E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Obesity and Chronic Kidney disease |
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E.1.1.1 | Medical condition in easily understood language |
Obesity and Kidney disease |
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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 | 20.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10038359 |
E.1.2 | Term | Renal and urinary disorders |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10027433 |
E.1.2 | Term | Metabolism and nutrition disorders |
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 compare the effect of tirzepatide MTD (10 or 15 mg) QW and placebo on kidney oxygenation after 52 weeks of treatment, in participants with and without T2D |
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E.2.2 | Secondary objectives of the trial |
To compare the effect of tirzepatide MTD (10 or 15 mg) QW and placebo after 52 weeks of treatment, in participants with and without T2D, in participants with T2D, and in participants without T2D on: - body weight Mean percent change from baseline in body weight - renal sinus fat Mean change from baseline in renal sinus fat (cm2) assessed using MRI - renal fat content Mean change from baseline in renal fat content using MRI-PDFF - renal blood flow |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Participants without diabetes must have HbA1c of ≤ 6.5 %. 2. Participants with diabetes must have HbA1c ≥ 7 % to ≤ 10.5 % at screening visit. 3. Participants must be at least 18 years of age or the legal age of consent in the juristiction where the study is taking place. 4. Participants must have a BMI ≥ 27kg/cm2 at screening visit 5. Participants must be diagnosed with CKD having a eGFR ≥30 to ≤ 60 mL/min1.73 m2 or eGFR ≥ 30 to 75 mL/min/1.73 m2 if UACR > 30 mg/g, calculated by CKD-EPI eqn., as determined by central labs at screening visit. 6. Participants must have been receiving an ACE or ARBi that is considered the maximal appropriate dose by the investigator for treatment of CKD or hypertension (unless patient has low blood pressure or hypotension), The dose must have been unchanged for 30 days before screening visit. |
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E.4 | Principal exclusion criteria |
1. For participants with T2D the following exclusion criteria apply: 2. Participants have a history of proliferative diabetic retinopathy or diabetic macular edema or non-proliferative edema or non-proliferative diabetic retinopathy that requires acute treatment. 3. Participants who have uncontrolled diabtes (such as diabetic ketoacidosis) at screening or randomization, in the judgement of the physician 4. For participants without T2D the following exclusion criteria apply: 5. Have T1DM or a history of ketoacidosis ot hypersmolar state/coma 6. Have self reported change in body weight >5kgs within the 90 days prior to screening visit 7. Have had or plan to have surgical treatment for obesity (excluding liposuction or abdominoplasty if performed >1 year prior to screening) 8. Have or plan to have endoscopic and or device based therapy for obesity or have had device removal within the last 180 days e.g. mucosal ablation, gastric artery, ambolization, intragastric balloon and duodenal jejunal bypass device. 9. Have eGFr < 30 mL/min/1.73 m2 calculated by CKD-EPI equation. 10. Have a history of unstable or rapidly progressing renal disease according to investigator judgement. 11. Have a history of a congenital or hereditary kidney disease, like polycystic kidney disease or congenital urinary tract malformations |
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean change from baseline in kidney oxygenation |
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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) |
Mean percent change from baseline in body weight Mean change from baseline in renal sinus fat (cm2) assessed using MRI Mean change from baseline in renal fat content using MRI-PDFF Mean change from baseline in renal blood flow using phase-contrast MRI |
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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 | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 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 | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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 |
Canada |
Mexico |
United States |
Austria |
Netherlands |
Denmark |
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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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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 | 9 |
E.8.9.1 | In the Member State concerned days | |
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 | 9 |