Co-administration of Tesofensine/Metoprolol in Subjects With Prader-Willi Syndrome (PWS)

Study Overview
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Brief Summary
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Two-centre, double-blind, placebo-controlled, randomized, and multiple-dose clinical study.

Detailed Description
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Two-centre, double-blind, placebo-controlled, randomized, and multiple-dose clinical study. Study medication will be administered for 91 days. The study will be conducted in two steps: Step 1 - 10-15 adult subjects with PWS will be treated. DSMB review and SUKL review - following the completion of the treatment of the adult subjects, unblinded efficacy, safety, PK data as well as all data from the study in subjects with type 2 diabetes (TM001) will be reviewed by an independent Data Safety Monitoring Board (DSMB) and State Institute for Drug Control (SUKL). Following the SUKL's approval the study will proceed to: Step 2 - 10-15 children with PWS.

Official Title
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A Double-blind, Randomized, Placebo-controlled, Multiple-dose, Multi-centre Safety and Efficacy Study of Co-administration of Tesofensine/Metoprolol in Subjects With Prader-Willi Syndrome (PWS)

Conditions
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Confirmed Genetic Diagnosis of Prader-Willi Syndrome

Intervention / Treatment
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* Drug: Tesofensine/Metoprolol
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females Confirmed genetic diagnosis of Prader-Willi syndrome Age: Step 1: Adults aged 18-30 b. Step 2: Children aged 12-17 BMI: Step 1: Adults with ≥25 kg/m2 Step 2: Children with a BMI >85th percentile for the same age and sex Normal BP or well managed hypertension (only if dose of BP medication(s) has been stable for >2 months) Normal lipid profile or well managed dyslipidemia (only if dose of lipid-lowering medication(s) has been stable for >2 months) On stable dose of growth hormone >2 months Exclusion Criteria: Hypersensitivity to tesofensine/metoprolol Type 1 diabetes Heart failure NYHA level II or greater, decompensated heart failure Previous myocardial infarction or stroke Diagnosis of schizophrenia, bipolar disorder, personality disorder or other DSM-III disorders, which in the investigator's opinion will interfere significantly with study compliance

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two-centre, double-blind, placebo-controlled, randomized, and multiple-dose clinical study.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tesofensine/Metoprolol<br>Tesofensine + metoprolol administered once a day, in the morning with a meal | Drug: Tesofensine/Metoprolol<br>* Study medication will be administered for 91 days.<br>* Other names: Metoprolol;|
| Placebo Comparator: Tesofensine/Metoprolol placebo<br>Placebo tablets matching tesofensine + metoprolol administered once a day, in the morning with meal | Drug: Placebos<br>* Study medication will be administered for 91 days.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline on body weight in subjects with PWS | To examine the effect of co-administration of tesofensine/metoprolol on body weight in subjects with PWS | 0-91 days |