E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | |
E.1.1.1 | Medical condition in easily understood language |
Heart failure is a condition where the heart does not have enough strength to pump blood all the way round the body efficiently, and causes edema, shortness of breath and reduced physical capacity. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000803 |
E.1.2 | Term | Acute heart failure |
E.1.2 | System Organ Class | 100000004849 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008908 |
E.1.2 | Term | Chronic heart failure |
E.1.2 | System Organ Class | 100000004849 |
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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 compare the pharmacokinetics of metformin in type 2 diabetic patients with heart failure in acute and chronic state. To investigate the influence of polymorphisms in genes encoding the metformin transporter proteins on metformin trough levels in type 2 diabetic heart failure patients. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Substudy A: To compare the pharmacokinetics of metformin in type 2 diabetic patients with heart failure in acute and chronic state.
Substudy B: To investigate the influence of polymorphisms in genes encoding the metformin transporter proteins on metformin trough levels in type 2 diabetic heart failure patients. |
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E.3 | Principal inclusion criteria |
Substudy A: • Patients with decompensated heart failure • Increased need for diuretics as judged by the clinicians • LVEF < 45% measured during admission or within 12 months prior to inclusion • NYHA-class I, II, III or IV • Ability to understand the written patient information and to give informed consent • Diabetes Type 2 (and in metformin treatment for > 1 month) • Stable dosage of metformin treatment for at least 1 week prior to examination
Substudy B: • Patients with heart failure • LVEF < 45% within 12 months prior to inclusion • NYHA-class I, II, III or IV • Ability to understand the written patient information and to give informed consent • Diabetes Type 2 (and in metformin treatment for > 1 month) • Stable dosage of metformin treatment for at least 1 week prior to examination |
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E.4 | Principal exclusion criteria |
Substudy A: • Severe cardiac failure, defined as o systolic blood pressure continuously < 85 mmHg o signs of tissue hypoperfusion (oliguria < 30 mL/h, altered level of consciousness, rapid deterioration of kidney function) o Need for intravenous inotropic support • Age < 18 years • Current abuse of alcohol or drugs • Adjustment or discontinuation of metformin dose during admission before examination
Substudy B: • Age < 18 years • Current abuse of alcohol or drugs |
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E.5 End points |
E.5.1 | Primary end point(s) |
Substudy A: Changes in renal clearance of metformin between patients with acute and chronic heart failure.
Substudy B: Mean trough steady-state concentrations (Css,min) of metformin with emphasis on the intra-interindividual variability in heart failure patients. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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 | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
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 | 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 | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |