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
Conditions
Sponsors
Saniona A/S
Eligibility
Sex/Gender
All
Inclusion criteria
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 estradiol, low FSH, low LH, and amenorrhea. If premenopausal the diagnosis should be confirmed at a time point prior to initiating treatment with estradiol/gestagen. Postmenopausal women with hypogonadotropic hypogonadism must have amenorrhea and low FSH and low LH for 1 year. 5. Diagnosis of HO secondary to damage to the hypothalamus Note: Diagnosis of HO secondary to damage to the hypothalamus includes suprasellar tumor, suprasellar surgery, traumatic injury, or irradiation (focal or local), confirmed by medical history documenting temporal relationship between damage and increase in body weight and substantiated as applicable by imaging visualizing tumor, description of surgical procedure, description of radiation therapy, and need for hormone replacement therapy 6. 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 7. Body mass index (BMI; body weight [kg] / height [m2]) of 30.0 to 60.0 kg/m2, inclusive, at Screening 8. Documented stable body weight (gain/loss 2 months prior to Screening, as judged by the Investigator 10. Type 2 diabetes mellitus (T2DM) is allowed, provided that all of the following criteria are met: a. Hemoglobin A1c (HbA1c) =65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: 1.Genotypic cytochrome CYP2D6-poor metabolizers and CYP2D6 ultra-rapid metabolizers, as confirmed by central laboratory at Screening 2.Use of any prohibited medication 3.Sitting BP that meets the following criteria after 5 minutes of rest at Screening: a.Subjects with systolic BP >145 mmHg or 95 mmHg or 95 bpm or 450 msec for males and >470 msec for females at Screening based on central review 6.Hypersensitivity or contraindication to tesofensine or metoprolol 7.Type 1 diabetes mellitus 8.History of clinically significant cardiac disorders as determined by the Investigator 9.Medical history of stroke or transient ischemic attack 10.Subjects who experienced any of the following clinical symptoms or conditions within 90 days prior to Screening, as described by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) and clinical judgment supported by the Brief Psychiatric Rating Scale (BPRS) administered centrally: a.Delusions; b.Hallucinations; c.Major depressive disorder; d.Hypomania; or e.Suicidality; 11.Subjects who answer “yes” to the self-mutilation/self-injury question in the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening and/or Baseline 12.Physical impairment which, in the Investigator’s opinion, will interfere significantly with study compliance 13.History of bulimia or anorexia nervosa 14.Uncontrolled endocrine disorders 15.Underlying liver impairment as evidenced by abnormal liver function test results at Screening, including alanine aminotransferase or aspartate aminotransferase abnormalities >3 x the upper limit of normal (ULN), or total bilirubin >1.5 x ULN (except in cases of diagnosed Gilbert’s Syndrome) 16.Underlying kidney impairment, defined as estimated glomerular filtration rate <= 60 mL/min/1.73 m2 (using the Schwartz equation), as determined by Screening laboratory assessments performed by the central laboratory 17.Subject has a rare hereditary problem of fructose intolerance, glucose galactose malabsorption, or sucrase-isomaltase insufficiency; 18.Subject without sufficient comprehension, communication ability, and cooperation to enable compliance with the study procedures and assessments 19.Subject who, in the Investigator’s judgment, is actively suicidal and therefore deemed to be at significant risk for suicide, or: a. Subjects who answer "yes" to Question 4 of the C-SSRS on the "Suicidal Ideation" portion and the ideation occurred within 6 months prior to screening; or b. Subjects who answer "yes" to Question 5 of the C-SSRS on the "Suicidal Ideation" portion and the ideation occurred within 6 months prior to screening; or c. Subjects who answer "yes" to any of the suicide-related behaviors on the "Suicidal Behavior" portion of and the behavior occurred within 2 years prior to Screening 20.Subjects with a history of substance abuse, including cannabinoids and/or alcohol use disorders, as per DSM-5, or a positive urine drug test (including amphetamines, cocaine, opiates, phencyclidine, tetrahydrocannabinol, barbiturates, and benzodiazepines) at Screening 21.Participation in another interventional study (eg, of a drug, over-the-counter product, device, weight loss program, therapy) within 90 days prior to Screening or any prior participation in a tesofensine or Tesomet clinical study) 22.Subjects who have a co-existing medical con
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives of the study is to examine the efficacy of Tesomet on body weight;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 ;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.;Timepoint(s) of evaluation of this end point: from Baseline to Week 36. | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
Australia, Belgium, Denmark, France, Germany, Israel, Italy, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactClinical Trials Information
Medpace
Outcome results
None listed