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 |
Obesity and associated disorders such as impaired metabolism of lipids and glucose |
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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 |
To evaluate the effect of Mirabegron treatment on brown fat activity measured by MRI in South Asians compared with white Caucasians. |
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E.2.2 | Secondary objectives of the trial |
The secondary objecties of the study are to assess: 1. differences in the effect of Mirabegron treatment on a) resting energy expenditure, b) plasma lipid levels c) and sympathetic output between South Asian and white Caucasian individuals. 2. differences between indirect BAT activation by cold exposure and direct BAT activation with Mirabegron treatment. 3. MRI scan as novel way to visualize BAT activity 4. the effect of mild cold exposure and Mirabegron on plasma lipoprotein profiles
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male volunteers. 10 white Caucasians, born in the Netherlands. 10 South Asians, living in the Netherlands. • Age: 18-30 years • BMI ≤ 25 kg/m2
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E.4 | Principal exclusion criteria |
• BMI > 25 kg/m2 • Recent excessive weight loss or exercise • Alcohol and/ or drugs abuse • Excessieve smoking (>10 cigarettes/day) • Any significant chronic disease, including diabetes, Renal, hepatic or endocrine disease • Heart disease or arrhythmias • Thyroid disease or thyroid medication • Hypertension • Use of medication known to influence glucose and/or lipid metabolism or BAT activity (e.g. beta blockers or calcium channel blockers) • Use of drugs that influence cardiac function or affect QT time • Use of MAO inhibitor • Use of systemic corticosteroids in previous six weeks • Recent participation in other research projects (within the last 3 months), participation in 2 or more projects in one year • Contraindications for undergoing an MRI scan. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- BAT activity measured by MRI scan |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
3 hours after either mild cold exposure, administration of Mirabgeron or a placebo. |
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E.5.2 | Secondary end point(s) |
- Fasted REE by indirect calorimetry - Change in supraclavicular skin temperature (as measured with iButtons) - Fasting serum markers for lipid metabolism (total cholesterol, HDL-C, LDL-C, triglycerides, free fatty acids) and dynamic changes in lipoproteins. - Fasting serum markers for sympathetic output (norepinephrine, epinephrine)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
3 hours after either mild cold exposure, administration of Mirabgeron or a placebo. |
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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 | No |
E.8.1.6 | Cross over | Yes |
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 | 3 |
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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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 | 6 |
E.8.9.1 | In the Member State concerned days | |