A 24-week phase 2, double-blind, placebo-controlled, single-centre safety and efficacy study to evaluate overall safety and tolerability of co-administration of tesofensine and metoprolol in subjects with obesity caused by an injury in hypothalamus (HIO), and with a 24-week open-label extension, in total 48 weeks

Phase 1

• Conditions: Hypothalmic injury-induced obesity (HIO); MedDRA version: 20.1Level: LLTClassification code 10013367Term: Disorders of the pituitary gland and its hypothalamic controlSystem Organ Class: 100000004860; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2018-003672-12-DK
• Lead Sponsor: Saniona A/S

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-11-28
• Last Update Posted: 18 January 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 25

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 < 86 mmol/mol
• Subjects taking GLP-1 analogues must have been on stable dose for >3 months
• Fasting plasma glucose <11.0 mmol/l measured on site
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 22
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3

Exclusion Criteria

1. BP =160/90 mmHg
2. HR = 90, <50 bpm
3. Hypersensitivity to tesofensine/metoprolol or any component of the products
4. Type 1 diabetes, Cushings disease, acromegaly, hypophysitis, infiltrative diseases or Prader-Willi syndrome
5. Heart failure New York Heart Association (NYHA) level II or greater, decompensated heart failure
6. Previous myocardial infarction or stroke within the last 5 years
7. Diagnosis of schizophrenia, bipolar disorder, personality disorder or other DSM-III disorders, or any other psychiatric condition, which in the investigator’s opinion will interfere significantly with study compliance
8. Physical impairment, which in the investigator’s opinion will interfere significantly with study compliance
9. Any clinically significant cardiac arrhythmia
10. Treatment with calcium channel blockers and beta blockers
11. Concomitant use of monoaminooxidase inhibitors
12. Use of recreational medication
13. Bulimia or anorexia nervosa
14. Any agent used for weight loss in the past 3 months, except GLP-1 compounds
15. Untreated hypo- or hyperthyroidism
16. Clinically significant liver (>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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified