Hypothalmic injury-induced obesity (HIO) MedDRA version: 20.1 Level: LLT Classification code 10013367 Term: Disorders of the pituitary gland and its hypothalamic control System Organ Class: 100000004860
Conditions
Interventions
Product Name: Tesofensine
Product Code: NS2330
Pharmaceutical Form: Tablet
INN or Proposed INN: Tesofensine
Current Sponsor code: NS2330
Concentration unit: g gram(s)
Concentration type: equal
Concent
Sponsors
Saniona A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Informed consent obtained before any trial-related activities 2. Males and females, aged 18-75 3. Confirmed diagnosis of HIO 4. BMI =27 kg/m2 (where overweight is related to the HIO) 5. Well managed and stable substitution of hypopituitarism >2 months as judged by the investigator 6. Normal blood pressure or well managed hypertension (only if dose of BP medication(s) has been stable for >2 months) 7. Type 2 diabetes is allowed, but the following criteria must be met: • HbA1c 3 months • Fasting plasma glucose =65 years) yes F.1.3.1 Number of subjects for this age range 3
Exclusion criteria
Exclusion criteria: 1. BP =160/90 mmHg 2. HR = 90, 3x ULN) and/or kidney impairment 17. More than 5% weight loss within the last 3 months 18. Subject is pregnant or lactating or intends to become pregnant or is of childbearing potential and not using an adequate contraceptive method (Spiral or hormonal contraception, birth control pills, implant, transdermal patch, vaginal ring or depot injection) 19. Male subjects not agreeing to use a condom without spermicide or oil-containing products (e.g., lubricants) during sexual activity with female partners of childbearing potential throughout the trial until at least 8 weeks after the last administration of IMP 20. Any contraindication for metoprolol according to the Summary of Product Characteristics (SmPC), e.g. severe peripheral arterial disease, untreated pheochromocytoma, concomitant intravenous administration of calcium antagonists of verapamil and diltiazem, due to the risk of hypotension, AV conduction disturbances, or left ventricular insufficiency 21. Subject has lactose intolerance or a rare hereditary problem of fructose intolerance, glucose galactose malabsorption or sucrase isomaltase insufficiency 22. Subject is unable to understand and communicate in Danish language or to understand the protocol requirements, instructions and study-related restrictions, the nature, scope and possible consequences of the clinical study or is unlikely to comply with the study requirements; e.g., uncooperative attitude and improbability of completing the clinical study 23. PHQ-9 (Patient Health Questionnaire): a. If a score of at least 5 in question 1 and 2 coming from the area of “More than half the days” or Nearly every day” or b. PHQ-9 score = 10 when counts from questions 3-5 have been subtracted or c. If a tic in question 6 in “More than half the days” or “Nearly every day” or d. Any score > 0 on question 9 at screening and baseline 24. Any suicidal behaviour within the past 30 days since screening 25. Subject has been enrolled in another clinical study within the past three months 26. Any other clinically meaningful condition, which in the opinion of the investigator, would make participation potentially unsafe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To examine overall safety and tolerability of co-administration of 0.5 mg tesofensine/50 mg metoprolol treatment over 24 weeks in subjects with HIO;Secondary Objective: • To examine the effect on satiety, appetite, body weight, body composition, quality of life, craving for something sweet, salty, savory and fatty, thirst, glycaemic control and lipid profile, HR and BP from from Baseline to week 24, from Baseline to week 48 and from week 24 to week 48 following co-administration of 0.5 mg tesofensine/50 mg metoprolol treatment in subjects with HIO. • To establish profile of trough values of tesofensine, its N-desmethyl-metabolite (NS2360) and metoprolol following co-administration of 0.5 mg tesofensine/50 mg metoprolol treatment in subjects with HIO. • To evaluate the effect on BP and HR from Baseline to week 24 by 24 hours (24H) home monitoring of BP and 48 H home monitoring of HR. • To evaluate overall safety and tolerability from week 24 to week 48 following co-administration of 0.5 mg tesofensine/50 mg metoprolol treatment in subjects with HIO.;Primary end point(s): Safety and tolerability will be judged from all safety data collected in the period, including number and type of treatment emergent adverse events, laboratory data, blood pressure and heart rate.;Timepoint(s) of evaluation of this end point: 24 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints: • Change in satiety and appetite using the CSS Baseline to week 24, from Baseline to week 48 and from week 24 to week 48 • Change in body weight from Baseline to week 24, from Baseline to week 48 and from week 24 to week 48 • Change in body composition i.e. body fat and lean body mass by Dual-energy X-ray absorptiometry (DEXA) from Baseline to week 24, from Baseline to week 48 and from week 24 to week 48 • Change in quality of life by the use of the SF-36 questionnaire from Baseline to week 24, from Baseline to week 48 and from week 24 to week 48 • Change in craving for something sweet, salty, savory and fatty by the use of Visual Analogue Scale (VAS) scales from Baseline to week 24, from Baseline to week 48 and from week 24 to week 48 • Change in thirst by the use of a VAS scale from Baseline to week 24, from Baseline to week 48 and from week 24 to week 48 • Change on glycaemic control and lipid profile from Baseline to week 24, from Baseline to week 48 and from week 24 to week 48 • Change in waist circumference from Baseline to week 24, from Baseline to week 48 and from week 24 to week 48 Secondary safety and PK endpoints: • Change on HR and BP from Baseline to week 48 and from week 24 to week 48 • Trough values of tesofensine, Metropolol and N-desmethyl-metabolite (NS2360) - Active arm: the first 24 weeks and then continuously up to week 48. - Placebo arm: start of treatment at week 25 and then continuously up to week 48. • Change of 24H BP/48H HR and QT from Baseline to V5 and V8 and from V5 to V8 measured by home monitoring • Number and type of AE’s from week 24 to week 48;Timepoint(s) of evaluation of this end point: Weeks 24 and 48. For trough values: - Active arm: the first 24 weeks and then continuously up to week 48. - Placebo arm: start of treatment at week 25 and then continuously up to week 48. | — |
Countries
Denmark
Contacts
Public ContactKim Krogsgaard
Saniona A/S
Outcome results
None listed