Study of Tesomet With Open-label Extension in Subjects With Hypothalamic Obesity (HO)

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 18 years of age or older, with HO

Official Title
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A Phase 2b, Double-blind, Randomized, Placebo-controlled, Dose-finding, Multi-center, 36-week Safety and Efficacy Study With Open-label Extension (OLE) Period of Tesomet in Subjects With Hypothalamic Obesity

Conditions
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Hypothalamic Obesity

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, if applicable, their parent or legal guardian must be willing to provide informed consent Diagnosis of HO secondary to damage to the hypothalamus Female subjects must be of non-childbearing potential At least 6 months since completion of therapy (chemotherapy, surgery, or radiation with resulting injury to the hypothalamus and/or the pituitary) with stable disease and lack of recurrence BMI 30.0 to 60.0 kg/m², inclusive Documented stable body weight (gain/loss <10%) for at least 90 days prior to Screening Stable and well-managed pituitary replacement (eg, glucocorticoid, thyroid hormone, estrogen/progestin or testosterone, desmopressin, or growth hormone) for >2 months prior to Screening 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: Systolic BP >145 mmHg or <100 mmHg; or Diastolic BP >95 mmHg or <70 mmHg Type 1 diabetes mellitus History of major depressive disorder within 2 years prior to Screening, or any history of other severe psychiatric disorder (eg, schizophrenia, bipolar disorder) Uncontrolled endocrine disorders (eg, Cushing syndrome, Addison's, hypothyroidism, hyperthyroidism) History of bulimia or anorexia nervosa Use of prohibited medications, including current use of selective serotonin reuptake inhibitors / serotonin-norepinephrine reuptake inhibitors (SSRIs/SNRIs)

Ages Eligible for Study
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Minimum Age: 18 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 36 weeks during the double-blind period; then if continued eligible for OLE, once-daily dosing for 36 weeks at 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 36 weeks during the double-blind period; then if continued eligible for OLE, once-daily dosing for 36 weeks at 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 36 weeks during the double-blind period; then if continued eligible for OLE, once-daily dosing for 36 weeks at 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 36 weeks during the double-blind period; then if continued eligible for OLE, once-daily dosing for 36 weeks at 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 |
| --- | --- | --- |
| Body weight (%) | Percentage change in body weight | Baseline to Week 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body weight loss | Proportion of subjects who meet pre-specified thresholds for body weight loss | Week 36 | 
| Body weight (kg) | Change in body weight in kilograms | Baseline to Week 36 | 
| Waist circumference (cm) | Change in waist circumference in centimeters | Baseline to Week 36 | 
| Body Mass Index (BMI) | Change in BMI | Baseline to Week 36 |