Overweight and Obesity
Conditions
Brief summary
Novo Nordisk are doing this study 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 healthcare professional. Blood samples will be taken at 12 visits. Women cannot take part if pregnant, breast-feeding or planning to get pregnant during the study period. If participants are a woman and are able to become pregnant, participants will be checked for pregnancy via urine tests.
Interventions
DRUGsemaglutide 50 mg
Participants will have semaglutide for 68 weeks and will have 1 tablet every morning. Dose gradually increased to 50 mg.
DRUGplacebo (semaglutide)
Participants will have placebo tablets for 68 weeks and will have 1 tablet every morning.
Sponsors
Novo Nordisk A/S
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 No maximum
Healthy volunteers
No
Inclusion criteria
Participants are eligible to be included in the study only if all the following criteria apply: * 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 above 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 greater than or equal to 2 weight related comorbidities (treated or untreated) according to the JASSO guideline or BMI greater than or equal to 35.0 kg/m\^2 with greater than or equal to1 weight related comorbidity (treated or untreated) according to the JASSO guideline. At least one comorbidity should be hypertension, dyslipidaemia or type 2 diabetes (T2D) * History of at least one self-reported unsuccessful dietary effort to lose body weight For participants with T2D at screening the following inclusion criteria apply in addition to criteria 1-4: * Diagnosed with T2D greater than or equal to 180 days prior to 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 drugs (OADs) alone or in any combination (metformin, α-glucosidase (AGI), sulphonylureas (SU), glinides, SGLT2i (sodium-glucose co-transporter 2 inhibitor) or thiazolidinediones) * HbA1c 7.0-10.0% (53-86 mmol/mol) (both inclusive) as measured by central laboratory at screening
Exclusion criteria
Participants without T2D only: * HbA1c greater than or equal to 6.5% (48 mmol/mol) as measured by the central laboratory at screening * History of type 1 or type 2 diabetes * Treatment with glucose-lowering agent(s) within 90 days prior to screening * Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of eGFR brlow 15 ml/min/1.73 m\^2 according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation as defined by kidney disease improving global outcomes (KDIGO) 2012 classification by the central laboratory at screening Participants with T2D at screening only: * Treatment with any medication for the indication of diabetes other than stated in the inclusion criteria within the past 60 days prior to screening * Receipt of any other anti-diabetic investigational drug within 90 days prior to screening for this study, or receipt of any investigational drugs not affecting diabetes within 30 days prior to screening for this study * Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed by an ophthalmologist or another suitably qualified health care provider 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. * Renal impairment measured as eGFR value of below 30 mL/min/1.73 m\^2 according to CKD EPI creatinine equation as defined by KDIGO 2012 classification by the central laboratory at screening * In participants treated with SGLT2i, renal impairment measured as eGFR value of below 60 mL/min/1.73 m\^2 according to CKD EPI creatinine equation as defined by KDIGO 2012 classification by the central laboratory at screening The following criteria apply to all participants: Obesity-related: * Treatment with any medication indicated for weight management within 90 days prior to screening * Previous or planned (during the study period) obesity treatment with surgery or a weight loss device. However, the following are allowed: (1) liposuction and/or abdominoplasty, if performed greater than 1 year prior to screening, (2) lap banding, if the band has been removed greater than 1 year prior to screening, (3) intragastric balloon, if the balloon has been removed greater than 1 year prior to screening or (4) duodenal-jejunal bypass sleeve, if the sleeve has been removed greater than 1 year prior to screening * Uncontrolled thyroid disease per investigators discretion * A self-reported change in body weight greater than 5 kg (11 lbs) within 90 days before screening irrespective of medical records
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Body Weight | Baseline (week 0), week 68 | Percent change in body weight from baseline (week 0) to week 68 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site. |
| Number of Participants Who Achieved Body Weight Reduction Greater Than or Equal (>=) to 5% (Yes/No) | At week 68 | Number of participants who achieved \>=5% weight reduction at week 68 is presented. In the reported data, 'Yes' infers the number of participants who have achieved greater than or equal to 5% weight reduction, whereas 'No' infers the number of participants who have not achieved greater than or equal to 5% weight reduction. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Very Low-Density Lipoproteins (VLDL): Ratio to Baseline | Baseline (week 0), week 68 | Change in VLDL measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75). |
| Change From Baseline in Triglycerides: Ratio to Baseline | Baseline (week 0), week 68 | Change in triglycerides measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75). |
| Change From Baseline in Free Fatty Acids: Ratio to Baseline | Baseline (week 0), week 68 | Change in free fatty acids measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75). |
| Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) : Ratio to Baseline | Baseline (week 0), week 68 | Change in hsCRP measured as milligrams per liter (mg/L) from baseline (week 0) to week 68 is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site. |
| Number of Treatment Emergent Adverse Events (TEAEs) | Week 0 to week 75 | An adverse event (AE) defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of an investigational medicinal product (IMP), whether or not considered related to the IMP. All AEs mentioned are treatment emergent adverse events (TEAE) defined as an event with onset during the on-treatment observation period. On-treatment: the date of first trial product administration (week 0) to the date of last trial product administration (week 68) excluding potential off-treatment time intervals of more than 3 consecutive days. For the evaluation of adverse events the lag time for each on-treatment time interval is 7 weeks. |
