Research Study Investigating How Well Semaglutide Works in People Suffering From Overweight or Obesity

Obesity Clinical Trial

— STEP 4  

Official title:

Effect and Safety of Semaglutide 2.4 mg Once-weekly in Subjects With Overweight or Obesity Who Have Reached Target Dose During run-in Period

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03548987
• Other study ID #: NN9536-4376
• Secondary ID: U1111-1201-08982
• Status: Completed
• Phase: Phase 3
• Start date: June 4, 2018
• Est. completion date: March 20, 2020

Study information

• Verified date: January 2022
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will look at the change in participant's body weight from the start to the end of the study. This 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, the participant will have talks with study staff about healthy food choices, how to be more physically active and what a participant can do to lose weight.

The participant will get semaglutide for the first 20 weeks. Then the participant will get either semaglutide or "dummy" medicine - which treatment the participant gets after the 20 weeks is decided by chance. The participants will need to take 1 injection once a week. The study medicine is injected with a thin needle in a skin fold in the stomach, thigh or upper arm. The study will last for about 1.5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 902
• Est. completion date: March 20, 2020
• Est. primary completion date: February 22, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female, age greater than or equal to 18 years at the time of signing informed consent

• Body mass index greater than or equal to 30 kg/sqm or greater than or equal to 27 kg/sqm with the presence of at least one of the following weight related comorbidities (treated or untreated): hypertension, dyslipidaemia, obstructive sleep apnoea or cardiovascular disease

• History of at least one self-reported unsuccessful dietary effort to lose body weight

Exclusion Criteria:

• Haemoglobin A1c greater than or equal to 48 mmol/mol (6.5%) as measured by central laboratory at screening

• A self-reported change in body weight more than 5 kg (11 lbs) within 90 days before screening irrespective of medical records

Related Conditions & MeSH terms

• Metabolism and Nutrition Disorder
• Nutrition Disorders
• Obesity
• Overweight

Intervention

Drug:
• Semaglutide
Subcutaneous (under the skin) injection of semaglutide once-weekly.
• Placebo
Subcutaneous (under the skin) injection of semaglutide placebo once-weekly.

Locations

Country	Name	City	State
Denmark	Novo Nordisk Investigational Site	Frederiksberg C
Denmark	Novo Nordisk Investigational Site	Køge
Israel	Novo Nordisk Investigational Site	Haifa
Israel	Novo Nordisk Investigational Site	Jerusalem
Israel	Novo Nordisk Investigational Site	Kfar Saba
Israel	Novo Nordisk Investigational Site	Petah-Tikva
Israel	Novo Nordisk Investigational Site	Tel Hashomer
Israel	Novo Nordisk Investigational Site	Tel-Aviv
Netherlands	Novo Nordisk Investigational Site	Amsterdam
Netherlands	Novo Nordisk Investigational Site	Amsterdam
Netherlands	Novo Nordisk Investigational Site	Arnhem
Portugal	Novo Nordisk Investigational Site	Braga
Portugal	Novo Nordisk Investigational Site	Coimbra
Portugal	Novo Nordisk Investigational Site	Matosinhos
Portugal	Novo Nordisk Investigational Site	Porto
Portugal	Novo Nordisk Investigational Site	Porto
Portugal	Novo Nordisk Investigational Site	Vila Nova de Gaia
South Africa	Novo Nordisk Investigational Site	Brits	North West
South Africa	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal
South Africa	Novo Nordisk Investigational Site	Johannesburg	Gauteng
South Africa	Novo Nordisk Investigational Site	Johannesburg	Gauteng
South Africa	Novo Nordisk Investigational Site	Pretoria	Gauteng
South Africa	Novo Nordisk Investigational Site	Pretoria	Gauteng
Spain	Novo Nordisk Investigational Site	Almeria
Spain	Novo Nordisk Investigational Site	Madrid
Spain	Novo Nordisk Investigational Site	Madrid
Spain	Novo Nordisk Investigational Site	Sabadell
Spain	Novo Nordisk Investigational Site	Sevilla
Spain	Novo Nordisk Investigational Site	Sevilla
Spain	Novo Nordisk Investigational Site	Sevilla
Sweden	Novo Nordisk Investigational Site	Malmö
Sweden	Novo Nordisk Investigational Site	Stockholm
Sweden	Novo Nordisk Investigational Site	Uppsala
Switzerland	Novo Nordisk Investigational Site	Genève 14
Switzerland	Novo Nordisk Investigational Site	Olten
Switzerland	Novo Nordisk Investigational Site	St. Gallen
Switzerland	Novo Nordisk Investigational Site	St. Gallen
Switzerland	Novo Nordisk Investigational Site	Zollikerberg
Switzerland	Novo Nordisk Investigational Site	Zürich
Ukraine	Novo Nordisk Investigational Site	Kharkiv
Ukraine	Novo Nordisk Investigational Site	Kyiv
Ukraine	Novo Nordisk Investigational Site	Kyiv
Ukraine	Novo Nordisk Investigational Site	Kyiv
Ukraine	Novo Nordisk Investigational Site	Odesa
United States	Novo Nordisk Investigational Site	Alpharetta	Georgia
United States	Novo Nordisk Investigational Site	Anniston	Alabama
United States	Novo Nordisk Investigational Site	Arlington	Virginia
United States	Novo Nordisk Investigational Site	Austin	Texas
United States	Novo Nordisk Investigational Site	Baton Rouge	Louisiana
United States	Novo Nordisk Investigational Site	Bristol	Tennessee
United States	Novo Nordisk Investigational Site	Bristol	Tennessee
United States	Novo Nordisk Investigational Site	Buckley	Michigan
United States	Novo Nordisk Investigational Site	Chattanooga	Tennessee
United States	Novo Nordisk Investigational Site	Cincinnati	Ohio
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Dayton	Ohio
United States	Novo Nordisk Investigational Site	Elkridge	Maryland
United States	Novo Nordisk Investigational Site	Fresno	California
United States	Novo Nordisk Investigational Site	Greensboro	North Carolina
United States	Novo Nordisk Investigational Site	Greenville	North Carolina
United States	Novo Nordisk Investigational Site	Louisville	Kentucky
United States	Novo Nordisk Investigational Site	New York	New York
United States	Novo Nordisk Investigational Site	Omaha	Nebraska
United States	Novo Nordisk Investigational Site	Raleigh	North Carolina
United States	Novo Nordisk Investigational Site	Richmond	Virginia
United States	Novo Nordisk Investigational Site	Roswell	Georgia
United States	Novo Nordisk Investigational Site	Salisbury	North Carolina
United States	Novo Nordisk Investigational Site	San Diego	California
United States	Novo Nordisk Investigational Site	Suwanee	Georgia
United States	Novo Nordisk Investigational Site	Wenatchee	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Denmark,  Israel,  Netherlands,  Portugal,  South Africa,  Spain,  Sweden,  Switzerland,  Ukraine, 

References & Publications (2)

Kushner RF, Calanna S, Davies M, Dicker D, Garvey WT, Goldman B, Lingvay I, Thomsen M, Wadden TA, Wharton S, Wilding JPH, Rubino D. Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5. Obesity (Silver Spring). 2020 Jun;28(6):1050-1061. doi: 10.1002/oby.22794. — View Citation

Rubino D, Abrahamsson N, Davies M, Hesse D, Greenway FL, Jensen C, Lingvay I, Mosenzon O, Rosenstock J, Rubio MA, Rudofsky G, Tadayon S, Wadden TA, Dicker D; STEP 4 Investigators. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Lo — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Randomisation to Week 68 in Body Weight (%)	Change in body weight from baseline (week 20) to week 68 is presented. The endpoint was evaluated based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75). On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).	Randomisation (week 20) to week 68
Secondary	Change in Waist Circumference	Change in waist circumference from baseline (week 20) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Secondary	Change in Systolic Blood Pressure	Change in systolic blood pressure from week 20 to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Secondary	Change in Diastolic Blood Pressure	Change in diastolic blood pressure from week 20 to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Secondary	Change in Physical Functioning Score (Short Form 36 [SF-36])	SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary and mental component summary). The 0-100 scale scores from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively. Change from week 20 in the domain scores and component summary scores were evaluated at week 68. A positive change score indicates an improvement since baseline. These endpoints were evaluated based on the data from in-trial observation period which is the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Secondary	Change in Body Weight [Kilogram (Kg)]	Change in body weight from week 20 to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomisation (week 20) to week 68
Secondary	Change in Body Mass Index (BMI)	Change in BMI from week 20 to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Secondary	Change in Haemoglobin A1c (HbA1c) [%]	Change in HbA1c from week 20 to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Secondary	Change in HbA1c [Millimoles Per Mole (mmol/Mol)]	Change in HbA1c from week 20 to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Secondary	Change in Fasting Plasma Glucose [Milligrams Per Deciliter (mg/dL)]	Change in fasting plasma glucose from week 20 to week 68 is presented.The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Secondary	Change in Fasting Plasma Glucose [Millimoles Per Litre (mmol/L)]	Change in fasting plasma glucose from week 20 to week 68 is presented.The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Secondary	Change in Fasting Serum Insulin	Change in fasting serum insulin from baseline (week 20) to week 68 [measured as milli-international units per milliliter (mIU/mL)] is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Secondary	Change in Total Cholesterol	Change in fasting total cholesterol from baseline (week 20) to week 68 (measured as mmol/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Secondary	Change in High-density Lipoproteins (HDL)	Change in fasting HDL from baseline (week 20) to week 68 (measured as mmol/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Secondary	Change in Low-density Lipoproteins (LDL)	Change in fasting LDL from baseline (week 20) to week 68 (measured as mmol/L) is presented as ratio to baseline.The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Secondary	Change in Very Low-density Lipoproteins (VLDL)	Change in fasting VLDL from baseline (week 20) to week 68 (measured as mmol/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Secondary	Change in Free Fatty Acids	Change in fasting free fatty acids from baseline (week 20) to week 68 (measured as mmol/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Secondary	Change in Triglycerides	Change in fasting triglycerides from baseline (week 20) to week 68 (measured as mmol/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomization (week 20) to week 68
Secondary	Subjects Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score	The number of participants achieving at least a 4.3-point increase in SF-36 physical functioning score from baseline (week 20) to week 68 is presented. In the reported data, 'Yes' infers number of participants who have achieved 4.3 points of increase of the score and 'No' infers number of participants who have not achieved 4.3 points of increase of the score. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomisation (week 20) to week 68
Secondary	Subjects Who Gain Weight (Yes/no)	The number of participants with weight gain from the start of the randomised period (week 20) to week 68 is presented. In the reported data, 'Yes' infers number of participants who have gained weight and 'No' infers number of participants who have not gained weight. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Randomisation (week 20) to week 68
