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CompletedNCT03845075Updated Feb 13, 2024Results posted

48 Weeks, Study to Evaluate Overall Safety and Tolerability of Co-administration of Tesofensine and Metoprolol in Subjects With Hypothalamic Injury-induced Obesity (HIO)

A Phase 2 interventional study of Tesofensine/Metoprolol and Placebo in Hypothalamic Injury-induced Obesity (HIO), sponsored by Saniona. Completed at 1 site in Denmark. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2024-02-13.

Sponsored by Saniona · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
21
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study 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
Read the 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.

02

Conditions studied

  • Hypothalamic Injury-induced Obesity (HIO)
03

In context

Obesity

6,296 studies on the registry are indexed under Obesity; 1,692 are open to participants now.

This study's enrollment of 21 is below the median of 78 across 4,878 interventional studies indexed under Obesity.

Browse Obesity studies →

Lead sponsor

Saniona is the lead sponsor of 8 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts 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

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
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
21 participants (actual)

Study arms

  • Experimental
    active arm

    The active medication arm will be given co-administration of 0.5 mg tesofensine/50 mg metoprolol daily for 24 weeks.

    Drug: Tesofensine/Metoprolol

  • Placebo comparator
    placebo arm

    The placebo arm will receive matching placebo tesofensine and placebo metoprolol.

    Drug: Placebo

Interventions

  • DrugTesofensine/Metoprolol

    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

06

What researchers measure

Primary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

07

Results

Posted Feb 13, 2024

Participant flow

Part 1 - DB
Participant flow — Part 1 - DB
MilestoneTesofensine/MetoprololPlaceboTesofensine/Metoprolol -> Tesofensine/MetoprololPlacebo -> Tesofensine/Metoprolol
Started14800
Completed12600
Not completed2200
Withdrew: Withdrawal by subject1100
Withdrew: Adverse event0100
Withdrew: Screen failure, but received 1 dose of study drug in error1000
Part 2 - OLE
Participant flow — Part 2 - OLE
MilestoneTesofensine/MetoprololPlaceboTesofensine/Metoprolol -> Tesofensine/MetoprololPlacebo -> Tesofensine/Metoprolol
Started00126
Completed00126
Not completed0000

