Obesity
Conditions
Brief summary
This study is open to adults, aged 18 to 75 years, with overweight or obesity. People with body mass index (BMI) of 27 or higher to join the study. People who have diabetes cannot participate. The purpose of this study is to find out whether a medicine called BI 456906 helps people lose weight. Participants are put into 5 groups by chance. 4 groups get different doses of BI 456906. The fifth group gets placebo. Participants get BI 456906 or placebo as injections under the skin once a week. Placebo injections look like BI 456906 injections but do not contain any medicine. Participants are in the study for about a year. During this time, there are about 20 in-person visits to the study site. At the study site visits, doctors measure participants' body weight. Results are compared between the BI 456906 groups and the placebo group. The doctors also regularly check the general health of the participants.
Interventions
DRUGBI 456906
BI 456906
DRUGPlacebo
Placebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in Body Weight From Baseline to Week 46 | Baseline, Week 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36, 40, and 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Weight Loss of ≥ 10% of Baseline Weight at Week 46 | At baseline and 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. |
| Weight Loss of ≥ 15% of Baseline Weight at Week 46 | At baseline and 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. |
| Absolute Change in Body Weight From Baseline to Week 46 | Baseline, Week 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36, 40, and 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. |
| Weight Loss of ≥ 5% of Baseline Weight at Week 46 | At baseline and 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. |
| Absolute Change in Systolic Blood Pressure From Baseline to Week 46 | Baseline, Week 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36, 40, and 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. |
| Absolute Change in Diastolic Blood Pressure From Baseline to Week 46 | Baseline, Week 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36, 40, and 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. |
| Absolute Change in Waist Circumference From Baseline to Week 46 | Baseline, Week 6, 12, 18, 24, 32, 40, and 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. |
Countries
Australia, Belgium, Canada, China, Germany, Netherlands, New Zealand, Poland, South Korea, Sweden, United Kingdom, United States
Participant flow
Recruitment details
This was a randomised, double-blinded, parallel-design, placebo-controlled, multi-national, and multi-centre study with four different BI 456906 maintenance doses (ranging from 0.6 mg/week to 4.8 mg/week) in patients with obesity or overweight (body mass index (BMI) \>=27 kg/m\^2), and without diabetes mellitus.
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 77 |
| 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. | 78 |
| 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. | 76 |
| 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. | 76 |
| 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 |
| Total | 384 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Dose Escalation Period | Adverse Event | 9 | 10 | 12 | 17 | 3 |
| Dose Escalation Period | Adverse event: COVID-infection | 4 | 1 | 2 | 1 | 0 |
| Dose Escalation Period | Burden of study procedures | 2 | 1 | 1 | 1 | 5 |
| Dose Escalation Period | Change of residence | 0 | 0 | 1 | 0 | 0 |
| Dose Escalation Period | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 |
| Dose Escalation Period | Not treated | 1 | 0 | 0 | 0 | 0 |
| Dose Escalation Period | Other not specified below | 3 | 3 | 2 | 1 | 3 |
| Dose Escalation Period | Perceived lack of efficacy | 0 | 0 | 0 | 0 | 6 |
| Dose Escalation Period | Protocol Violation | 2 | 2 | 0 | 2 | 1 |
| Dose Escalation Period | Withdrawal by Subject | 2 | 0 | 0 | 0 | 2 |
| Maintenance Period | Adverse Event | 2 | 8 | 5 | 4 | 1 |
| Maintenance Period | Adverse event: COVID infection | 0 | 1 | 0 | 0 | 0 |
| Maintenance Period | Burden of study procedures | 1 | 2 | 0 | 1 | 0 |
| Maintenance Period | Change of residence | 0 | 1 | 0 | 0 | 1 |
| Maintenance Period | COVID-related | 0 | 0 | 1 | 1 | 0 |
| Maintenance Period | Lost to Follow-up | 1 | 0 | 1 | 0 | 1 |
| Maintenance Period | Missing | 1 | 0 | 0 | 0 | 0 |
| Maintenance Period | Other than listed above | 2 | 0 | 3 | 2 | 6 |
| Maintenance Period | Perceived lack of efficacy | 0 | 2 | 1 | 0 | 1 |
| Maintenance Period | Protocol Violation | 1 | 0 | 0 | 0 | 1 |
| Maintenance Period | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | 0.6 mg BI 456906 - Planned Maintenance Treatment (Maintenance Dose Assigned at Randomisation) | 2.4 mg BI 456906 - Planned Maintenance Treatment | 3.6 mg BI 456906 - Planned Maintenance Treatment | 4.8 mg BI 456906 - Planned Maintenance Treatment | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 48.6 Years STANDARD_DEVIATION 12.6 | 49.0 Years STANDARD_DEVIATION 13.1 | 50.3 Years STANDARD_DEVIATION 11.8 | 47.6 Years STANDARD_DEVIATION 13.5 | 50.0 Years STANDARD_DEVIATION 13.5 | 48.9 Years STANDARD_DEVIATION 12.8 |
| Body weight at baseline | 106.98 Kilogram (kg) STANDARD_DEVIATION 18.71 | 106.57 Kilogram (kg) STANDARD_DEVIATION 22.97 | 104.68 Kilogram (kg) STANDARD_DEVIATION 19.63 | 105.86 Kilogram (kg) STANDARD_DEVIATION 17.39 | 104.32 Kilogram (kg) STANDARD_DEVIATION 22.95 | 105.68 Kilogram (kg) STANDARD_DEVIATION 20.39 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 1 Participants | 2 Participants | 6 Participants | 5 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 74 Participants | 77 Participants | 74 Participants | 70 Participants | 72 Participants | 367 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 9 Participants | 9 Participants | 7 Participants | 7 Participants | 40 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 8 Participants | 3 Participants | 8 Participants | 8 Participants | 37 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 59 Participants | 60 Participants | 63 Participants | 59 Participants | 60 Participants | 301 Participants |
| Sex: Female, Male Female | 51 Participants | 54 Participants | 51 Participants | 53 Participants | 53 Participants | 262 Participants |
| Sex: Female, Male Male | 26 Participants | 24 Participants | 25 Participants | 23 Participants | 24 Participants | 122 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 92 | 0 / 92 | 0 / 71 | 0 / 54 | 0 / 77 |
| other Total, other adverse events | 70 / 92 | 79 / 92 | 64 / 71 | 46 / 54 | 48 / 77 |
| serious Total, serious adverse events | 2 / 92 | 3 / 92 | 4 / 71 | 4 / 54 | 5 / 77 |
Outcome results
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.
Time frame: Baseline, Week 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36, 40, and 46.
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.6 mg BI 456906 - Planned Maintenance Treatment (Maintenance Dose Assigned at Randomisation) | Percentage Change in Body Weight From Baseline to Week 46 | -6.19 Percentage change | Standard Error 1.07 |
| 2.4 mg BI 456906 - Planned Maintenance Treatment | Percentage Change in Body Weight From Baseline to Week 46 | -12.51 Percentage change | Standard Error 1.01 |
| 3.6 mg BI 456906 - Planned Maintenance Treatment | Percentage Change in Body Weight From Baseline to Week 46 | -13.22 Percentage change | Standard Error 1.04 |
| 4.8 mg BI 456906 - Planned Maintenance Treatment | Percentage Change in Body Weight From Baseline to Week 46 | -14.94 Percentage change | Standard Error 1.01 |
| Placebo | Percentage Change in Body Weight From Baseline to Week 46 | -2.82 Percentage change | Standard Error 1.06 |
Comparison: 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%).p-value: <0.0001MCP-Mod - Linear model fit
Comparison: 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%).p-value: <0.0001MCP-Mod - Exponential model fit
Comparison: 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%).p-value: <0.0001MCP-Mod - Emax1 model fit
Comparison: 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%).p-value: <0.0001MCP-Mod - Emax2 model fit
Comparison: 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%).p-value: <0.0001MCP-Mod - Sigmoid Emax model fit
Comparison: No formal hypotheses were tested.p-value: 0.025795% CI: [-6.33, -0.41]Mixed Models Analysis
Comparison: No formal hypotheses were tested.p-value: <0.000195% CI: [-12.57, -6.81]Mixed Models Analysis
Comparison: No formal hypotheses were tested.p-value: <0.000195% CI: [-13.32, -7.49]Mixed Models Analysis
Comparison: No formal hypotheses were tested.p-value: <0.000195% CI: [-15, -9.24]Mixed Models Analysis
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.
Time frame: Baseline, Week 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36, 40, and 46.
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.6 mg BI 456906 - Planned Maintenance Treatment (Maintenance Dose Assigned at Randomisation) | Absolute Change in Body Weight From Baseline to Week 46 | -7.21 Kilogram (kg) | Standard Error 1.06 |
| 2.4 mg BI 456906 - Planned Maintenance Treatment | Absolute Change in Body Weight From Baseline to Week 46 | -14.75 Kilogram (kg) | Standard Error 1.03 |
| 3.6 mg BI 456906 - Planned Maintenance Treatment | Absolute Change in Body Weight From Baseline to Week 46 | -15.64 Kilogram (kg) | Standard Error 1.04 |
| 4.8 mg BI 456906 - Planned Maintenance Treatment | Absolute Change in Body Weight From Baseline to Week 46 | -18.47 Kilogram (kg) | Standard Error 1.04 |
| Placebo | Absolute Change in Body Weight From Baseline to Week 46 | -2.68 Kilogram (kg) | Standard Error 1.04 |
Comparison: No formal hypotheses were tested.p-value: 0.002595% CI: [-7.44, -1.61]Mixed Models Analysis
Comparison: No formal hypotheses were tested.p-value: <0.000195% CI: [-14.94, -9.19]Mixed Models Analysis
Comparison: No formal hypotheses were tested.p-value: <0.000195% CI: [-15.85, -10.07]Mixed Models Analysis
Comparison: No formal hypotheses were tested.p-value: <0.000195% CI: [-18.67, -12.9]Mixed Models Analysis
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.
Time frame: Baseline, Week 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36, 40, and 46.
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.6 mg BI 456906 - Planned Maintenance Treatment (Maintenance Dose Assigned at Randomisation) | Absolute Change in Diastolic Blood Pressure From Baseline to Week 46 | -3.31 Millimeter of mercury (mmHg) | Standard Error 0.9 |
| 2.4 mg BI 456906 - Planned Maintenance Treatment | Absolute Change in Diastolic Blood Pressure From Baseline to Week 46 | -4.36 Millimeter of mercury (mmHg) | Standard Error 0.9 |
| 3.6 mg BI 456906 - Planned Maintenance Treatment | Absolute Change in Diastolic Blood Pressure From Baseline to Week 46 | -4.31 Millimeter of mercury (mmHg) | Standard Error 0.87 |
| 4.8 mg BI 456906 - Planned Maintenance Treatment | Absolute Change in Diastolic Blood Pressure From Baseline to Week 46 | -4.80 Millimeter of mercury (mmHg) | Standard Error 0.89 |
| Placebo | Absolute Change in Diastolic Blood Pressure From Baseline to Week 46 | -1.87 Millimeter of mercury (mmHg) | Standard Error 0.89 |
Comparison: No formal hypotheses were tested.p-value: 0.256995% CI: [-3.92, 1.05]Mixed Models Analysis
Comparison: No formal hypotheses were tested.p-value: 0.049595% CI: [-4.97, 0]Mixed Models Analysis
Comparison: No formal hypotheses were tested.p-value: 0.050695% CI: [-4.9, 0.01]Mixed Models Analysis
Comparison: No formal hypotheses were tested.p-value: 0.020295% CI: [-5.4, -0.46]Mixed Models Analysis
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.
Time frame: Baseline, Week 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 28, 32, 36, 40, and 46.
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.6 mg BI 456906 - Planned Maintenance Treatment (Maintenance Dose Assigned at Randomisation) | Absolute Change in Systolic Blood Pressure From Baseline to Week 46 | -6.19 Millimeter of mercury (mmHg) | Standard Error 1.47 |
| 2.4 mg BI 456906 - Planned Maintenance Treatment | Absolute Change in Systolic Blood Pressure From Baseline to Week 46 | -8.08 Millimeter of mercury (mmHg) | Standard Error 1.48 |
| 3.6 mg BI 456906 - Planned Maintenance Treatment | Absolute Change in Systolic Blood Pressure From Baseline to Week 46 | -8.66 Millimeter of mercury (mmHg) | Standard Error 1.44 |
| 4.8 mg BI 456906 - Planned Maintenance Treatment | Absolute Change in Systolic Blood Pressure From Baseline to Week 46 | -8.62 Millimeter of mercury (mmHg) | Standard Error 1.46 |
| Placebo | Absolute Change in Systolic Blood Pressure From Baseline to Week 46 | -2.46 Millimeter of mercury (mmHg) | Standard Error 1.46 |
Comparison: No formal hypotheses were tested.p-value: 0.073395% CI: [-7.82, 0.35]Mixed Models Analysis
Comparison: No formal hypotheses were tested.p-value: <0.007295% CI: [-9.71, 1.53]Mixed Models Analysis
Comparison: No formal hypotheses were tested.p-value: 0.002795% CI: [-10.23, -2.17]Mixed Models Analysis
Comparison: No formal hypotheses were tested.p-value: 0.003395% CI: [-10.25, -2.06]Mixed Models Analysis
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.
Time frame: Baseline, Week 6, 12, 18, 24, 32, 40, and 46.
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.6 mg BI 456906 - Planned Maintenance Treatment (Maintenance Dose Assigned at Randomisation) | Absolute Change in Waist Circumference From Baseline to Week 46 | -8.32 Centimeter (cm) | Standard Error 1.22 |
| 2.4 mg BI 456906 - Planned Maintenance Treatment | Absolute Change in Waist Circumference From Baseline to Week 46 | -14.99 Centimeter (cm) | Standard Error 1.21 |
| 3.6 mg BI 456906 - Planned Maintenance Treatment | Absolute Change in Waist Circumference From Baseline to Week 46 | -14.96 Centimeter (cm) | Standard Error 1.19 |
| 4.8 mg BI 456906 - Planned Maintenance Treatment | Absolute Change in Waist Circumference From Baseline to Week 46 | -16.01 Centimeter (cm) | Standard Error 1.19 |
| Placebo | Absolute Change in Waist Circumference From Baseline to Week 46 | -3.96 Centimeter (cm) | Standard Error 1.2 |
Comparison: No formal hypotheses were tested.p-value: 0.011695% CI: [-7.74, -0.98]Mixed Models Analysis
Comparison: No formal hypotheses were tested.p-value: <0.000195% CI: [-14.39, -7.66]Mixed Models Analysis
Comparison: No formal hypotheses were tested.p-value: <0.000195% CI: [-14.33, -7.67]Mixed Models Analysis
Comparison: No formal hypotheses were tested.p-value: <0.000195% CI: [-15.39, -8.71]Mixed Models Analysis
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.
Time frame: At baseline and at Week 46.
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0.6 mg BI 456906 - Planned Maintenance Treatment (Maintenance Dose Assigned at Randomisation) | Weight Loss of ≥ 10% of Baseline Weight at Week 46 | 33.9 Percentage of participants |
| 2.4 mg BI 456906 - Planned Maintenance Treatment | Weight Loss of ≥ 10% of Baseline Weight at Week 46 | 65.5 Percentage of participants |
| 3.6 mg BI 456906 - Planned Maintenance Treatment | Weight Loss of ≥ 10% of Baseline Weight at Week 46 | 65.6 Percentage of participants |
| 4.8 mg BI 456906 - Planned Maintenance Treatment | Weight Loss of ≥ 10% of Baseline Weight at Week 46 | 68.8 Percentage of participants |
| Placebo | Weight Loss of ≥ 10% of Baseline Weight at Week 46 | 11.1 Percentage of participants |
Comparison: 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.p-value: 0.01295% CI: [1.29, 8.02]Regression, Logistic
Comparison: 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.p-value: <0.000195% CI: [4.36, 25.86]Regression, Logistic
Comparison: 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.p-value: <0.000195% CI: [4.02, 23.79]Regression, Logistic
Comparison: 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.p-value: <0.000195% CI: [5.91, 35.55]Regression, Logistic
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.
Time frame: At baseline and at Week 46.
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0.6 mg BI 456906 - Planned Maintenance Treatment (Maintenance Dose Assigned at Randomisation) | Weight Loss of ≥ 15% of Baseline Weight at Week 46 | 12.5 Percentage of particpants |
| 2.4 mg BI 456906 - Planned Maintenance Treatment | Weight Loss of ≥ 15% of Baseline Weight at Week 46 | 37.9 Percentage of particpants |
| 3.6 mg BI 456906 - Planned Maintenance Treatment | Weight Loss of ≥ 15% of Baseline Weight at Week 46 | 45.9 Percentage of particpants |
| 4.8 mg BI 456906 - Planned Maintenance Treatment | Weight Loss of ≥ 15% of Baseline Weight at Week 46 | 54.7 Percentage of particpants |
| Placebo | Weight Loss of ≥ 15% of Baseline Weight at Week 46 | 5.6 Percentage of particpants |
Comparison: 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.p-value: 0.265495% CI: [0.56, 8.02]Regression, Logistic
Comparison: 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.p-value: 0.000295% CI: [2.89, 30.95]Regression, Logistic
Comparison: 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.p-value: <0.000195% CI: [3.62, 38.36]Regression, Logistic
Comparison: 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.p-value: <0.000195% CI: [6.47, 68.28]Regression, Logistic
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.
Time frame: At baseline and at Week 46.
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0.6 mg BI 456906 - Planned Maintenance Treatment (Maintenance Dose Assigned at Randomisation) | Weight Loss of ≥ 5% of Baseline Weight at Week 46 | 60.7 Percentage of participants |
| 2.4 mg BI 456906 - Planned Maintenance Treatment | Weight Loss of ≥ 5% of Baseline Weight at Week 46 | 81.0 Percentage of participants |
| 3.6 mg BI 456906 - Planned Maintenance Treatment | Weight Loss of ≥ 5% of Baseline Weight at Week 46 | 82.0 Percentage of participants |
| 4.8 mg BI 456906 - Planned Maintenance Treatment | Weight Loss of ≥ 5% of Baseline Weight at Week 46 | 82.8 Percentage of participants |
| Placebo | Weight Loss of ≥ 5% of Baseline Weight at Week 46 | 25.9 Percentage of participants |
Comparison: 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.p-value: 0.001595% CI: [1.57, 6.84]Regression, Logistic
Comparison: 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.p-value: <0.000195% CI: [4, 19.46]Regression, Logistic
Comparison: 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.p-value: <0.000195% CI: [3.41, 16.41]Regression, Logistic
Comparison: 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.p-value: <0.000195% CI: [4.77, 24.31]Regression, Logistic