Research Study to Investigate How Well Semaglutide Tablets Taken Once Daily Work in People Who Are Overweight or Living With Obesity (OASIS 1)

Study Overview
=================
Brief Summary
-----------------
This study is being conducted to see if semaglutide tablets can be used as a treatment to help people living with overweight or obesity lose weight. This study will look at the change in participants body weight. Participants will either get semaglutide tablets (new medicine) or placebo tablets ('dummy' medicine that looks like semaglutide but has no effect on the body). For a fair comparison, people are divided into two groups at random by a computer. This process is called randomisation. Semaglutide tablets are new medicine being tested to treat overweight and obesity. Doctors in many countries can already prescribe semaglutide tablets at lower doses to treat type 2 diabetes. Participants will get semaglutide or placebo tablets for 68 weeks and will need to take 1 tablet every morning In addition to taking the medicine, participants will have talks with study staff about: healthy food choices how to be more physically active what participants can do to lose weight The study will last for about 1½ year.Participants will have 14 clinic visits and 7 phone calls with the study doctor. Blood samples will be taken at 10 visits. Participants will have a test to check their heart done at 3 visits. Women cannot take part if pregnant, breast-feeding or plan to get pregnant during the study period. If participant is a woman and is able to become pregnant, participant will be checked for pregnancy via urine tests.

Official Title
-----------------
Efficacy and Safety of Oral Semaglutide 50 mg Once Daily in Subjects With Overweight or Obesity (OASIS 1)

Conditions
-----------------
Obesity, Overweight

Intervention / Treatment
-----------------
* Drug: Oral semaglutide
* Drug: Placebo (semaglutide)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female, age greater than or equal to 18 years at the time of signing informed consent Body mass index (BMI): 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 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: HbA1c greater than or equal to 6.5% (48 mmol/mol) as measured by the central laboratory at screening A self-reported change in body weight greater than 5 kg (11 lbs) within 90 days before screening irrespective of medical records

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral semaglutide<br>Participants will receive once daily semaglutide tables in a dose escalating manner for 68 weeks: 3 mg (week 1-4), 7 mg (week 5-8), 14 mg (week 9-12), 25 mg (week 13-16) and 50 mg (week 17-68) | Drug: Oral semaglutide<br>* Participants will receive a daily dose of oral semaglutide.<br>|
| Placebo Comparator: Oral semaglutide placebo<br>All participants are given once daily dose for 68 weeks | Drug: Placebo (semaglutide)<br>* Oral placebo (semaglutide) once daily. Planned treatment duration will be 68 weeks.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative change in body weight | percentage-point | From baseline (week 0) to end of treatment (week 68) | 
| Achievement of body weight reduction greater than or equal to 5% (Yes/No) | Count of participants | At end-of-treatment (week 68) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Achievement of body weight reduction greater than or equal to 10% (Yes/No) | Count of participants | At end of treatment (week 68) | 
| Change in Short Form-36 (SF-36) Physical Function | Score points | From baseline (week 0) to end of treatment (week 68) | 
| Change in IWQOL-Lite-CT Physical Function | Score points | From baseline (week 0) to end of treatment (week 68) | 
| Change in waist circumference | measured in cm | From baseline (week 0) to end of treatment (week 68) | 
| Achievement of body weight reduction greater than or equal to 15% (Yes/No) | Count of participants | At end of treatment (week 68) | 
| Achievement of body weight reduction greater than or equal to 20% (Yes/No) | Count of participants | At end of treatment (week 68) | 
| Change in body mass index (BMI) | measured in kg/m^2 | From baseline (week 0) to end of treatment (week 68) | 
| Change in systolic blood pressure | measured in mmHg | From baseline (week 0) to end of treatment (week 68) | 
| Change in diastolic blood pressure | measured in mmHg | From randomisation (week 0) to end of treatment (week 68) | 
| Change in HbA1c (glycated haemoglobin) | percentage-point | From baseline (week 0) to end of treatment (week 68) | 
| Change in fasting plasma glucose (FPG) | measured in mg/dL | From baseline (week 0) to end of treatment (week 68) | 
| Change in fasting serum insulin | Ratio to baseline | From baseline (week 0) to end of treatment (week 68) | 
| Change in lipids: Total cholesterol | Ratio to baseline | From baseline (week 0) to end of treatment (week 68) | 
| Change in lipids: HDL (high density lipoprotein) cholesterol | Ratio to baseline | From baseline (week 0) to end of treatment (week 68) | 
| Change in lipids: LDL (low-density lipoprotein) cholesterol | Ratio to baseline | From baseline (week 0) to end of treatment (week 68) | 
| Change in lipids: VLDL (very-low density lipoprotein) cholesterol | Ratio to baseline | From baseline (week 0) to end of treatment (week 68) | 
| Change in lipids: Triglycerides | Ratio to baseline | From baseline (week 0) to end of treatment (week 68) | 
| Change in lipids: Free fatty acids | Ratio to baseline | From baseline (week 0) to end of treatment (week 68) | 
| Change in high sensitivity C-Reactive Protein | Ratio to baseline | From baseline (week 0) to end of treatment (week 68) | 
| Number of treatment emergent adverse events | Count of events | From baseline (week 0) to end-of-trial (week 75) | 
| Number of serious adverse events | Count of events | From baseline (week 0) to end-of-trial (week 75) |