemical structures
  7. History of severe or multiple allergies
  8. GFR (as calculated by the Cockroft-Gault equation) < 60 ml/min at Screening
  9. State after kidney transplantation
  10. Laboratory safety value(s) outside the reference range and deemed clinically relevant by the Investigator
  11. 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
  12. Pregnancy or breast feeding
  13. Systolic blood pressure outside the range of 100-160 mmHg or diastolic blood pressure above 90 mmHg at Screening
  14. Acute myocardial infarction or cerebral event (stroke/TIA) within six months prior to Screening
  15. Uncontrolled unstable angina pectoris or history of pericarditis, myocarditis, endocarditis
  16. Increased risk of thromboembolism, e.g. subjects with a history of deep leg vein thrombosis or family history of deep leg vein thrombosis, as judged by the Investigator
  17. Hemodynamic relevant aortic stenosis, Aortic aneurysm
  18. Repeated episodes of severe hypoglycaemia within six months prior to Screening
  19. History of diabetic ketoacidosis, praecoma diabeticum, or diabetic coma
  20. Recurrent urogenital infections
  21. Haematuria
  22. History of pancreatitis
  23. Progressive fatal disease
  24. Elective surgery planned during study participation
  25. Acute or scheduled investigation with iodine containing radiopaque material
  26. History of drug or alcohol abuse in the past two years
  27. Donation of blood, major blood loss (>=500 ml), or major surgery within the last three months prior to Screening
  28. Active hepatitis B, measured by positive tests of surface antigen HBsAg and/or active hepatitis C, measured by positive hepatitis C virus antibody tests (HCV) at Screening
  29. Positive human immunodeficiency virus (HIV) antibodies or HIV 1 Ag at Screening

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02304081


Locations
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Germany
Profil Mainz GmbH & Co. KG
Mainz, Germany, 55116
Sponsors and Collaborators
Prof. Dr. Thomas Forst
Investigators
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Principal Investigator: Thomas Forst, Prof. Dr. Profil Mainz GmbH & Co KG, Rheinstraße 4c, 55116 Mainz
Additional Information:
Publications of Results:

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Responsible Party: Prof. Dr. Thomas Forst, Chief Executive Officer (Prof. Dr.), Profil Mainz GmbH & Co KG
ClinicalTrials.gov Identifier: NCT02304081    
Other Study ID Numbers: 95/8010-DASA-001
First Posted: December 1, 2014    Key Record Dates
Last Update Posted: June 20, 2018
Last Verified: June 2018
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Saxagliptin
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents