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] - 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 | 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 investigate the cause for the discrepancy in predicted and observed weight loss with empagliflozin by measuring appetite hormone regulation. |
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E.2.2 | Secondary objectives of the trial |
To determine the effects of empagliflozin on energy expenditure and change in total body weight and body composition. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and postmenopausal female participants aged between 30-70 years of age inclusive 2. Type 2 diabetes on diet and lifestyle control or stable dose of metformin only for at least 3 months 3. Stable weight (less than 5% change in body weight in last 3 months) – determined by self-reporting or documentation in clinical records 4. HbA1c 48-86mmol/mol (6.5 - 10%) 5. eGFR≥60ml/min/1.73m2 6. BMI ≥ 25kg/m2 7. Able and willing to give informed consent 8. Able to understand English.
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E.4 | Principal exclusion criteria |
1. Females who are not postmenopausal (as menstrual cycle can affect appetite hormone concentrations) which is defined as “2 years post last menstrual period <50 years of age or 1 year post last menstrual period >50 years of age.” 2. Type 2 diabetes on any other glucose lowering treatment except metformin 3. Patients with Type 1 diabetes 4. Patients on loop diuretics 5. Age <29 years and >70 years 6. BMI <25kg/m2 7. Not able to give informed consent 8. Not able to understand English 9. Moderate to severe renal impairment (eGFR<60ml/min/1.73m2) 10. Unstable diabetes i.e. HbA1c >86mmol/mol (10%), recent hospital admission with diabetic emergency in last 3 months 11. Patients with familial renal glycosuria 12. Patients with recurrent balanitis, vaginal or urinary tract infections 13. Shift workers 14. Patients who have participated in another study of an investigational medicinal product in the last 3 months 15. Active malignancy 16. Serious illness with a life-expectancy of less than 1 year. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in appetite hormone concentrations (specifically total PYY) between baseline and 24 weeks: - this will be measured by sequential blood sampling during visits 1-5. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At baseline (0 weeks), 2 weeks, 6 weeks, 12 weeks and 24 weeks (study end). |
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E.5.2 | Secondary end point(s) |
The secondary outcomes are to determine the effects of empagliflozin on energy expenditure and change in total body weight and body composition.
Secondary endpoints, which are exploratory, are effect on:- (i) Appetite hormones ghrelin and GLP-1 and appetite perception (ii) Total body weight and change in body composition (fat and fat free mass) (iii) Resting energy expenditure (iv) Physical activity (v) Change in blood and urine biochemical parameters.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At baseline (0 weeks), 2 weeks, 6 weeks, 12 weeks and 24 weeks (study end). |
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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 | 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 | 4 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |