Saxagliptin in Combination With Dapagliflozin - Effects on Islet Cell Function

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02304081
• Date of registration: 11/11/2014
• Prospective Registration: Yes
• Primary sponsor: Prof. Dr. Thomas Forst
• Public title: Saxagliptin in Combination With Dapagliflozin - Effects on Islet Cell Function
• Scientific 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
• Date of first enrolment: January 2015
• Target sample size: 64
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02304081
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 4

Countries of recruitment

Germany

Contacts

• Name: Thomas Forst, Prof. Dr.
• Affiliation: Profil Mainz GmbH & Co KG, Rheinstraße 4c, 55116 Mainz

Key inclusion & exclusion 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



Age minimum: 30 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Type2 Diabetes Mellitus

Intervention(s)

Drug: Saxagliptin

Drug: Placebo for Saxagliptin

Primary Outcome(s)

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(s)

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)]

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)]

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)]

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)]

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)]

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)]

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)]

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)]

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)]

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)]

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)]

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)]

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)]

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)]

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)]

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)]

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)]

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)]

Secondary ID(s)

95/8010-DASA-001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors