A Study to Test Whether Different Doses of BI 456906 Are Effective in Treating Adults With Type 2 Diabetes.

Study Overview
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Brief Summary
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This study is open to adults with type 2 diabetes who take metformin but still have too high blood sugar. The purpose of the study is to find the best dose of BI 456906 that reduces blood sugar. The study also looks at whether BI 456906 helps the participants lose weight. Participants are in the study for about 23 weeks. During this time, most participants visit the study site about 13 times. Some participants visit the study site about 20 times. At the start of the study, the participants are put into 7 groups. The participants in groups 1 to 6 get injections under the skin once or twice every week. Some participants get different doses of BI 456906 and other participants get placebo. Placebo injections look like the BI 456906 injections, but contain no medicine. Participants in group 7 get semaglutide injections every week. Semaglutide is another medicine for adults with type 2 diabetes. During the study, the doctors regularly take blood samples from the participants and measure their body weight. The changes in blood sugar levels and body weight are compared between the groups. The doctors also check the general health of the participants.

Official Title
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A Phase II, Randomized, Parallel Group, Dose-finding Study of Subcutaneously Administered BI 456906 for 16 Weeks, Compared With Placebo and Open-label Semaglutide in Patients With Type 2 Diabetes Mellitus.

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: BI 456906
* Drug: Placebo
* Drug: Semaglutide


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Signed and dated written informed consent in accordance with International conference on harmonization - Good clinical practice (ICH GCP) and local legislation. Male and female patients 18 years to 75 years (both inclusive) of age on the day of signing informed consent. Diagnosis of Type 2 diabetes mellitus (T2DM) at least 6 months prior to informed consent. Glycosylated hemoglobin A1c (HbA1c) 7.0%-10.0% (both inclusive) at screening. Treatment with a stable dose of metformin ≥ 1000mg/day for at least 3 months prior to screening. Body mass index (BMI) 25 kg/m2-50 kg/m2 (both inclusive) at screening. Women of childbearing potential must be ready and able to use highly effective methods of birth control. Exclusion criteria: Patients with type 1 diabetes. Exposure to semaglutide, or other Glucagon-like-peptide 1 receptor (GLP-1R) agonists (including combination products) within 3 months prior to screening, or any previous exposure to BI 456906. Any additional oral anti-hyperglycemic medication beyond metformin within 3 months prior to screening. Use of insulin for glycemic control within 12 months prior to screening. Resting Heart Rate >100 bpm or blood pressure ≥160/95 mmHg at screening. A marked baseline prolongation of QT/QTc (Fridericia) interval or any other clinically significant Electrocardiogram (ECG) finding at screening. Body weight change of +/- 5% or more in the past 3 months or on anti-obesity therapies at any time during the 6 months prior to screening. Continuous oral pharmacotherapy to treat any clinical condition during the Trial. Following medications are allowed: metformin, anti-hypertensives (any medication known to cause heart block or bradycardia such as beta-blockers, verapamil and diltiazem are excluded unless used to treat heart rate control or hypertension), Hormone replacement therapy including thyroid hormone, lipid lowering, proton pump inhibitors, H2 blockers for Gastric esophageal reflux disease (GERD), analgesics, sleep medications antihistamines selective Alpha receptor blocker for benign prostatic hyperplasia Patients must be on a stable dose for at least 3 months Prior to Screening Any suicidal behavior in the past 2 years, any suicidal ideation of type 4 or 5 in the Columbia-suicide severity rating scale (C-SSRS) in the past 3 months at screening. Chronic or relevant acute infections. Women who are pregnant, nursing, or who plan to become pregnant while in the trial. Further exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 456906 0.3 mg<br> | Drug: BI 456906<br>* Solution for Injection<br>|
| Experimental: BI 456906 0.9 mg<br> | Drug: BI 456906<br>* Solution for Injection<br>|
| Experimental: BI 456906 1.8 mg<br> | Drug: BI 456906<br>* Solution for Injection<br>|
| Experimental: BI 456906 2.7 mg<br> | Drug: BI 456906<br>* Solution for Injection<br>|
| Experimental: BI 456906 1.2 twice weekly (2.4) mg<br> | Drug: BI 456906<br>* Solution for Injection<br>|
| Experimental: BI 456906 1.8 twice weekly (3.6) mg<br> | Drug: BI 456906<br>* Solution for Injection<br>|
| Active Comparator: Semaglutide<br> | Drug: Semaglutide<br>* Solution for Injection<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Solution for Injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change in HbA1c From Baseline to 16 Weeks | Absolute change in glycosylated hemoglobin A1c (HbA1c) from baseline to 16 weeks after treatment start is presented. The measurements for this outcome were performed at baseline and at Week 17. Absolute change from baseline in HbA1c to 16 weeks after treatment start was calculated by subtracting the baseline HbA1c value from the HbA1c value at Week 17. | At baseline and at Week 17 (16 weeks after treatment start). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Key Secondary Endpoint: The Relative Change in Body Weight From Baseline to 16 Weeks | The relative change in body weight from baseline to 16 weeks after treatment start is presented. The measurements for this outcome were performed at baseline and at Week 17. The relative change in body weight from baseline to 16 weeks after treatment start was calculated as (body weight at Week 17 - body weight at baseline/body weight at baseline) * 100. | At baseline and at Week 17 (16 weeks after treatment start ). | 
| The Absolute Change in Body Weight From Baseline to 16 Weeks | The absolute change in body weight from baseline to 16 weeks after treatment start is presented. Measurements for this outcome were performed at baseline and at Week 17. The absolute change in body weight from baseline to 16 weeks after treatment start was calculated as: body weight at Week 17- body weight at baseline. | At baseline and at Week 17 (16 weeks after treatment start). | 
| The Absolute Change in Waist Circumference From Baseline to 16 Weeks | The absolute change in waist circumference from baseline to 16 weeks after treatment start is presented. Measurements for this outcome were performed at baseline and at Week 17. The absolute change in waist circumference from baseline to 16 weeks after treatment start was calculated as: waist circumference at Week 17- waist circumference at baseline. | At baseline and at Week 17 (16 weeks after treatment start). | 
| Percentage of Patients With 5 % or Greater Body Weight Loss From Baseline to 16 Weeks | The percentage of patients with 5 percent (%) or greater body weight loss from baseline to 16 weeks after treatment start is presented. Measurements for this outcome were performed at baseline and at Week 17. | At baseline and at Week 17 (16 weeks after treatment start). | 
| Percentage of Patients With 10% or Greater Body Weight Loss From Baseline to 16 Weeks | The percentage of patients with 10 % or greater body weight loss from baseline to 16 weeks after treatment start is presented. Measurements for this outcome were performed at baseline and at Week 17. | At baseline and at Week 17 (16 weeks after treatment start). |