Outcome measures

PrimaryNumber 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
Reported as:
Count of participants · Participants
Number of Participants With Treatment Emergent Adverse Events
ParticipantsTesofensine/MetoprololPlacebo
Number of Participants With Treatment Emergent Adverse Events127
PrimaryNumber 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
Reported as:
Count of participants · Participants
Number of Participants With at Least One Mild, Moderate or Severe Adverse Event
ParticipantsTesofensine/MetoprololPlacebo
At least one mild AE117
At least one moderate AE105
At least one severe AE22
PrimaryParticipants (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
Reported as:
Count of participants · Participants
Participants (Number and Percentage) With and Type of Serious Adverse Events
ParticipantsTesofensine/MetoprololPlacebo
At least one SAE21
Preferred Term: Anxiety10
Preferred Term: Craniopharyngioma10
Preferred Term: Hyponatraemia01
Preferred Term: Post procedural complication10
PrimarySafety 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
Reported as:
Mean · mmHg
Safety as Assessed by Systolic Blood Pressure [mmHg]
mmHgTesofensine/MetoprololPlacebo
Baseline124.0 ± 9134.5 ± 16
Week 4126.6 ± 12131.8 ± 17
Week 8129.2 ± 17126.3 ± 23
Week 12126.3 ± 13126.2 ± 14
Week 16123.9 ± 14126.0 ± 17
Week 20127.3 ± 12129.2 ± 18
Week 24125.3 ± 16130.5 ± 22
Statistical analysis
  • Tesofensine/Metoprolol vs Placebo · ANCOVA · p = 0.4671 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 3.60 · 95% CI -6.58 to 13.78Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol vs Placebo · ANCOVA · p = 0.1808 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 10.11 · 95% CI -5.14 to 25.36Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol vs Placebo · ANCOVA · p = 0.4171 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 4.63 · 95% CI -7.08 to 16.33Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol vs Placebo · ANCOVA · p = 0.3116 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 5.33 · 95% CI -5.43 to 16.10Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol vs Placebo · ANCOVA · p = 0.2353 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 5.80 · 95% CI -4.12 to 15.72Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol vs Placebo · ANCOVA · p = 0.3037 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 5.86 · 95% CI -5.76 to 17.48Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
PrimarySafety 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
Reported as:
Mean · mmHg
Safety as Assessed by Diastolic Blood Pressure [mmHg]
mmHgTesofensine/MetoprololPlacebo
Baseline83.2 ± 1485.9 ± 8
Week 484.2 ± 886.8 ± 8
Week 884.5 ± 986.0 ± 9
Week 1281.5 ± 1086.5 ± 8
Week 1681.4 ± 980.3 ± 13
Week 2084.3 ± 985.7 ± 9
Week 2483.1 ± 984.2 ± 13
Statistical analysis
  • Tesofensine/Metoprolol vs Placebo · ANCOVA · p = 0.6543 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -1.31 · 95% CI -7.33 to 4.72Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol vs Placebo · ANCOVA · p = 0.7941 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 0.94 · 95% CI -6.50 to 8.38Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol vs Placebo · ANCOVA · p = 0.5937 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -2.00 · 95% CI -9.72 to 5.73Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol vs Placebo · ANCOVA · p = 0.5423 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 2.56 · 95% CI -6.11 to 11.23Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol vs Placebo · ANCOVA · p = 0.7226 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 1.20 · 95% CI -5.77 to 8.16Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol vs Placebo · ANCOVA · p = 0.7912 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 1.15 · 95% CI -7.85 to 10.16Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
PrimarySafety 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
Reported as:
Mean · bpm
Safety as Assessed by Heart Rate [Bpm]
bpmTesofensine/MetoprololPlacebo
Baseline75.5 ± 878.9 ± 11
Week 471.9 ± 975.9 ± 12
Week 872.7 ± 876.0 ± 13
Week 1274.2 ± 1073.3 ± 8
Week 1673.8 ± 1374.8 ± 6
Week 2074.8 ± 1177.2 ± 13
Week 2473.6 ± 1071.5 ± 9
Statistical analysis
  • Tesofensine/Metoprolol vs Placebo · ANCOVA · p = 0.7023 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -1.35 · 95% CI -8.67 to 5.97Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol vs Placebo · ANCOVA · p = 0.9012 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -0.48 · 95% CI -8.58 to 7.61Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol vs Placebo · ANCOVA · p = 0.6138 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 2.14 · 95% CI -6.63 to 10.92Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol vs Placebo · ANCOVA · p = 0.7889 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 1.23 · 95% CI -8.26 to 10.72Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol vs Placebo · ANCOVA · p = 0.9536 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 0.30 · 95% CI -10.34 to 10.94Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol vs Placebo · ANCOVA · p = 0.5551 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 2.70 · 95% CI -6.72 to 12.12Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
PrimarySafety 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
Reported as:
Count of participants · Participants
Safety as Assessed by Hematology Parameters
ParticipantsTesofensine/MetoprololPlacebo
Hemoglobin: Baseline - Low00
Hemoglobin: Baseline - High01
Hemoglobin: Week 12 - Low00
Hemoglobin: Week 12 - High00
Hemoglobin: Week 24 - Low10
Hemoglobin: Week 24 - High00
Platelets: Baseline - Low00
Platelets: Baseline - High10
Platelets: Week 12 - Low00
Platelets: Week 12 - High10
Platelets: Week 24 - Low00
Platelets: Week 24 - High10
WBC: Baseline - Low00
WBC: Baseline - High32
WBC: Week 12 - Low00
WBC: Week 12 - High51
WBC: Week 24 - Low00
WBC: Week 24 - High01
Neutrophils: Baseline - Low10
Neutrophils: Baseline - High11
Neutrophils: Week 12 - Low00
Neutrophils: Week 12 - High41
Neutrophils: Week 24 - Low10
Neutrophils: Week 24 - High11
Monocytes: Baseline - Low00
Monocytes: Baseline - High00
Monocytes: Week 12 - Low00
Monocytes: Week 12 - High10
Monocytes: Week 24 - Low00
Monocytes: Week 24 - High10
Lymphocytes: Baseline - Low01
Lymphocytes: Baseline - High12
Lymphocytes: Week 12 - Low01
Lymphocytes: Week 12 - High00
Lymphocytes: Week 24 - Low00
Lymphocytes: Week 24 - High10
PrimarySafety 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
Reported as:
Count of participants · Participants
Safety as Assessed by Electrolytes and Creatinine
ParticipantsTesofensine/MetoprololPlacebo
Sodium: Baseline - Low00
Sodium: Baseline - High22
Sodium: Week 4 - Low00
Sodium: Week 4 - High00
Sodium: Week 8 - Low00
Sodium: Week 8 - High11
Sodium: Week 12 - Low00
Sodium: Week 12 - High10
Sodium: Week 16 - Low00
Sodium: Week 16 - High10
Sodium: Week 20 - Low00
Sodium: Week 20 - High22
Sodium: Week 24 - Low10
Sodium: Week 24 - High01
Potassium: Baseline - Low00
Potassium: Baseline - High01
Potassium: Week 4 - Low21
Potassium: Week 4 - High01
Potassium: Week 8 - Low20
Potassium: Week 8 - High00
Potassium: Week 12 - Low10
Potassium: Week 12 - High00
Potassium: Week 16 - Low10
Potassium: Week 16 - High01
Potassium: Week 20 - Low10
Potassium: Week 20 - High00
Potassium: Week 24 - Low01
Potassium: Week 24 - High00
Creatinine: Baseline - Low32
Creatinine: Baseline - High00
Creatinine: Week 4 - Low24
Creatinine: Week 4 - High00
Creatinine: Week 8 - Low23
Creatinine: Week 8 - High00
Creatinine: Week 12 - Low22
Creatinine: Week 12 - High00
Creatinine: Week 16 - Low32
Creatinine: Week 16 - High00
Creatinine: Week 20 - Low42
Creatinine: Week 20 - High00
Creatinine: Week 24 - Low31
Creatinine: Week 24 - High00
PrimarySafety 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
Reported as:
Count of participants · Participants
Safety as Assessed by Liver and Kidney Function Tests
ParticipantsTesofensine/MetoprololPlacebo
GGT: Baseline - Low00
GGT: Baseline - High51
GGT: Week 12 - Low01
GGT: Week 12 - High52
GGT: Week 24 - Low00
GGT: Week 24 - High40
AST: Baseline - Low00
AST: Baseline - High00
AST: Week 12 - Low00
AST: Week 12 - High00
AST: Week 24 - Low00
AST: Week 24 - High00
ALT: Baseline - Low00
ALT: Baseline - High00
ALT: Week 12 - Low00
ALT: Week 12 - High10
ALT: Week 24 - Low00
ALT: Week 24 - High00
ALP: Baseline - Low00
ALP: Baseline - High10
ALP: Week 12 - Low00
ALP: Week 12 - High20
ALP: Week 24 - Low00
ALP: Week 24 - High10
GFR: Baseline - Low00
GFR: Baseline - High00
GFR: Week 12 - Low00
GFR: Week 12 - High00
GFR: Week 24 - Low00
GFR: Week 24 - High00
Urea: Baseline - Low11
Urea: Baseline - High00
Urea: Week 12 - Low20
Urea: Week 12 - High00
Urea: Week 24 - Low10
Urea: Week 24 - High00
SecondaryComposite 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
Reported as:
Mean · score on a scale
Composite Satiety Score (CSS)
score on a scaleTesofensine/Metoprolol -> Tesofensine/MetoprololPlacebo -> Tesofensine/Metoprolol
Baseline to Week 244.5 ± 20.66.5 ± 19.3
Baseline to Week 484.2 ± 15.111.2 ± 14.3
Week 24 to Week 48-0.3 ± 14.44.7 ± 12.5
Statistical analysis
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.7782 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -2.52 · 95% CI -21.23 to 16.20(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate.
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.3130 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -7.26 · 95% CI -22.09 to 7.56(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate.
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.4033 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -5.73 · 95% CI -19.92 to 8.47(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate.
SecondaryBody 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
Reported as:
Mean · kg
Body Weight
kgTesofensine/Metoprolol -> Tesofensine/MetoprololPlacebo -> Tesofensine/Metoprolol
Baseline to Week 24-7.93 ± 6.59-0.15 ± 4.74
Baseline to Week 48-6.53 ± 7.36-5.65 ± 8.90
Week 24 to Week 481.40 ± 4.05-5.50 ± 6.20
Statistical analysis
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.0325 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -7.50 · 95% CI -14.29 to -0.71(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate.
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.9394 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -0.32 · 95% CI -9.04 to 8.40(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate.
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol · ANCOVA · p = 0.0135 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 6.91 · 95% CI 1.65 to 12.18(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate.
SecondaryBody 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
Reported as:
Mean · kg
Body Composition - Fat Mass
kgTesofensine/Metoprolol -> Tesofensine/MetoprololPlacebo -> Tesofensine/Metoprolol
Baseline to Week 24-5.31 ± 5.34-1.04 ± 3.75
Baseline to Week 48-4.87 ± 5.31-3.77 ± 5.81
Week 24 to Week 480.44 ± 3.50-2.73 ± 3.37
Statistical analysis
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.1048 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -4.17 · 95% CI -9.31 to 0.98(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate.
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.7189 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -0.99 · 95% CI -6.75 to 4.77(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate.
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.1053 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 3.09 · 95% CI -0.73 to 6.91(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate.
SecondaryBody 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
Reported as:
Mean · kg
Body Composition - Lean Body Mass
kgTesofensine/Metoprolol -> Tesofensine/MetoprololPlacebo -> Tesofensine/Metoprolol
Baseline to Week 24-2.85 ± 1.880.55 ± 1.32
Baseline to Week 48-1.81 ± 2.18-1.87 ± 3.36
Week 24 to Week 481.04 ± 1.18-2.42 ± 3.51
Statistical analysis
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.0033 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -3.12 · 95% CI -5.02 to -1.21(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate.
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.6663 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 0.58 · 95% CI -2.24 to 3.41(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate.
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.0058 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 3.59 · 95% CI 1.21 to 5.98(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate.
SecondaryGlycemic 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
Reported as:
Mean · mmol/mol
Glycemic Control - HbA1c
mmol/molTesofensine/Metoprolol -> Tesofensine/MetoprololPlacebo -> Tesofensine/Metoprolol
Baseline to Week 24-6.00 ± 15.39-0.17 ± 2.40
Baseline to Week 48-5.33 ± 14.79-0.17 ± 2.23
Week 24 to Week 480.67 ± 1.300.00 ± 0.63
Statistical analysis
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.0713 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -3.02 · 95% CI -6.34 to 0.30(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate.
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.1457 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -2.48 · 95% CI -5.92 to 0.96(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate.
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.1837 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 0.85 · 95% CI -0.45 to 2.15(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate.
SecondaryGlycemic 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
Reported as:
Mean · mmol/L
Glycemic Control - Fasting Plasma Glucose
mmol/LTesofensine/Metoprolol -> Tesofensine/MetoprololPlacebo -> Tesofensine/Metoprolol
Baseline to Week 24-0.29 ± 0.64-0.28 ± 0.57
Baseline to Week 48-0.11 ± 0.530.08 ± 0.37
Week 24 to Week 480.18 ± 0.460.37 ± 0.59
Statistical analysis
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.7926 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -0.05 · 95% CI -0.42 to 0.33(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate.
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.2124 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -0.27 · 95% CI -0.72 to 0.17(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate.
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.6084 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -0.14 · 95% CI -0.72 to 0.43(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate.
SecondaryCraving 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
Reported as:
Mean · score on a scale
Craving for Something Sweet, Salty, Meat/Fish, or Fatty
score on a scaleTesofensine/Metoprolol -> Tesofensine/MetoprololPlacebo -> Tesofensine/Metoprolol
Desire for something sweet from baseline to week 249.0 ± 36.616.2 ± 30.8
Desire for something sweet from baseline to week 482.1 ± 35.835.3 ± 32.9
Desire for something sweet from week 24 to week 48-6.9 ± 20.219.2 ± 30.7
Desire for something salty from baseline to week 24-2.3 ± 27.913.2 ± 21.5
Desire for something salty from baseline to week 48-3.4 ± 28.833.3 ± 30.9
Desire for something salty from week 24 to week 48-1.2 ± 8.520.2 ± 22.7
Desire for meat/fish from baseline to week 247.3 ± 42.68.8 ± 34.0
Desire for meat/fish from baseline to week 4814.0 ± 44.135.0 ± 34.6
Desire for meat/fish from week 24 to week 486.8 ± 18.626.2 ± 34.2
Desire for something fatty from baseline to week 2418.2 ± 22.62.2 ± 11.3
Desire for something fatty from baseline to week 485.2 ± 25.722.5 ± 26.3
Desire for something fatty from week 24 to week 48-13.0 ± 15.620.3 ± 28.0
Statistical analysis
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.0905 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 16.00 · 95% CI -2.85 to 34.85(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate.
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.6285 (P-value from ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 6.65 · 95% CI -22.05 to 35.36(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate.
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.5884 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -6.81 · 95% CI -33.05 to 19.43(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate.
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.8533 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 2.98 · 95% CI -30.73 to 36.68(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate.
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.1529 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -17.33 · 95% CI -41.87 to 7.20(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.3399 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -11.75 · 95% CI -37.15 to 13.65(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.0673 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -23.95 · 95% CI -49.84 to 1.93(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.1657 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -22.60 · 95% CI -55.65 to 10.46(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.0108 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -30.18 · 95% CI -52.31 to -8.06(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.1710 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -14.79 · 95% CI -36.71 to 7.13(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.0083 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -19.86 · 95% CI -33.80 to -5.93(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.0631 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -22.98 · 95% CI -47.39 to 1.43(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
SecondaryThirst

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
Reported as:
Mean · score on a scale
Thirst
score on a scaleTesofensine/Metoprolol -> Tesofensine/MetoprololPlacebo -> Tesofensine/Metoprolol
From baseline to week 24-2.4 ± 28.9-18.8 ± 23.2
From baseline to week 48-6.3 ± 25.8-16.7 ± 18.8
From week 24 to week 48-3.8 ± 16.52.2 ± 20.5
Statistical analysis
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.8082 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -2.56 · 95% CI -24.65 to 19.53(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.9034 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -1.42 · 95% CI -25.94 to 23.10(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.4658 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -7.00 · 95% CI -26.93 to 12.93(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
SecondaryWaist 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
Reported as:
Mean · cm
Waist Circumference
cmTesofensine/Metoprolol -> Tesofensine/MetoprololPlacebo -> Tesofensine/Metoprolol
From baseline to week 24-7.08 ± 6.93-1.17 ± 4.40
From baseline to week 48-5.75 ± 5.26-3.00 ± 6.51
From week 24 to week 481.33 ± 4.01-1.83 ± 2.64
Statistical analysis
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.0537 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -5.68 · 95% CI -11.46 to 0.10(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.3772 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -2.69 · 95% CI -8.98 to 3.61(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.1171 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 3.03 · 95% CI -0.85 to 6.91(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
SecondaryLipid 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
Reported as:
Mean · mmol/L
Lipid Profile
mmol/LTesofensine/Metoprolol -> Tesofensine/MetoprololPlacebo -> Tesofensine/Metoprolol
Change in total cholesterol from baseline to week 24-0.17 ± 0.46-0.17 ± 0.45
Change in total cholesterol from baseline to week 48-0.01 ± 0.60-0.22 ± 0.75
Change in total cholesterol from week 24 to week 480.16 ± 0.48-0.05 ± 0.69
Change in HDL cholesterol from baseline to week 240.04 ± 0.21-0.02 ± 0.37
Change in HDL cholesterol from baseline to week 480.09 ± 0.260.03 ± 0.25
Change in HDL cholesterol from week 24 to week 480.05 ± 0.240.05 ± 0.16
Change in LDL cholesterol from baseline to week 24-0.23 ± 0.39-0.20 ± 0.43
Change in LDL cholesterol from baseline to week 48-0.15 ± 0.38-0.32 ± 0.53
Change in LDL cholesterol from week 24 to week 480.08 ± 0.28-0.12 ± 0.45
Change in triglycerides from baseline to week 24-0.08 ± 0.77-0.30 ± 0.76
Change in triglycerides from baseline to week 48-0.07 ± 0.77-0.48 ± 0.28
Change in triglycerides from week 24 to week 480.01 ± 0.69-0.18 ± 0.66
Statistical analysis
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.8623 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -0.05 · 95% CI -0.59 to 0.50(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.8327 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 0.03 · 95% CI -0.25 to 0.30(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.8080 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -0.06 · 95% CI -0.53 to 0.42(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.5791 · Ls mean difference: 0.22 · 95% CI -0.62 to 1.07(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.9337 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 0.03 · 95% CI -0.71 to 0.77(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.9305 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 0.01 · 95% CI -0.21 to 0.23(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.6910 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 0.09 · 95% CI -0.40 to 0.59(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.2688 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 0.35 · 95% CI -0.30 to 1.01(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.8262 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 0.06 · 95% CI -0.54 to 0.67(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.8293 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -0.02 · 95% CI -0.20 to 0.17(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.5486 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 0.11 · 95% CI -0.27 to 0.49(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.3226 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 0.24 · 95% CI -0.26 to 0.75(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
SecondaryQuality 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
Reported as:
Mean · score on a scale
Quality of Life - SF-36
score on a scaleTesofensine/Metoprolol -> Tesofensine/MetoprololPlacebo -> Tesofensine/Metoprolol
Physical component from baseline to week 240.90 ± 7.591.36 ± 3.74
Physical component from baseline to week 480.70 ± 5.982.41 ± 4.82
Physical component from week 24 to week 48-0.21 ± 6.801.05 ± 3.64
Mental component from baseline to week 24-3.08 ± 11.44-0.49 ± 2.02
Mental component from baseline to week 48-1.46 ± 7.740.49 ± 1.74
Mental component from week 24 to week 481.62 ± 11.460.98 ± 2.29
Statistical analysis
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.8420 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 0.59 · 95% CI -5.55 to 6.73(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.6693 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -1.74 · 95% CI -10.15 to 6.67(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.5444 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -1.83 · 95% CI -8.12 to 4.46(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.5595 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -1.85 · 95% CI -8.47 to 4.76(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.4331 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -2.07 · 95% CI -7.54 to 3.41(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.6427 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -1.44 · 95% CI -7.90 to 5.03(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
SecondaryNumber 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
Reported as:
Count of participants · Participants
Number of Participants With Adverse Event(s) and/or Serious Adverse Event(s) - Open-label Extension
ParticipantsTesofensine/Metoprolol -> Tesofensine/MetoprololPlacebo -> Tesofensine/Metoprolol
Infections and infestations64
Gastrointestinal disorders53
Musculoskeletal and connective tissue disorders71
Nervous system disorders34
General disorders and administration site conditions40
Psychiatric disorders22
Cardiac disorders03
Injury, poisoning and procedural complications11
Vascular disorders02
Blood and lymphatic system disorders10
Investigations10
Respiratory, thoracic and mediastinal disorders10
SecondaryBlood 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
Reported as:
Mean · mmHg
Blood Pressure (Change)
mmHgTesofensine/Metoprolol -> Tesofensine/MetoprololPlacebo -> Tesofensine/Metoprolol
Change in Systolic BP from baseline to week 242.0 ± 13-4.2 ± 8
Change in Systolic BP from baseline to week 485.8 ± 14-9.7 ± 13
Change in Systolic BP from week 24 to wek 485.0 ± 11-5.5 ± 14
Change in Diastolic BP from baseline to week 242.8 ± 11-2.0 ± 11
Change in Diastolic BP from baseline to week 486.5 ± 12-1.0 ± 13
Change in Diastolic BP from week 24 to week 484.2 ± 91.0 ± 10
Statistical analysis
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.3037 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 5.86 · 95% CI -5.76 to 17.48(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.7912 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 1.15 · 95% CI -7.85 to 10.16(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.1773 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 10.29 · 95% CI -5.25 to 25.83(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.7980 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 1.32 · 95% CI -9.55 to 12.20(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.1580 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 7.77 · 95% CI -3.40 to 18.94(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.7021 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 1.64 · 95% CI -7.36 to 10.64(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
Secondary24 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
Reported as:
Mean · mmHg
24 Hours Blood Pressure
mmHgTesofensine/MetoprololPlacebo
Systolic BP mean change from baseline to week 12-8.0 ± 200.7 ± 14
Systolic BP mean change from baseline to week 242.3 ± 20-8.4 ± 17
Diastolic BP mean change from baseline to week 120.2 ± 93.7 ± 8
Diastolic BP mean change from baseline to week 243.7 ± 8-2.8 ± 9
Statistical analysis
  • Tesofensine/Metoprolol vs Placebo · ANCOVA · p = 0.8728 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 1.50 · 95% CI -18.17 to 21.18(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol vs Placebo · ANCOVA · p = 0.5714 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 2.46 · 95% CI -6.61 to 11.54(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol vs Placebo · ANCOVA · p = 0.2322 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -10.15 · 95% CI -27.51 to 7.22(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol vs Placebo · ANCOVA · p = 0.4321 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -3.46 · 95% CI -12.61 to 5.68(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
SecondaryPlasma 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
Reported as:
Geometric mean · μg/L
Plasma Trough Concentrations
μg/LTesofensine/Metoprolol -> Tesofensine/MetoprololPlacebo -> Tesofensine/Metoprolol
Tesofensine Week 1212.03 ± 38.6—
Tesofensine Week 2412.34 ± 55.4—
Tesofensine Week 3611.01 ± 54.419.10 ± 56.1
Tesofensine Week 486.78 ± 394.715.11 ± 70.2
NS2360 metab. Week 123.39 ± 48.5—
NS2360 metab. Week 243.96 ± 71.9—
NS2360 metab. Week 363.39 ± 57.16.51 ± 56.3
NS2360 metab. Week 482.44 ± 157.36.02 ± 67.7
Metoprolol Week 1210.83 ± 120.8—
Metoprolol Week 249.07 ± 281.4—
Metoprolol Week 368.97 ± 309.610.62 ± 206.0
Metoprolol Week 487.29 ± 156.97.30 ± 578.8
Secondary48 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
Reported as:
Count of participants · Participants
48 Hours Heart Rate and QT Interval at Baseline, Week 12 and Week 24
ParticipantsTesofensine/MetoprololPlacebo
ECG interretation baseline — Normal148
ECG interretation baseline — Abnormal00
ECG interretation at week 12 — Normal96
ECG interretation at week 12 — Abnormal30
ECG interretation at week 24 — Normal116
ECG interretation at week 24 — Abnormal10
48 hour heart rate at baseline — Normal138
48 hour heart rate at baseline — Abnormal00
48 hour heart rate at week 12 — Normal106
48 hour heart rate at week 12 — Abnormal20
48 hour heart rate at week 24 — Normal126
48 hour heart rate at week 24 — Abnormal00
SecondaryHeart 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
Reported as:
Mean · bpm
Heart Rate (Change)
bpmTesofensine/Metoprolol -> Tesofensine/MetoprololPlacebo -> Tesofensine/Metoprolol
Change in Heart Rate from baseline to week 24-2.4 ± 11-7.0 ± 12
Change in Heart Rate from baseline to week 480.1 ± 70.7 ± 20
Change in Heart Rate from week 24 to week 484.2 ± 87.7 ± 10
Statistical analysis
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.5551 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: 2.70 · 95% CI -6.72 to 12.12(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.7256 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -2.13 · 95% CI -14.88 to 10.63(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate
  • Tesofensine/Metoprolol -> Tesofensine/Metoprolol vs Placebo -> Tesofensine/Metoprolol · ANCOVA · p = 0.4822 (P-value from an ANCOVA model with treatment as factor and baseline as covariate.) · Ls mean difference: -3.29 · 95% CI -13.05 to 6.48(Tesofensine/Metoprolol -\> Tesofensine/Metoprolol) - (Placebo -\> Tesofensine/Metoprolol). Estimate and 95% CI are based on a least squares (LS) mean difference from an ANCOVA model with treatment as factor and baseline as covariate

Adverse events

Collected over Part 1 (double-blind part): From the first dose of double-blind study drug during Part 1 until the last dose during Part 1 (24 weeks duration). Part 2 (open-label extension part): From the first dose of open-label study drug during Part 2 until the last dose during Part 2 (24 weeks duration).. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Tesofensine/Metoprolol0/14 (0%)2/14 (14.3%)12/14 (85.7%)
Placebo0/8 (0%)1/8 (12.5%)7/8 (87.5%)
Tesofensine/Metoprolol -> Tesofensine/Metoprolol0/11 (0%)1/11 (9.1%)11/11 (100%)
Placebo -> Tesofensine/Metoprolol0/6 (0%)0/6 (0%)6/6 (100%)
Most frequent serious events
Most frequent serious events
EventTesofensine/MetoprololPlaceboTesofensine/Metoprolol -> Tesofensine/MetoprololPlacebo -> Tesofensine/Metoprolol
HyponatraemiaMetabolism and nutrition disorders0/141/80/110/6
Abdominal pain upperGastrointestinal disorders0/140/81/110/6
Post procedural complicationInjury, poisoning and procedural complications1/140/80/110/6
CraniopharyngiomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/140/80/110/6
AnxietyPsychiatric disorders1/140/80/110/6
Most frequent other events
Showing 10 of 63
Most frequent other events
EventTesofensine/MetoprololPlaceboTesofensine/Metoprolol -> Tesofensine/MetoprololPlacebo -> Tesofensine/Metoprolol
Sleep disorderPsychiatric disorders7/141/82/111/6
PalpitationsCardiac disorders0/141/80/113/6
Dry mouthGastrointestinal disorders6/140/80/112/6
DizzinessNervous system disorders6/143/81/111/6
Abdominal pain upperGastrointestinal disorders3/143/80/111/6
ArthralgiaMusculoskeletal and connective tissue disorders0/140/84/110/6
HeadacheNervous system disorders5/140/81/112/6
Viral upper respiratory tract infectionInfections and infestations2/140/81/112/6
NauseaGastrointestinal disorders2/142/82/110/6
VomitingGastrointestinal disorders1/142/80/110/6

Baseline characteristics

Age, Continuous
Age, Continuous(years)Tesofensine/MetoprololPlaceboTotal
Mean45.4 ± 13.344.4 ± 18.345.0 ± 14.9
Sex: Female, Male
Sex: Female, Male(Participants)Tesofensine/MetoprololPlaceboTotal
Female11617
Male325
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Tesofensine/MetoprololPlaceboTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American000
White14822
More than one race000
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(Participants)Tesofensine/MetoprololPlaceboTotal
Denmark14822
Weight
Weight(kg)Tesofensine/MetoprololPlaceboTotal
Mean114.34 ± 18.14112.16 ± 27.04113.55 ± 21.18
08

Study locations

1 site
  • Rigshospitalet
    Copenhagen, 210, Denmark
09

References and documents

Study documents

  • Study protocol · Dec 10, 2019
  • Statistical analysis plan · May 17, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 13, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03845075
Lead sponsor
Saniona
Responsible party
Sponsor
First posted
Feb 19, 2019
Start date
Feb 25, 2019
Primary completion
Oct 16, 2020
Completion
Oct 16, 2020
Results posted
Feb 13, 2024
Last update
Feb 13, 2024

Study contacts

Ulla Feldt-Rasmussen, MD, DMSc
principal investigator · Department of Medical Endocrinology and metabolism Rigshospitalet,Copenhagen, DK

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
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