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 |
|
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 | 14.0 |
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 |
|
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 |
The aim of this study is to compare the effects of single dose, double dose and split double dose aspirin (ASA) on platelet function in ASA-naïve patients with Type 2 diabetes but with no cardiovascular disease. Our hypothesis is that the high residual platelet reactivity commonly seen in ASA-treated diabetes patients might be overcome by giving higher or more frequent ASA doses. The change in platelet reactivity between baseline and the post single dose, split dose or double dose treatment period will be measured by the 'VerifyNowTM' ASA Point-of-Care test. |
|
E.2.2 | Secondary objectives of the trial |
To determine whether the mechanism(s) for aspirin (ASA) “treatment failure” or “high platelet reactivity” in type 2 diabetics is/are COX-1 dependent or independent. (COX-1 is an important enzyme in the platelet that is affected by aspirin). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients will be eligible for the study if they: • Have type 2 diabetes (defined according to the European Association for the Study of Diabetes guidelines) • Are aged ≥18 years and <55 years • Have not had a coronary event or other indication requiring ASA • Have been on stable doses of antihyperglycaemic medication, i.e. the type of medication or dose used has not been changed for at least 3 months. • Have HbA1c levels ≤8.0% • Have triglycerides ≤2mmol/l |
|
E.4 | Principal exclusion criteria |
Patients will be ineligible for the study if they: • Have cardiovascular disease, including coronary heart disease, stroke and peripheral artery disease • Have been taking aspirin (ASA), non-steroidal anti-inflammatory drugs, any antiplatelet or antithrombotic drugs within the last 30 days • Have a history of peptic ulcer disease • Are treated with insulin • Have high blood pressure (>150 mmHg systolic or >100 mmHg diastolic) • Have a known bleeding disorder • Have a known gastro-intestinal disorder • Have evidence of severe hepatic disease or ALT >3 times of the upper limit. • Have evidence of renal dysfunction or eGFR <40ml/min/1.73m2 • Have a contraindication to ASA, such as allergy or active bleeding • Have a planned intervention or surgery in the next 3 months • Are pregnant or lactating women • Have a history of any medical condition that would place them at risk as a result of a blood donation • Are currently taking part, or have completed, an Investigational Medicinal Product (IMP) trial within the last 3 months • Are felt to be unsuitable for the trial as decided by a principal investigator |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the change in platelet reactivity between baseline and post the single dose, split double dose, and double dose treatment periods, as measured by the 'VerifyNowTM' ASA Point-of-Care test after two weeks treatment on each of the three dose regimens. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline results taken at the randomisation visit will be compared to those results obtained following the three study interventions. |
|
E.5.2 | Secondary end point(s) |
Secondary endpoints include a variety of COX-1 dependent and independent platelet function tests, and indirect and direct measures of platelet function, after two weeks treatment on each of the three dose regimens as follows: - Change in serum TXB2 level between baseline and on ASA treatments - Change in urinary dTxB2 levels between baseline and on ASA treatments - Change in platelet function between baseline and on ASA treatments as measured by LTA - Change in platelet function between baseline and on ASA treatments as measured by PFA-100 - Change in platelet function between baseline and on ASA treatments as measured by WBA - Change in platelet function between baseline and on ASA treatments as measured by IPF |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline results taken at the randomisation visit will be compared to those results obtained following the three study interventions. |
|
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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | 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 | 3 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |