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 | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012613 |
E.1.2 | Term | Diabetes mellitus non-insulin-dependent |
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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 investigate the beneficial effect of saxagliptin compared to placebo on endothelial and vascular function of the retinal circulation. By applying Scanning-Laser-Doppler-Flowmetry, the retinal capillary flow will be measured at baseline and its change to 1) Flicker light (repeated flashes that cause vasodilation) and 2) after i.v. L-NMMA application (known to block NO synthase thereby analysing the basal NO activity in the retinal circulation). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of saxagliptin on metabolic parameters (HbA1c, glucose levels, [fasting, postprandial] adiponectin, lipids, insulin, insulin sensitivity [HOMA-index]and lipids)
To evaluate the effect of saxagliptin on other biomarkers (oxidative stress [e.g isoprostanes, GSH/GSSG ratio] and/or inflammatory markers [e.g IL-6, hsCRP]
To evaluate the effect of saxagliptin on carotid-to-femoral pulse wave velocity and aortic pulse wave contour [aortic augmentation index]
To evaluate the effect of saxagliptin on urinary albumine-to-creatinine ratio (UACR)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Type 2 diabetes mellitus defined by fasting glucose ≥126 mg/dl or HbA1c ≥6.5% or on blood glucose lowering medication
Age of 18 -75 years
Male and Female patients are eligible. Females of child bearing potential or within two years of the menopause are only eligible if pregnancy test at the screening visit is negative and they use adequate contraceptive precautions during the trial. Adequate contraceptive precautions include precaution with a Pearl-Index <1 (oral contraceptive pill, subdermal contraceptive rod - Implanon®, intra-uterine spiral, tubular sterilization).
The patient must demonstrate that she/he is able and willing to perform blood glucose measurements as necessary for Home Blood Glucose Monitoring by herself/himself after it was demonstrated to her/him. |
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E.4 | Principal exclusion criteria |
Any other form of diabetes mellitus than type 2 diabetes mellitus
Patients with more than on one blood glucose lowering medication or on insulin therapy
Last measured HbA1c ≥ 10%
Fasting plasma glucose > 240 mg/dl
Blood pressure levels ≥180/110 mmHg
Body mass index >50 kg/m²
Triglyceride levels > 500 mg/dl
HDL-cholesterol levels <25 mg/dl
Estimated creatinine clearance < 50 ml/min/1.73m²
Macroalbuminuria defined by urinary albumine-to-creatinine ratio > 300 mg/g
Known liver function test >3 times upper limit of normal
Pregnant or breast-feeding patients
Current or previous (within 6 months) treatment with an incretin-based therapy such as DPP 4 inhibitors and/or GLP-1 mimetics
Patients with a history of a hypersensitivity reaction or anaphylaxia in response to a previous treatment to a DPP 4 inhibitor and/or GLP-1 mimetics
Any patient currently receiving chronic (>30 consecutive days) treatment with an oral steroid)
Acute cardiovascular event (including myocardial infarction, unstable angina pectoris, percutaneous coronary intervention, heart failure, stroke, TIA. PRIND, intracerebral bleeding) <6 months prior to screening visit (visit 1)
Diabetic retinopathy
History of epilepsia or history of seizures
Patients being treated for severe auto immune disease such as lupus
Involvement in the planning and/or conduct of the study (applies to both AstraZeneca and BMS or representative staff and/or staff at the study site)
Previous randomisation in the present study
Participation in another clinical study within 30 days prior to visit 1
Individuals at risk for poor protocol or medication compliance
Subject who do not give written consent, that pseudonymous data will be transferred in line with the duty of documentation and the duty of notification according to § 12 and § 13 GCP-V
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary parameter is the change of retinal capillary flow in reponse to L-NMMA. |
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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 | 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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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.8.3 |
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 | Yes |
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 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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |