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

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

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

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.

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:

  1. Female and male subjects 18 to 65 years of age: 27 to 60 kg/m2; or
  2. 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:

  1. Adult subjects with systolic BP >/=145 mmHg or <100 mmHg; or
  2. Adult subjects with diastolic BP >/=95 mmHg or <70 mmHg; or
  3. 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