E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 diabetes with renal complications |
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E.1.1.1 | Medical condition in easily understood language |
Type 2 diabetes with increased protein in the urine |
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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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
E.1.2 | System Organ Class | 100000004861 |
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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 the effect of treatment with semaglutide 1.34 mg/ml in combination with empagliflozin 25 mg, compared to treatment with empagliflozin 25 mg in combination with placebo on albuminuria in participants with type 2 diabetes and albuminuria. |
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E.2.2 | Secondary objectives of the trial |
To compare the effects of combination of empagliflozin 25 mg with either semaglutide 1.34 mg/ml or placebo treatment on: • Glycaemic control • Inflammation and endothelial dysfunction • 24h blood pressure • Kidney function (GFR) • Vasoactive hormones
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Given written informed consent 2. Male or female patients ≥ 18 years with type 2 diabetes (WHO criteria). 3. UACR > 100 mg/g within a year of informed consent documented in the medical files. 4. eGFR ≥ 30 ml/min/1.73 m2 (estimated by CKD-EPI formula) within 3 months of informed consent documented in the medical files. The eGFR measured at visit 0 has to meet the criteria as well. 5. Fertile female must use chemical, hormonal and mechanical contraceptives, be in menopause (i.e. must not have had regular menstrual bleeding for at least one year), have undergone bilateral oophorectomy or have been surgically sterilized or hysterectomised at least six months prior to screening 6. Treated with maximal tolerated dose of an angiotensin-converting-enzyme inhibitor or an angiotensin II receptor blocker, 4 weeks prior to randomisation. If the participants are not treated with maximal tolerated dosis the investigator will increase the dose 4 weeks prior randomisation if tolerated. 7. Ability to communicate with the investigator and understand informed consent.
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E.4 | Principal exclusion criteria |
1. Type 1 diabetes 2. Known or suspected hypersensitivity to trial product(s) or related products 3. Cancer (except basal cell skin cancer or squamous cell skin cancer) or any other clinically significant disorder, except for conditions associated with type 2 diabetes history, which in the investigators opinion could interfere with the results of the trial 4. Cardiac disease defined as: Decompensated heart failure (NYHA class III-IV) and or diagnosis of unstable angina pectoris and/or myocadial infarction within the last 6 months. 5. Previous bowel resection 6. Body mass index < 18.5 kg/m2 7. Females of childbearing potential who are pregnant, breast-feeding, intend to become pregnant or are not using adequate contraceptive methods 8. Known or suspected abuse of alcohol or narcotics. 9. Participant in another intervention study
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in albuminuria (UACR) from randomisation to end of week 52 measured in three morning spot urine samples. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At randomisation and after 26 weeks of treatment |
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E.5.2 | Secondary end point(s) |
• Change in HbA1c from randomisation to end of week 52. Change in measured kidney function (GFR) from randomisation to week 52. Change in 24 hour blood pressure from randomisation to week 52. Change in vasoactive hormones from randomisation to week 52. o Plasma renin concentration, plasma renin activity, angiotensin I, angiotensin II, aldosterone and copeptin. Change in inflammatory and endothelial biomarkers from randomisation to week 52. o Von Willebrand factor, sVCAM-1, sICAM-1, E-selectin, b-leucocytes, s-CRP, IL-6, osteopontin and TNF-α.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At randomisation and after 26 weeks of treatment |
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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 | 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) | Yes |
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 | 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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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 |