| Number of Serious Adverse Events (SAEs) | Week 0 to week 75 | A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose results in death, or is life-threatening, or requires inpatient hospitalization or causes prolongation of existing hospitalization results in persistent or significant disability/incapacity, or may have caused a congenital anomaly/birth defect, or requires intervention to prevent permanent impairment or damage. SAE results occurred from week 0 to week 75 is presented based on the on-treatment observation, which was defined as the date of first trial product administration (week 0) to the date of last trial product administration (week 68) excluding potential off-treatment time intervals of more than 3 consecutive days. For the evaluation of adverse events the lag time for each on-treatment time interval is 7 weeks. |
| Change From Baseline in Low-Density Lipoproteins (LDL): Ratio to Baseline | Baseline (week 0), week 68 | Change in LDL measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75). |
| Number of Participants Who Achieved Body Weight Reduction Greater Than or Equal (>=) to 10% (Yes/No) | At week 68 | Number of participants who achieved \>=10% weight reduction at week 68 is presented. In the reported data, 'Yes' infers the number of participants who have achieved greater than or equal to 10% weight reduction, whereas 'No' infers the number of participants who have not achieved greater than or equal to 10% weight reduction. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site. |
| Change From Baseline in Impact of Weight on Quality of Life-Lite for Clinical Trials (IWQOL-Lite for CT) - Physical Function Domain (5-items) Score | Baseline (week 0), week 68 | 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 patient'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. Results for Physical Function Domain are presented in this outcome measure. The outcome measure was evaluated based on the data from in-trial observation period which is the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site. |
| Number of Participants Who Achieved Body Weight Reduction Greater Than or Equal (>=) to 15% (Yes/No) | At week 68 | Number of participants who achieved \>=15% weight reduction at week 68 is presented. In the reported data, 'Yes' infers the number of participants who have achieved greater than or equal to 15% weight reduction, whereas 'No' infers the number of participants who have not achieved greater than or equal to 15% weight reduction. The outcome measure was evaluated based on in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75). |
| Number of Participants Who Achieved Body Weight Reduction Greater Than or Equal (>=) to 20% (Yes/No) | At week 68 | Number of participants who achieved \>=20% weight reduction at week 68 is presented. In the reported data, 'Yes' infers the number of participants who have achieved greater than or equal to 20% weight reduction, whereas 'No' infers the number of participants who have not achieved greater than or equal to 20% weight reduction. The outcome measure was evaluated based on in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75). |
| Change From Baseline in Body Mass Index (BMI) | Baseline (week 0), week 68 | Change in BMI from baseline (week 0) to week 68 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75). |
| Change From Baseline in Waist Circumference Measured According to the JASSO (Japan Society for the Study of Obesity) Guideline | Baseline (week 0), week 68 | Change in waist circumference measured according to JASSO guideline from baseline (week 0) to week 68 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75). |
| Change From Baseline in Visceral Fat Area (VFA) Measured by CT Scan in a Subset of the Japanese Study Population (%) | Baseline (week 0), week 68 | Change in VFA measured by CT Scan in a subset of the japanese study population from baseline (week 0) to week 68 is presented in %. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75). |
| Change From Baseline in Visceral Fat Area (VFA) Measured by CT Scan in a Subset of the Japanese Study Population (Centimeter Square [cm^2]) | Baseline (week 0), week 68 | Change in VFA measured by CT Scan in a subset of the japanese study population from baseline (week 0) to week 68 is presented in cm\^2. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75). |
| Change From Baseline in Systolic Blood Pressure | Baseline (week 0), week 68 | Change in systolic blood pressure from baseline (week 0) to week 68 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75). |
| Change From Baseline in Diastolic Blood Pressure | Baseline (week 0), week 68 | Change in diastolic blood pressure from baseline (week 0) to week 68 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75). |
| Change From Baseline in Glycosylated Haemoglobin (HbA1c) | Baseline (week 0), week 68 | Change in glycosylated haemoglobin (HbA1c) from baseline (week 0) to week 68 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75). |
| Change From Baseline in Total Cholesterol: Ratio to Baseline | Baseline (week 0), week 68 | Change in total cholesterol measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75). |
| Change From Baseline in High-Density Lipoproteins (HDL): Ratio to Baseline | Baseline (week 0), week 68 | Change in HDL measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75). |
Countries
Japan, South Korea
Contacts
STUDY_DIRECTORClinical Transparency (dept. 1452)
Novo Nordisk A/S
Participant flow
Recruitment details
The trial was conducted at 13 sites in 2 countries as follows: Japan (9 sites) and South Korea (4 sites).
Pre-assignment details
Participants were randomised in 2:1 ratio to receive 50 milligram (mg) oral semaglutide or semaglutide matching placebo once weekly. The trial had a 68-week treatment period (16 weeks of dose escalation period and 52 weeks of maintenance period) followed by a 7-week follow-up period.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 50 Years STANDARD_DEVIATION 11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 67 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 201 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 87 Participants |
| Sex: Female, Male Male | 81 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 134 | 0 / 66 |
| other Total, other adverse events | 106 / 134 | 47 / 66 |
| serious Total, serious adverse events | 8 / 134 | 6 / 66 |
Outcome results
None listed