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
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
21
During Part 1 subjects will be randomized to treatment with co-administration of 0.5 mg tesofensine/50mg metoprolol (active medication)
During Part 1 subjects will be randomized to matching placebo tesofensine and placebo metoprolol
Rigshospitalet
Copenhagen, Denmark
Number of Participants With Treatment Emergent Adverse Events
Number and percentage of participants with adverse events in each of the two treatment arms
Time frame: from Baseline to week 24
Number of Participants With at Least One Mild, Moderate or Severe Adverse Event
Number and percentage of participants with mild, moderate or severe adverse events in each of the two treatment arms.
Time frame: from Baseline to week 24
Participants (Number and Percentage) With and Type of Serious Adverse Events
Number and percentage of participants with at least one serious adverse event, indicating type, in each of the two treatment arms
Time frame: from Baseline to week 24
Safety as Assessed by Systolic Blood Pressure [mmHg]
Systolic blood pressure in mmHg measured at each visit in each of the two treatment arms
Time frame: from Baseline to week 24
Safety as Assessed by Diastolic Blood Pressure [mmHg]
Diastolic blood pressure in mmHg measured at each visit in each of the two treatment arms
Time frame: from Baseline to week 24
Safety as Assessed by Heart Rate [Bpm]
Heart rate measured in beats per minute (bpm) at each visit in each of the two treatment arms
Time frame: from Baseline to week 24
Safety as Assessed by Hematology Parameters
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
Time frame: from Baseline to week 24
Safety as Assessed by Electrolytes and Creatinine
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
Time frame: from Baseline to week 24
Safety as Assessed by Liver and Kidney Function Tests
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
Time frame: from Baseline to week 24
Composite Satiety Score (CSS)
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)
Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Body Weight
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
Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Body Composition - Fat Mass
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.
Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Body Composition - Lean Body Mass
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.
Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Glycemic Control - HbA1c
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.
Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Glycemic Control - Fasting Plasma Glucose
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.
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Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Craving for Something Sweet, Salty, Meat/Fish, or Fatty
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.
Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Thirst
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.
Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Waist Circumference
Change in waist circumference from baseline to week 24, from baseline to week 48, and from week 24 to week 48. mITT observed values.
Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Lipid Profile
Change in lipid profile from baseline to week 24, from baseline to week 48, and from week 24 to week 48. mITT observed values.
Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Quality of Life - SF-36
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.
Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension
Number of participants with adverse event(s) and/or serious adverse event(s) reported from week 24 to week 48
Time frame: from week 24 to week 48
Blood Pressure (Change)
Change in blood pressure from baseline to week 24, from baseline to week 48, and from week 24 to week 48. mITT observed values.
Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
24 Hours Blood Pressure
Changes in 24 hours blood pressure from baseline to week 12 and baseline to week 24
Time frame: from baseline to week 12 and baseline to week 24
Plasma Trough Concentrations
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.
Time frame: baseline to week 48
48 Hours Heart Rate and QT Interval at 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.
Time frame: baseline, week 12 and week 24
Heart Rate (Change)
Change in heart rate from baseline to week 24, from baseline to week 48, and from week 24 to week 48. mITT observed values.
Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48