A Study to Test Whether Different Doses of BI 456906 Help... | NCT04667377

ID	Type	Description	Link
2020-002479-37	EudraCT Number

A Study to Test Whether Different Doses of BI 456906 Help... | NCT04667377 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Intervention Names
0.6 mg BI 456906	Experimental	Drug: BI 456906
Placebo group	Placebo Comparator	Drug: Placebo
2.4 mg BI456906	Experimental	Drug: BI 456906
3.6 mg BI 456906	Experimental	Drug: BI 456906
4.8 mg BI 456906	Experimental	Drug: BI 456906

Name	Type	Description	Arm Group Labels	Other Names
BI 456906	Drug	BI 456906	0.6 mg BI 456906 2.4 mg BI456906 3.6 mg BI 456906 4.8 mg BI 456906

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage Change in Body Weight From Baseline to Week 46	Percentage change in body weight from baseline to Week 46 was modeled using a mixed model for repeated measures (MMRM) with fixed effects for baseline body weight as a continuous linear covariate, and treatment, gender, visit, treatment by visit interaction and baseline by visit interaction as factors, using visit (Week 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36, 40, and 46) as repeated measures, an unstructured covariance matrix to model within subject measurements, adjusted mean (standard error) at Week 46 is reported. For analysis, all available post-baseline body weight measurements (on- and off-treatment) were used, except those for participants who discontinued treatment early due to COVID-19. For these participants only on-treatment values were used. That is, a hypothetical strategy was used for intercurrent event (ICE) "COVID-19 pandemic-related early treatment discontinuation", a treatment policy strategy for ICE "non-pandemic-related early treatment discontinuation".	Baseline, Week 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36, 40, and 46.

Secondary Outcomes

Measure	Description	Time Frame
Weight Loss of ≥ 5% of Baseline Weight at Week 46	Weight loss of greater than or equal to 5 percent (≥5%) of baseline weight at Week 46 (yes/no), reported as percentage of participants who achieved a weight loss of ≥5% of baseline weight at Week 46. For analysis, all available post-baseline body weight measurements (on- and off-treatment) were used, except those for participants who discontinued treatment early due to COVID-19. For these participants only on-treatment values were used. Percentages were rounded to one decimal place.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Adult ≥ 18 years and < 75 years of age at screening
Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.
Obesity or Overweight defined as BMI ≥27 kg/m2 at screening
A minimum absolute body weight of 70 kg for females and 80 kg for males at screening
Male or female participants. Women of childbearing potential (WOCBP)1 must be willing and able to use two forms of effective contraception where at least one form is highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.
Patients must have undergone at least one previous unsuccessful nonsurgical weight-loss attempt per investigator's judgement

Exclusion criteria:

Body weight change of over +/- 5% or more in the past 12 weeks prior to randomization. There must be documentation of weight in the past 12 weeks before randomization.
Obesity induced by an endocrinologic disorder (i.e. Cushing Syndrome, hypogonadism, growh hormone deficiency. However, well controlled hypothyroidism, polycystic ovarian disease are still allowed)
A HbA1c ≥ 6.5% at screening or diagnosed with type 1 or type 2 diabetes mellitus
Exposure to Glucagon like peptide-1 receptor agonist (GLP-1Ra) based therapies within three months prior to screening
Any suicidal behaviour in the past 2 years, any suicidal ideation of type 4 or 5 in the Columbia-Suicide Severity Rating Scale (CSSRS) within 3 months before screening, or during screening period
History of major depressive disorder within 2 years before randomization
Major depressive symptoms (defined as a screening Patient Health Questionnaire-9 [PHQ-9] score ≥15) at screening and/or during screening period
Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders at screening
Chronic or relevant acute infections (including but not limited to respiratory tract infections, urinary tract infection, bladder infection, enterocolitis, abscess, tuberculosis, meningitis, influenza, Epstein-Barr virus, HIV/AIDS, and hepatitis B or C, and severe acute respiratory syndrome coronavirus type 19 (SARS CoV-2) (as confirmed by Polychain reaction (PCR) test)), within 2 weeks from screening or during screening.
Further exclusion criteria apply

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
Diablo Clinical Research		Walnut Creek	California	94598	United States
L-MARC Research Center

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
42331726	Derived	Ekinci EI, Maldonado SG, Unseld A, Martinez JA, Hennige AM, Schoelch C. Dual Glucagon and GLP-1 Receptor Agonist Survodutide Improves Biomarkers of Beta-Cell Function and Insulin Sensitivity in People With Type 2 Diabetes or Living With Overweight/Obesity. Diabetes Obes Metab. 2026 Jun 22. doi: 10.1111/dom.70861. Online ahead of print.
39821928

Label	URL
Related Info	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	0.6 mg BI 456906 - Planned Maintenance Treatment (Maintenance Dose Assigned at Randomisation)	Participants with obesity or overweight were administered a solution for injection of BI 456906, by a weekly subcutaneous injection of two syringes (0.5 mL filling volume per syringe) on the same injection day, of 0.3 mg on Week 1 and 2, and 0.6 mg on Week 3 to Week 20 (dose escalation phase, with fixed dose escalation from Week 1 to Week 10 and flexible dose escalation from Week 11 to Week 20). From Week 21 to Week 46 (maintenance dosing phase) participants stayed on the dose of 0.6 mg BI 456906. Participant not tolerating the assigned dose escalation schedule due to gastrointestinal adverse events had the option of dose adjustment during the flexible part of the dose escalation phase (Week 11 - 20) which could lead to a maintenance dose lower than the dose the participant was randomised to.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Apr 29, 2022	Oct 4, 2023

Type	Comment	Reasons
Other not specified below		FG0003 subjects FG0013 subjects FG0022 subjects FG0031 subjects FG0043 subjects
Protocol Violation		FG0002 subjects FG0012 subjects FG0020 subjects FG0032 subjects FG004
Burden of study procedures		FG0002 subjects FG0011 subjects FG0021 subjects FG0031 subjects FG004
Change of residence		FG0000 subjects FG0010 subjects FG0021 subjects FG0030 subjects FG004
Perceived lack of efficacy		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004
Adverse Event		FG0009 subjects FG00110 subjects FG00212 subjects FG00317 subjects FG004
Adverse event: COVID-infection		FG0004 subjects FG0011 subjects FG0022 subjects FG0031 subjects FG004
Not treated		FG0001 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004
Withdrawal by Subject		FG0002 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004
Lost to Follow-up		FG0000 subjects FG0011 subjects FG0020 subjects FG0030 subjects FG004

Maintenance Period

Type	Comment	Milestone Data
STARTED		FG00055 subjects FG00160 subjects FG00259 subjects FG00355 subjects FG00457 subjects
COMPLETED	Completed = Completed trial medication	FG00047 subjects FG00145 subjects FG00248 subjects FG00347 subjects
NOT COMPLETED		FG0008 subjects FG00115 subjects FG00211 subjects FG0038 subjects FG004

Type	Comment	Reasons
Perceived lack of efficacy		FG0000 subjects FG0012 subjects FG0021 subjects FG003

Arm/Group Information

ID	Title	Description
BG000	0.6 mg BI 456906 - Planned Maintenance Treatment (Maintenance Dose Assigned at Randomisation)	Participants with obesity or overweight were administered a solution for injection of BI 456906, by a weekly subcutaneous injection of two syringes (0.5 mL filling volume per syringe) on the same injection day, of 0.3 mg on Week 1 and 2, and 0.6 mg on Week 3 to Week 20 (dose escalation phase, with fixed dose escalation from Week 1 to Week 10 and flexible dose escalation from Week 11 to Week 20). From Week 21 to Week 46 (maintenance dosing phase) participants stayed on the dose of 0.6 mg BI 456906. Participant not tolerating the assigned dose escalation schedule due to gastrointestinal adverse events had the option of dose adjustment during the flexible part of the dose escalation phase (Week 11 - 20) which could lead to a maintenance dose lower than the dose the participant was randomised to.
BG001	2.4 mg BI 456906 - Planned Maintenance Treatment	Participants with obesity or overweight were administered a solution for injection of BI 456906, by a weekly subcutaneous injection of two syringes (0.5 mL filling volume per syringe) on the same injection day, of 0.3 mg on Week 1 and Week 2, 0.6 mg on Week 3 and Week 4, 0.9 mg on Week 5 and Week 6, 1.2 mg on Week 7 to Week 10, 1.8 mg on Week 11 to Week 14 and 2.4 mg on Week 15 to Week 20 (dose escalation phase, with fixed dose escalation from Week 1 to Week 10 and flexible dose escalation from Week 11 to Week 20). From Week 21 to Week 46 (maintenance dosing phase) participants stayed on the dose of 2.4 mg BI 456906. Participant not tolerating the assigned dose escalation schedule due to gastrointestinal adverse events had the option of dose adjustment during the flexible part of the dose escalation phase (Week 11 - 20) which could lead to a maintenance dose lower than the dose the participant was randomised to.
BG002	3.6 mg BI 456906 - Planned Maintenance Treatment	Participants with obesity or overweight were administered a solution for injection of BI 456906, by a weekly subcutaneous injection of two syringes (0.5 mL filling volume per syringe) on the same injection day, of 0.3 mg on Week 1 and Week 2, 0.6 mg on Week 3 and Week 4, 0.9 mg on Week 5 and Week 6, 1.2 mg on Week 7 to Week 10, 1.8 mg on Week 11 and Week 12, 2.4 mg on Week 13 and Week 14, 3.0 mg on Week 15 and Week 16, and 3.6 mg on Week 17 to Week 20 (dose escalation phase, with fixed dose escalation from Week 1 to Week 10 and flexible dose escalation from Week 11 to Week 20). From Week 21 to Week 46 (maintenance dosing phase) participants stayed on the dose of 3.6 mg BI 456906. Participant not tolerating the assigned dose escalation schedule due to gastrointestinal adverse events had the option of dose adjustment during the flexible part of the dose escalation phase (Week 11 - 20) which could lead to a maintenance dose lower than the dose the participant was randomised to.
BG003	4.8 mg BI 456906 - Planned Maintenance Treatment	Participants with obesity or overweight were administered a solution for injection of BI 456906, by a weekly subcutaneous injection of two syringes (0.5 mL filling volume per syringe) on the same injection day, of 0.3 mg on Week 1 and Week 2, 0.6 mg on Week 3 and Week 4, 0.9 mg on Week 5 and Week 6, 1.2 mg on Week 7 and Week 8, 1.8 mg on Week 9 and Week 10, 2.4 mg on Week 11 and Week 12, 3.3 mg on Week 13 and Week 14, 4.2 mg on Week 15 and Week 16, and 4.8 mg on Week 17 to Week 20 (dose escalation phase, with fixed dose escalation from Week 1 to Week 10 and flexible dose escalation from Week 11 to Week 20). From Week 21 to Week 46 (maintenance dosing phase) participants stayed on the dose of 4.8 mg BI 456906. Participant not tolerating the assigned dose escalation schedule due to gastrointestinal adverse events had the option of dose adjustment during the flexible part of the dose escalation phase (Week 11 - 20) which could lead to a maintenance dose lower than the dose the participant was randomised to.
BG004	Placebo	Participants with obesity or overweight were administered a solution for injection of Placebo, by a weekly subcutaneous injection of two syringes on the same injection day, for 46 weeks.
BG005	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00048.6± 12.6 BG00149.0± 13.1 BG00250.3± 11.8 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00051 BG00154 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0003 BG0011 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Body weight at baseline

Mean

Standard Deviation

Kilogram (kg)

Title

Denominators

Categories

Title	Measurements
	BG000106.98± 18.71 BG001106.57± 22.97 BG002

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

Percentage Change in Body Weight From Baseline to Week 46

Percentage change in body weight from baseline to Week 46 was modeled using a mixed model for repeated measures (MMRM) with fixed effects for baseline body weight as a continuous linear covariate, and treatment, gender, visit, treatment by visit interaction and baseline by visit interaction as factors, using visit (Week 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36, 40, and 46) as repeated measures, an unstructured covariance matrix to model within subject measurements, adjusted mean (standard error) at Week 46 is reported. For analysis, all available post-baseline body weight measurements (on- and off-treatment) were used, except those for participants who discontinued treatment early due to COVID-19. For these participants only on-treatment values were used. That is, a hypothetical strategy was used for intercurrent event (ICE) "COVID-19 pandemic-related early treatment discontinuation", a treatment policy strategy for ICE "non-pandemic-related early treatment discontinuation".

Full analysis set (all randomised participants who received at least one dose of study treatment and who have analysable data for at least one efficacy endpoint) using planned maintenance treatment. Number of participants analysed = Participants with available data for the outcome measure.

Posted

Least Squares Mean

Standard Error

Percentage change

Baseline, Week 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36, 40, and 46.

ID	Title	Description
OG000	0.6 mg BI 456906 - Planned Maintenance Treatment (Maintenance Dose Assigned at Randomisation)	Participants with obesity or overweight were administered a solution for injection of BI 456906, by a weekly subcutaneous injection of two syringes (0.5 mL filling volume per syringe) on the same injection day, of 0.3 mg on Week 1 and 2, and 0.6 mg on Week 3 to Week 20 (dose escalation phase, with fixed dose escalation from Week 1 to Week 10 and flexible dose escalation from Week 11 to Week 20). From Week 21 to Week 46 (maintenance dosing phase) participants stayed on the dose of 0.6 mg BI 456906. Participant not tolerating the assigned dose escalation schedule due to gastrointestinal adverse events had the option of dose adjustment during the flexible part of the dose escalation phase (Week 11 - 20) which could lead to a maintenance dose lower than the dose the participant was randomised to.
OG001	2.4 mg BI 456906 - Planned Maintenance Treatment	Participants with obesity or overweight were administered a solution for injection of BI 456906, by a weekly subcutaneous injection of two syringes (0.5 mL filling volume per syringe) on the same injection day, of 0.3 mg on Week 1 and Week 2, 0.6 mg on Week 3 and Week 4, 0.9 mg on Week 5 and Week 6, 1.2 mg on Week 7 to Week 10, 1.8 mg on Week 11 to Week 14 and 2.4 mg on Week 15 to Week 20 (dose escalation phase, with fixed dose escalation from Week 1 to Week 10 and flexible dose escalation from Week 11 to Week 20). From Week 21 to Week 46 (maintenance dosing phase) participants stayed on the dose of 2.4 mg BI 456906. Participant not tolerating the assigned dose escalation schedule due to gastrointestinal adverse events had the option of dose adjustment during the flexible part of the dose escalation phase (Week 11 - 20) which could lead to a maintenance dose lower than the dose the participant was randomised to.
OG002	3.6 mg BI 456906 - Planned Maintenance Treatment	Participants with obesity or overweight were administered a solution for injection of BI 456906, by a weekly subcutaneous injection of two syringes (0.5 mL filling volume per syringe) on the same injection day, of 0.3 mg on Week 1 and Week 2, 0.6 mg on Week 3 and Week 4, 0.9 mg on Week 5 and Week 6, 1.2 mg on Week 7 to Week 10, 1.8 mg on Week 11 and Week 12, 2.4 mg on Week 13 and Week 14, 3.0 mg on Week 15 and Week 16, and 3.6 mg on Week 17 to Week 20 (dose escalation phase, with fixed dose escalation from Week 1 to Week 10 and flexible dose escalation from Week 11 to Week 20). From Week 21 to Week 46 (maintenance dosing phase) participants stayed on the dose of 3.6 mg BI 456906. Participant not tolerating the assigned dose escalation schedule due to gastrointestinal adverse events had the option of dose adjustment during the flexible part of the dose escalation phase (Week 11 - 20) which could lead to a maintenance dose lower than the dose the participant was randomised to.

Units	Counts
Participants	OG00076 OG00178 OG00276 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-6.19± 1.07 OG001-12.51± 1.01 OG002-13.22± 1.04 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001 OG002 OG003 OG004	A flat vs. non-flat dose-response relationship across the 4 doses of BI 456906 and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different potential dose-response patterns (Linear, Exponential, Emax1, Emax2, Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 2.5%).	MCP-Mod - Linear model fit		<0.0001	P-value is adjusted for multiplicity.													Other

Secondary

Weight Loss of ≥ 5% of Baseline Weight at Week 46

Weight loss of greater than or equal to 5 percent (≥5%) of baseline weight at Week 46 (yes/no), reported as percentage of participants who achieved a weight loss of ≥5% of baseline weight at Week 46. For analysis, all available post-baseline body weight measurements (on- and off-treatment) were used, except those for participants who discontinued treatment early due to COVID-19. For these participants only on-treatment values were used. Percentages were rounded to one decimal place.

Posted

Number

Percentage of participants

At baseline and at Week 46.

ID	Title	Description
OG000	0.6 mg BI 456906 - Planned Maintenance Treatment (Maintenance Dose Assigned at Randomisation)	Participants with obesity or overweight were administered a solution for injection of BI 456906, by a weekly subcutaneous injection of two syringes (0.5 mL filling volume per syringe) on the same injection day, of 0.3 mg on Week 1 and 2, and 0.6 mg on Week 3 to Week 20 (dose escalation phase, with fixed dose escalation from Week 1 to Week 10 and flexible dose escalation from Week 11 to Week 20). From Week 21 to Week 46 (maintenance dosing phase) participants stayed on the dose of 0.6 mg BI 456906. Participant not tolerating the assigned dose escalation schedule due to gastrointestinal adverse events had the option of dose adjustment during the flexible part of the dose escalation phase (Week 11 - 20) which could lead to a maintenance dose lower than the dose the participant was randomised to.

Secondary

Weight Loss of ≥ 10% of Baseline Weight at Week 46

Weight loss of greater than or equal to 10 percent (≥10%) of baseline weight at Week 46 (yes/no), reported as percentage of participants who achieved a weight loss of ≥10% of baseline weight at Week 46. For analysis, all available post-baseline body weight measurements (on- and off-treatment) were used, except those for participants who discontinued treatment early due to COVID-19. For these participants only on-treatment values were used. Percentages were rounded to one decimal place.

Posted

Number

Percentage of participants

At baseline and at Week 46.

ID	Title	Description
OG000	0.6 mg BI 456906 - Planned Maintenance Treatment (Maintenance Dose Assigned at Randomisation)	Participants with obesity or overweight were administered a solution for injection of BI 456906, by a weekly subcutaneous injection of two syringes (0.5 mL filling volume per syringe) on the same injection day, of 0.3 mg on Week 1 and 2, and 0.6 mg on Week 3 to Week 20 (dose escalation phase, with fixed dose escalation from Week 1 to Week 10 and flexible dose escalation from Week 11 to Week 20). From Week 21 to Week 46 (maintenance dosing phase) participants stayed on the dose of 0.6 mg BI 456906. Participant not tolerating the assigned dose escalation schedule due to gastrointestinal adverse events had the option of dose adjustment during the flexible part of the dose escalation phase (Week 11 - 20) which could lead to a maintenance dose lower than the dose the participant was randomised to.

Secondary

Weight Loss of ≥ 15% of Baseline Weight at Week 46

Weight loss of greater than or equal to 15 percent (≥15%) of baseline weight at Week 46 (yes/no), reported as percentage of participants who achieved a weight loss of ≥15% of baseline weight at Week 46. For analysis, all available post-baseline body weight measurements (on- and off-treatment) were used, except those for participants who discontinued treatment early due to COVID-19. For these participants only on-treatment values were used. Percentages were rounded to one decimal place.

Posted

Number

Percentage of particpants

At baseline and at Week 46.

ID	Title	Description
OG000	0.6 mg BI 456906 - Planned Maintenance Treatment (Maintenance Dose Assigned at Randomisation)	Participants with obesity or overweight were administered a solution for injection of BI 456906, by a weekly subcutaneous injection of two syringes (0.5 mL filling volume per syringe) on the same injection day, of 0.3 mg on Week 1 and 2, and 0.6 mg on Week 3 to Week 20 (dose escalation phase, with fixed dose escalation from Week 1 to Week 10 and flexible dose escalation from Week 11 to Week 20). From Week 21 to Week 46 (maintenance dosing phase) participants stayed on the dose of 0.6 mg BI 456906. Participant not tolerating the assigned dose escalation schedule due to gastrointestinal adverse events had the option of dose adjustment during the flexible part of the dose escalation phase (Week 11 - 20) which could lead to a maintenance dose lower than the dose the participant was randomised to.

Secondary

Absolute Change in Body Weight From Baseline to Week 46

Absolute change in body weight from baseline to Week 46 was modeled using a mixed model for repeated measures (MMRM) with fixed effects for baseline body weight as a continuous linear covariate, and treatment, gender, visit, treatment by visit interaction and baseline by visit interaction as factors, using visit (Week 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36, 40, and 46) as repeated measures and an unstructured covariance matrix to model within subject measurements, adjusted mean (standard error) at Week 46 is reported. MMRM analysis was performed on the FAS, using planned maintenance treatment (dose assigned at randomisation) and including only on-treatment data, regardless of whether early treatment discontinuation was COVID-19 related.

Full analysis set (FAS, all randomised participants who received at least one dose of study treatment and who have analysable data for at least one efficacy endpoint), using planned maintenance treatment. Number of participants analysed = Participants with available data for the outcome measure.

Posted

Least Squares Mean

Standard Error

Kilogram (kg)

Baseline, Week 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36, 40, and 46.

ID	Title	Description
OG000	0.6 mg BI 456906 - Planned Maintenance Treatment (Maintenance Dose Assigned at Randomisation)	Participants with obesity or overweight were administered a solution for injection of BI 456906, by a weekly subcutaneous injection of two syringes (0.5 mL filling volume per syringe) on the same injection day, of 0.3 mg on Week 1 and 2, and 0.6 mg on Week 3 to Week 20 (dose escalation phase, with fixed dose escalation from Week 1 to Week 10 and flexible dose escalation from Week 11 to Week 20). From Week 21 to Week 46 (maintenance dosing phase) participants stayed on the dose of 0.6 mg BI 456906. Participant not tolerating the assigned dose escalation schedule due to gastrointestinal adverse events had the option of dose adjustment during the flexible part of the dose escalation phase (Week 11 - 20) which could lead to a maintenance dose lower than the dose the participant was randomised to.

Secondary

Absolute Change in Waist Circumference From Baseline to Week 46

Absolute change in waist circumference from baseline to Week 46 was modeled using a mixed model for repeated measures (MMRM) with fixed effects for baseline waist circumference as a continuous linear covariate, and treatment, gender, visit, treatment by visit interaction and baseline by visit interaction as factors, using visit (Week 6, 12, 18, 24, 32, 40, and 46) as repeated measures and an unstructured covariance matrix to model within subject measurements, adjusted mean (standard error) at Week 46 is reported. MMRM analysis was performed on the FAS, using planned maintenance treatment (dose assigned at randomisation) and including only on-treatment data, regardless of whether early treatment discontinuation was COVID-19 related.

Posted

Least Squares Mean

Standard Error

Centimeter (cm)

Baseline, Week 6, 12, 18, 24, 32, 40, and 46.

ID	Title	Description
OG000	0.6 mg BI 456906 - Planned Maintenance Treatment (Maintenance Dose Assigned at Randomisation)	Participants with obesity or overweight were administered a solution for injection of BI 456906, by a weekly subcutaneous injection of two syringes (0.5 mL filling volume per syringe) on the same injection day, of 0.3 mg on Week 1 and 2, and 0.6 mg on Week 3 to Week 20 (dose escalation phase, with fixed dose escalation from Week 1 to Week 10 and flexible dose escalation from Week 11 to Week 20). From Week 21 to Week 46 (maintenance dosing phase) participants stayed on the dose of 0.6 mg BI 456906. Participant not tolerating the assigned dose escalation schedule due to gastrointestinal adverse events had the option of dose adjustment during the flexible part of the dose escalation phase (Week 11 - 20) which could lead to a maintenance dose lower than the dose the participant was randomised to.

Secondary

Absolute Change in Systolic Blood Pressure From Baseline to Week 46

Absolute change in systolic blood pressure from baseline to Week 46 was modeled using a mixed model for repeated measures (MMRM) with fixed effects for baseline systolic blood pressure as a continuous linear covariate, and treatment, gender, visit, treatment by visit interaction and baseline by visit interaction as factors, using visit Week 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36, 40, and 46) as repeated measures and an unstructured covariance matrix to model within subject measurements, adjusted mean (standard error) at Week 46 is reported. MMRM analysis was performed on the FAS, using planned maintenance treatment (dose assigned at randomisation) and including only on-treatment data, regardless of whether early treatment discontinuation was COVID-19 related.

Posted

Least Squares Mean

Standard Error

Millimeter of mercury (mmHg)

Baseline, Week 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36, 40, and 46.

ID	Title	Description
OG000	0.6 mg BI 456906 - Planned Maintenance Treatment (Maintenance Dose Assigned at Randomisation)	Participants with obesity or overweight were administered a solution for injection of BI 456906, by a weekly subcutaneous injection of two syringes (0.5 mL filling volume per syringe) on the same injection day, of 0.3 mg on Week 1 and 2, and 0.6 mg on Week 3 to Week 20 (dose escalation phase, with fixed dose escalation from Week 1 to Week 10 and flexible dose escalation from Week 11 to Week 20). From Week 21 to Week 46 (maintenance dosing phase) participants stayed on the dose of 0.6 mg BI 456906. Participant not tolerating the assigned dose escalation schedule due to gastrointestinal adverse events had the option of dose adjustment during the flexible part of the dose escalation phase (Week 11 - 20) which could lead to a maintenance dose lower than the dose the participant was randomised to.

Secondary

Absolute Change in Diastolic Blood Pressure From Baseline to Week 46

Absolute change in diastolic blood pressure from baseline to Week 46 was modeled using a mixed model for repeated measures (MMRM) with fixed effects for baseline diastolic blood pressure as a continuous linear covariate, and treatment, gender, visit, treatment by visit interaction and baseline by visit interaction as factors, using visit Week 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36, 40, and 46) as repeated measures and an unstructured covariance matrix to model within subject measurements, adjusted mean (standard error) at Week 46 is reported. MMRM analysis was performed on the FAS, using planned maintenance treatment (dose assigned at randomisation) and including only on-treatment data, regardless of whether early treatment discontinuation was COVID-19 related.

Posted

Least Squares Mean

Standard Error

Millimeter of mercury (mmHg)

Baseline, Week 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36, 40, and 46.

