E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate alpha- and beta-cell function during combination treatment with dapagliflozin plus saxagliptin compared to dapagliflozin alone in subjects with T2DM on stable metformin background therapy |
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E.2.2 | Secondary objectives of the trial |
•evaluate the effect of dapagliflozin treatment on alpha- and beta-cell function in subjects with T2DM
•evaluate insulin resistance during combination treatment with dapagliflozin plus saxagliptin compared to dapagliflozin alone in subjects with T2DM
•evaluate the effect of dapagliflozin treatment on insulin resistance in subjects with T2DM
•evaluate body weight during combination treatment with dapagliflozin plus saxagliptin compared to dapagliflozin alone in subjects with T2DM
•evaluate the effect of dapagliflozin treatment on body weight in subjects with T2DM
•evaluate the risk of hypoglycaemia during combination treatment with dapagliflozin plus saxagliptin compared to dapagliflozin alone in subjects with T2DM
•evaluate the effect of dapagliflozin treatment on the risk of hypoglycaemic events in subjects with T2DM |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Diabetes mellitus type 2
2. HbA1c 7.0%–9.9%, both inclusive
3. Treatment with metformin for at least six months (daily dose 1500 – 3000 mg)
4. Age 30–75 years, both inclusive
5. BMI 25–35 kg/m^2, both inclusive
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E.4 | Principal 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
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E.5 End points |
E.5.1 | Primary end point(s) |
• Glucagon / insulin ratio during hyperglycaemic clamp phase (AUCGluc270–390min / AUCIns270–390min) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Endpoint measurements will be performed at baseline (Visit 2) as well as after Treatment Phase 1 (Visit 3) and after Treatment Phase 2 (Visit 3) |
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E.5.2 | Secondary end point(s) |
•Glucagon release during hyperglycaemic clamp phase (AUCGluc270–390min; pg/ml*min)
•First phase glucagon release during hyperglycaemic clamp phase (AUCGluc270–290min; pg/ml*min)
•First phase insulin release during hyperglycaemic clamp phase (AUCIns270–290min; pmol/l*min)
•Second phase insulin release during hyperglycaemic clamp phase (AUCIns290–390min; pmol/l*min)
•First Phase glucagon / insulin ratio during hyperglycaemic clamp phase (AUCGluc270–290min / AUCIns270–290min)
•Second Phase glucagon / insulin ratio during hyperglycaemic clamp phase (AUCGluc290–390min / AUCIns290–390min)
•Intact proinsulin release during hyperglycaemic clamp (AUCIP270–390min ; pmol/l*min)
•Insulin / proinsulin ratio during hyperglycaemic clamp (AUCIns270–390min / AUCIP270–390min)
•C-Peptide release during hyperglycaemic clamp (AUCC-Pep270–390min ; pmol/l*min)
•C-Peptide/Insulin ratio during hyperglycaemic clamp (AUCC-Pep270–390min / AUCIP270–390min)
•M-Value during euglycaemic-hyperinsulinaemic clamp phase (mg/kg*min)
•HOMAIR Index
•Body Weight (kg)
•Fasting Adiponectin (µg/ml)
•Fasting Plasma Glucose (mg/dl)
•HbA1C (mmol/mol; %)
•QuantoseTM Score
•Blood Lipids (Triglycerides [mg/dl]; total, HDL, LDL cholesterol [mg/dl])
•Incidence of treatment-emergent hypoglycaemic episodes from baseline (first administration of trial medication on Visit 2) until end of treatment (last administration of trial medication on Visit 4)
•Changes in clinical and laboratory safety variables from baseline until end of treatment
•Incidence of adverse events from baseline until end of Treatment
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Endpoint measurements will be performed at baseline (Visit 2) as well as after Treatment Phase 1 (Visit 3) and after Treatment Phase 2 (Visit 3) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 15 |