E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prader Willi syndrome (PWS) |
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E.1.1.1 | Medical condition in easily understood language |
Prader Willi syndrome is genetic condition that affects many parts and organ system of the body. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036476 |
E.1.2 | Term | Prader-Willi syndrome |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The purpose of this study is to investigate the safety and efficacy of co-administration of tesofensine/metoprolol treatment versus placebo in adult and pediatric subjects with Prader-Willi syndrome. The primary objective is to examine the effect of co-administration of tesofensine/metoprolol on body weight in subjects with PWS in an open
labeled extension study. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
1. To establish pharmacokinetic profile of tesofensine and metoprolol in subjects with PWS
2. To examine the change in hyperphagia-related behaviour in subjects with PWS by use of the Hyperphagia Questionnaire for Clinical Trials (HQ-CT)
3. To examine the effect of co-administration of tesofensine/metoprolol on glycaemic control and lipid profile in subjects with PWS
4. To examine the effect of co-administration of tesofensine/metoprolol on HR and BP in subjects with PWS
5. To examine the effects of co-administration of tesofensine/metoprolol on body composition in subjects with PWS
6. To evaluate overall safety and tolerability of co-administration of the tesofensine/metoprolol in subjects with PWS
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All male and female pediatric subjects with confirmed diagnosis of PWS who completed the double blind phase (12 weeks) and the first OLE, will be invited to participate in the second open label 12 weeks extension phase, if deemed eligible by the Investigators. |
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E.4 | Principal exclusion criteria |
If subject/parents decide to not participate in OLE II, subject will finish the study based on the Protocol Amendment 1.6. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for this study is percent change from baseline to end of treatment periods in mean body weight. |
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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) |
Secondary endpoints include:
1. Steady state concentrations of tesofensine and metoprolol as measured by trough values
2. Uptake and initial plateau concentrations of metoprolol as measured
by samples taken 2 and 4 hours after dose administration
3. Change from baseline to end of the treatment periods in total HQCT score
4. Change from baseline to end of treatment periods in mean body weight (kg)
5. Change from baseline to end of treatment periods in fat- and fat-free mass (%) by dual X-ray absorptiometry (DXA)
6. Change from baseline to end of treatment periods in HR (bpm), SBP (mmHg), DBP (mmHg)
7. AEs, clinical labs, ECG
There are additional exploratory endpoints:
1. Change from baseline to end of treatment periods in FPG, insulin
2. Change from baseline to end of treatment periods in lipid profile
3. Change from baseline to end of treatment periods in waist circumference (cm) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From baseline to end of study 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 | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |