E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 evaluate if treatment with Lixisenatide for 24 weeks reduces Ao-PWV in T2DM with DN. |
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E.2.2 | Secondary objectives of the trial |
To evaluate if treatment with Lixisenatide reduces albumin excretion rate (AER), central aortic pressure, augmentation index, sodium balance, ANP, post prandial sodium, brachial artery pressure and other secondary exploratory objectives. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Written informed consent T2DM patients aged ≥40 years with DN defined as a history of an elevated AER [albumin:creatinine ratio (ACR) ≥2.5mg/mmol in men and ≥3mg/mmol in women or AER ≥20mcg/min] or positive urine dipstick result for proteinuria or urine protein creatinine ratios (PCR)>15 mg/mmol or clinical evidence of diabetic nephropathy] in the absence of other causes of renal damage or urinary tract infections, estimated glomerular filtration rate (eGFR)* ≥30 ml/min; On anti-hypertensive therapy with renin angiotensin system (RAS) inhibitor at a stable dose for at least 1 month prior to randomisation HbA1c ≥6.5% on anti-diabetic medications Body mass index ≥30 kg/m2 or ≥27 kg/m2 (people from black, Asian and other minority ethnic groups and for whom insulin therapy would have significant occupational implications or weight loss would benefit other significant obesity-related comorbidities) * by Modification of Diet in Renal Disease (MDRD) Study equation [186 x (Creat / 88.4)-1.154 x (Age)-0.203 x (0.742 if female) x (1.210 if black) ]
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E.4 | Principal exclusion criteria |
Patients with eGFR<30 ml/min; Patients with recent (within 1 year) history of CVD event; Patients with uncontrolled hypertension defined as systolic BP and diastolic BP greater than 180 and 110mmHg respectively; Pregnancy or lactation; Females of child bearing potential or males able to father a child who do not agree to use suitable methods of contraception (as specified in section 4.7 of the Protocol) Patients with non diabetic renal disease; Patients expected to receive an increase in the dose of RAS inhibitors during the course of study; History of pancreatitis; Active gastrointestinal (GI) or biliary disease; Planned major GI surgery that can/could affect upper GI function; History or family history of thyroid cancer or multiple endocrine neoplasia 2; Known allergy/intolerance to GLP-1 receptor agonist treatment, metacresol or any of the IMP or placebo components. Subjects involved in current research or have recently (within 30 days) been involved in any research involving an IMP prior to recruitment. Subjects with insufficient understanding of the Trial or unable to comply with study requirements Subjects on basal insulin and a sulphonylurea at randomisation visit. Patients already on a GLP-1 receptor agonist therapy
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end point will be change from baseline in Ao-PWV. The primary end point is change in Ao-PWV following 24 weeks with Lixisenatide as compared to 24 weeks of placebo treatment. |
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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) |
Exploratory secondary endpoints include changes in: - albumin excretion rate (AER), - central aortic pressure, - augmentation index, - sodium balance, - atrial natriuretic peptide (ANP), - post prandial sodium (at 2hrs and area under curve), - brachial artery pressure - panel of vascular and inflammatory markers [which will include VCAM-1, ICAM-1, MMP 2 and 9, serum elastase activity, high sensitive CRP] - AGE (known to be associated with arterial stiffness and albuminuria and potentially affected by GLP-1 agonists). - Samples will also be collected and for future analyses of cardio-renal and metabolic markers.
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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 | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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) | 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 | 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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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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The trial will be closed when all participants have made their final visit, the data entered into the database and all queries resolved and the database locked. |
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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 | 0 |