Hypothalamic Injury-induced Obesity (HIO)
Conditions
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.
Interventions
During Part 1 subjects will be randomized to treatment with co-administration of 0.5 mg tesofensine/50mg metoprolol (active medication)
DRUGPlacebo
During Part 1 subjects will be randomized to matching placebo tesofensine and placebo metoprolol
Sponsors
Saniona
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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)
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
| 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 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 |
| 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 |
| 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 |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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 |
| 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. |
| 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) |
| 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. |
| 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. |
| 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. |
| 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 |
| 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 - 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Denmark
Participant flow
Pre-assignment details
A total of 35 subjects with HIO were screened; 13 subjects were screen failures. A total of 21 unique subjects were assigned 22 randomization numbers. One subject was a screen failure who was randomized in error, and withdrawn after receiving 1 dose of tesofensine/metoprolol; this subject was later rescreened and rerandomized to placebo. This subject is summarized for both tesofensine/metoprolol and placebo (ie, considered as 2 independent subjects).
Participants by arm
| Arm | Count |
|---|---|
| Tesofensine/Metoprolol Subjects were randomized to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol (active medication) once daily for 24 weeks during Part 1. | 14 |
| Placebo Subjects were randomized to receive matching placebo tablets once daily for 24 weeks during Part 1. | 8 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Part 1 - DB | Adverse Event | 0 | 1 | 0 | 0 |
| Part 1 - DB | Screen failure, but received 1 dose of study drug in error | 1 | 0 | 0 | 0 |
| Part 1 - DB | Withdrawal by Subject | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Tesofensine/Metoprolol | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 45.4 years STANDARD_DEVIATION 13.3 | 44.4 years STANDARD_DEVIATION 18.3 | 45.0 years STANDARD_DEVIATION 14.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 8 Participants | 22 Participants |
| Region of Enrollment Denmark | 14 Participants | 8 Participants | 22 Participants |
| Sex: Female, Male Female | 11 Participants | 6 Participants | 17 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants |
| Weight | 114.34 kg STANDARD_DEVIATION 18.14 | 112.16 kg STANDARD_DEVIATION 27.04 | 113.55 kg STANDARD_DEVIATION 21.18 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 8 | 0 / 11 | 0 / 6 |
| other Total, other adverse events | 12 / 14 | 7 / 8 | 11 / 11 | 6 / 6 |
| serious Total, serious adverse events | 2 / 14 | 1 / 8 | 1 / 11 | 0 / 6 |
Outcome results
Primary
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
Population: Safety Analysis Set: all subjects who took at least one dose of the IMPs (active substances or placebos)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tesofensine/Metoprolol | Number of Participants With at Least One Mild, Moderate or Severe Adverse Event | At least one mild AE | 11 Participants |
| Tesofensine/Metoprolol | Number of Participants With at Least One Mild, Moderate or Severe Adverse Event | At least one moderate AE | 10 Participants |
| Tesofensine/Metoprolol | Number of Participants With at Least One Mild, Moderate or Severe Adverse Event | At least one severe AE | 2 Participants |
| Placebo | Number of Participants With at Least One Mild, Moderate or Severe Adverse Event | At least one mild AE | 7 Participants |
| Placebo | Number of Participants With at Least One Mild, Moderate or Severe Adverse Event | At least one moderate AE | 5 Participants |
| Placebo | Number of Participants With at Least One Mild, Moderate or Severe Adverse Event | At least one severe AE | 2 Participants |
Primary
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
Population: Safety Analysis Set: all subjects who took at least one dose of the IMPs (active substances or placebos)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tesofensine/Metoprolol | Number of Participants With Treatment Emergent Adverse Events | 12 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events | 7 Participants |
Primary
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
Population: Safety Analysis Set: all subjects who took at least one dose of the IMPs (active substances or placebos)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tesofensine/Metoprolol | Participants (Number and Percentage) With and Type of Serious Adverse Events | Preferred Term: Anxiety | 1 Participants |
| Tesofensine/Metoprolol | Participants (Number and Percentage) With and Type of Serious Adverse Events | Preferred Term: Hyponatraemia | 0 Participants |
| Tesofensine/Metoprolol | Participants (Number and Percentage) With and Type of Serious Adverse Events | Preferred Term: Craniopharyngioma | 1 Participants |
| Tesofensine/Metoprolol | Participants (Number and Percentage) With and Type of Serious Adverse Events | Preferred Term: Post procedural complication | 1 Participants |
| Tesofensine/Metoprolol | Participants (Number and Percentage) With and Type of Serious Adverse Events | At least one SAE | 2 Participants |
| Placebo | Participants (Number and Percentage) With and Type of Serious Adverse Events | Preferred Term: Post procedural complication | 0 Participants |
| Placebo | Participants (Number and Percentage) With and Type of Serious Adverse Events | At least one SAE | 1 Participants |
| Placebo | Participants (Number and Percentage) With and Type of Serious Adverse Events | Preferred Term: Anxiety | 0 Participants |
| Placebo | Participants (Number and Percentage) With and Type of Serious Adverse Events | Preferred Term: Craniopharyngioma | 0 Participants |
| Placebo | Participants (Number and Percentage) With and Type of Serious Adverse Events | Preferred Term: Hyponatraemia | 1 Participants |
Primary
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
Population: Safety Analysis Set: all subjects who took at least one dose of the IMPs (active substances or placebos). Subjects with an assessment at given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tesofensine/Metoprolol | Safety as Assessed by Diastolic Blood Pressure [mmHg] | Week 8 | 84.5 mmHg | Standard Deviation 9 |
| Tesofensine/Metoprolol | Safety as Assessed by Diastolic Blood Pressure [mmHg] | Week 16 | 81.4 mmHg | Standard Deviation 9 |
| Tesofensine/Metoprolol | Safety as Assessed by Diastolic Blood Pressure [mmHg] | Week 4 | 84.2 mmHg | Standard Deviation 8 |
| Tesofensine/Metoprolol | Safety as Assessed by Diastolic Blood Pressure [mmHg] | Week 20 | 84.3 mmHg | Standard Deviation 9 |
| Tesofensine/Metoprolol | Safety as Assessed by Diastolic Blood Pressure [mmHg] | Week 12 | 81.5 mmHg | Standard Deviation 10 |
| Tesofensine/Metoprolol | Safety as Assessed by Diastolic Blood Pressure [mmHg] | Week 24 | 83.1 mmHg | Standard Deviation 9 |
| Tesofensine/Metoprolol | Safety as Assessed by Diastolic Blood Pressure [mmHg] | Baseline | 83.2 mmHg | Standard Deviation 14 |
| Placebo | Safety as Assessed by Diastolic Blood Pressure [mmHg] | Week 24 | 84.2 mmHg | Standard Deviation 13 |
| Placebo | Safety as Assessed by Diastolic Blood Pressure [mmHg] | Baseline | 85.9 mmHg | Standard Deviation 8 |
| Placebo | Safety as Assessed by Diastolic Blood Pressure [mmHg] | Week 4 | 86.8 mmHg | Standard Deviation 8 |
| Placebo | Safety as Assessed by Diastolic Blood Pressure [mmHg] | Week 8 | 86.0 mmHg | Standard Deviation 9 |
| Placebo | Safety as Assessed by Diastolic Blood Pressure [mmHg] | Week 12 | 86.5 mmHg | Standard Deviation 8 |
| Placebo | Safety as Assessed by Diastolic Blood Pressure [mmHg] | Week 16 | 80.3 mmHg | Standard Deviation 13 |
| Placebo | Safety as Assessed by Diastolic Blood Pressure [mmHg] | Week 20 | 85.7 mmHg | Standard Deviation 9 |
Comparison: Week 4; Safety set; LOCFp-value: 0.654395% CI: [-7.33, 4.72]ANCOVA
Comparison: Week 8; Safety set; LOCFp-value: 0.794195% CI: [-6.5, 8.38]ANCOVA
Comparison: Week 12; Safety set; LOCFp-value: 0.593795% CI: [-9.72, 5.73]ANCOVA
Comparison: Week 16; Safety set; LOCFp-value: 0.542395% CI: [-6.11, 11.23]ANCOVA
Comparison: Week 20; Safety set; LOCFp-value: 0.722695% CI: [-5.77, 8.16]ANCOVA
Comparison: Week 24; Safety set; LOCFp-value: 0.791295% CI: [-7.85, 10.16]ANCOVA
Primary
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
Population: Safety Analysis Set: all subjects who took at least one dose of the IMPs (active substances or placebos). Subjects with an assessment at given timepoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Sodium: Week 20 - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Sodium: Baseline - High | 2 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Sodium: Week 4 - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Sodium: Week 4 - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Sodium: Week 8 - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Sodium: Week 8 - High | 1 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Sodium: Week 12 - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Sodium: Week 12 - High | 1 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Sodium: Week 16 - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Sodium: Week 16 - High | 1 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Sodium: Baseline - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Sodium: Week 20 - High | 2 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Sodium: Week 24 - Low | 1 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Sodium: Week 24 - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Potassium: Baseline - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Potassium: Baseline - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Potassium: Week 4 - Low | 2 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Potassium: Week 4 - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Potassium: Week 8 - Low | 2 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Potassium: Week 8 - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Potassium: Week 12 - Low | 1 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Potassium: Week 12 - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Potassium: Week 16 - Low | 1 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Potassium: Week 16 - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Potassium: Week 20 - Low | 1 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Potassium: Week 20 - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Potassium: Week 24 - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Potassium: Week 24 - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Creatinine: Baseline - Low | 3 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Creatinine: Baseline - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Creatinine: Week 4 - Low | 2 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Creatinine: Week 4 - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Creatinine: Week 8 - Low | 2 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Creatinine: Week 8 - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Creatinine: Week 12 - Low | 2 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Creatinine: Week 12 - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Creatinine: Week 16 - Low | 3 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Creatinine: Week 16 - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Creatinine: Week 20 - Low | 4 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Creatinine: Week 20 - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Creatinine: Week 24 - Low | 3 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Electrolytes and Creatinine | Creatinine: Week 24 - High | 0 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Creatinine: Week 4 - High | 0 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Sodium: Baseline - Low | 0 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Potassium: Week 12 - High | 0 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Sodium: Baseline - High | 2 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Creatinine: Week 20 - High | 0 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Sodium: Week 4 - Low | 0 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Potassium: Week 16 - Low | 0 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Sodium: Week 4 - High | 0 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Creatinine: Week 8 - Low | 3 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Sodium: Week 8 - Low | 0 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Potassium: Week 16 - High | 1 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Sodium: Week 8 - High | 1 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Creatinine: Week 16 - High | 0 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Sodium: Week 12 - Low | 0 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Potassium: Week 20 - Low | 0 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Sodium: Week 12 - High | 0 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Creatinine: Week 8 - High | 0 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Sodium: Week 16 - Low | 0 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Potassium: Week 20 - High | 0 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Sodium: Week 16 - High | 0 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Creatinine: Week 24 - High | 0 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Sodium: Week 20 - Low | 0 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Potassium: Week 24 - Low | 1 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Sodium: Week 20 - High | 2 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Creatinine: Week 12 - Low | 2 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Sodium: Week 24 - Low | 0 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Potassium: Week 24 - High | 0 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Sodium: Week 24 - High | 1 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Creatinine: Week 20 - Low | 2 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Potassium: Baseline - Low | 0 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Creatinine: Baseline - Low | 2 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Potassium: Baseline - High | 1 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Creatinine: Week 12 - High | 0 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Potassium: Week 4 - Low | 1 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Creatinine: Baseline - High | 0 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Potassium: Week 4 - High | 1 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Creatinine: Week 24 - Low | 1 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Potassium: Week 8 - Low | 0 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Creatinine: Week 4 - Low | 4 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Potassium: Week 8 - High | 0 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Creatinine: Week 16 - Low | 2 Participants |
| Placebo | Safety as Assessed by Electrolytes and Creatinine | Potassium: Week 12 - Low | 0 Participants |
Primary
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
Population: Safety Analysis Set: all subjects who took at least one dose of the IMPs (active substances or placebos). Subjects with an assessment at given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tesofensine/Metoprolol | Safety as Assessed by Heart Rate [Bpm] | Week 8 | 72.7 bpm | Standard Deviation 8 |
| Tesofensine/Metoprolol | Safety as Assessed by Heart Rate [Bpm] | Week 16 | 73.8 bpm | Standard Deviation 13 |
| Tesofensine/Metoprolol | Safety as Assessed by Heart Rate [Bpm] | Week 4 | 71.9 bpm | Standard Deviation 9 |
| Tesofensine/Metoprolol | Safety as Assessed by Heart Rate [Bpm] | Week 20 | 74.8 bpm | Standard Deviation 11 |
| Tesofensine/Metoprolol | Safety as Assessed by Heart Rate [Bpm] | Week 12 | 74.2 bpm | Standard Deviation 10 |
| Tesofensine/Metoprolol | Safety as Assessed by Heart Rate [Bpm] | Week 24 | 73.6 bpm | Standard Deviation 10 |
| Tesofensine/Metoprolol | Safety as Assessed by Heart Rate [Bpm] | Baseline | 75.5 bpm | Standard Deviation 8 |
| Placebo | Safety as Assessed by Heart Rate [Bpm] | Week 24 | 71.5 bpm | Standard Deviation 9 |
| Placebo | Safety as Assessed by Heart Rate [Bpm] | Baseline | 78.9 bpm | Standard Deviation 11 |
| Placebo | Safety as Assessed by Heart Rate [Bpm] | Week 4 | 75.9 bpm | Standard Deviation 12 |
| Placebo | Safety as Assessed by Heart Rate [Bpm] | Week 8 | 76.0 bpm | Standard Deviation 13 |
| Placebo | Safety as Assessed by Heart Rate [Bpm] | Week 12 | 73.3 bpm | Standard Deviation 8 |
| Placebo | Safety as Assessed by Heart Rate [Bpm] | Week 16 | 74.8 bpm | Standard Deviation 6 |
| Placebo | Safety as Assessed by Heart Rate [Bpm] | Week 20 | 77.2 bpm | Standard Deviation 13 |
Comparison: Week 4; Safety set; LOCFp-value: 0.702395% CI: [-8.67, 5.97]ANCOVA
Comparison: Week 8; Safety set; LOCFp-value: 0.901295% CI: [-8.58, 7.61]ANCOVA
Comparison: Week 12; Safety set; LOCFp-value: 0.613895% CI: [-6.63, 10.92]ANCOVA
Comparison: Week 16; Safety set; LOCFp-value: 0.788995% CI: [-8.26, 10.72]ANCOVA
Comparison: Week 20; Safety set; LOCFp-value: 0.953695% CI: [-10.34, 10.94]ANCOVA
Comparison: Week 24; Safety set; LOCFp-value: 0.555195% CI: [-6.72, 12.12]ANCOVA
Primary
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
Population: Safety Analysis Set: all subjects who took at least one dose of the IMPs (active substances or placebos). Subjects with an assessment at given timepoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Neutrophils: Baseline - Low | 1 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Platelets: Week 12 - High | 1 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Neutrophils: Baseline - High | 1 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Hemoglobin: Week 12 - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Neutrophils: Week 12 - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Platelets: Week 24 - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Neutrophils: Week 12 - High | 4 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Hemoglobin: Week 24 - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Neutrophils: Week 24 - Low | 1 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Platelets: Week 24 - High | 1 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Neutrophils: Week 24 - High | 1 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Hemoglobin: Baseline - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Monocytes: Baseline - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | WBC: Baseline - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Monocytes: Baseline - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Platelets: Baseline - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Monocytes: Week 12 - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | WBC: Baseline - High | 3 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Monocytes: Week 12 - High | 1 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Hemoglobin: Week 12 - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Monocytes: Week 24 - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | WBC: Week 12 - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Monocytes: Week 24 - High | 1 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Platelets: Baseline - High | 1 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Lymphocytes: Baseline - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | WBC: Week 12 - High | 5 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Lymphocytes: Baseline - High | 1 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Hemoglobin: Baseline - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Lymphocytes: Week 12 - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | WBC: Week 24 - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Lymphocytes: Week 12 - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Platelets: Week 12 - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Lymphocytes: Week 24 - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | WBC: Week 24 - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Lymphocytes: Week 24 - High | 1 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Hematology Parameters | Hemoglobin: Week 24 - Low | 1 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Lymphocytes: Week 24 - High | 0 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Hemoglobin: Baseline - High | 1 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Hemoglobin: Week 12 - Low | 0 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Hemoglobin: Week 12 - High | 0 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Hemoglobin: Week 24 - Low | 0 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Hemoglobin: Week 24 - High | 0 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Platelets: Baseline - Low | 0 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Platelets: Baseline - High | 0 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Platelets: Week 12 - Low | 0 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Platelets: Week 12 - High | 0 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Platelets: Week 24 - Low | 0 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Platelets: Week 24 - High | 0 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | WBC: Baseline - Low | 0 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | WBC: Baseline - High | 2 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | WBC: Week 12 - Low | 0 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | WBC: Week 12 - High | 1 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | WBC: Week 24 - Low | 0 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | WBC: Week 24 - High | 1 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Neutrophils: Baseline - Low | 0 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Neutrophils: Baseline - High | 1 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Neutrophils: Week 12 - Low | 0 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Neutrophils: Week 12 - High | 1 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Neutrophils: Week 24 - Low | 0 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Neutrophils: Week 24 - High | 1 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Monocytes: Baseline - Low | 0 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Monocytes: Baseline - High | 0 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Monocytes: Week 12 - Low | 0 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Monocytes: Week 12 - High | 0 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Monocytes: Week 24 - Low | 0 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Monocytes: Week 24 - High | 0 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Lymphocytes: Baseline - Low | 1 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Lymphocytes: Baseline - High | 2 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Lymphocytes: Week 12 - Low | 1 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Lymphocytes: Week 12 - High | 0 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Lymphocytes: Week 24 - Low | 0 Participants |
| Placebo | Safety as Assessed by Hematology Parameters | Hemoglobin: Baseline - Low | 0 Participants |
Primary
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
Population: Safety Analysis Set: all subjects who took at least one dose of the IMPs (active substances or placebos). Subjects with an assessment at given timepoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | ALP: Baseline - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | GGT: Week 24 - High | 4 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | ALP: Baseline - High | 1 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | AST: Week 24 - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | ALP: Week 12 - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | GGT: Week 12 - High | 5 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | ALP: Week 12 - High | 2 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | AST: Week 24 - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | ALP: Week 24 - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | AST: Baseline - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | ALP: Week 24 - High | 1 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | ALT: Baseline - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | GFR: Baseline - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | GGT: Week 12 - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | GFR: Baseline - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | ALT: Baseline - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | GFR: Week 12 - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | AST: Baseline - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | GFR: Week 12 - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | ALT: Week 12 - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | GFR: Week 24 - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | GGT: Week 24 - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | GFR: Week 24 - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | ALT: Week 12 - High | 1 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | Urea: Baseline - Low | 1 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | AST: Week 12 - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | Urea: Baseline - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | ALT: Week 24 - Low | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | Urea: Week 12 - Low | 2 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | GGT: Baseline - High | 5 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | Urea: Week 12 - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | ALT: Week 24 - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | Urea: Week 24 - Low | 1 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | AST: Week 12 - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | Urea: Week 24 - High | 0 Participants |
| Tesofensine/Metoprolol | Safety as Assessed by Liver and Kidney Function Tests | GGT: Baseline - Low | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | Urea: Week 24 - High | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | GGT: Baseline - Low | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | GGT: Baseline - High | 1 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | GGT: Week 12 - Low | 1 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | GGT: Week 12 - High | 2 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | GGT: Week 24 - Low | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | GGT: Week 24 - High | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | AST: Baseline - Low | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | AST: Baseline - High | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | AST: Week 12 - Low | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | AST: Week 12 - High | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | AST: Week 24 - Low | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | AST: Week 24 - High | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | ALT: Baseline - Low | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | ALT: Baseline - High | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | ALT: Week 12 - Low | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | ALT: Week 12 - High | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | ALT: Week 24 - Low | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | ALT: Week 24 - High | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | ALP: Baseline - Low | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | ALP: Baseline - High | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | ALP: Week 12 - Low | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | ALP: Week 12 - High | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | ALP: Week 24 - Low | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | ALP: Week 24 - High | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | GFR: Baseline - Low | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | GFR: Baseline - High | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | GFR: Week 12 - Low | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | GFR: Week 12 - High | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | GFR: Week 24 - Low | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | GFR: Week 24 - High | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | Urea: Baseline - Low | 1 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | Urea: Baseline - High | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | Urea: Week 12 - Low | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | Urea: Week 12 - High | 0 Participants |
| Placebo | Safety as Assessed by Liver and Kidney Function Tests | Urea: Week 24 - Low | 0 Participants |
Primary
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
Population: Safety Analysis Set: all subjects who took at least one dose of the IMPs (active substances or placebos). Subjects with an assessment at given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tesofensine/Metoprolol | Safety as Assessed by Systolic Blood Pressure [mmHg] | Week 8 | 129.2 mmHg | Standard Deviation 17 |
| Tesofensine/Metoprolol | Safety as Assessed by Systolic Blood Pressure [mmHg] | Week 16 | 123.9 mmHg | Standard Deviation 14 |
| Tesofensine/Metoprolol | Safety as Assessed by Systolic Blood Pressure [mmHg] | Week 4 | 126.6 mmHg | Standard Deviation 12 |
| Tesofensine/Metoprolol | Safety as Assessed by Systolic Blood Pressure [mmHg] | Week 20 | 127.3 mmHg | Standard Deviation 12 |
| Tesofensine/Metoprolol | Safety as Assessed by Systolic Blood Pressure [mmHg] | Week 12 | 126.3 mmHg | Standard Deviation 13 |
| Tesofensine/Metoprolol | Safety as Assessed by Systolic Blood Pressure [mmHg] | Week 24 | 125.3 mmHg | Standard Deviation 16 |
| Tesofensine/Metoprolol | Safety as Assessed by Systolic Blood Pressure [mmHg] | Baseline | 124.0 mmHg | Standard Deviation 9 |
| Placebo | Safety as Assessed by Systolic Blood Pressure [mmHg] | Week 24 | 130.5 mmHg | Standard Deviation 22 |
| Placebo | Safety as Assessed by Systolic Blood Pressure [mmHg] | Baseline | 134.5 mmHg | Standard Deviation 16 |
| Placebo | Safety as Assessed by Systolic Blood Pressure [mmHg] | Week 4 | 131.8 mmHg | Standard Deviation 17 |
| Placebo | Safety as Assessed by Systolic Blood Pressure [mmHg] | Week 8 | 126.3 mmHg | Standard Deviation 23 |
| Placebo | Safety as Assessed by Systolic Blood Pressure [mmHg] | Week 12 | 126.2 mmHg | Standard Deviation 14 |
| Placebo | Safety as Assessed by Systolic Blood Pressure [mmHg] | Week 16 | 126.0 mmHg | Standard Deviation 17 |
| Placebo | Safety as Assessed by Systolic Blood Pressure [mmHg] | Week 20 | 129.2 mmHg | Standard Deviation 18 |
Comparison: Week 4; Safety set; LOCFp-value: 0.467195% CI: [-6.58, 13.78]ANCOVA
Comparison: Week 8; Safety set; LOCFp-value: 0.180895% CI: [-5.14, 25.36]ANCOVA
Comparison: Week 12; Safety set; LOCFp-value: 0.417195% CI: [-7.08, 16.33]ANCOVA
Comparison: Week 16; Safety set; LOCFp-value: 0.311695% CI: [-5.43, 16.1]ANCOVA
Comparison: Week 20; Safety set; LOCFp-value: 0.235395% CI: [-4.12, 15.72]ANCOVA
Comparison: Week 24; Safety set; LOCFp-value: 0.303795% CI: [-5.76, 17.48]ANCOVA
Secondary
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
Population: Number of participants analyzed:~Tesofensine/Metoprolol - Baseline/Week 12/Week 24: 14/12/9 Placebo - Baseline/Week 12/Week24: 8/6/5
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tesofensine/Metoprolol | 24 Hours Blood Pressure | Systolic BP mean change from baseline to week 12 | -8.0 mmHg | Standard Deviation 20 |
| Tesofensine/Metoprolol | 24 Hours Blood Pressure | Systolic BP mean change from baseline to week 24 | 2.3 mmHg | Standard Deviation 20 |
| Tesofensine/Metoprolol | 24 Hours Blood Pressure | Diastolic BP mean change from baseline to week 24 | 3.7 mmHg | Standard Deviation 8 |
| Tesofensine/Metoprolol | 24 Hours Blood Pressure | Diastolic BP mean change from baseline to week 12 | 0.2 mmHg | Standard Deviation 9 |
| Placebo | 24 Hours Blood Pressure | Diastolic BP mean change from baseline to week 12 | 3.7 mmHg | Standard Deviation 8 |
| Placebo | 24 Hours Blood Pressure | Systolic BP mean change from baseline to week 12 | 0.7 mmHg | Standard Deviation 14 |
| Placebo | 24 Hours Blood Pressure | Diastolic BP mean change from baseline to week 24 | -2.8 mmHg | Standard Deviation 9 |
| Placebo | 24 Hours Blood Pressure | Systolic BP mean change from baseline to week 24 | -8.4 mmHg | Standard Deviation 17 |
Comparison: From baseline to week 24; mITT LOCF. (Change in systolic blood pressure mean)p-value: 0.872895% CI: [-18.17, 21.18]ANCOVA
Comparison: From baseline to week 24; mITT LOCF. (Change in diastolic blood pressure mean)p-value: 0.571495% CI: [-6.61, 11.54]ANCOVA
Comparison: From baseline to week 12; mITT LOCF. (Change in systolic blood pressure mean)p-value: 0.232295% CI: [-27.51, 7.22]ANCOVA
Comparison: From baseline to week 12; mITT LOCF. (Change in diastolic blood pressure mean)p-value: 0.432195% CI: [-12.61, 5.68]ANCOVA
Secondary
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
Population: 21 sub. were assign. 22 randomization no.~1 sub. was screen failure received 1 dose of Tesomet prior to being withdrawn at baseline. Sub. was re-screened and randomized as new sub. receiving PBO. As this sub. was assigned 2 randomization no., 1 under each arm, the sub. is summarized for both arms. The 2 randomization no. are considered as 2 sub.~14 sub. were randomized to receive Tesomet and 8 sub. received PBO. 4 sub. (2 Tesomet, 2 PBO) terminated study before end of 24W DB period.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Tesofensine/Metoprolol | 48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24 | ECG interretation baseline | Normal | 14 Participants |
| Tesofensine/Metoprolol | 48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24 | ECG interretation baseline | Abnormal | 0 Participants |
| Tesofensine/Metoprolol | 48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24 | ECG interretation at week 12 | Normal | 9 Participants |
| Tesofensine/Metoprolol | 48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24 | ECG interretation at week 12 | Abnormal | 3 Participants |
| Tesofensine/Metoprolol | 48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24 | ECG interretation at week 24 | Normal | 11 Participants |
| Tesofensine/Metoprolol | 48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24 | ECG interretation at week 24 | Abnormal | 1 Participants |
| Tesofensine/Metoprolol | 48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24 | 48 hour heart rate at baseline | Normal | 13 Participants |
| Tesofensine/Metoprolol | 48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24 | 48 hour heart rate at baseline | Abnormal | 0 Participants |
| Tesofensine/Metoprolol | 48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24 | 48 hour heart rate at week 12 | Normal | 10 Participants |
| Tesofensine/Metoprolol | 48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24 | 48 hour heart rate at week 12 | Abnormal | 2 Participants |
| Tesofensine/Metoprolol | 48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24 | 48 hour heart rate at week 24 | Normal | 12 Participants |
| Tesofensine/Metoprolol | 48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24 | 48 hour heart rate at week 24 | Abnormal | 0 Participants |
| Placebo | 48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24 | 48 hour heart rate at week 24 | Normal | 6 Participants |
| Placebo | 48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24 | ECG interretation baseline | Normal | 8 Participants |
| Placebo | 48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24 | 48 hour heart rate at baseline | Normal | 8 Participants |
| Placebo | 48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24 | ECG interretation baseline | Abnormal | 0 Participants |
| Placebo | 48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24 | 48 hour heart rate at week 12 | Abnormal | 0 Participants |
| Placebo | 48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24 | ECG interretation at week 12 | Normal | 6 Participants |
| Placebo | 48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24 | 48 hour heart rate at baseline | Abnormal | 0 Participants |
| Placebo | 48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24 | ECG interretation at week 12 | Abnormal | 0 Participants |
| Placebo | 48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24 | 48 hour heart rate at week 24 | Abnormal | 0 Participants |
| Placebo | 48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24 | ECG interretation at week 24 | Normal | 6 Participants |
| Placebo | 48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24 | 48 hour heart rate at week 12 | Normal | 6 Participants |
| Placebo | 48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24 | ECG interretation at week 24 | Abnormal | 0 Participants |
Secondary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tesofensine/Metoprolol | Blood Pressure (Change) | Change in Systolic BP from baseline to week 24 | 2.0 mmHg | Standard Deviation 13 |
| Tesofensine/Metoprolol | Blood Pressure (Change) | Change in Systolic BP from baseline to week 48 | 5.8 mmHg | Standard Deviation 14 |
| Tesofensine/Metoprolol | Blood Pressure (Change) | Change in Systolic BP from week 24 to wek 48 | 5.0 mmHg | Standard Deviation 11 |
| Tesofensine/Metoprolol | Blood Pressure (Change) | Change in Diastolic BP from baseline to week 24 | 2.8 mmHg | Standard Deviation 11 |
| Tesofensine/Metoprolol | Blood Pressure (Change) | Change in Diastolic BP from baseline to week 48 | 6.5 mmHg | Standard Deviation 12 |
| Tesofensine/Metoprolol | Blood Pressure (Change) | Change in Diastolic BP from week 24 to week 48 | 4.2 mmHg | Standard Deviation 9 |
| Placebo | Blood Pressure (Change) | Change in Diastolic BP from baseline to week 48 | -1.0 mmHg | Standard Deviation 13 |
| Placebo | Blood Pressure (Change) | Change in Systolic BP from baseline to week 24 | -4.2 mmHg | Standard Deviation 8 |
| Placebo | Blood Pressure (Change) | Change in Diastolic BP from baseline to week 24 | -2.0 mmHg | Standard Deviation 11 |
| Placebo | Blood Pressure (Change) | Change in Systolic BP from baseline to week 48 | -9.7 mmHg | Standard Deviation 13 |
| Placebo | Blood Pressure (Change) | Change in Diastolic BP from week 24 to week 48 | 1.0 mmHg | Standard Deviation 10 |
| Placebo | Blood Pressure (Change) | Change in Systolic BP from week 24 to wek 48 | -5.5 mmHg | Standard Deviation 14 |
Comparison: From baseline to week 24; safety set LOCF. (Change in systolic blood pressure)p-value: 0.303795% CI: [-5.76, 17.48]ANCOVA
Comparison: From baseline to week 24; safety set LOCF. (Change in diastolic blood pressure)p-value: 0.791295% CI: [-7.85, 10.16]ANCOVA
Comparison: From baseline to week 48; safety set LOCF. (Change in systolic blood pressure)p-value: 0.177395% CI: [-5.25, 25.83]ANCOVA
Comparison: From baseline to week 48; safety set LOCF. (Change in diastolic blood pressure)p-value: 0.79895% CI: [-9.55, 12.2]ANCOVA
Comparison: From week 24 to week 48; safety set LOCF. (Change in systolic blood pressure)p-value: 0.15895% CI: [-3.4, 18.94]ANCOVA
Comparison: From week 24 to week 48; safety set LOCF. (Change in diastolic blood pressure)p-value: 0.702195% CI: [-7.36, 10.64]ANCOVA
Secondary
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
Population: Modified Intention-to-treat (mITT) Population: all subjects who entered Part 2 (open-label extension) and had nonmissing baseline assessments and at least 1 post-Part 1 assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tesofensine/Metoprolol | Body Composition - Fat Mass | Baseline to Week 24 | -5.31 kg | Standard Deviation 5.34 |
| Tesofensine/Metoprolol | Body Composition - Fat Mass | Baseline to Week 48 | -4.87 kg | Standard Deviation 5.31 |
| Tesofensine/Metoprolol | Body Composition - Fat Mass | Week 24 to Week 48 | 0.44 kg | Standard Deviation 3.5 |
| Placebo | Body Composition - Fat Mass | Baseline to Week 24 | -1.04 kg | Standard Deviation 3.75 |
| Placebo | Body Composition - Fat Mass | Baseline to Week 48 | -3.77 kg | Standard Deviation 5.81 |
| Placebo | Body Composition - Fat Mass | Week 24 to Week 48 | -2.73 kg | Standard Deviation 3.37 |
Comparison: Baseline to Week 24; mITT observed.p-value: 0.104895% CI: [-9.31, 0.98]ANCOVA
Comparison: Baseline to Week 48; mITT observed.p-value: 0.718995% CI: [-6.75, 4.77]ANCOVA
Comparison: Week 24 to Week 48; mITT observed.p-value: 0.105395% CI: [-0.73, 6.91]ANCOVA
Secondary
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
Population: Modified Intention-to-treat (mITT) Population: all subjects who entered Part 2 (open-label extension) and had nonmissing baseline assessments and at least 1 post-Part 1 assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tesofensine/Metoprolol | Body Composition - Lean Body Mass | Baseline to Week 24 | -2.85 kg | Standard Deviation 1.88 |
| Tesofensine/Metoprolol | Body Composition - Lean Body Mass | Baseline to Week 48 | -1.81 kg | Standard Deviation 2.18 |
| Tesofensine/Metoprolol | Body Composition - Lean Body Mass | Week 24 to Week 48 | 1.04 kg | Standard Deviation 1.18 |
| Placebo | Body Composition - Lean Body Mass | Baseline to Week 24 | 0.55 kg | Standard Deviation 1.32 |
| Placebo | Body Composition - Lean Body Mass | Baseline to Week 48 | -1.87 kg | Standard Deviation 3.36 |
| Placebo | Body Composition - Lean Body Mass | Week 24 to Week 48 | -2.42 kg | Standard Deviation 3.51 |
Comparison: Baseline to Week 24; mITT observedp-value: 0.003395% CI: [-5.02, -1.21]ANCOVA
Comparison: Baseline to Week 48; mITT LOCFp-value: 0.666395% CI: [-2.24, 3.41]ANCOVA
Comparison: Week 24 to Week 48; mITT LOCFp-value: 0.005895% CI: [1.21, 5.98]ANCOVA
Secondary
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
Population: Modified Intention-to-treat (mITT) Population: all subjects who entered Part 2 (open-label extension) and had nonmissing baseline assessments and at least 1 post-Part 1 assessment. Last observation carried forward (LOCF) approach.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tesofensine/Metoprolol | Body Weight | Baseline to Week 24 | -7.93 kg | Standard Deviation 6.59 |
| Tesofensine/Metoprolol | Body Weight | Baseline to Week 48 | -6.53 kg | Standard Deviation 7.36 |
| Tesofensine/Metoprolol | Body Weight | Week 24 to Week 48 | 1.40 kg | Standard Deviation 4.05 |
| Placebo | Body Weight | Baseline to Week 24 | -0.15 kg | Standard Deviation 4.74 |
| Placebo | Body Weight | Baseline to Week 48 | -5.65 kg | Standard Deviation 8.9 |
| Placebo | Body Weight | Week 24 to Week 48 | -5.50 kg | Standard Deviation 6.2 |
Comparison: Baseline to Week 24p-value: 0.032595% CI: [-14.29, -0.71]ANCOVA
Comparison: Baseline to Week 48p-value: 0.939495% CI: [-9.04, 8.4]ANCOVA
Comparison: Week 24 to Week 28p-value: 0.013595% CI: [1.65, 12.18]ANCOVA
Secondary
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
Population: Modified Intention-to-treat (mITT) Population: all subjects who entered Part 2 (open-label extension) and had nonmissing baseline assessments and at least 1 post-Part 1 assessment. Last observation carried forward (LOCF) approach.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tesofensine/Metoprolol | Composite Satiety Score (CSS) | Baseline to Week 24 | 4.5 score on a scale | Standard Deviation 20.6 |
| Tesofensine/Metoprolol | Composite Satiety Score (CSS) | Baseline to Week 48 | 4.2 score on a scale | Standard Deviation 15.1 |
| Tesofensine/Metoprolol | Composite Satiety Score (CSS) | Week 24 to Week 48 | -0.3 score on a scale | Standard Deviation 14.4 |
| Placebo | Composite Satiety Score (CSS) | Baseline to Week 24 | 6.5 score on a scale | Standard Deviation 19.3 |
| Placebo | Composite Satiety Score (CSS) | Baseline to Week 48 | 11.2 score on a scale | Standard Deviation 14.3 |
| Placebo | Composite Satiety Score (CSS) | Week 24 to Week 48 | 4.7 score on a scale | Standard Deviation 12.5 |
Comparison: Baseline to Week 24p-value: 0.778295% CI: [-21.23, 16.2]ANCOVA
Comparison: Baseline to Week 48p-value: 0.31395% CI: [-22.09, 7.56]ANCOVA
Comparison: Week 24 to Week 48p-value: 0.403395% CI: [-19.92, 8.47]ANCOVA
Secondary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tesofensine/Metoprolol | Craving for Something Sweet, Salty, Meat/Fish, or Fatty | Desire for something sweet from baseline to week 24 | 9.0 score on a scale | Standard Deviation 36.6 |
| Tesofensine/Metoprolol | Craving for Something Sweet, Salty, Meat/Fish, or Fatty | Desire for something sweet from baseline to week 48 | 2.1 score on a scale | Standard Deviation 35.8 |
| Tesofensine/Metoprolol | Craving for Something Sweet, Salty, Meat/Fish, or Fatty | Desire for something sweet from week 24 to week 48 | -6.9 score on a scale | Standard Deviation 20.2 |
| Tesofensine/Metoprolol | Craving for Something Sweet, Salty, Meat/Fish, or Fatty | Desire for something salty from baseline to week 24 | -2.3 score on a scale | Standard Deviation 27.9 |
| Tesofensine/Metoprolol | Craving for Something Sweet, Salty, Meat/Fish, or Fatty | Desire for something salty from baseline to week 48 | -3.4 score on a scale | Standard Deviation 28.8 |
| Tesofensine/Metoprolol | Craving for Something Sweet, Salty, Meat/Fish, or Fatty | Desire for something salty from week 24 to week 48 | -1.2 score on a scale | Standard Deviation 8.5 |
| Tesofensine/Metoprolol | Craving for Something Sweet, Salty, Meat/Fish, or Fatty | Desire for meat/fish from baseline to week 24 | 7.3 score on a scale | Standard Deviation 42.6 |
| Tesofensine/Metoprolol | Craving for Something Sweet, Salty, Meat/Fish, or Fatty | Desire for meat/fish from baseline to week 48 | 14.0 score on a scale | Standard Deviation 44.1 |
| Tesofensine/Metoprolol | Craving for Something Sweet, Salty, Meat/Fish, or Fatty | Desire for meat/fish from week 24 to week 48 | 6.8 score on a scale | Standard Deviation 18.6 |
| Tesofensine/Metoprolol | Craving for Something Sweet, Salty, Meat/Fish, or Fatty | Desire for something fatty from baseline to week 24 | 18.2 score on a scale | Standard Deviation 22.6 |
| Tesofensine/Metoprolol | Craving for Something Sweet, Salty, Meat/Fish, or Fatty | Desire for something fatty from baseline to week 48 | 5.2 score on a scale | Standard Deviation 25.7 |
| Tesofensine/Metoprolol | Craving for Something Sweet, Salty, Meat/Fish, or Fatty | Desire for something fatty from week 24 to week 48 | -13.0 score on a scale | Standard Deviation 15.6 |
| Placebo | Craving for Something Sweet, Salty, Meat/Fish, or Fatty | Desire for something fatty from baseline to week 48 | 22.5 score on a scale | Standard Deviation 26.3 |
| Placebo | Craving for Something Sweet, Salty, Meat/Fish, or Fatty | Desire for something sweet from baseline to week 24 | 16.2 score on a scale | Standard Deviation 30.8 |
| Placebo | Craving for Something Sweet, Salty, Meat/Fish, or Fatty | Desire for meat/fish from baseline to week 24 | 8.8 score on a scale | Standard Deviation 34 |
| Placebo | Craving for Something Sweet, Salty, Meat/Fish, or Fatty | Desire for something sweet from baseline to week 48 | 35.3 score on a scale | Standard Deviation 32.9 |
| Placebo | Craving for Something Sweet, Salty, Meat/Fish, or Fatty | Desire for something fatty from baseline to week 24 | 2.2 score on a scale | Standard Deviation 11.3 |
| Placebo | Craving for Something Sweet, Salty, Meat/Fish, or Fatty | Desire for something sweet from week 24 to week 48 | 19.2 score on a scale | Standard Deviation 30.7 |
| Placebo | Craving for Something Sweet, Salty, Meat/Fish, or Fatty | Desire for meat/fish from baseline to week 48 | 35.0 score on a scale | Standard Deviation 34.6 |
| Placebo | Craving for Something Sweet, Salty, Meat/Fish, or Fatty | Desire for something salty from baseline to week 24 | 13.2 score on a scale | Standard Deviation 21.5 |
| Placebo | Craving for Something Sweet, Salty, Meat/Fish, or Fatty | Desire for something fatty from week 24 to week 48 | 20.3 score on a scale | Standard Deviation 28 |
| Placebo | Craving for Something Sweet, Salty, Meat/Fish, or Fatty | Desire for something salty from baseline to week 48 | 33.3 score on a scale | Standard Deviation 30.9 |
| Placebo | Craving for Something Sweet, Salty, Meat/Fish, or Fatty | Desire for meat/fish from week 24 to week 48 | 26.2 score on a scale | Standard Deviation 34.2 |
| Placebo | Craving for Something Sweet, Salty, Meat/Fish, or Fatty | Desire for something salty from week 24 to week 48 | 20.2 score on a scale | Standard Deviation 22.7 |
Comparison: Baseline to week 24; mITT observed. (Like to eat something fatty)p-value: 0.090595% CI: [-2.85, 34.85]ANCOVA
Comparison: Baseline to Week 24; mITT observed. (Like some meat/fish)p-value: 0.628595% CI: [-22.05, 35.36]ANCOVA
Comparison: Baseline to Week 24; mITT observed. (Eat something salty).p-value: 0.588495% CI: [-33.05, 19.43]ANCOVA
Comparison: Baseline to Week 24; mITT observed. (Eat something sweet).p-value: 0.853395% CI: [-30.73, 36.68]ANCOVA
Comparison: Baseline to Week 48; mITT LOCF. (Like to eat something fatty).p-value: 0.152995% CI: [-41.87, 7.2]ANCOVA
Comparison: Baseline to Week 48; mITT LOCF. (Like some meat/fish).p-value: 0.339995% CI: [-37.15, 13.65]ANCOVA
Comparison: Baseline to Week 48; mITT LOCF. (Eat something salty).p-value: 0.067395% CI: [-49.84, 1.93]ANCOVA
Comparison: Baseline to Week 48; mITT LOCF. (Eat something sweet).p-value: 0.165795% CI: [-55.65, 10.46]ANCOVA
Comparison: Week 24 to week 48; mITT LOCF. (Like to eat something fatty).p-value: 0.010895% CI: [-52.31, -8.06]ANCOVA
Comparison: Week 24 to week 48; mITT LOCF. (Like some meat/fish).p-value: 0.17195% CI: [-36.71, 7.13]ANCOVA
Comparison: Week 24 to week 48; mITT LOCF. (Eat something salty).p-value: 0.008395% CI: [-33.8, -5.93]ANCOVA
Comparison: Week 24 to week 48; mITT LOCF. (Eat something sweet).p-value: 0.063195% CI: [-47.39, 1.43]ANCOVA
Secondary
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.
Time frame: from baseline to week 24, from baseline to week 48 and from week 24 to week 48
Population: Modified Intention-to-treat (mITT) Population: all subjects who entered Part 2 (open-label extension) and had nonmissing baseline assessments and at least 1 post-Part 1 assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tesofensine/Metoprolol | Glycemic Control - Fasting Plasma Glucose | Baseline to Week 24 | -0.29 mmol/L | Standard Deviation 0.64 |
| Tesofensine/Metoprolol | Glycemic Control - Fasting Plasma Glucose | Baseline to Week 48 | -0.11 mmol/L | Standard Deviation 0.53 |
| Tesofensine/Metoprolol | Glycemic Control - Fasting Plasma Glucose | Week 24 to Week 48 | 0.18 mmol/L | Standard Deviation 0.46 |
| Placebo | Glycemic Control - Fasting Plasma Glucose | Baseline to Week 24 | -0.28 mmol/L | Standard Deviation 0.57 |
| Placebo | Glycemic Control - Fasting Plasma Glucose | Baseline to Week 48 | 0.08 mmol/L | Standard Deviation 0.37 |
| Placebo | Glycemic Control - Fasting Plasma Glucose | Week 24 to Week 48 | 0.37 mmol/L | Standard Deviation 0.59 |