ID	Title	Description
OG000	0.6 mg BI 456906 - Planned Maintenance Treatment (Maintenance Dose Assigned at Randomisation)	Participants with obesity or overweight were administered a solution for injection of BI 456906, by a weekly subcutaneous injection of two syringes (0.5 mL filling volume per syringe) on the same injection day, of 0.3 mg on Week 1 and 2, and 0.6 mg on Week 3 to Week 20 (dose escalation phase, with fixed dose escalation from Week 1 to Week 10 and flexible dose escalation from Week 11 to Week 20). From Week 21 to Week 46 (maintenance dosing phase) participants stayed on the dose of 0.6 mg BI 456906. Participant not tolerating the assigned dose escalation schedule due to gastrointestinal adverse events had the option of dose adjustment during the flexible part of the dose escalation phase (Week 11 - 20) which could lead to a maintenance dose lower than the dose the participant was randomised to.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	0.6 mg BI 456906 - Actual Maintenance Treatment	Participants with obesity or overweight were administered a solution for injection of BI 456906, by a weekly subcutaneous injection of two syringes (0.5 mL filling volume per syringe) on the same injection day, of 0.3 mg on Week 1 and 2, and 0.6 mg on Week 3 to Week 20 (dose escalation phase, with fixed dose escalation from Week 1 to Week 10 and flexible dose escalation from Week 11 to Week 20). From Week 21 to Week 46 (maintenance dosing phase) participants stayed on the dose of 0.6 mg BI 456906. Participant not tolerating the assigned dose escalation schedule due to gastrointestinal adverse events had the option of dose adjustment during the flexible part of the dose escalation phase (Week 11 - 20) which could lead to a maintenance dose lower than the dose the participant was randomised to.	92	2	92	70	92
EG001	2.4 mg BI 456906 - Actual Maintenance Treatment	Participants with obesity or overweight were administered a solution for injection of BI 456906, by a weekly subcutaneous injection of two syringes (0.5 mL filling volume per syringe) on the same injection day, of 0.3 mg on Week 1 and Week 2, 0.6 mg on Week 3 and Week 4, 0.9 mg on Week 5 and Week 6, 1.2 mg on Week 7 to Week 10, 1.8 mg on Week 11 to Week 14 and 2.4 mg on Week 15 to Week 20 (dose escalation phase, with fixed dose escalation from Week 1 to Week 10 and flexible dose escalation from Week 11 to Week 20). From Week 21 to Week 46 (maintenance dosing phase) participants stayed on the dose of 2.4 mg BI 456906. Participant not tolerating the assigned dose escalation schedule due to gastrointestinal adverse events had the option of dose adjustment during the flexible part of the dose escalation phase (Week 11 - 20) which could lead to a maintenance dose lower than the dose the participant was randomised to.	92	3	92	79	92
EG002	3.6 mg BI 456906 - Actual Maintenance Treatment	Participants with obesity or overweight were administered a solution for injection of BI 456906, by a weekly subcutaneous injection of two syringes (0.5 mL filling volume per syringe) on the same injection day, of 0.3 mg on Week 1 and Week 2, 0.6 mg on Week 3 and Week 4, 0.9 mg on Week 5 and Week 6, 1.2 mg on Week 7 to Week 10, 1.8 mg on Week 11 and Week 12, 2.4 mg on Week 13 and Week 14, 3.0 mg on Week 15 and Week 16, and 3.6 mg on Week 17 to Week 20 (dose escalation phase, with fixed dose escalation from Week 1 to Week 10 and flexible dose escalation from Week 11 to Week 20). From Week 21 to Week 46 (maintenance dosing phase) participants stayed on the dose of 3.6 mg BI 456906. Participant not tolerating the assigned dose escalation schedule due to gastrointestinal adverse events had the option of dose adjustment during the flexible part of the dose escalation phase (Week 11 - 20) which could lead to a maintenance dose lower than the dose the participant was randomised to.	71	4	71	64	71
EG003	4.8 mg BI 456906 - Actual Maintenance Treatment	Participants with obesity or overweight were administered a solution for injection of BI 456906, by a weekly subcutaneous injection of two syringes (0.5 mL filling volume per syringe) on the same injection day, of 0.3 mg on Week 1 and Week 2, 0.6 mg on Week 3 and Week 4, 0.9 mg on Week 5 and Week 6, 1.2 mg on Week 7 and Week 8, 1.8 mg on Week 9 and Week 10, 2.4 mg on Week 11 and Week 12, 3.3 mg on Week 13 and Week 14, 4.2 mg on Week 15 and Week 16, and 4.8 mg on Week 17 to Week 20 (dose escalation phase, with fixed dose escalation from Week 1 to Week 10 and flexible dose escalation from Week 11 to Week 20). From Week 21 to Week 46 (maintenance dosing phase) participants stayed on the dose of 4.8 mg BI 456906. Participant not tolerating the assigned dose escalation schedule due to gastrointestinal adverse events had the option of dose adjustment during the flexible part of the dose escalation phase (Week 11 - 20) which could lead to a maintenance dose lower than the dose the participant was randomised to.	54	4	54	46	54
EG004	Placebo	Participants with obesity or overweight were administered a solution for injection of Placebo, by a weekly subcutaneous injection of two syringes on the same injection day, for 46 weeks.	77	5	77	48	77

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Deafness	Ear and labyrinth disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0011 affected92 at risk EG0020 affected71 at risk EG0030 affected54 at risk EG0040 affected77 at risk
Nausea	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected92 at risk EG0010 affected92 at risk EG0020 affected71 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected92 at risk EG0010 affected92 at risk EG0020 affected71 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0010 affected92 at risk EG0020 affected71 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0010 affected92 at risk EG0020 affected71 at risk EG003
COVID-19 pneumonia	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0010 affected92 at risk EG0020 affected71 at risk EG003
Cellulitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0011 affected92 at risk EG0020 affected71 at risk EG003
Tonsillitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0010 affected92 at risk EG0020 affected71 at risk EG003
Tooth abscess	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0010 affected92 at risk EG0020 affected71 at risk EG003
Incisional hernia	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0010 affected92 at risk EG0021 affected71 at risk EG003
Wrist fracture	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0010 affected92 at risk EG0021 affected71 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected92 at risk EG0010 affected92 at risk EG0020 affected71 at risk EG003
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0010 affected92 at risk EG0020 affected71 at risk EG003
Bowen's disease	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0001 affected92 at risk EG0010 affected92 at risk EG0020 affected71 at risk EG003
Glioblastoma multiforme	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0010 affected92 at risk EG0020 affected71 at risk EG003
Intraductal proliferative breast lesion	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0010 affected92 at risk EG0021 affected71 at risk EG003
Malignant melanoma in situ	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0011 affected92 at risk EG0020 affected71 at risk EG003
Renal failure	Renal and urinary disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected92 at risk EG0010 affected92 at risk EG0020 affected71 at risk EG003
Endometrial hyperplasia	Reproductive system and breast disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0010 affected92 at risk EG0020 affected71 at risk EG003
Uterine prolapse	Reproductive system and breast disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0010 affected92 at risk EG0020 affected71 at risk EG003
Pulmonary congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0010 affected92 at risk EG0020 affected71 at risk EG003
Angioedema	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0010 affected92 at risk EG0021 affected71 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal distension	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0004 affected92 at risk EG0014 affected92 at risk EG0027 affected71 at risk EG0033 affected54 at risk EG0043 affected77 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0004 affected92 at risk EG00110 affected92 at risk EG0025 affected71 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0003 affected92 at risk EG0015 affected92 at risk EG0028 affected71 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG00011 affected92 at risk EG00119 affected92 at risk EG00222 affected71 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG00022 affected92 at risk EG00121 affected92 at risk EG00217 affected71 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0007 affected92 at risk EG0019 affected92 at risk EG0028 affected71 at risk EG003
Eructation	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0004 affected92 at risk EG0016 affected92 at risk EG0025 affected71 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0002 affected92 at risk EG0017 affected92 at risk EG00210 affected71 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 affected92 at risk EG0010 affected92 at risk EG0021 affected71 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG00036 affected92 at risk EG00160 affected92 at risk EG00245 affected71 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG00013 affected92 at risk EG00128 affected92 at risk EG00228 affected71 at risk EG003
Fatigue	General disorders	MedDRA 25.0	Systematic Assessment	EG0006 affected92 at risk EG0015 affected92 at risk EG00213 affected71 at risk EG003
Injection site bruising	General disorders	MedDRA 25.0	Systematic Assessment	EG0003 affected92 at risk EG0013 affected92 at risk EG0022 affected71 at risk EG003
COVID-19	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG00018 affected92 at risk EG00111 affected92 at risk EG00217 affected71 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0008 affected92 at risk EG0015 affected92 at risk EG0026 affected71 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0002 affected92 at risk EG0011 affected92 at risk EG0025 affected71 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0004 affected92 at risk EG0012 affected92 at risk EG0026 affected71 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG00011 affected92 at risk EG00110 affected92 at risk EG00216 affected71 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG00010 affected92 at risk EG0013 affected92 at risk EG0028 affected71 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0007 affected92 at risk EG0012 affected92 at risk EG0024 affected71 at risk EG003
Dizziness	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 affected92 at risk EG0018 affected92 at risk EG00210 affected71 at risk EG003
Headache	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0008 affected92 at risk EG0017 affected92 at risk EG00210 affected71 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 25.0	Systematic Assessment	EG0003 affected92 at risk EG0015 affected92 at risk EG0021 affected71 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0002 affected92 at risk EG0012 affected92 at risk EG0024 affected71 at risk EG003

Ancestor Terms

ID	Term
D050177	Overweight
D044343	Overnutrition
D009748	Nutrition Disorders
D009750	Nutritional and Metabolic Diseases
D001835	Body Weight
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Estimate Comment	Non-Inferiority Type	Non-Inferiority Comment
OG000 OG004	Logistic regression after multiple imputation. Analysis based on all available post-baseline body weight measurements (on-treatment (first intake of study drug until 28 days after last intake of study drug) and off-treatment), except those for participants who discontinued treatment early due to COVID-19. For these participants only on-treatment values were used.	Regression, Logistic	Logistic regression with treatment group and gender as factors and baseline body weight as a continuous linear covariate.	0.0015	P-value is considered nominal.	Odds Ratio (OR)	3.28	2-Sided	95	1.57	6.84	Odds ratio is calculated as BI 456906 / Placebo.	Other	Missing body weight measurements were multiply imputed using MMRM with treatment, gender, baseline body weight as factors. "Percentage change in body weight from baseline to Week 46" and "Body weight loss ≥ 5% at Week 46 (yes/no)" were derived per participant in each of the 1000 imputed datasets. Each dataset was analysed by a logistic regression. Multiple estimates from multiple imputation runs were summarised using Rubin's method.
OG001 OG004	Logistic regression after multiple imputation. Analysis based on all available post-baseline body weight measurements (on-treatment (first intake of study drug until 28 days after last intake of study drug) and off-treatment), except those for participants who discontinued treatment early due to COVID-19. For these participants only on-treatment values were used.	Regression, Logistic	Logistic regression with treatment group and gender as factors and baseline body weight as a continuous linear covariate.	<.0001	P-value is considered nominal.	Odds Ratio (OR)	8.83	2-Sided	95	4.00	19.46	Odds ratio is calculated as BI 456906 / Placebo.	Other	Missing body weight measurements were multiply imputed using MMRM with treatment, gender, baseline body weight as factors. "Percentage change in body weight from baseline to Week 46" and "Body weight loss ≥ 5% at Week 46 (yes/no)" were derived per participant in each of the 1000 imputed datasets. Each dataset was analysed by a logistic regression. Multiple estimates from multiple imputation runs were summarised using Rubin's method.
OG002 OG004	Logistic regression after multiple imputation. Analysis based on all available post-baseline body weight measurements (on-treatment (first intake of study drug until 28 days after last intake of study drug) and off-treatment), except those for participants who discontinued treatment early due to COVID-19. For these participants only on-treatment values were used.	Regression, Logistic	Logistic regression with treatment group and gender as factors and baseline body weight as a continuous linear covariate.	<.0001	P-value is considered nominal.	Odds Ratio (OR)	7.48	2-Sided	95	3.41	16.41	Odds ratio is calculated as BI 456906 / Placebo.	Other	Missing body weight measurements were multiply imputed using MMRM with treatment, gender, baseline body weight as factors. "Percentage change in body weight from baseline to Week 46" and "Body weight loss ≥ 5% at Week 46 (yes/no)" were derived per participant in each of the 1000 imputed datasets. Each dataset was analysed by a logistic regression. Multiple estimates from multiple imputation runs were summarised using Rubin's method.
OG003 OG004	Logistic regression after multiple imputation. Analysis based on all available post-baseline body weight measurements (on-treatment (first intake of study drug until 28 days after last intake of study drug) and off-treatment), except those for participants who discontinued treatment early due to COVID-19. For these participants only on-treatment values were used.	Regression, Logistic	Logistic regression with treatment group and gender as factors and baseline body weight as a continuous linear covariate.	<.0001	P-value is considered nominal.	Odds Ratio (OR)	10.77	2-Sided	95	4.77	24.31	Odds ratio is calculated as BI 456906 / Placebo.	Other	Missing body weight measurements were multiply imputed using MMRM with treatment, gender, baseline body weight as factors. "Percentage change in body weight from baseline to Week 46" and "Body weight loss ≥ 5% at Week 46 (yes/no)" were derived per participant in each of the 1000 imputed datasets. Each dataset was analysed by a logistic regression. Multiple estimates from multiple imputation runs were summarised using Rubin's method.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Estimate Comment	Non-Inferiority Type	Non-Inferiority Comment
OG000 OG004	Logistic regression after multiple imputation. Analysis based on all available post-baseline body weight measurements (on-treatment (first intake of study drug until 28 days after last intake of study drug) and off-treatment), except those for participants who discontinued treatment early due to COVID-19. For these participants only on-treatment values were used.	Regression, Logistic	Logistic regression with treatment group and gender as factors and baseline body weight as a continuous linear covariate.	0.0120	P-value is considered nominal.	Odds Ratio (OR)	3.22	2-Sided	95	1.29	8.02	Odds ratio is calculated as BI 456906 / Placebo.	Other	Missing body weight measurements were multiply imputed using MMRM with treatment, gender, baseline body weight as factors. "Percentage change in body weight from baseline to Week 46" and "Body weight loss ≥ 10% at Week 46 (yes/no)" were derived per participant in each of the 1000 imputed datasets. Each dataset was analysed by a logistic regression. Multiple estimates from multiple imputation runs were summarised using Rubin's method.
OG001 OG004	Logistic regression after multiple imputation. Analysis based on all available post-baseline body weight measurements (on-treatment (first intake of study drug until 28 days after last intake of study drug) and off-treatment), except those for participants who discontinued treatment early due to COVID-19. For these participants only on-treatment values were used.	Regression, Logistic	Logistic regression with treatment group and gender as factors and baseline body weight as a continuous linear covariate.	<.0001	P-value is considered nominal.	Odds Ratio (OR)	10.62	2-Sided	95	4.36	25.86	Odds ratio is calculated as BI 456906 / Placebo.	Other	Missing body weight measurements were multiply imputed using MMRM with treatment, gender, baseline body weight as factors. "Percentage change in body weight from baseline to Week 46" and "Body weight loss ≥ 10% at Week 46 (yes/no)" were derived per participant in each of the 1000 imputed datasets. Each dataset was analysed by a logistic regression. Multiple estimates from multiple imputation runs were summarised using Rubin's method.
OG002 OG004	Logistic regression after multiple imputation. Analysis based on all available post-baseline body weight measurements (on-treatment (first intake of study drug until 28 days after last intake of study drug) and off-treatment), except those for participants who discontinued treatment early due to COVID-19. For these participants only on-treatment values were used.	Regression, Logistic	Logistic regression with treatment group and gender as factors and baseline body weight as a continuous linear covariate.	<.0001	P-value is considered nominal.	Odds Ratio (OR)	9.78	2-Sided	95	4.02	23.79	Odds ratio is calculated as BI 456906 / Placebo.	Other	Missing body weight measurements were multiply imputed using MMRM with treatment, gender, baseline body weight as factors. "Percentage change in body weight from baseline to Week 46" and "Body weight loss ≥ 10% at Week 46 (yes/no)" were derived per participant in each of the 1000 imputed datasets. Each dataset was analysed by a logistic regression. Multiple estimates from multiple imputation runs were summarised using Rubin's method.
OG003 OG004	Logistic regression after multiple imputation. Analysis based on all available post-baseline body weight measurements (on-treatment (first intake of study drug until 28 days after last intake of study drug) and off-treatment), except those for participants who discontinued treatment early due to COVID-19. For these participants only on-treatment values were used.	Regression, Logistic	Logistic regression with treatment group and gender as factors and baseline body weight as a continuous linear covariate.	<.0001	P-value is considered nominal.	Odds Ratio (OR)	14.50	2-Sided	95	5.91	35.55	Odds ratio is calculated as BI 456906 / Placebo.	Other	Missing body weight measurements were multiply imputed using MMRM with treatment, gender, baseline body weight as factors. "Percentage change in body weight from baseline to Week 46" and "Body weight loss ≥ 10% at Week 46 (yes/no)" were derived per participant in each of the 1000 imputed datasets. Each dataset was analysed by a logistic regression. Multiple estimates from multiple imputation runs were summarised using Rubin's method.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Estimate Comment	Non-Inferiority Type	Non-Inferiority Comment
OG000 OG004	Logistic regression after multiple imputation. Analysis based on all available post-baseline body weight measurements (on-treatment (first intake of study drug until 28 days after last intake of study drug) and off-treatment), except those for participants who discontinued treatment early due to COVID-19. For these participants only on-treatment values were used.	Regression, Logistic	Logistic regression with treatment group and gender as factors and baseline body weight as a continuous linear covariate.	0.2654	P-value is considered nominal.	Odds Ratio (OR)	2.13	2-Sided	95	0.56	8.02	Odds ratio is calculated as BI 456906 / Placebo.	Other	Missing body weight measurements were multiply imputed using MMRM with treatment, gender, baseline body weight as factors. "Percentage change in body weight from baseline to Week 46" and "Body weight loss ≥ 15% at Week 46 (yes/no)" were derived per participant in each of the 1000 imputed datasets. Each dataset was analysed by a logistic regression. Multiple estimates from multiple imputation runs were summarised using Rubin's method.
OG001 OG004	Logistic regression after multiple imputation. Analysis based on all available post-baseline body weight measurements (on-treatment (first intake of study drug until 28 days after last intake of study drug) and off-treatment), except those for participants who discontinued treatment early due to COVID-19. For these participants only on-treatment values were used.	Regression, Logistic	Logistic regression with treatment group and gender as factors and baseline body weight as a continuous linear covariate.	0.0002	P-value is considered nominal.	Odds Ratio (OR)	9.47	2-Sided	95	2.89	30.95	Odds ratio is calculated as BI 456906 / Placebo.	Other	Missing body weight measurements were multiply imputed using MMRM with treatment, gender, baseline body weight as factors. "Percentage change in body weight from baseline to Week 46" and "Body weight loss ≥ 15% at Week 46 (yes/no)" were derived per participant in each of the 1000 imputed datasets. Each dataset was analysed by a logistic regression. Multiple estimates from multiple imputation runs were summarised using Rubin's method.
OG002 OG004	Logistic regression after multiple imputation. Analysis based on all available post-baseline body weight measurements (on-treatment (first intake of study drug until 28 days after last intake of study drug) and off-treatment), except those for participants who discontinued treatment early due to COVID-19. For these participants only on-treatment values were used.	Regression, Logistic	Logistic regression with treatment group and gender as factors and baseline body weight as a continuous linear covariate.	<.0001	P-value is considered nominal.	Odds Ratio (OR)	11.79	2-Sided	95	3.62	38.36	Odds ratio is calculated as BI 456906 / Placebo.	Other	Missing body weight measurements were multiply imputed using MMRM with treatment, gender, baseline body weight as factors. "Percentage change in body weight from baseline to Week 46" and "Body weight loss ≥ 15% at Week 46 (yes/no)" were derived per participant in each of the 1000 imputed datasets. Each dataset was analysed by a logistic regression. Multiple estimates from multiple imputation runs were summarised using Rubin's method.
OG003 OG004	Logistic regression after multiple imputation. Analysis based on all available post-baseline body weight measurements (on-treatment (first intake of study drug until 28 days after last intake of study drug) and off-treatment), except those for participants who discontinued treatment early due to COVID-19. For these participants only on-treatment values were used.	Regression, Logistic	Logistic regression with treatment group and gender as factors and baseline body weight as a continuous linear covariate.	<.0001	P-value is considered nominal.	Odds Ratio (OR)	21.02	2-Sided	95	6.47	68.28	Odds ratio is calculated as BI 456906 / Placebo.	Other	Missing body weight measurements were multiply imputed using MMRM with treatment, gender, baseline body weight as factors. "Percentage change in body weight from baseline to Week 46" and "Body weight loss ≥ 15% at Week 46 (yes/no)" were derived per participant in each of the 1000 imputed datasets. Each dataset was analysed by a logistic regression. Multiple estimates from multiple imputation runs were summarised using Rubin's method.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Estimate Comment	Non-Inferiority Type	Non-Inferiority Comment
OG000 OG004	No formal hypotheses were tested.	Mixed Models Analysis	Kenward-Roger approximation was used to estimate the denominator degrees of freedom.	0.0025	P-value is considered nominal.	Difference of adjusted means	-4.53	Standard Error of the Mean	1.48	2-Sided	95	-7.44	-1.61	Difference was calculated as BI 456906 - placebo.	Other	MMRM with fixed effects for baseline body weight as a continuous linear covariate, and treatment, gender, visit, treatment by visit interaction and baseline by visit interaction as factors, using visit as repeated measures and an unstructured covariance matrix to model within subject measurements.
OG001 OG004	No formal hypotheses were tested.	Mixed Models Analysis	Kenward-Roger approximation was used to estimate the denominator degrees of freedom.	<.0001	P-value is considered nominal.	Difference of adjusted means	-12.07	Standard Error of the Mean	1.46	2-Sided	95	-14.94	-9.19	Difference was calculated as BI 456906 - placebo.	Other	MMRM with fixed effects for baseline body weight as a continuous linear covariate, and treatment, gender, visit, treatment by visit interaction and baseline by visit interaction as factors, using visit as repeated measures and an unstructured covariance matrix to model within subject measurements.
OG002 OG004	No formal hypotheses were tested.	Mixed Models Analysis	Kenward-Roger approximation was used to estimate the denominator degrees of freedom.	<.0001	P-value is considered nominal.	Difference of adjusted means	-12.96	Standard Error of the Mean	1.47	2-Sided	95	-15.85	-10.07	Difference was calculated as BI 456906 - placebo at week 46.	Other	MMRM with fixed effects for baseline body weight as a continuous linear covariate, and treatment, gender, visit, treatment by visit interaction and baseline by visit interaction as factors, using visit as repeated measures and an unstructured covariance matrix to model within subject measurements.
OG003 OG004	No formal hypotheses were tested.	Mixed Models Analysis	Kenward-Roger approximation was used to estimate the denominator degrees of freedom.	<.0001	P-value is considered nominal.	Difference of adjusted means	-15.78	Standard Error of the Mean	1.47	2-Sided	95	-18.67	-12.90	Difference was calculated as BI 456906 - placebo at week 46.	Other	MMRM with fixed effects for baseline body weight as a continuous linear covariate, and treatment, gender, visit, treatment by visit interaction and baseline by visit interaction as factors, using visit as repeated measures and an unstructured covariance matrix to model within subject measurements.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Estimate Comment	Non-Inferiority Type	Non-Inferiority Comment
