48 Weeks, Study to Evaluate Overall Safety and Tolerability of Co-administration of Tesofensine and Metoprolol in Subjects With Hypothalamic Injury-induced Obesity (HIO)
- Conditions
- Hypothalamic Injury-induced Obesity (HIO)
- Interventions
- Drug: Placebo
- Registration Number
- NCT03845075
- Lead Sponsor
- Saniona
- Brief Summary
Double-blind, randomized, placebo-controlled, single- center study followed by an open-label extension period.
• The study will have two parts:
* Part 1: 24 weeks double-blind treatment (DB), followed by
* Part 2: 24 weeks open-label extension (OLE) - all subjects still participating at the end of Part 1 will be given an option to continue for additional 24 weeks on the active drug if evaluated eligible by the Investigator
- Detailed Description
Part 1 - the double-blind (DB) part: The active medication arm will be given co-administration of 0.5 mg tesofensine/50 mg metoprolol daily for 24 weeks. The placebo arm will receive matching placebo tablets.
Part 2 - the open-label extension (OLE) part: All active participants at the end of the double-blind part will be given the active medication 0.5 mg tesofensine/50 mg metoprolol daily for 24 weeks.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 21
- Informed consent obtained before any trial-related activities
- Males and females, aged 18-75
- Confirmed diagnosis of HIO
- BMI ≥27 kg/m2 (where overweight is related to the HIO)
- Blood Pressure (BP) ≥160/90 mmHg
- Heart rate (HR) ≥ 90, <50 bpm
- Type 1 diabetes, Cushings disease, acromegaly, hypophysitis, infiltrative diseases or Prader-Willi syndrome
- Heart failure New York Heart Association (NYHA) level II or greater, decompensated heart failure
- Previous myocardial infarction or stroke within the last 5 years
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description placebo arm Placebo The placebo arm will receive matching placebo tesofensine and placebo metoprolol. active arm Tesofensine/Metoprolol The active medication arm will be given co-administration of 0.5 mg tesofensine/50 mg metoprolol daily for 24 weeks.
- Primary Outcome Measures
Name Time Method Safety as Assessed by Liver and Kidney Function Tests from Baseline to week 24 Number and percentage of deviations from normal range (as defined by the investigational site's laboratory) for gamma glutamyl transferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), glomerular filtration rate (GFR), and urea at baseline, week 12, and week 24 in each of the two treatment arms
Participants (Number and Percentage) With and Type of Serious Adverse Events from Baseline to week 24 Number and percentage of participants with at least one serious adverse event, indicating type, in each of the two treatment arms
Safety as Assessed by Diastolic Blood Pressure [mmHg] from Baseline to week 24 Diastolic blood pressure in mmHg measured at each visit in each of the two treatment arms
Number of Participants With Treatment Emergent Adverse Events from Baseline to week 24 Number and percentage of participants with adverse events in each of the two treatment arms
Safety as Assessed by Heart Rate [Bpm] from Baseline to week 24 Heart rate measured in beats per minute (bpm) at each visit in each of the two treatment arms
Safety as Assessed by Hematology Parameters from Baseline to week 24 Number and percentage of deviations from normal range (as defined by the investigational site's laboratory) for hemoglobin, platelet counts, white cells count, differential counts at baseline, week 12 and week 24 in each of the two treatment arms
Safety as Assessed by Electrolytes and Creatinine from Baseline to week 24 Number and percentage of deviations from normal range (as defined by the investigational site's laboratory) for sodium, potassium, creatinine at each visit in each of the two treatment arms
Number of Participants With at Least One Mild, Moderate or Severe Adverse Event from Baseline to week 24 Number and percentage of participants with mild, moderate or severe adverse events in each of the two treatment arms.
Safety as Assessed by Systolic Blood Pressure [mmHg] from Baseline to week 24 Systolic blood pressure in mmHg measured at each visit in each of the two treatment arms
- Secondary Outcome Measures
Name Time Method Body Composition - Fat Mass from baseline to week 24, from baseline to week 48 and from week 24 to week 48 Change in body fat mass as measured in kg by DXA scan measured at baseline, week 24 and week 48 for each of the two treatment arms. mITT observed values.
Quality of Life - SF-36 from baseline to week 24, from baseline to week 48 and from week 24 to week 48 Change in quality of life by use of the Short Form 36 Health Survey (SF-36) scores from baseline to week 24, from baseline to week 48, and from week 24 to week 48
The physical component summary score includes the aggregated scores for scales of physical functioning, role-physical, bodily pain, and general health. The mental health component summary score includes the aggregated scores for scales of vitality, social functioning, role-emotional, and mental health. Scores range from 0 to 100; higher score indicates better health.
mITT observed values.Blood Pressure (Change) from baseline to week 24, from baseline to week 48 and from week 24 to week 48 Change in blood pressure from baseline to week 24, from baseline to week 48, and from week 24 to week 48. mITT observed values.
24 Hours Blood Pressure from baseline to week 12 and baseline to week 24 Changes in 24 hours blood pressure from baseline to week 12 and baseline to week 24
Plasma Trough Concentrations baseline to week 48 Plasma trough concentrations of tesofensine, metabolite NS2360 and metoprolol for the active arm (the first 24 weeks and then continuously up to week 48) and placebo arm (start of treatment at week 25 and then continuously up to week 48). mITT observed values.
Body Weight from 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 48 and from week 24 to week 48 measured at each visit for each of the two treatment arms
Body Composition - Lean Body Mass from baseline to week 24, from baseline to week 48 and from week 24 to week 48 Change in lean body mass as measured in kg by DXA scan measured at baseline, week 24 and week 48 for each of the two treatment arms. mITT observed values.
Lipid Profile from baseline to week 24, from baseline to week 48 and from week 24 to week 48 Change in lipid profile from baseline to week 24, from baseline to week 48, and from week 24 to week 48. mITT observed values.
Glycemic Control - HbA1c from baseline to week 24, from baseline to week 48 and from week 24 to week 48 Change in HbA1c from baseline to week 24, baseline to week 48 and week 24 to week 48 for each of the two treatment arms. mITT observed values.
Thirst 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 visual analog scale (VAS) from baseline to week 24, from baseline to week 48, and from week 24 to week 48
The VAS consisted of a 100-mm horizontal line; subjects placed a vertical line on the VAS to indicate the level of intensity of their thirst. The VAS value is the distance in mm (0-100 mm) from the left end of the line to the subject's vertical line (higher value represents an increase in perception of thirst).
mITT observed values.Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension from week 24 to week 48 Number of participants with adverse event(s) and/or serious adverse event(s) reported from week 24 to week 48
Heart Rate (Change) from baseline to week 24, from baseline to week 48 and from week 24 to week 48 Change in heart rate from baseline to week 24, from baseline to week 48, and from week 24 to week 48. mITT observed values.
Waist Circumference 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. mITT observed values.
Composite Satiety Score (CSS) from baseline to week 24, from baseline to week 48 and from week 24 to week 48 Change in satiety and appetite using the CSS from Baseline to week 24, from Baseline to week 48 and from week 24 to week 48 measured at each visit for each of the two treatment arms
Full name of the scale: composite satiety score (CSS), sometimes referred to as "appetite suppression score". Range of values is 0-100; lower the value, hungrier a person is. CSS = (satiety + fullness + \[100 - hunger\] + \[100 - prospective food consumption\]) / 4. The four variables included are measured by visual analog scales (0-100 mm)Glycemic Control - Fasting Plasma Glucose from baseline to week 24, from baseline to week 48 and from week 24 to week 48 Change in fasting plasma glucose from baseline to week 24, baseline to week 48 and week 24 to week 48 measured at each visit for each of the two treatments arms. mITT observed values.
Craving for Something Sweet, Salty, Meat/Fish, or Fatty from baseline to week 24, from baseline to week 48 and from week 24 to week 48 Change in craving for something sweet, salty, meat/fish, or fatty by the use of visual analogue scales (VAS) from baseline to week 24, from baseline to week 48, and from week 24 to week 48
The VAS consisted of a 100-mm horizontal line; subjects placed a vertical line on the VAS to indicate the level of intensity of their food craving. The VAS value is the distance in mm (0-100 mm) from the left end of the line to the subject's vertical line (higher value represents less craving).
mITT observed values.48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24 baseline, week 12 and week 24 For Part 1, 48 hours HR and QT interval from week 12 to week 24 were not recorded in the database and analysis of changes not evaluated. Instead, abnormal findings over visits were summarized.
Abnormal ECG findings detected in the three Tesomet treated subjects are:
* QTc prolongation (466 ms)
* Bradycardia (56 bpm)
* QTc prolongation (460 ms) All were considered not clinically significant.
Trial Locations
- Locations (1)
Rigshospitalet
🇩🇰Copenhagen, Denmark