E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes mellitus type 2. |
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E.1.1.1 | Medical condition in easily understood language |
Disease characterized by increased concentration of glucose (sugar) in blood and disorder of glucose metabolism. |
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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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012601 |
E.1.2 | Term | 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 characterize the effect of dapagliflozin on the renal tubular function using 1HNMR spectroscopy. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives: To assess the effects of the coadministration of dapagliflozin with chlorothalidone on the extracellular volume status and electrolyte concentrations in diabetic patients with hypertension. The doses of blood pressure-lowering drugs for controlling BP (< 140/90 mmHg) will be assessed at the end of the dapagliflozin monotherapy period and at the end of the dapagliflozin-chlorothalidone coadministration period. Safety objective: Safety monitoring will be performed at monthly intervals. On each visit, the presence of adverse events will be assessed by history, detailed physical examination and appropriate laboratory tests. Exploratory objectives: As NMR spectroscopy is a non-selective technique, novel, unexpected, metabolites related to the disease process can be revealed and identified from their characteristic spectrum. The drug-induced changes in the concentrations of these metabolites will be recorded and the mechanisms that underlie them will be investigated. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provision of informed consent prior to any study specific procedures 2. Female and/or male aged 18-70 years. Women with childbearing potential can only be included in the study if a serological pregnancy test is negative and a safe contraception method is used throughout the study. 3. Uncontrolled type 2 diabetes mellitus (HbA1c > 7%) on metformin monotherapy (≥ 2000 mg qd or maximum tolerated dose) 4. Stage 1 hypertension (BP 140-159/90-99 mmHg)
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E.4 | Principal exclusion criteria |
1. Known primary kidney disease (eGFR < 60 ml/min) 2. History of cardiovascular disease 3. Type 1 diabetes 4. History of heart failure 5. Diseases that shorten the life expectancy (cancers, degenerative neurological disorders etc.) 6. Pregnancy-lactation 7. Patients with eGFR values lower than 45 ml/min (on repeated measurements) during the study period will be excluded |
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E.5 End points |
E.5.1 | Primary end point(s) |
To characterize the effect of dapagliflozin on the renal tubular function using 1HNMR spectroscopy. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At baseline, at week 13 and week 17. |
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E.5.2 | Secondary end point(s) |
Secondary objectives: To assess the effects of the coadministration of dapagliflozin with chlorothalidone on the extracellular volume status and electrolyte concentrations in diabetic patients with hypertension. In addition, the doses of blood pressure-lowering drugs needed to control BP values (< 140/90 mmHg) will be assessed at the end of the dapagliflozin monotherapy period as well as at the end of the dapagliflozin-chlorothalidone coadministration period. Safety objective: Safety monitoring will be performed at monthly intervals. On each visit, the presence of adverse events will be assessed by history, detailed physical examination and appropriate laboratory tests (glucose, uric acid, urea, creatinine, electrolytes, complete blood count and urinalysis). In addition, patients will be instructed to contact the study personnel in case of an emergency situation, whereas an adverse event reporting system will be available throughout the study. In the case of a serious adverse event requiring hospitalization the participant will be excluded from the study. Exploratory objectives: As NMR spectroscopy is a non-selective technique, novel, unexpected, metabolites related to the disease process can be revealed and identified from their characteristic spectrum. The drug-induced changes in the concentrations of these metabolites will be recorded and the mechanisms that underlie them will be investigated. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary: according to the timepoint of collection of each specific variable (e.g. at weeks 5, 9, 13, 17) as applicable. Safety: data collection and assessment of assessment are continuous. The safety data will be analyzed at the end of the study.
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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 | No |
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 | No |
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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |