48 Weeks, Study to Evaluate Overall Safety and Tolerabili... | NCT03845075

Label	Type	Description	Intervention Names
active arm	Experimental	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 arm	Placebo Comparator	The placebo arm will receive matching placebo tesofensine and placebo metoprolol.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Tesofensine/Metoprolol	Drug	During Part 1 subjects will be randomized to treatment with co-administration of 0.5 mg tesofensine/50mg metoprolol (active medication)	active arm

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events	Number and percentage of participants with adverse events in each of the two treatment arms	from Baseline to week 24
Number of Participants With at Least One Mild, Moderate or Severe Adverse Event	Number and percentage of participants with mild, moderate or severe adverse events in each of the two treatment arms.	from Baseline to week 24
Participants (Number and Percentage) With and Type of Serious Adverse Events	Number and percentage of participants with at least one serious adverse event, indicating type, in each of the two treatment arms	from Baseline to week 24
Safety as Assessed by Systolic Blood Pressure [mmHg]	Systolic blood pressure in mmHg measured at each visit in each of the two treatment arms	from Baseline to week 24
Safety as Assessed by Diastolic Blood Pressure [mmHg]	Diastolic blood pressure in mmHg measured at each visit in each of the two treatment arms	from Baseline to week 24
Safety as Assessed by Heart Rate [Bpm]	Heart rate measured in beats per minute (bpm) at each visit in each of the two treatment arms	from Baseline to week 24
Safety as Assessed by Hematology Parameters	Number and percentage of deviations from normal range (as defined by the investigational site's laboratory) for hemoglobin, platelet counts, white cells count, differential counts at baseline, week 12 and week 24 in each of the two treatment arms

Secondary Outcomes

Measure	Description	Time Frame
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)

Name	Affiliation	Role
Ulla Feldt-Rasmussen, MD, DMSc	Department of Medical Endocrinology and metabolism Rigshospitalet,Copenhagen, DK	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Rigshospitalet		Copenhagen		210	Denmark

ID	Title	Description
FG000	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.
FG001	Placebo

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Dec 10, 2019	Apr 21, 2020

ID	Title	Description
BG000	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.
BG001	Placebo	Subjects were randomized to receive matching placebo tablets once daily for 24 weeks during Part 1.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00014 BG0018 BG00222

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Treatment Emergent Adverse Events

Number and percentage of participants with adverse events in each of the two treatment arms

Safety Analysis Set: all subjects who took at least one dose of the IMPs (active substances or placebos)

Posted

Count of Participants

Participants

from Baseline to week 24

ID	Title	Description
OG000	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.
OG001	Placebo	Subjects were randomized to receive matching placebo tablets once daily for 24 weeks during Part 1.

Units	Counts
Participants	OG00014 OG0018

Title

Denominators

Categories

Title	Measurements
	OG00012 OG0017

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.

Safety Analysis Set: all subjects who took at least one dose of the IMPs (active substances or placebos)

Posted

Count of Participants

Participants

from Baseline to week 24

ID	Title	Description
OG000	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.
OG001	Placebo	Subjects were randomized to receive matching placebo tablets once daily for 24 weeks during Part 1.

Units	Counts
Participants	OG000

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

Safety Analysis Set: all subjects who took at least one dose of the IMPs (active substances or placebos)

Posted

Count of Participants

Participants

from Baseline to week 24

ID	Title	Description
OG000	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.
OG001	Placebo	Subjects were randomized to receive matching placebo tablets once daily for 24 weeks during Part 1.

Units	Counts
Participants	OG000

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

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.

Posted

Mean

Standard Deviation

mmHg

from Baseline to week 24

ID	Title	Description
OG000	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.
OG001	Placebo	Subjects were randomized to receive matching placebo tablets once daily for 24 weeks during Part 1.

Units	Counts
Participants	OG000

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

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.

Posted

Mean

Standard Deviation

mmHg

from Baseline to week 24

ID	Title	Description
OG000	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.
OG001	Placebo	Subjects were randomized to receive matching placebo tablets once daily for 24 weeks during Part 1.

Units	Counts
Participants	OG000

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

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.

Posted

Mean

Standard Deviation

bpm

from Baseline to week 24

ID	Title	Description
OG000	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.
OG001	Placebo	Subjects were randomized to receive matching placebo tablets once daily for 24 weeks during Part 1.

Units	Counts
Participants	OG000

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

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.

Posted

Count of Participants

Participants

from Baseline to week 24

ID	Title	Description
OG000	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.
OG001	Placebo	Subjects were randomized to receive matching placebo tablets once daily for 24 weeks during Part 1.

Units	Counts
Participants	OG000

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

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.

Posted

Count of Participants

Participants

from Baseline to week 24

ID	Title	Description
OG000	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.
OG001	Placebo	Subjects were randomized to receive matching placebo tablets once daily for 24 weeks during Part 1.

Units	Counts
Participants	OG000

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

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.

Posted

Count of Participants

Participants

from Baseline to week 24

ID	Title	Description
OG000	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.
OG001	Placebo	Subjects were randomized to receive matching placebo tablets once daily for 24 weeks during Part 1.

Units	Counts
Participants

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)

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.

Posted

Mean

Standard Deviation

score on a scale

from baseline to week 24, from baseline to week 48 and from week 24 to week 48

ID	Title	Description
OG000	Tesofensine/Metoprolol -> Tesofensine/Metoprolol	Subjects who received co-administration of 0.5 mg tesofensine/50 mg metoprolol (active medication) once daily for 24 weeks during Part 1 continued to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.
OG001	Placebo -> Tesofensine/Metoprolol	Subjects who received matching placebo tablets once daily for 24 weeks during Part 1 were switched to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.

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

Posted

Mean

Standard Deviation

from baseline to week 24, from baseline to week 48 and from week 24 to week 48

ID	Title	Description
OG000	Tesofensine/Metoprolol -> Tesofensine/Metoprolol	Subjects who received co-administration of 0.5 mg tesofensine/50 mg metoprolol (active medication) once daily for 24 weeks during Part 1 continued to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.
OG001	Placebo -> Tesofensine/Metoprolol	Subjects who received matching placebo tablets once daily for 24 weeks during Part 1 were switched to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.

Units	Counts

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.

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.

Posted

Mean

Standard Deviation

from baseline to week 24, from baseline to week 48 and from week 24 to week 48

ID	Title	Description
OG000	Tesofensine/Metoprolol -> Tesofensine/Metoprolol	Subjects who received co-administration of 0.5 mg tesofensine/50 mg metoprolol (active medication) once daily for 24 weeks during Part 1 continued to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.
OG001	Placebo -> Tesofensine/Metoprolol	Subjects who received matching placebo tablets once daily for 24 weeks during Part 1 were switched to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.

Units	Counts
Participants

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.

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.

Posted

Mean

Standard Deviation

from baseline to week 24, from baseline to week 48 and from week 24 to week 48

ID	Title	Description
OG000	Tesofensine/Metoprolol -> Tesofensine/Metoprolol	Subjects who received co-administration of 0.5 mg tesofensine/50 mg metoprolol (active medication) once daily for 24 weeks during Part 1 continued to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.
OG001	Placebo -> Tesofensine/Metoprolol	Subjects who received matching placebo tablets once daily for 24 weeks during Part 1 were switched to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.

Units	Counts
Participants

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.

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.

Posted

Mean

Standard Deviation

mmol/mol

from baseline to week 24, from baseline to week 48 and from week 24 to week 48

ID	Title	Description
OG000	Tesofensine/Metoprolol -> Tesofensine/Metoprolol	Subjects who received co-administration of 0.5 mg tesofensine/50 mg metoprolol (active medication) once daily for 24 weeks during Part 1 continued to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.
OG001	Placebo -> Tesofensine/Metoprolol	Subjects who received matching placebo tablets once daily for 24 weeks during Part 1 were switched to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.

Units	Counts
Participants

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.

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.

Posted

Mean

Standard Deviation

mmol/L

from baseline to week 24, from baseline to week 48 and from week 24 to week 48

ID	Title	Description
OG000	Tesofensine/Metoprolol -> Tesofensine/Metoprolol	Subjects who received co-administration of 0.5 mg tesofensine/50 mg metoprolol (active medication) once daily for 24 weeks during Part 1 continued to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.
OG001	Placebo -> Tesofensine/Metoprolol	Subjects who received matching placebo tablets once daily for 24 weeks during Part 1 were switched to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.

Units	Counts

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.

Posted

Mean

Standard Deviation

score on a scale

from baseline to week 24, from baseline to week 48 and from week 24 to week 48

ID	Title	Description
OG000	Tesofensine/Metoprolol -> Tesofensine/Metoprolol	Subjects who received co-administration of 0.5 mg tesofensine/50 mg metoprolol (active medication) once daily for 24 weeks during Part 1 continued to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.
OG001	Placebo -> Tesofensine/Metoprolol	Subjects who received matching placebo tablets once daily for 24 weeks during Part 1 were switched to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.

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.

Posted

Mean

Standard Deviation

score on a scale

from baseline to week 24, from baseline to week 48 and from week 24 to week 48

ID	Title	Description
OG000	Tesofensine/Metoprolol -> Tesofensine/Metoprolol	Subjects who received co-administration of 0.5 mg tesofensine/50 mg metoprolol (active medication) once daily for 24 weeks during Part 1 continued to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.
OG001	Placebo -> Tesofensine/Metoprolol	Subjects who received matching placebo tablets once daily for 24 weeks during Part 1 were switched to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.

Units	Counts

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.

Posted

Mean

Standard Deviation

from baseline to week 24, from baseline to week 48 and from week 24 to week 48

ID	Title	Description
OG000	Tesofensine/Metoprolol -> Tesofensine/Metoprolol	Subjects who received co-administration of 0.5 mg tesofensine/50 mg metoprolol (active medication) once daily for 24 weeks during Part 1 continued to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.
OG001	Placebo -> Tesofensine/Metoprolol	Subjects who received matching placebo tablets once daily for 24 weeks during Part 1 were switched to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.

Units	Counts
Participants	OG000

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.

Posted

Mean

Standard Deviation

mmol/L

from baseline to week 24, from baseline to week 48 and from week 24 to week 48

ID	Title	Description
OG000	Tesofensine/Metoprolol -> Tesofensine/Metoprolol	Subjects who received co-administration of 0.5 mg tesofensine/50 mg metoprolol (active medication) once daily for 24 weeks during Part 1 continued to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.
OG001	Placebo -> Tesofensine/Metoprolol	Subjects who received matching placebo tablets once daily for 24 weeks during Part 1 were switched to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.

Units	Counts
Participants	OG000

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.

Posted

Mean

Standard Deviation

score on a scale

from baseline to week 24, from baseline to week 48 and from week 24 to week 48

ID	Title	Description
OG000	Tesofensine/Metoprolol -> Tesofensine/Metoprolol	Subjects who received co-administration of 0.5 mg tesofensine/50 mg metoprolol (active medication) once daily for 24 weeks during Part 1 continued to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.
OG001	Placebo -> Tesofensine/Metoprolol	Subjects who received matching placebo tablets once daily for 24 weeks during Part 1 were switched to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.

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

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.

Posted

Count of Participants

Participants

from week 24 to week 48

ID	Title	Description
OG000	Tesofensine/Metoprolol -> Tesofensine/Metoprolol	Subjects who received co-administration of 0.5 mg tesofensine/50 mg metoprolol (active medication) once daily for 24 weeks during Part 1 continued to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.
OG001	Placebo -> Tesofensine/Metoprolol	Subjects who received matching placebo tablets once daily for 24 weeks during Part 1 were switched to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.

Units	Counts
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.

Posted

Mean

Standard Deviation

mmHg

from baseline to week 24, from baseline to week 48 and from week 24 to week 48

ID	Title	Description
OG000	Tesofensine/Metoprolol -> Tesofensine/Metoprolol	Subjects who received co-administration of 0.5 mg tesofensine/50 mg metoprolol (active medication) once daily for 24 weeks during Part 1 continued to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.
OG001	Placebo -> Tesofensine/Metoprolol	Subjects who received matching placebo tablets once daily for 24 weeks during Part 1 were switched to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.

Units	Counts
Participants	OG000

Secondary

24 Hours Blood Pressure

Changes in 24 hours blood pressure from baseline to week 12 and baseline to week 24

Number of participants analyzed:

Tesofensine/Metoprolol - Baseline/Week 12/Week 24: 14/12/9 Placebo - Baseline/Week 12/Week24: 8/6/5

Posted

Mean

Standard Deviation

mmHg

from baseline to week 12 and baseline to week 24

ID	Title	Description
OG000	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.
OG001	Placebo	Subjects were randomized to receive matching placebo tablets once daily for 24 weeks during Part 1.

Units	Counts
Participants	OG000

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.

The Placebo -> Tesofensine/Metoprolol group did not start treatment before week 25

Posted

Geometric Mean

Geometric Coefficient of Variation

μg/L

baseline to week 48

ID	Title	Description
OG000	Tesofensine/Metoprolol -> Tesofensine/Metoprolol	Subjects who received co-administration of 0.5 mg tesofensine/50 mg metoprolol (active medication) once daily for 24 weeks during Part 1 continued to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.
OG001	Placebo -> Tesofensine/Metoprolol	Subjects who received matching placebo tablets once daily for 24 weeks during Part 1 were switched to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.

Units	Counts
Participants

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.

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.

Posted

Count of Participants

Participants

baseline, week 12 and week 24

ID	Title	Description
OG000	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.
OG001	Placebo	Subjects were randomized to receive matching placebo tablets once daily for 24 weeks during Part 1.

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.

Posted

Mean

Standard Deviation

bpm

from baseline to week 24, from baseline to week 48 and from week 24 to week 48

ID	Title	Description
OG000	Tesofensine/Metoprolol -> Tesofensine/Metoprolol	Subjects who received co-administration of 0.5 mg tesofensine/50 mg metoprolol (active medication) once daily for 24 weeks during Part 1 continued to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.
OG001	Placebo -> Tesofensine/Metoprolol	Subjects who received matching placebo tablets once daily for 24 weeks during Part 1 were switched to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.

Units	Counts
Participants	OG000

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain upper	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0003 events3 affected14 at risk EG0015 events3 affected8 at risk EG0020 events0 affected11 at risk EG0031 events1 affected6 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0006 events6 affected14 at risk EG0010 events0 affected8 at risk EG0020 events0 affected11 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0003 events2 affected14 at risk EG0012 events2 affected8 at risk EG0023 events2 affected11 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0012 events2 affected8 at risk EG0020 events0 affected11 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0002 events2 affected14 at risk EG0010 events0 affected8 at risk EG0022 events2 affected11 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0012 events2 affected8 at risk EG0021 events1 affected11 at risk EG003
Faeces hard	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0002 events2 affected14 at risk EG0010 events0 affected8 at risk EG0020 events0 affected11 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected8 at risk EG0020 events0 affected11 at risk EG003
Dizziness	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0009 events6 affected14 at risk EG0016 events3 affected8 at risk EG0021 events1 affected11 at risk EG003
Headache	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0006 events5 affected14 at risk EG0010 events0 affected8 at risk EG0021 events1 affected11 at risk EG003
Presyncope	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected8 at risk EG0020 events0 affected11 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0011 events1 affected8 at risk EG0021 events1 affected11 at risk EG003
Viral tonsillitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0012 events2 affected8 at risk EG0020 events0 affected11 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0002 events2 affected14 at risk EG0010 events0 affected8 at risk EG0021 events1 affected11 at risk EG003
Eye infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected8 at risk EG0020 events0 affected11 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected8 at risk EG0021 events1 affected11 at risk EG003
Gingivitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected8 at risk EG0020 events0 affected11 at risk EG003
Influenza	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected8 at risk EG0020 events0 affected11 at risk EG003
Sinusitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected8 at risk EG0020 events0 affected11 at risk EG003
Tonsillitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected8 at risk EG0020 events0 affected11 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected8 at risk EG0021 events1 affected11 at risk EG003
Sleep disorder	Psychiatric disorders	MedDRA 22.0	Systematic Assessment	EG0007 events7 affected14 at risk EG0011 events1 affected8 at risk EG0022 events2 affected11 at risk EG003
Paranoia	Psychiatric disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected8 at risk EG0020 events0 affected11 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected8 at risk EG0020 events0 affected11 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected8 at risk EG0021 events1 affected11 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected8 at risk EG0020 events0 affected11 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected8 at risk EG0020 events0 affected11 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected8 at risk EG0020 events0 affected11 at risk EG003
Fatigue	General disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0011 events1 affected8 at risk EG0021 events1 affected11 at risk EG003
Pyrexia	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected8 at risk EG0021 events1 affected11 at risk EG003
Energy increased	General disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected8 at risk EG0020 events0 affected11 at risk EG003
Hyperhydrosis	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0003 events3 affected14 at risk EG0010 events0 affected8 at risk EG0020 events0 affected11 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected8 at risk EG0020 events0 affected11 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected8 at risk EG0020 events0 affected11 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0002 events1 affected14 at risk EG0010 events0 affected8 at risk EG0020 events0 affected11 at risk EG003
Viral upper respiratory tract infection	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected8 at risk EG0020 events0 affected11 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected8 at risk EG0020 events0 affected11 at risk EG003
Palpitations	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected8 at risk EG0020 events0 affected11 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected8 at risk EG0020 events0 affected11 at risk EG003
Blood pressure increased	Investigations	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected8 at risk EG0020 events0 affected11 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected8 at risk EG0021 events1 affected11 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected8 at risk EG0021 events1 affected11 at risk EG003
Onychomycosis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected8 at risk EG0021 events1 affected11 at risk EG003
Oral herpes	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected8 at risk EG0020 events0 affected11 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected8 at risk EG0020 events0 affected11 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected8 at risk EG0024 events4 affected11 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected8 at risk EG0021 events1 affected11 at risk EG003
Joint stiffness	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected8 at risk EG0021 events1 affected11 at risk EG003
Dyskinesia	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected8 at risk EG0020 events0 affected11 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected8 at risk EG0021 events1 affected11 at risk EG003
Restless legs syndrome	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected8 at risk EG0020 events0 affected11 at risk EG003
Influenza like illness	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected8 at risk EG0021 events1 affected11 at risk EG003
Oedema peripheral	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected8 at risk EG0021 events1 affected11 at risk EG003
Depressed mood	Psychiatric disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected8 at risk EG0021 events1 affected11 at risk EG003
Hallucination, auditory	Psychiatric disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected8 at risk EG0020 events0 affected11 at risk EG003
Arthropod bite	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected8 at risk EG0020 events0 affected11 at risk EG003
Wound	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected8 at risk EG0023 events1 affected11 at risk EG003
Orthostatic hypotension	Vascular disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected8 at risk EG0020 events0 affected11 at risk EG003
Hot flush	Vascular disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected8 at risk EG0020 events0 affected11 at risk EG003
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected8 at risk EG0021 events1 affected11 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected8 at risk EG0021 events1 affected11 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected8 at risk EG0021 events1 affected11 at risk EG003
Nasal discomfort	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected8 at risk EG0021 events1 affected11 at risk EG003

ID	Term
D050198	Phenoxypropanolamines
D011412	Propanolamines
D000605	Amino Alcohols
D000438	Alcohols
D009930	Organic Chemicals
D020005	Propanols
D000588	Amines

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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	2	14	12	14
EG001	Placebo	Subjects were randomized to receive matching placebo tablets once daily for 24 weeks during Part 1.	8	1	8	7	8
EG002	Tesofensine/Metoprolol -> Tesofensine/Metoprolol	Subjects who received co-administration of 0.5 mg tesofensine/50 mg metoprolol (active medication) once daily for 24 weeks during Part 1 continued to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.	11	1	11	11	11
EG003	Placebo -> Tesofensine/Metoprolol	Subjects who received matching placebo tablets once daily for 24 weeks during Part 1 were switched to receive co-administration of 0.5 mg tesofensine/50 mg metoprolol once daily for an additional 24 weeks in Part 2.	6	0	6	6	6