Study of Tesomet With Open-label Extension in Subjects With Prader-Willi Syndrome

Study Overview
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Brief Summary
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This study will evaluate the safety and efficacy of Tesomet (tesofensine + metoprolol) in subjects with PWS.

Detailed Description
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For the double-blind portion of the study, dosing will be initiated in a subgroup of adults who are 18-65 years of age. Following independent Data Monitoring Board review of subgroup safety data, and review and confirmation to proceed by FDA, enrollment of subjects <18 years of age will commence.

Official Title
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A Phase 2b, Double-blind, Randomized, Placebo-controlled, Multi-center, 16-week Dose Finding, Safety and Efficacy Study With Open-label Extension (OLE) Period of Tesomet in Subjects With Prader-Willi Syndrome

Conditions
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Prader-Willi Syndrome

Intervention / Treatment
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* Other: Placebo
* Drug: Tesomet


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Subject and their legally authorized representative must be willing to provide informed consent Confirmed genetic diagnosis of PWS Body mass index (BMI) within the following range at Screening: Female and male subjects 18 to 65 years of age: 27 to 60 kg/m2; or Female and male subjects 13 to 17 years of age with BMI that is at least 85th percentile for age and sex; Female subjects must be of non-child-bearing potential Documented stable body weight Moderate hyperphagia at Screening and at Baseline Participants must have a reliable and stable caregiver who should be able to spend an adequate amount of time with the participants to be able to address behaviors, activities and symptoms Male subjects who are sexually active must be surgically sterile Key Exclusion Criteria: Females who are pregnant, breastfeeding, or actively intending to become pregnant during the study Sitting BP that meets the following criteria after 5 minutes of rest at Screening: Adult subjects with systolic BP >/=145 mmHg or <100 mmHg; or Adult subjects with diastolic BP >/=95 mmHg or <70 mmHg; or Adolescent subjects with a systolic or diastolic BP that is 95th percentile or greater for age and sex Type 1 diabetes mellitus History of dementia (eg, Alzheimer's disease, Parkinson's disease) History of bulimia or anorexia nervosa History of major depressive disorder within 2 years prior to Screening, or any history of other severe psychiatric disorder (eg, schizophrenia, bipolar disorder), or symptoms of delusions, hallucinations, or mania/hypomania within 90 days prior to Screening, as described by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) Uncontrolled endocrine disorders (eg, Cushing syndrome, Addison's, hypothyroidism, hyperthyroidism) Medical condition or recent systemic infection that, in the opinion of the Investigator, could impact the safety of the subject Use of prohibited medications, including current use of SSRIs/SNRIs

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 65 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Once-daily PO for 16 weeks during the double-blind period; then if eligible for OLE, once-daily dosing for 36 weeks of the highest tolerated Tesomet dose from the double-blind period | Other: Placebo<br>* Inactive comparator<br>Drug: Tesomet<br>* Fixed-dose combination<br>* Other names: metoprolol;|
| Experimental: Tesomet Low Dose<br>Once-daily PO for 16 weeks during the double-blind period; then if eligible for OLE, once-daily dosing for 36 weeks of the highest tolerated dose from the double-blind period | Drug: Tesomet<br>* Fixed-dose combination<br>* Other names: metoprolol;|
| Experimental: Tesomet Medium Dose<br>Once-daily PO for 16 weeks during the double-blind period; then if eligible for OLE, once-daily dosing for 36 weeks of the highest tolerated dose from the double-blind period | Drug: Tesomet<br>* Fixed-dose combination<br>* Other names: metoprolol;|
| Experimental: Tesomet High Dose<br>Once-daily PO for 16 weeks during the double-blind period; then if eligible for OLE, once-daily dosing for 36 weeks of the highest tolerated dose from the double-blind period | Drug: Tesomet<br>* Fixed-dose combination<br>* Other names: metoprolol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hyperphagia | Change in Hyperphagia Questionnaire for Clinical Trials (HQ-CT) total score | Baseline to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Body Weight | Percentage change in body weight | Baseline to Week 16 | 
| Hyperphagia Severity (Caregiver) | Change in caregiver rating of hyperphagia severity | Baseline to Week 16 | 
| Hyperphagia Change (Caregiver) | Proportion of caregiver responses for change in subject's hyperphagia | Week 16 | 
| PWS Severity (Clinician) | Change in clinician rating of the subject's PWS severity | Baseline to Week 16 | 
| Overall Status Change (Clinician) | Proportion of clinician responses for change in subject's overall clinical status | Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hyperphagia