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

Novo Nordisk A/S375 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

375

Conditions

Overweight

Interventions

SemaglutideDRUG

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

Placebo (semaglutide)DRUG

Semaglutide placebo administered s.c. as an adjunct to a reduced-calorie diet and increased physical activity regimen for 44 weeks

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (33)

Instituto de Ciências Farmacêuticas de Estudos e Pesquisas

Aparecida de Goiânia, Goiás, Brazil

CPCLIN - Centro de Pesquisas Clínicas

São Paulo, São Paulo, Brazil

The First Affiliated Hospital of Anhui Medical University-Endocrinology

Hefei, Anhui, China

Chinese People's Liberation Army General Hospital-Endocrinology

Beijing, Beijing Municipality, China

Beijing Luhe Hospital Capital Medical University

Beijing, Beijing Municipality, China

Outcomes

Primary Outcomes

Change From Baseline in Body Weight (Percentage [%])

Change from baseline at week 0 to week 44 in body weight (%) is presented.The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: Baseline (week 0), week 44

Number of Participants Who Achieved Body Weight Reduction Greater Than or Equal (>=) to 5% (Yes/No)

Number of participants who achieved \>=5% weight reduction at week 44 for in-trial observation period 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. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: At week 44

Secondary Outcomes

Number of Participants Who Achieved Body Weight Reduction Greater Than or Equal (>=) to 10% (Yes/No)

Number of participants who achieved \>=10% weight reduction at week 44 for in-trial observation period 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. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: At week 44

Number of Participants Who Achieved Body Weight Reduction Greater Than or Equal (>=) to 15% (Yes/No)

Number of participants who achieved \>=15% weight reduction at week 44 for in-trial observation period 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. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: At week 44

Change From Baseline in Waist Circumference

Change in waist circumference from baseline (week 0) to week 44 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: Baseline (week 0), week 44

Change From Baseline in Body Weight (Kilogram [kg])

Change in body weight from baseline (week 0) to week 44 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: Baseline (week 0), week 44

Change From Baseline in Body Mass Index (BMI)

Change in BMI from baseline (week 0) to week 44 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: Baseline (week 0), week 44

Number of Participants Who Achieved Body Weight Reduction Greater Than or Equal (>=) to 20% (Yes/No)

Number of participants who achieved \>=20% weight reduction at week 44 for in-trial observation period 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. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: At week 44

Change From Baseline in Systolic Blood Pressure

Change in systolic blood pressure from baseline (week 0) to week 44 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: Baseline (week 0), week 44

Change From Baseline in Short Form-36 (SF-36) - Physical Functioning Score

SF-36 is a 36-item participants-reported survey of participants health that measures the partici-pants overall health-related quality of life (HRQoL). SF-36 questionnaire measured 8 domains of functional health and well-being as well as 2 component summary scores (physical component summary and mental component summary). This outcome measure shows results for 'physical functioning domain'. Physical function domain score ranges from 0 to 100, with higher values indicating better functional health and well-being. Change from baseline (week 0) in the domain scores were evaluated at week 44. These outcome measures were evaluated based on data from in-trial observation period which is the uninterrupted time interval from (week 0) to (week 51).

Time frame: Baseline (week 0), week 44

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

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 participants 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 participants overall health-related quality of life (HRQoL). All IWQOL-Lite-CT composite and physical function domain scores range from 0 to 100, with higher scores reflecting better levels of functioning. This outcome measure shows results for 'physical function domain'. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: Baseline (week 0), week 44

Change From Baseline in Glycosylated Haemoglobin (HbA1c) (Percentage [%])

Change in glycosylated haemoglobin (HbA1c) (%) from baseline (week 0) to week 44 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: Baseline (week 0), week 44

Change From Baseline in HbA1c (Millimoles Per Mole [mmol/Mol])

Change in HbA1c (mmol/mol) from baseline (week 0) to week 44 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: Baseline (week 0), week 44

Change From Baseline in Fasting Plasma Glucose (FPG) (Milligrams Per Deciliter [mg/dL])

Change in fasting plasma glucose (mg/dL) from baseline (week 0) to week 44 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: Baseline (week 0), week 44

Change From Baseline in FPG (Millimoles Per Liter [mmol/L])

Change in FPG (mmol/L) from baseline (week 0) to week 44 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: Baseline (week 0), week 44

Change From Baseline in Fasting Serum Insulin: Ratio to Baseline

Change in fasting serum insulin measured as milli-international units per milliliter (mIU/mL) from baseline (week 0) to week 44 is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: Baseline (week 0), week 44

