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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to demonstrate non-inferiority of treatment with linagliptin in comparison with placebo (as add-on therapy on top of standard of care) with respect to time to first occurrence of any of the adjudicated components of the primary composite endpoint in patients with type 2 diabetes mellitus |
|
E.2.2 | Secondary objectives of the trial |
If non-inferiority has been demonstrated, then the primary composite endpoint will be tested for superiority and the composite renal endpoint will be investigated separately with a test on superiority |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Documented diagnosis of T2DM before visit 1(screening).
2) Male or female patients who are drug-naïve or pre-treated with any antidiabetic background medication, excluding treatment with GLP-1 receptor agonists, DPP-4 inhibitors or SGLT-2 inhibitors if =>consecutive 7 days.
3) Stable antidiabetic background medication (unchanged daily dose) for at least 8 weeks prior to randomization. If insulin is part of the background therapy, the average daily insulin dose should not have changed by more than 10% within the 8 weeks prior to randomization compared with the daily insulin dose at randomization.
4) HbA1c of => 6.5% and <= 10.0% at Visit 1 (screening)
5) Age => 18 years at Visit 1(screening). For Japan only: Age => 20 years at Visit 1
6) Body Mass Index (BMI) <= 45 kg/m2 at Visit 1 (screening)
7) Signed and dated written informed consent by date of Visit 1(screening) in accordance with Good Clinical Practice (GCP) and local legislation prior to any study related procedure
8) High risk of CV events
|
|
E.4 | Principal exclusion criteria |
1) Type 1 diabetes mellitus.
2) Treatment (=> 7 consecutive days) with GLP-1 receptor agonists, other DPP-4 inhibitors or SGLT-2 inhibitors prior to informed consent. Note: This also includes clinical trials where these antidiabetic drugs have been provided to the patient.
3) Active liver disease or impaired hepatic function, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase (AP) => 3 x upper limit of normal (ULN) as determined at Visit 1.
4) eGFR <15 ml/min 1.73 m2 (severe renal impairment or ESRD, MDRD formula), as determined during screening at Visit 1 and/or the need for maintenance dialysis.
5) Any previous (or planned within next 12 months) bariatric surgery (open or laparascopic) or intervention (gastric sleeve).
6) Pre-planned coronary artery re-vascularisation (PCI, CABG) or any previous PCI and/or CABG <= 2 months prior informed consent
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
1: Time to the first occurence of any of the following adjudication confirmed components of the primary composite endpoint (3-point MACE): CV death, non-fatal MI or non fatal stroke |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1: Time to first occurance of any of the following by adjudication confirmed components: Composite renal endpoint (renal death, sustained end stage renal disease [ESRD], sustained decrease of 40% or more in eGFR. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1: 54 months
2: 54 months
|
|
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 | No |
E.6.10 | Pharmacogenetic | Yes |
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 | 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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 21 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 160 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Brazil |
Bulgaria |
Canada |
Chile |
China |
Colombia |
Croatia |
Czech Republic |
Germany |
Hungary |
India |
Israel |
Japan |
Korea, Republic of |
Malaysia |
Mexico |
Netherlands |
Poland |
Portugal |
Romania |
Russian Federation |
South Africa |
Spain |
Taiwan |
Ukraine |
United Kingdom |
United States |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
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 | 5 |
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 |