Research Study Looking at How Well Semaglutide Tablets Taken Once Daily Work in People Who Have a Body Weight Above the Healthy Range

Study Overview
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Brief Summary
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This study will look how well semaglutide tablets taken once daily helps people with body weight above the healthy range. Participants will either get semaglutide 25 milligram (mg) once daily or placebo once daily. This study will last for 72 weeks, which includes 1-week screening period, 64 weeks of treatment period and 7 weeks of follow up period.

Official Title
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Efficacy and Safety of Oral Semaglutide 25 mg Once Daily in Adults With Overweight or Obesity

Conditions
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Overweight, Obesity

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: Informed consent obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study Male or female, age greater than or equal to 18 years at the time of signing informed consent Body mass index (BMI) of Greater than or equal to 27.0 kg/m^2 with the presence of at least one of the following weight-related complications (treated or untreated): hypertension, dyslipidaemia, obstructive sleep apnoea or cardiovascular (CV) disease OR Greater than or equal to 30.0 kg/m^2 History of at least one self-reported unsuccessful dietary effort to lose body weight Exclusion Criteria: A self-reported change in body weight greater than 5 kg (11 pound [lbs]) within 90 days before screening irrespective of medical records HbA1c greater than or equal to 6.5 percent (48 mmol/mol) as measured by the central laboratory at screening

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: Oral semaglutide 25 mg<br>Participants will receive semaglutide tablets orally once daily. Participants will receive semaglutide in a dose escalation manner for 64 weeks: 3 mg (weeks 0 to 4), 7 mg (weeks 5 to 8), 14 mg (weeks 9 to 12), and 25 mg (weeks 13 to 64). | Drug: Semaglutide<br>* Semaglutide tablets orally once daily for 64 weeks.<br>|
| Placebo Comparator: Oral semaglutide placebo<br>Participants will receive placebo tablets matched to semaglutide orally once daily for 64 weeks. | Drug: Placebo semaglutide<br>* Semaglutide placebo-matching tablets orally once daily for 64 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative change in body weight | Measured in percentage (%). | From baseline (week 0) to end of treatment (week 64) | 
| Number of participants who achieve body weight loss equal to or above 5 percent (yes/no) | Measured as count of participants. | At end of treatment (week 64) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who achieve body weight loss equal to or above 10 percent (yes/no) | Measured as count of participants. | At end of treatment (week 64) | 
| Number of participants who achieve body weight loss equal to or above 15 percent (yes/no) | Measured as count of participants. | At end of treatment (week 64) | 
| Number of participants who achieve body weight loss equal to or above 20 percent (yes/no) | Measured as count of participants. | At end of treatment (week 64) | 
| Change in Impact of Weight on Quality of Life-Lite-Clinical Trials version (IWQOL-Lite-CT) (Physical Function Domain [5-items] Score) | The Impact of Weight on Quality of Life Clinical Trials Version (IWQOL-Lite-CT) is designed to assess the impact of changes in weight on participant's quality of life within the context of clinical trials. IWQOL-Lite-CT is a 20-item questionnaire-based instrument used to assess the impact of body weight changes on participant's overall health-related quality of life (HRQoL). All IWQOL-Lite-CT composite scores range from 0 to 100, with higher scores reflecting better levels of functioning. | From baseline (week 0) to end of treatment (week 64) | 
| Change in body mass index (BMI) | Measured in kilogram per square meter (kg/m^2). | From baseline (week 0) to end of treatment (week 64) | 
| Change in waist circumference | Measured in centimeter (cm). | From baseline (week 0) to end of treatment (week 64) | 
| Change in systolic blood pressure | Measured in millimeter of mercury (mmHg). | From baseline (week 0) to end of treatment (week 64) | 
| Change in diastolic blood pressure | Measured in mmHg. | From randomisation (week 0) to end of treatment (week 64) | 
| Change in glycated haemoglobin (HbA1c) | Measured in percentage point (%-point). | From baseline (week 0) to end of treatment (week 64) | 
| Change in lipid: Total cholesterol (ratio to baseline) | Change from baseline in total cholesterol at week 64 will be presented as ratio to baseline. | From baseline (week 0) to end of treatment (week 64) | 
| Change in lipid: High-density lipoprotein (HDL) cholesterol (ratio to baseline) | Change from baseline in HDL cholesterol at week 64 will be presented as ratio to baseline. | From baseline (week 0) to end of treatment (week 64) | 
| Change in lipid: Low-density lipoprotein (LDL) cholesterol (ratio to baseline) | Change from baseline in LDL cholesterol at week 64 will be presented as ratio to baseline. | From baseline (week 0) to end of treatment (week 64) | 
| Change in lipid: Very-low-density lipoprotein (VLDL) cholesterol (ratio to baseline) | Change from baseline in VLDL cholesterol at week 64 will be presented as ratio to baseline. | From baseline (week 0) to end of treatment (week 64) | 
| Change in lipid: Triglycerides (ratio to baseline) | Change from baseline in triglycerides at week 64 will be presented as ratio to baseline. | From baseline (week 0) to end of treatment (week 64) | 
| Change in lipid: Free fatty acids (ratio to baseline) | Change from baseline in free fatty acids at week 64 will be presented as ratio to baseline. | From baseline (week 0) to end of treatment (week 64) | 
| Change in high sensitivity C Reactive Protein | Change from baseline in high sensitivity C Reactive Protein at week 64 will be presented as ratio to baseline. | From baseline (week 0) to end of treatment (week 64) | 
| Change in fasting plasma glucose (FPG) | Change from baseline in FPG at week 64 will be presented as ratio to baseline. | From baseline (week 0) to end of treatment (week 64) | 
| Change in fasting serum insulin | Change from baseline in fasting serum insulin at week 64 will be presented as ratio to baseline. | From baseline (week 0) to end of treatment (week 64) | 
| Number of treatment emergent adverse events | Measured as count of events. | From baseline (week 0) to end of study (week 71) | 
| Number of treatment emergent serious adverse events | Measured as count of events. | From baseline (week 0) to end of study (week 71) |