Comparison: Baseline to Week 24; mITT LOCFp-value: 0.792695% CI: [-0.42, 0.33]ANCOVA
Comparison: Baseline to Week 48; mITT LOCFp-value: 0.212495% CI: [-0.72, 0.17]ANCOVA
Comparison: Week 24 to Week 48; mITT LOCFp-value: 0.608495% CI: [-0.72, 0.43]ANCOVA
Secondary
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
Population: Modified Intention-to-treat (mITT) Population: all subjects who entered Part 2 (open-label extension) and had nonmissing baseline assessments and at least 1 post-Part 1 assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tesofensine/Metoprolol | Glycemic Control - HbA1c | Baseline to Week 24 | -6.00 mmol/mol | Standard Deviation 15.39 |
| Tesofensine/Metoprolol | Glycemic Control - HbA1c | Baseline to Week 48 | -5.33 mmol/mol | Standard Deviation 14.79 |
| Tesofensine/Metoprolol | Glycemic Control - HbA1c | Week 24 to Week 48 | 0.67 mmol/mol | Standard Deviation 1.3 |
| Placebo | Glycemic Control - HbA1c | Week 24 to Week 48 | 0.00 mmol/mol | Standard Deviation 0.63 |
| Placebo | Glycemic Control - HbA1c | Baseline to Week 24 | -0.17 mmol/mol | Standard Deviation 2.4 |
| Placebo | Glycemic Control - HbA1c | Baseline to Week 48 | -0.17 mmol/mol | Standard Deviation 2.23 |
Comparison: Baseline to Week 24; mITT observedp-value: 0.071395% CI: [-6.34, 0.3]ANCOVA
Comparison: Baseline to Week 48; mITT LOCFp-value: 0.145795% CI: [-5.92, 0.96]ANCOVA
Comparison: Week 24 to Week 48; mITT LOCFp-value: 0.183795% CI: [-0.45, 2.15]ANCOVA
Secondary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tesofensine/Metoprolol | Heart Rate (Change) | Change in Heart Rate from baseline to week 24 | -2.4 bpm | Standard Deviation 11 |
| Tesofensine/Metoprolol | Heart Rate (Change) | Change in Heart Rate from baseline to week 48 | 0.1 bpm | Standard Deviation 7 |
| Tesofensine/Metoprolol | Heart Rate (Change) | Change in Heart Rate from week 24 to week 48 | 4.2 bpm | Standard Deviation 8 |
| Placebo | Heart Rate (Change) | Change in Heart Rate from baseline to week 24 | -7.0 bpm | Standard Deviation 12 |
| Placebo | Heart Rate (Change) | Change in Heart Rate from baseline to week 48 | 0.7 bpm | Standard Deviation 20 |
| Placebo | Heart Rate (Change) | Change in Heart Rate from week 24 to week 48 | 7.7 bpm | Standard Deviation 10 |
Comparison: From baseline to week 24; safety set LOCF. (Change in heart rate)p-value: 0.555195% CI: [-6.72, 12.12]ANCOVA
Comparison: From baseline to week 48; safety set LOCF. (Change in heart rate)p-value: 0.725695% CI: [-14.88, 10.63]ANCOVA
Comparison: From week 24 to week 48; safety set LOCF. (Change in heart rate)p-value: 0.482295% CI: [-13.05, 6.48]ANCOVA
Secondary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tesofensine/Metoprolol | Lipid Profile | Change in total cholesterol from baseline to week 24 | -0.17 mmol/L | Standard Deviation 0.46 |
| Tesofensine/Metoprolol | Lipid Profile | Change in total cholesterol from baseline to week 48 | -0.01 mmol/L | Standard Deviation 0.6 |
| Tesofensine/Metoprolol | Lipid Profile | Change in total cholesterol from week 24 to week 48 | 0.16 mmol/L | Standard Deviation 0.48 |
| Tesofensine/Metoprolol | Lipid Profile | Change in HDL cholesterol from baseline to week 24 | 0.04 mmol/L | Standard Deviation 0.21 |
| Tesofensine/Metoprolol | Lipid Profile | Change in HDL cholesterol from baseline to week 48 | 0.09 mmol/L | Standard Deviation 0.26 |
| Tesofensine/Metoprolol | Lipid Profile | Change in HDL cholesterol from week 24 to week 48 | 0.05 mmol/L | Standard Deviation 0.24 |
| Tesofensine/Metoprolol | Lipid Profile | Change in LDL cholesterol from baseline to week 24 | -0.23 mmol/L | Standard Deviation 0.39 |
| Tesofensine/Metoprolol | Lipid Profile | Change in LDL cholesterol from baseline to week 48 | -0.15 mmol/L | Standard Deviation 0.38 |
| Tesofensine/Metoprolol | Lipid Profile | Change in LDL cholesterol from week 24 to week 48 | 0.08 mmol/L | Standard Deviation 0.28 |
| Tesofensine/Metoprolol | Lipid Profile | Change in triglycerides from baseline to week 24 | -0.08 mmol/L | Standard Deviation 0.77 |
| Tesofensine/Metoprolol | Lipid Profile | Change in triglycerides from baseline to week 48 | -0.07 mmol/L | Standard Deviation 0.77 |
| Tesofensine/Metoprolol | Lipid Profile | Change in triglycerides from week 24 to week 48 | 0.01 mmol/L | Standard Deviation 0.69 |
| Placebo | Lipid Profile | Change in triglycerides from baseline to week 48 | -0.48 mmol/L | Standard Deviation 0.28 |
| Placebo | Lipid Profile | Change in total cholesterol from baseline to week 24 | -0.17 mmol/L | Standard Deviation 0.45 |
| Placebo | Lipid Profile | Change in LDL cholesterol from baseline to week 24 | -0.20 mmol/L | Standard Deviation 0.43 |
| Placebo | Lipid Profile | Change in total cholesterol from baseline to week 48 | -0.22 mmol/L | Standard Deviation 0.75 |
| Placebo | Lipid Profile | Change in triglycerides from baseline to week 24 | -0.30 mmol/L | Standard Deviation 0.76 |
| Placebo | Lipid Profile | Change in total cholesterol from week 24 to week 48 | -0.05 mmol/L | Standard Deviation 0.69 |
| Placebo | Lipid Profile | Change in LDL cholesterol from baseline to week 48 | -0.32 mmol/L | Standard Deviation 0.53 |
| Placebo | Lipid Profile | Change in HDL cholesterol from baseline to week 24 | -0.02 mmol/L | Standard Deviation 0.37 |
| Placebo | Lipid Profile | Change in triglycerides from week 24 to week 48 | -0.18 mmol/L | Standard Deviation 0.66 |
| Placebo | Lipid Profile | Change in HDL cholesterol from baseline to week 48 | 0.03 mmol/L | Standard Deviation 0.25 |
| Placebo | Lipid Profile | Change in LDL cholesterol from week 24 to week 48 | -0.12 mmol/L | Standard Deviation 0.45 |
| Placebo | Lipid Profile | Change in HDL cholesterol from week 24 to week 48 | 0.05 mmol/L | Standard Deviation 0.16 |
Comparison: Baseline to Week 24; mITT observed. (Change in total cholesterol)p-value: 0.862395% CI: [-0.59, 0.5]ANCOVA
Comparison: Baseline to Week 24; mITT observed. (Change in HDL cholesterol)p-value: 0.832795% CI: [-0.25, 0.3]ANCOVA
Comparison: Baseline to Week 24; mITT observed. (Change in LDL cholesterol)p-value: 0.80895% CI: [-0.53, 0.42]ANCOVA
Comparison: Baseline to Week 24; mITT observed. (Change in triglycerides)p-value: 0.579195% CI: [-0.62, 1.07]ANCOVA
Comparison: Baseline to Week 48; mITT LOCF. (Change in cholesterol)p-value: 0.933795% CI: [-0.71, 0.77]ANCOVA
Comparison: Baseline to Week 48; mITT LOCF. (Change in HDL cholesterol)p-value: 0.930595% CI: [-0.21, 0.23]ANCOVA
Comparison: Baseline to Week 48; mITT LOCF. (Change in LDL cholesterol)p-value: 0.69195% CI: [-0.4, 0.59]ANCOVA
Comparison: Baseline to Week 48; mITT LOCF. (Change in triglycerides)p-value: 0.268895% CI: [-0.3, 1.01]ANCOVA
Comparison: Week 24 to week 48; mITT LOCF. (Change in cholesterol)p-value: 0.826295% CI: [-0.54, 0.67]ANCOVA
Comparison: Week 24 to week 48; mITT LOCF. (Change in HDL cholesterol)p-value: 0.829395% CI: [-0.2, 0.17]ANCOVA
Comparison: Week 24 to week 48; mITT LOCF. (Change in LDL cholesterol)p-value: 0.548695% CI: [-0.27, 0.49]ANCOVA
Comparison: Week 24 to week 48; mITT LOCF. (Change in triglycerides)p-value: 0.322695% CI: [-0.26, 0.75]ANCOVA
Secondary
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
Population: One subject was excluded from safety analysis (in the Tesofensine/Metoprolol -\> Tesofensine/Metoprolol arm) since subject discontinued Tesomet treatment in Part 1 but continued in Part 2 without being dosed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tesofensine/Metoprolol | Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension | Infections and infestations | 6 Participants |
| Tesofensine/Metoprolol | Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension | Gastrointestinal disorders | 5 Participants |
| Tesofensine/Metoprolol | Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension | Musculoskeletal and connective tissue disorders | 7 Participants |
| Tesofensine/Metoprolol | Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension | Nervous system disorders | 3 Participants |
| Tesofensine/Metoprolol | Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension | General disorders and administration site conditions | 4 Participants |
| Tesofensine/Metoprolol | Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension | Psychiatric disorders | 2 Participants |
| Tesofensine/Metoprolol | Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension | Cardiac disorders | 0 Participants |
| Tesofensine/Metoprolol | Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension | Injury, poisoning and procedural complications | 1 Participants |
| Tesofensine/Metoprolol | Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension | Vascular disorders | 0 Participants |
| Tesofensine/Metoprolol | Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension | Blood and lymphatic system disorders | 1 Participants |
| Tesofensine/Metoprolol | Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension | Investigations | 1 Participants |
| Tesofensine/Metoprolol | Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension | Respiratory, thoracic and mediastinal disorders | 1 Participants |
| Placebo | Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension | Investigations | 0 Participants |
| Placebo | Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension | Infections and infestations | 4 Participants |
| Placebo | Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension | Cardiac disorders | 3 Participants |
| Placebo | Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension | Gastrointestinal disorders | 3 Participants |
| Placebo | Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension | Blood and lymphatic system disorders | 0 Participants |
| Placebo | Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension | Musculoskeletal and connective tissue disorders | 1 Participants |
| Placebo | Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension | Injury, poisoning and procedural complications | 1 Participants |
| Placebo | Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension | Nervous system disorders | 4 Participants |
| Placebo | Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| Placebo | Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension | General disorders and administration site conditions | 0 Participants |
| Placebo | Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension | Vascular disorders | 2 Participants |
| Placebo | Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension | Psychiatric disorders | 2 Participants |
Secondary
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
Population: The Placebo -\> Tesofensine/Metoprolol group did not start treatment before week 25
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tesofensine/Metoprolol | Plasma Trough Concentrations | Metoprolol Week 12 | 10.83 μg/L | Geometric Coefficient of Variation 120.8 |
| Tesofensine/Metoprolol | Plasma Trough Concentrations | Metoprolol Week 24 | 9.07 μg/L | Geometric Coefficient of Variation 281.4 |
| Tesofensine/Metoprolol | Plasma Trough Concentrations | Metoprolol Week 36 | 8.97 μg/L | Geometric Coefficient of Variation 309.6 |
| Tesofensine/Metoprolol | Plasma Trough Concentrations | Tesofensine Week 36 | 11.01 μg/L | Geometric Coefficient of Variation 54.4 |
| Tesofensine/Metoprolol | Plasma Trough Concentrations | Metoprolol Week 48 | 7.29 μg/L | Geometric Coefficient of Variation 156.9 |
| Tesofensine/Metoprolol | Plasma Trough Concentrations | Tesofensine Week 12 | 12.03 μg/L | Geometric Coefficient of Variation 38.6 |
| Tesofensine/Metoprolol | Plasma Trough Concentrations | NS2360 metab. Week 12 | 3.39 μg/L | Geometric Coefficient of Variation 48.5 |
| Tesofensine/Metoprolol | Plasma Trough Concentrations | NS2360 metab. Week 24 | 3.96 μg/L | Geometric Coefficient of Variation 71.9 |
| Tesofensine/Metoprolol | Plasma Trough Concentrations | NS2360 metab. Week 36 | 3.39 μg/L | Geometric Coefficient of Variation 57.1 |
| Tesofensine/Metoprolol | Plasma Trough Concentrations | Tesofensine Week 24 | 12.34 μg/L | Geometric Coefficient of Variation 55.4 |
| Tesofensine/Metoprolol | Plasma Trough Concentrations | NS2360 metab. Week 48 | 2.44 μg/L | Geometric Coefficient of Variation 157.3 |
| Tesofensine/Metoprolol | Plasma Trough Concentrations | Tesofensine Week 48 | 6.78 μg/L | Geometric Coefficient of Variation 394.7 |
| Placebo | Plasma Trough Concentrations | Metoprolol Week 48 | 7.30 μg/L | Geometric Coefficient of Variation 578.8 |
| Placebo | Plasma Trough Concentrations | Tesofensine Week 36 | 19.10 μg/L | Geometric Coefficient of Variation 56.1 |
| Placebo | Plasma Trough Concentrations | Tesofensine Week 48 | 15.11 μg/L | Geometric Coefficient of Variation 70.2 |
| Placebo | Plasma Trough Concentrations | NS2360 metab. Week 36 | 6.51 μg/L | Geometric Coefficient of Variation 56.3 |
| Placebo | Plasma Trough Concentrations | NS2360 metab. Week 48 | 6.02 μg/L | Geometric Coefficient of Variation 67.7 |
| Placebo | Plasma Trough Concentrations | Metoprolol Week 36 | 10.62 μg/L | Geometric Coefficient of Variation 206 |
Secondary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tesofensine/Metoprolol | Quality of Life - SF-36 | Physical component from baseline to week 24 | 0.90 score on a scale | Standard Deviation 7.59 |
| Tesofensine/Metoprolol | Quality of Life - SF-36 | Physical component from baseline to week 48 | 0.70 score on a scale | Standard Deviation 5.98 |
| Tesofensine/Metoprolol | Quality of Life - SF-36 | Physical component from week 24 to week 48 | -0.21 score on a scale | Standard Deviation 6.8 |
| Tesofensine/Metoprolol | Quality of Life - SF-36 | Mental component from baseline to week 24 | -3.08 score on a scale | Standard Deviation 11.44 |
| Tesofensine/Metoprolol | Quality of Life - SF-36 | Mental component from baseline to week 48 | -1.46 score on a scale | Standard Deviation 7.74 |
| Tesofensine/Metoprolol | Quality of Life - SF-36 | Mental component from week 24 to week 48 | 1.62 score on a scale | Standard Deviation 11.46 |
| Placebo | Quality of Life - SF-36 | Mental component from baseline to week 48 | 0.49 score on a scale | Standard Deviation 1.74 |
| Placebo | Quality of Life - SF-36 | Physical component from baseline to week 24 | 1.36 score on a scale | Standard Deviation 3.74 |
| Placebo | Quality of Life - SF-36 | Mental component from baseline to week 24 | -0.49 score on a scale | Standard Deviation 2.02 |
| Placebo | Quality of Life - SF-36 | Physical component from baseline to week 48 | 2.41 score on a scale | Standard Deviation 4.82 |
| Placebo | Quality of Life - SF-36 | Mental component from week 24 to week 48 | 0.98 score on a scale | Standard Deviation 2.29 |
| Placebo | Quality of Life - SF-36 | Physical component from week 24 to week 48 | 1.05 score on a scale | Standard Deviation 3.64 |
Comparison: From baseline to week 24; mITT LOCF. (Physical component score)p-value: 0.84295% CI: [-5.55, 6.73]ANCOVA
Comparison: From baseline to week 24; mITT LOCF. (Mental component score)p-value: 0.669395% CI: [-10.15, 6.67]ANCOVA
Comparison: From baseline to week 48; mITT LOCF. (Physical component score)p-value: 0.544495% CI: [-8.12, 4.46]ANCOVA
Comparison: From baseline to week 48; mITT LOCF. (Mental component score)p-value: 0.559595% CI: [-8.47, 4.76]ANCOVA
Comparison: Week 24 to week 48; mITT LOCF. (Physical component score)p-value: 0.433195% CI: [-7.54, 3.41]ANCOVA
Comparison: Week 24 to week 48; mITT LOCF. (Mental component score)p-value: 0.642795% CI: [-7.9, 5.03]ANCOVA
Secondary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tesofensine/Metoprolol | Thirst | From baseline to week 24 | -2.4 score on a scale | Standard Deviation 28.9 |
| Tesofensine/Metoprolol | Thirst | From baseline to week 48 | -6.3 score on a scale | Standard Deviation 25.8 |
| Tesofensine/Metoprolol | Thirst | From week 24 to week 48 | -3.8 score on a scale | Standard Deviation 16.5 |
| Placebo | Thirst | From baseline to week 24 | -18.8 score on a scale | Standard Deviation 23.2 |
| Placebo | Thirst | From baseline to week 48 | -16.7 score on a scale | Standard Deviation 18.8 |
| Placebo | Thirst | From week 24 to week 48 | 2.2 score on a scale | Standard Deviation 20.5 |
Comparison: Baseline to Week 24; mITT observed.p-value: 0.808295% CI: [-24.65, 19.53]ANCOVA
Comparison: Baseline to Week 48; mITT LOCF.p-value: 0.903495% CI: [-25.94, 23.1]ANCOVA
Comparison: Week 24 to week 48; mITT LOCF.p-value: 0.465895% CI: [-26.93, 12.93]ANCOVA
Secondary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tesofensine/Metoprolol | Waist Circumference | From baseline to week 24 | -7.08 cm | Standard Deviation 6.93 |
| Tesofensine/Metoprolol | Waist Circumference | From baseline to week 48 | -5.75 cm | Standard Deviation 5.26 |
| Tesofensine/Metoprolol | Waist Circumference | From week 24 to week 48 | 1.33 cm | Standard Deviation 4.01 |
| Placebo | Waist Circumference | From baseline to week 24 | -1.17 cm | Standard Deviation 4.4 |
| Placebo | Waist Circumference | From baseline to week 48 | -3.00 cm | Standard Deviation 6.51 |
| Placebo | Waist Circumference | From week 24 to week 48 | -1.83 cm | Standard Deviation 2.64 |
Comparison: Baseline to Week 24; mITT LOCF.p-value: 0.053795% CI: [-11.46, 0.1]ANCOVA
Comparison: Baseline to Week 48; mITT LOCF.p-value: 0.377295% CI: [-8.98, 3.61]ANCOVA
Comparison: Week 24 to week 48; mITT LOCF.p-value: 0.117195% CI: [-0.85, 6.91]ANCOVA