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

INTERVENTION: Product Name: Tesomet Pharmaceutical Form: Capsule INN or Proposed INN: Tesofensine CAS Number: 195875‐84‐4 Current Sponsor code: NS2330 Other descriptive name: TESOFENSINE CITRATE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 0.25‐ INN or Proposed INN: Metoprolol Other descriptive name: METOPROLOL SUCCINATE (PH. EUR.) Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 30‐ Pharmaceutical form of the placebo: Capsule Route of administration of the placebo: Oral use Product Name: Tesomet Pharmaceutical Form: Capsule INN or Proposed INN: Tesofensine CAS Number: 195875‐84‐4 Current Sponsor code: NS2330 Other descriptive name: TESOFENSINE CITRATE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 0.375‐ INN or Proposed INN: Metoprolol Other descriptive name: METOPROLOL SUCCINATE (PH. EUR.) Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 45‐ Pharmaceutical form of the placebo: Capsule Route of administration of the placebo: Oral use Product Name: Tesomet Pharmaceutical Form: Capsule INN or Proposed INN: Tesofensine CAS Number: 195875‐84‐4 Current Sponsor code: NS2330 Other descriptive name: TESOFENSINE CITRATE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 0.5‐ INN or Proposed INN: Metoprolol Other descriptive name: METOPROLOL SUCCINATE (PH. EUR.) Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 60‐ Pharmaceutical form of the placebo: Capsule Route of administration of the placebo: Oral use CONDITION: Hypothalamic Obesity ; MedDRA version: 20.1 Level: LLT Classification code 10013367 Term: Disorders of the pituitary gland and its hypothalamic control System Organ Class: 100000004860 Therapeutic area: Diseases [C] ‐ Nutritional and Metabolic Diseases [C18] PRIMARY OUTCOME: Main Objective: The primary objectives of the study is to examine the efficacy of Tesomet on body weight Primary end point(s): The primary efficacy endpoint of this study is the change in body weight (%) from Baseline to Week 36.; Safety endpoints for the double‐blind period include the following:; • The incidence of TEAEs of special interest, including specified cardiovascular events, or specified psychiatric events;; • The incidence of treatment‐emergent adverse events (TEAEs) and serious adverse events (SAEs);; • The incidence of MACE;; • Laboratory evaluation (chemistry and hematology) results at Baseline and at all site visits;; • Vital sign measurements at Baseline and at Weeks 8, 16, 24, and 36;; • ECG assessments at Baseline and at Weeks 8, 16, 24, and 36;; • Holter monitoring at Screening and at Weeks 12 and 36;; • Physical examination findings at Baseline and at Weeks 8, 16, 24, and 36;; • C‐SSRS administered by a trained rater at Baseline and at all visits; and; • Patient Health Questionnaire‐9 (PHQ‐9) self administered by the subject at Baseline and at all visits. Secondary Objective: The secondary objectives of the study are:; • To examine the proportion of subjects with at least 5% body weight loss from baseline; • To examine change in body weight; • To examine change from baseline in waist circumference; • To examine change from baseline in BMI; Timepoint(s) of evaluation of this end point: from Baseline to Week 36. SECONDARY OUTCOME: Secondary end point(s): • Proportion of subjects with at least 5% body weight loss at Week 36; ; • Change in body weight (kg) from Baseline to Week 36;; • Change in waist circumference (cm) from Baseline to Week 36; and; • Change in BMI from Baseline to Week 36.; ; Timepoint(s) of evaluation of this end point: Baseline to Week 36 INCLUSION CRITERIA: 1. Subject and, if applicable, their parent or legal guardian must be willing to sign and receive a copy of the informed consent form (ICF) after the nature and risk of study participation have been fully explained Note: Subjects under the age of consent should provide written assent with a written consent provided by a guardian, as per local requirements. 2. Female and male subjects >= 16 years of age at the time of informed consent 3. Female subjects of non‐childbearing potential (WONCBP) defined as: prior menarche, postmenopausal (no menses for 12 months without an alternative medical cause and FSH > 30mIU/ml at screening), permanently sterile (permanent sterilization methods include hysterectomy, or bilateral salpingectomy and bilateral oophorectomy =6 months prior to the first dose of study drug); 4. Female subjects who have a confirmed diagnosis (prior to screening) of hypogonadotropic hypogonadism as determined and documented by low estra