Secondary	Change in Body Weight	The body weight change (%) from week 0 to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Run-in (week 0) to week 68
Secondary	Subjects Who Achieve (Yes/no): Body Weight Reduction < 0%	The number of participants who achieved less than (<) 0% weight loss from week 0 to week 68 is presented. In the reported data, 'Yes' infers number of participants who have achieved <0% weight loss whereas 'No' infers number of participants who have not achieved <0% weight loss.The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Run-in (week 0) to week 68
Secondary	Subjects Who Achieve (Yes/no): Body Weight Reduction = 5%	The number of participants who achieved greater than or equal to (=) 5% weight loss from week 0 to week 68 is presented. In the reported data, 'Yes' infers number of participants who have achieved = 5% weight loss whereas 'No' infers number of participants who have not achieved = 5% weight loss. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Run-in (week 0) to week 68
Secondary	Subjects Who Achieve (Yes/no): Body Weight Reduction = 10%	The number of participants who achieved = 10% weight loss from week 0 to week 68 is presented. In the reported data, 'Yes' infers number of participants who have achieved = 10% weight loss whereas 'No' infers number of participants who have not achieved = 10% weight loss. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Run-in (week 0) to week 68
Secondary	Subjects Who Achieve (Yes/no): Body Weight Reduction = 15%	The number of participants who achieved = 15% weight loss from week 0 to week 68 is presented. In the reported data, 'Yes' infers number of participants who have achieved = 15% weight loss whereas 'No' infers number of participants who have not achieved = 15% weight loss. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).	Run-in (week 0) to week 68
Secondary	Number of Treatment-emergent Adverse Events (AEs)	An adverse event (AE) was 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 here are treatment emergent adverse events (TEAE) defined as an event that had onset date (or increase in severity) on or after the first day of exposure to treatment (week 0-20 run-in period). The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 7 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 7 consecutive missed doses (off-treatment period).	Run-in (week 0) to randomisation (week 20)
Secondary	Number of Treatment-emergent AEs	An AE was 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 here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to treatment (week 20-75). The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 7 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 7 consecutive missed doses (off-treatment period).	Randomisation (week 20) to week 75
Secondary	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. The SAEs occurred during run-in period from week 0 to week 20 is presented. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 7 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 7 consecutive missed doses (off-treatment period).	Run-in (week 0) to randomisation (week 20)
Secondary	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. The SAEs occurred during run-in period from week 0 to week 20 is presented. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 7 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 7 consecutive missed doses (off-treatment period).	Randomisation (week 20) to week 75
Secondary	Change in Pulse	Change in pulse rate from week 0 week to week 20 is presented. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).	Run-in (week 0) to randomisation (week 20)
Secondary	Change in Pulse	Change in pulse from week 20 and 68 is presented. The endpoint was evaluated based on the data from on-treatment observation period.On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).	Randomisation (week 20) to week 68
Secondary	Change in Amylase	Change in amylase (measured as units per liter [U/L]) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).	Run-in (week) 0 to randomization (week 20)
Secondary	Change in Amylase	Change in amylase (measured as U/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).	Randomisation (week 20) to week 68
Secondary	Change in Lipase	Change in lipase (measured as U/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).	Run-in (week 0) to randomization (week 20)
Secondary	Change in Lipase	Change in lipase (measured as U/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).	Randomisation (week 20) to week 68
Secondary	Change in Calcitonin	Change in calcitonin (measured as nanogram per liter (ng/L)]) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).	Run-in (week 0) to randomization (week 20)
Secondary	Change in Calcitonin	Change in calcitonin (measured as ng/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).	Randomisation (week 20) to week 68