Change From Baseline in Diastolic Blood Pressure

Change in diastolic blood pressure from baseline (week 0) to week 44 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: Baseline (week 0), week 44

Change From Baseline in Total Cholesterol: Ratio to Baseline

Change in total cholesterol measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 44 is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: Baseline (week 0), week 44

Change From Baseline in High-Density Lipoproteins (HDL)-Ratio to Baseline

Change in HDL measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 44 is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: Baseline (week 0), week 44

Change From Baseline in Low-Density Lipoproteins (LDL)-Ratio to Baseline

Change in LDL measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 44 is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: Baseline (week 0), week 44

Change From Baseline in Very Low-Density Lipoproteins (VLDL)-Ratio to Baseline

Change in VLDL measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 44 is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: Baseline (week 0), week 44

Change From Baseline in Free Fatty Acids-Ratio to Baseline

Change in free fatty acids measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 44 is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: Baseline (week 0), week 44

Change From Baseline in Triglycerides-Ratio to Baseline

Change in triglycerides measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 44 is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: Baseline (week 0), week 44

Change From Baseline in SF-36 All Domains (Except Physical Functioning) and 2 Component Summary Scores

SF-36 is a 36-item participant-reported survey of health that measures the overall HRQoL. SF-36 questionnaire measured 8 domains of functional health and well-being as well as 2 component summary scores (physical and mental component summary). This outcome measure shows results for all domains (except physical functioning) and 2 component summary scores. The score ranges from 0 to 100, with higher values indicating better functional health and well-being. Change from baseline week 0 in domain and component summary scores were evaluated at week 44 based on data from in-trial observation period which is uninterrupted time interval from (week 0) to (week 51).

Time frame: Baseline (week 0), week 44

Change From Baseline in IWQOL-Lite for Physical Domain Score, Psychological Domain Score and Total 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 participants 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 participants overall health-related quality of life (HRQoL). All IWQOL-Lite-CT composite scores for physical domain score, psychosocial domain score and total score ranges from 0 to 100, with higher scores reflecting better levels of functioning. This outcome measure shows results for 'physical and psychosocial domains, and for total'. The outcome measure was evaluated based on the data from in-trial observation period which is the uninterrupted time interval from start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: Baseline (week 0), week 44

Number of Participants Who Achieved Responder Definition Value for SF-36 Physical Functioning Score (Yes/No)

The number of participants experiencing a meaningful within participant improvement in SF-36 Physical function after 44 weeks was determined based on 3.7 threshold. The threshold of 3.7 is specific for overweight or obese population included in the study and calculated using participant global rating anchor questionnaires to reflect participants own perspective based on Food and Drug Administration (FDA) recommendations. In the reported data, "Yes" infers the number of participants who have achieved an improvement in score greater than or equal to the threshold and "No" infers number of participants who have not achieved an improvement in score greater than or equal to the threshold. The outcome measure was evaluated based on in-trial observation period which is the uninterrupted time interval from start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: At week 44

Number of Participants Who Achieved Responder Definition Value For IWQoL-Lite for CT Physical Function (5-items) Score (Yes/No)

The number of participants experiencing a meaningful within participant improvement in IWQOL-Lite-CT physical function after 44 weeks was determined based on thresholds of 14.6. The threshold of 14.6 is specific for the population with overweight or obesity included in the study and calculated using patient global rating anchor questionnaires to reflect participants own perspective based on FDA recommendations. In the reported data, "Yes" infers the number of participants who have achieved an improvement in score greater than or equal to the threshold and "No" infers the number of participants who have not achieved an improvement in score greater than or equal to the threshold. The outcome measure was evaluated based on in-trial observation period which is the uninterrupted time interval from start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: At week 44

Number of Participants With Type 2 Diabetes (T2D) Who Achieved HbA1c Less Than (<) 7.0 Percent (%) (53 mmol/Mol)

Number of participants with T2D who achieved HbA1c \< 7% (53 mmol/mol) at week 44 is presented. In the reported data, "Yes" infers the number of participants who have achieved HbA1c values less than the 7% and "No" infers the number of participants who have not achieved HbA1c values less than the 7%. The outcome measure was evaluated based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: At week 44

Number of Participants With T2D Who Achieved HbA1c Less Than or Equal to (<=) 6.5% (48 mmol/Mol)

Number of participants with T2D who achieved HbA1c \<= 6.5% (48 mmol/mol) at week 44 is presented. In the reported data, "Yes" infers the number of participants who have achieved HbA1c values less than or equal to 6.5% and "No" infers the number of participants who have not achieved HbA1c values less than or equal to 6.5%. The outcome measure was evaluated based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: At week 44

Change From Baseline in Glycaemic Category (Normo-Glycaemia, Pre-Diabetes, T2D) in Participants With no T2D at Baseline

Change from baseline in number of participants in glycaemic categories (normo-glycaemia, pre-diabetes and type 2 diabetes) at baseline (week 0) to week 44 are presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: Baseline (week 0), week 44

Change From Baseline in Number of Participants With Antihypertensive Medication (Decrease, No Change, Increase)

Change from baseline in number of participants in antihypertensive medication (decrease, no change, increase) at baseline (week 0) to week 44 are presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: Baseline (week 0), week 44

Change From Baseline in Number of Participants With Lipid-Lowering Medication (Decrease, No Change, Increase)

Change from baseline in number of participants in lipid-lowering medication (decrease, no change, increase) at baseline (week 0) to week 44 are presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: Baseline (week 0), week 44

Change From Baseline in Number of Participants With Concomitant Oral Antidiabetic Medication (Decrease, No Change, Increase) in Participants With No T2D at Baseline

Change from basline in number of participants with concomitant oral antidiabetic medication (decrease, no change, increase) at baseline (week 0) to week 44 are presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: Baseline (week 0), week 44

Change From Baseline in Number of Participants in Fatty Liver Index (FLI) Score Category

Change from baseline in number of participants in fatty liver index (FLI) at baseline (week 0) to week 44 are presented. The fatty liver index is based on an algorithm including body mass index, waist circumference, triglycerides and gamma-glutamyl-transferase. The FLI scores less than (\<) 30 indicates no hepatic steatosis (no fatty liver), FLI greater than or equal to (\>=) 30 to less than (\<) 60 indicates intermediate status of hepatic steatosis and \>=60 indicates severe/worse hepatic steatosis. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: Baseline (week 0), week 44

Number of Participants Who From Randomization Permanently Discontinued Randomized Trial Product

Number of participants who permanently discontinued randomized trial product from baseline (week 0) to week 44 are presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time frame: Baseline (week 0), week 44

Time to Permanent Discontinuation of Randomized Trial Product (Weeks)

Time to permanent discontinuation of randomised trial product from baseline (week 0) to week 44 is reported. Participants who permanently discontinued the randomised trial product during the in-trial observation period were only included in the analysis. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to date of last contact with trial site (week 51).

Time frame: Baseline (week 0), week 44

Number of Treatment Emergent Adverse Events (TEAEs)

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 a product, whether or not considered related to the product. All AEs mentioned are treatment emergent adverse events (TEAE) defined as an event with onset during the on-treatment observation period. On-treatment observation period: the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 44) plus a 7 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.

Time frame: Baseline (week 0), week 51

Number of Serious Adverse Events (SAEs)

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 51 is presented based on the on-treatment observation, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 44) plus a 7 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.

Time frame: Baseline (week 0), week 51

Number of Treatment Emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemia Episodes (Yes/No) in Participants With T2D at Week 0

Hypoglycaemic episodes with onset during on-treatment observation period were considered treatment-emergent. Number of treatment emergent severe or BG confirmed symptomatic hypoglycaemia episodes in participants with T2D at week 0 with onset during on-treatment observation period were presented.

Time frame: Baseline (week 0), week 51

Change From Baseline in Pulse

Change in pulse from baseline (week 0) to week 44 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 44) plus a 7 week follow-up period and excluding any off-treatment time intervals.

Time frame: Baseline (week 0), week 44

Change From Baseline in Amylase: Ratio to Baseline

Change in amylase measured in units/liter (U/L) from baseline (week 0) to week 44 is presented as ratio to baseline. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 44) plus a 7 week follow-up period and excluding any off-treatment time intervals.

Time frame: Baseline (week 0), week 44

Change From Baseline in Lipase: Ratio to Baseline

Change in lipase measured in units/liter (U/L) from baseline (week 0) to week 44 is presented as ratio to baseline. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 44) plus a 7 week follow-up period and excluding any off-treatment time intervals.

Time frame: Baseline (week 0), week 44

Change From Baseline in Calcitonin: Ratio to Baseline

Change in calcitonin measured in units/liter (U/L) from baseline (week 0) to week 44 is presented as ratio to baseline. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 44) plus a 7 week follow-up period and excluding any off-treatment time intervals.

Time frame: Baseline (week 0), week 44