OG000 OG004	No formal hypotheses were tested.	Mixed Models Analysis	Kenward-Roger approximation was used to estimate the denominator degrees of freedom.	0.0116	P-value is considered nominal.	Difference of adjusted means	-4.36	Standard Error of the Mean	1.71	2-Sided	95	-7.74	-0.98	Difference was calculated as BI 456906 - placebo.	Other	MMRM with fixed effects for baseline waist circumference as a continuous linear covariate, and treatment, gender, visit, treatment by visit interaction and baseline by visit interaction as factors, using visit as repeated measures and an unstructured covariance matrix to model within subject measurements.
OG001 OG004	No formal hypotheses were tested.	Mixed Models Analysis	Kenward-Roger approximation was used to estimate the denominator degrees of freedom.	<.0001	P-value is considered nominal.	Difference of adjusted means	-11.03	Standard Error of the Mean	1.71	2-Sided	95	-14.39	-7.66	Difference was calculated as BI 456906 - placebo.	Other	MMRM with fixed effects for baseline waist circumference as a continuous linear covariate, and treatment, gender, visit, treatment by visit interaction and baseline by visit interaction as factors, using visit as repeated measures and an unstructured covariance matrix to model within subject measurements.
OG002 OG004	No formal hypotheses were tested.	Mixed Models Analysis	Kenward-Roger approximation was used to estimate the denominator degrees of freedom.	<.0001	P-value is considered nominal.	Difference of adjusted means	-11.00	Standard Error of the Mean	1.69	2-Sided	95	-14.33	-7.67	Difference was calculated as BI 456906 - placebo.	Other	MMRM with fixed effects for baseline waist circumference as a continuous linear covariate, and treatment, gender, visit, treatment by visit interaction and baseline by visit interaction as factors, using visit as repeated measures and an unstructured covariance matrix to model within subject measurements.
OG003 OG004	No formal hypotheses were tested.	Mixed Models Analysis	Kenward-Roger approximation was used to estimate the denominator degrees of freedom.	<.0001	P-value is considered nominal.	Difference of adjusted means	-12.05	Standard Error of the Mean	1.69	2-Sided	95	-15.39	-8.71	Difference was calculated as BI 456906 - placebo.	Other	MMRM with fixed effects for baseline waist circumference as a continuous linear covariate, and treatment, gender, visit, treatment by visit interaction and baseline by visit interaction as factors, using visit as repeated measures and an unstructured covariance matrix to model within subject measurements.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Estimate Comment	Non-Inferiority Type	Non-Inferiority Comment
OG000 OG004	No formal hypotheses were tested.	Mixed Models Analysis	Kenward-Roger approximation was used to estimate the denominator degrees of freedom.	0.0733	P-value is considered nominal.	Difference of adjusted means	-3.73	Standard Error of the Mean	2.08	2-Sided	95	-7.82	0.35	Difference was calculated as BI 456906 - placebo.	Other	MMRM with fixed effects for baseline systolic blood pressure as a continuous linear covariate, and treatment, gender, visit, treatment by visit interaction and baseline by visit interaction as factors, using visit as repeated measures and an unstructured covariance matrix to model within subject measurements.
OG001 OG004	No formal hypotheses were tested.	Mixed Models Analysis	Kenward-Roger approximation was used to estimate the denominator degrees of freedom.	<.0072	P-value is considered nominal.	Difference of adjusted means	-5.62	Standard Error of the Mean	2.08	2-Sided	95	-9.71	1.53	Difference was calculated as BI 456906 - placebo.	Other	MMRM with fixed effects for baseline systolic blood pressure as a continuous linear covariate, and treatment, gender, visit, treatment by visit interaction and baseline by visit interaction as factors, using visit as repeated measures and an unstructured covariance matrix to model within subject measurements.
OG002 OG004	No formal hypotheses were tested.	Mixed Models Analysis	Kenward-Roger approximation was used to estimate the denominator degrees of freedom.	0.0027	P-value is considered nominal.	Difference of adjusted means	-6.20	Standard Error of the Mean	2.05	2-Sided	95	-10.23	-2.17	Difference was calculated as BI 456906 - placebo.	Other	MMRM with fixed effects for baseline systolic blood pressure as a continuous linear covariate, and treatment, gender, visit, treatment by visit interaction and baseline by visit interaction as factors, using visit as repeated measures and an unstructured covariance matrix to model within subject measurements.
OG003 OG004	No formal hypotheses were tested.	Mixed Models Analysis	Kenward-Roger approximation was used to estimate the denominator degrees of freedom.	0.0033	P-value is considered nominal.	Difference of adjusted means	-6.16	Standard Error of the Mean	2.08	2-Sided	95	-10.25	-2.06	Difference was calculated as BI 456906 - placebo.	Other	MMRM with fixed effects for baseline systolic blood pressure as a continuous linear covariate, and treatment, gender, visit, treatment by visit interaction and baseline by visit interaction as factors, using visit as repeated measures and an unstructured covariance matrix to model within subject measurements.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Estimate Comment	Non-Inferiority Type	Non-Inferiority Comment
OG000 OG004	No formal hypotheses were tested.	Mixed Models Analysis	Kenward-Roger approximation was used to estimate the denominator degrees of freedom.	0.2569	P-value is considered nominal.	Difference of adjusted means	-1.44	Standard Error of the Mean	1.26	2-Sided	95	-3.92	1.05	Difference was calculated as BI 456906 - placebo.	Other	MMRM with fixed effects for baseline diastolic blood pressure as a continuous linear covariate, and treatment, gender, visit, treatment by visit interaction and baseline by visit interaction as factors, using visit as repeated measures and an unstructured covariance matrix to model within subject measurements.
OG001 OG004	No formal hypotheses were tested.	Mixed Models Analysis	Kenward-Roger approximation was used to estimate the denominator degrees of freedom.	0.0495	P-value is considered nominal.	Difference of adjusted means	-2.49	Standard Error of the Mean	1.26	2-Sided	95	-4.97	-0.00	Difference was calculated as BI 456906 - placebo.	Other	MMRM with fixed effects for baseline diastolic blood pressure as a continuous linear covariate, and treatment, gender, visit, treatment by visit interaction and baseline by visit interaction as factors, using visit as repeated measures and an unstructured covariance matrix to model within subject measurements.
OG002 OG004	No formal hypotheses were tested.	Mixed Models Analysis	Kenward-Roger approximation was used to estimate the denominator degrees of freedom.	0.0506	P-value is considered nominal.	Difference of adjusted means	-2.44	Standard Error of the Mean	1.24	2-Sided	95	-4.90	0.01	Difference was calculated as BI 456906 -placebo.	Other	MMRM with fixed effects for baseline diastolic blood pressure as a continuous linear covariate, and treatment, gender, visit, treatment by visit interaction and baseline by visit interaction as factors, using visit as repeated measures and an unstructured covariance matrix to model within subject measurements.
OG003 OG004	No formal hypotheses were tested.	Mixed Models Analysis	Kenward-Roger approximation was used to estimate the denominator degrees of freedom.	0.0202	P-value is considered nominal.	Difference of adjusted means	-2.93	Standard Error of the Mean	1.25	2-Sided	95	-5.40	-0.46	Difference was calculated as BI 456906 - placebo.	Other	MMRM with fixed effects for baseline diastolic blood pressure as a continuous linear covariate, and treatment, gender, visit, treatment by visit interaction and baseline by visit interaction as factors, using visit as repeated measures and an unstructured covariance matrix to model within subject measurements.