E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
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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 define phenotypic differences that predict sulphonylurea response in order to identify aetiological differences in these distinct subgroups, by intensively studying: i. Beta cell response to intravenous glucose and tolbutamide to identify quantitative and qualitative differences in function ii. Insulin sensitivity iii. Pharmacokinetics
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E.2.2 | Secondary objectives of the trial |
a) To establish a cohort of patients who are adherent to sulphonylurea therapy, but whose response is either good or poor. b) To validate the initial determination of response from the database by correlation with a controlled re-challenge response, to allow future large-scale pharmacogenetics studies c) To investigate whether patients GG homozygous at rs12255372 of TCF7L2 respond better to sulphonylureas than those who are TT homozygous at this SNP
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Study 1. • Type 2 diabetes • Age >35 and < 70 • Age of diabetes diagnosis >35 and <70 • White European • Pre-SU HbA1c <=10% • HbA1c (on treatment) <= 9% • No established cardiovascular disease (previous established angina or myocardial infarction) • No established cerebrovascular disease (previous stroke or transient ischaemic attack) • No or stable (background) retinopathy (no unscheduled laser treatment in the last 6 months) • eGFR > 60mls/min • No frank proteinuria (on multistix 10SG) • No active foot ulceration or infection • Liver ALT within the laboratory reference range • Contactable by telephone
Study 2.
• Age >35 and < 70 • Age of diabetes diagnosis >35 and <70 • White European • HbA1c ≥ 7% and ≤ 9% • Not on SU and no previous SU intolerance • No established cardiovascular disease (previous established angina or myocardial infarction) • No established cerebrovascular disease (previous stroke or transient ischaemic attack) • No or stable (background) retinopathy (no unscheduled laser treatment in the last 6 months) • eGFR > 60 ml/min • No frank proteinuria (on multistix 10SG) • No active foot ulceration or infection • Liver ALT within the laboratory reference range • Contactable by telephone
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E.4 | Principal exclusion criteria |
• Type 1 diabetes • HbA1c >10% prior to commencing SU • HbA1c>9% on SU treatment Study 1 • Previous cardiovascular or cerebrovascular disease • Pre-proliferative or proliferative retinopathy • eGFR<60 ml/min • Proteinuria (multistix 10 SG) • Active foot ulceration or infection • Liver ALT outwith the reference range • Female planning to conceive within the study period • Any other significant medical reason for exclusion as determined by the investigator
Study 2
• Type 1 diabetes • HbA1c ≤ 7% or ≥ 9%. • Previous cardiovascular or cerebrovascular disease • Pre-proliferative or proliferative retinopathy • eGFR< 60 ml/min • Proteinuria (multistix 10 SG) • Active foot ulceration or infection • Liver ALT outwith the reference range • Female planning to conceive within the study period • Any other significant medical reason for exclusion as determined by the investigator
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E.5 End points |
E.5.1 | Primary end point(s) |
Study 1 and 2.
Change in HbA1c |
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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 | No |
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 | Yes |
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) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
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 | Yes |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
parallel group - each group gets the study drug and difference in response is compared between group |
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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 | 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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Last visit of last subject |
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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 | |
E.8.9.1 | In the Member State concerned days | |