Research Study of How Well Semaglutide Works in People Living With Overweight or Obesity

Study Overview
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Brief Summary
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This study will look at the change in body weight from the start to the end of the study. The purpose of the study is to compare the effect on body weight in people taking semaglutide (a new medicine) and people taking dummy medicine. In addition to taking the medicine participants will have talks with study staff about healthy food choices, how to be more physically active and what else they can do to lose weight. Participants will either get semaglutide or dummy medicine - which treatment is decided by chance. Participants will need to take 1 injection once a week. The study medicine is injected with a thin needle in a skinfold in the stomach, thigh or upper arm.• The study will last for about 1 year. Participants will have 11 clinic visits and 8 phone calls with the study doctor. Participants will have 3 clinic visits where they cannot eat and drink (water is allowed) for up to 8 hours before the visit and 1 clinic visit where they cannot eat and drink for up to 2 hours before the visit. (4 visits and 1 visit, respectively, if they have type 2 diabetes (T2D)). Participants will have 4 clinic visits where they will have blood samples taken. (5 visits if they have T2D). For China: Participants will have 9 clinic visits where they will have blood samples taken. Women cannot take part if pregnant, breast-feeding or planning to become pregnant during the study period.

Official Title
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Effect and Safety of Semaglutide 2.4 mg Once-weekly on Weight Management in Subjects With Overweight or Obesity

Conditions
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Overweight, Obesity, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Semaglutide
* Drug: Placebo (semaglutide)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, age 18 years or older at the time of signing informed consent History of at least one self-reported unsuccessful dietary effort to lose body weight For subjects without T2D at screening: Body mass index (BMI) of : greater than or equal to 30 kg/m^2 greater than or equal to 27 kg/m^2 with the presence of at least one of the following weight-related comorbidities (treated or untreated): hypertension, dyslipidaemia, obstructive sleep apnoea or cardiovascular disease For subjects with T2D at screening: Diagnosed with T2D above or equal to 180 days prior to the day of screening Treated with either: diet and exercise alone or stable treatment (same drug(s), dose and dosing frequency) for at least 60 days prior to the day of screening with up to 3 oral antidiabetic medications alone or in any combination (metformin, α-glucosidase inhibitor (AGI), SU, glinides, SGLT2i or glitazone) according to local label HbA1c 7.0-10.0% (53-86 mmol/mol) (both inclusive) BMI greater than or equal to 27 kg/m^2 Exclusion Criteria: A self-reported change in body weight above 5 kg (11 lbs) within 90 days before screening irrespective of medical records For subjects without T2D at screening: - HbA1c equal to or above 6.5% (48 mmol/mol) as measured by the central laboratory at screening For subjects with T2D at screening: Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of below 30 mL/min/1.73 m^2 (below 60 mL/min/1.73 m^2 in subjects treated with SGLT2i) according to CKDEPI creatinine equation as defined by KDIGO 2012 by the central laboratory at screening Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.

Ages Eligible for Study
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Minimum Age: 18 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: Semaglutide<br>Once-weekly injections of gradually increased doses of semaglutide | Drug: Semaglutide<br>* Semaglutide administered subcutaneously (s.c., under the skin) as well as diet and physical activity counselling for 44 weeks. Doses gradually increased to 2.4 mg<br>|
| Placebo Comparator: Placebo (semaglutide)<br>Once-weekly injections of gradually increased doses of semaglutide placebo | Drug: Placebo (semaglutide)<br>* Semaglutide placebo administered s.c. as an adjunct to a reduced-calorie diet and increased physical activity regimen for 44 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in body weight | Percent | From baseline at week 0 to week 44 | 
| Subjects who achieve body weight reduction equal to or above 5% (yes/no) | Number of subjects | From baseline at week 0 to week 44 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjects who achieve body weight reduction equal to or above 10% (yes/no) | Number of subjects | From baseline at week 0 to week 44 | 
| Subjects who achieve body weight reduction equal to or above 15% (yes/no) | Number of subjects | From baseline at week 0 to week 44 | 
| Change in waist circumference | cm | From baseline at week 0 to week 44 | 
| Change in systolic blood pressure | mmHg | From baseline at week 0 to week 44 | 
| Change in physical functioning score | Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health. | From baseline at week 0 to week 44 | 
| Change in physical function domain (5-items) score | The Impact of Weight on Quality of Life Lite for Clinical Trials Version (IWQoL-Lite for CT) questionnaire is a 20-item modified version of an instrument designed to assess weight-related quality of life. | From baseline at week 0 to week 44 | 
| Change in body weight | kg | From baseline at week 0 to week 44 | 
| Change in body mass index (BMI) | kg/m^2 | From baseline at week 0 to week 44 | 
| Change in glycosylated haemoglobin (HbA1c) | Percent | From baseline at week 0 to week 44 | 
| Change in HbA1c | mmol /mol | From baseline at week 0 to week 44 | 
| Change in fasting plasma glucose (FPG) | mg/dL | From baseline at week 0 to week 44 | 
| Change in fasting serum insulin | mIU/L | From baseline at week 0 to week 44 | 
| Change in diastolic blood pressure | mmHg | From baseline at week 0 to week 44 | 
| Change in lipids: Total cholesterol | mg/dL | From baseline at week 0 to week 44 | 
| Change in lipids: High density lipoprotein (HDL) cholesterol | mg/dL | From baseline at week 0 to week 44 | 
| Change in lipids: Low density lipoprotein (LDL) cholesterol | mg/dL | From baseline at week 0 to week 44 | 
| Change in lipids: Very low density lipoprotein (VLDL) cholesterol | mg/dL | From baseline at week 0 to week 44 | 
| Change in lipids: Free fatty acids (FFA) | mg/dL | From baseline at week 0 to week 44 | 
| Change in lipids: Triglycerides | mg/dL | From baseline at week 0 to week 44 | 
| Change in SF-36: role-physical score | Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health. | From baseline at week 0 to week 44 | 
| Change in SF-36: bodily pain score | Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health. | From baseline at week 0 to week 44 | 
| Change in SF-36: general health score | Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health. | From baseline at week 0 to week 44 | 
| Change in SF-36: vitality score | Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health. | From baseline at week 0 to week 44 | 
| Change in SF-36: social functioning score | Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health. | From baseline at week 0 to week 44 | 
| Change in SF-36: role-emotional score | Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health. | From baseline at week 0 to week 44 | 
| Change in SF-36: mental health score | Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health. | From baseline at week 0 to week 44 | 
| Change in SF-36: physical component summary | Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health. | From baseline at week 0 to week 44 | 
| Change in SF-36: mental component summary | Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health. | From baseline at week 0 to week 44 | 
| Change in IWQoL-Lite for CT: pain/discomfort domain score | The Impact of Weight on Quality of Life Lite for Clinical Trials Version (IWQoL-Lite for CT) questionnaire is a 20-item modified version of an instrument designed to assess weight-related quality of life. | From baseline at week 0 to week 44 | 
| Change in IWQoL-Lite for CT: psychosocial domain score | The Impact of Weight on Quality of Life Lite for Clinical Trials Version (IWQoL-Lite for CT) questionnaire is a 20-item modified version of an instrument designed to assess weight-related quality of life. | From baseline at week 0 to week 44 | 
| Change in IWQoL-Lite for CT: total score | The Impact of Weight on Quality of Life Lite for Clinical Trials Version (IWQoL-Lite for CT) questionnaire is a 20-item modified version of an instrument designed to assess weight-related quality of life. | From baseline at week 0 to week 44 | 
| Subjects who achieve responder definition value for SF-36 physical functioning score (yes/no) | Number of subjects | Week 44 | 
| Subjects who achieve responder definition value for IWQoL-Lite for CT physical function domain (5-items) score (yes/no) | Number of subjects | Week 44 | 
| Change in glycaemic category | Normo-glycaemia, pre-diabetes or T2D | From baseline at week 0 to week 44 | 
| Change in antihypertensive medication | Decrease, no change, increase | From baseline at week 0 to week 44 | 
| Change in lipid-lowering medication | Decrease, no change, increase | From baseline at week 0 to week 44 | 
| Change in concomitant oral antidiabetic medication | Decrease, no change, increase (only applies to subjects with T2D at week 0) | From baseline at week 0 to week 44 | 
| Change in fatty liver index (FLI) score category | Below 30, equal to or above 30 and below 60, equal to or above 60 | From baseline at week 0 to week 44 | 
| Subjects who have permanently discontinued randomised trial product (yes/no) | Number of subjects | From randomisation at week 0 to week 44 | 
| Time to permanent discontinuation of randomised trial product | Weeks | Week 0 - week 44 | 
| Number of treatment emergent adverse events (TEAEs) | Count | From week 0 to week 51 | 
| Number of serious adverse events (SAEs) | Count | From week 0 to week 51 | 
| Number of treatment emergent severe or blood glucose (BG) confirmed symptomatic hypoglycaemia episodes (yes/no) | Count (only applies to subjects with T2D at week 0) | From week 0 to week 51 | 
| Change in pulse | Beats per minute (bpm) | From baseline at week 0 to week 44 | 
| Change in amylase | U/L | From baseline at week 0 to week 44 | 
| Change in lipase | U/L | From baseline at week 0 to week 44 | 
| Change in calcitonin | ng/L | From baseline at week 0 to week 44 |