E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
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 characterise the relationship between plasma metformin pharmacokinetics and the presence of polymorphisms in human organic cation transporter genes in patients with type 2 diabetes mellitus on chronic metformin therapy. |
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E.2.2 | Secondary objectives of the trial |
To characterise the relationship between the plasma pharmacokinetics and the levels of vitamin B12 and lactate in patients with type 2 diabetes mellitus on chronic metformin therapy. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Subject is aged between 25 and 85 years of age inclusive. 2. Subject has given signed informed consent (written and witnessed). 3. Subject has a diagnosis of type 2 diabetes mellitus, regardless of how and when that diagnosis was established. 4. Subject’s anti-hyperglycaemic medication consists of metformin monotherapy, at a dosage of 500mg three times daily and that dosage has been established for a period of at least 3 months. 5. Subject has not missed any metformin doses for a period of at least 5 days and compliance has been assessed through a validated compliance questionnaire. 6. Subject is able to recall at least approximate timing of dosing (within 30 minutes). |
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E.4 | Principal exclusion criteria |
1. Subject is, in the opinion of the Investigator, not suitable to participate in the study. 2. Subject has a diagnosis of pernicious anaemia. 3. Subject is also prescribed additional anti-hyperglycaemic medication such as sulphonylureas, meglitinide analogues, thiazolidinediones or insulin. 4. Subject has taken any known inhibitor of OCT1 or OCT2, such as amantadine, cimetidine, clonidine, desipramine, midazolam, procainamide, quinidine, quinine, or verapamil in the last 4 weeks. 5. Subject has participated in strenuous physical activity, defined as more than typical walking pace, for a period of 8 hours prior to study entry. 6. Subject has an alcohol intake greater than the recommended weekly safe drinking limits (>21 units in men; >14 units in women).
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E.5 End points |
E.5.1 | Primary end point(s) |
1. OCT1 and OCT2 genotype Identification of the following SNPs will be undertaken: a) OCT1-M408V b) OCT1-M420del c) OCT1-R61C d) OCT2-A270S 2. Metformin pharmacokinetic (PK) parameters: a) Plasma metformin concentration (co-primary outcome measure) b) Predicted metformin clearance (co-primary outcome measure) c) Predicted metformin AUC (area under the plasma concentration-time curve) d) Predicted metformin Cmax
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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 | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |