Effectiveness of Semaglutide 2.4 mg vs. Commercially Available Medications for Chronic Weight Management in Participants With Obesity in a Multi-employer Setting in The US - a Pragmatic Clinical Study
Phase: PHASE4
Conditions: Obesity
Sponsor: Novo Nordisk A/S

Cover Page for Protocol
Sponsor name:
Novo Nordisk A/S
NCT number
1&7
Sponsor trial ID:
NN9536-4741
Official title of study:
Effectiveness of semaglutide 2.4 mg vs. commercially 
available medications for chronic weight management in 
participants with obesity in a multi-employer setting in the US 
– a pragmatic clinical study
Document date*:
15 September 2022
*Document date refers to the date on which the document was most recently updated.

Protocol
Date:
15 September 2022
Novo Nordisk
Study ID: NN9536-4741
Version:
2.0
Semaglutide 2.4 mg s.c.
Status:
Final
Page:
1 of 62
Protocol
Protocol Title: 
Effectiveness of semaglutide 2.4 mg vs. commercially available medications for chronic weight 
management in participants with obesity in a multi-employer setting in the US – a pragmatic 
clinical study
Substances: semaglutide 2.4 mg, orlistat, phentermine/topiramate, naltrexone/bupropion, 
liraglutide 3.0 mg
Universal Trial Number: U1111-1263-7301
Study phase: 4
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
CONFIDENTIAL
This confidential document is the property of Novo Nordisk. No unpublished information contained herein may be 
disclosed without prior written approval from Novo Nordisk. Access to this document must be restricted to relevant 
parties.

Protocol
Date:
15 September 2022
Novo Nordisk
Study ID: NN9536-4741
Version:
2.0
Semaglutide 2.4 mg s.c.
Status:
Final
Page:
2 of 62
Protocol amendment summary of changes table
Document History
Document version 
Date 
Applicable in country(-ies) and/or 
site(s)
Protocol version 2.0
15 September 2022
Yes
Original protocol version 1.0
01 February 2022
Submitted for IRB review
Protocol version 2.0 (15 September 2022)
This amendment is considered to be non-substantial because it neither substantially impacts the 
safety or rights of the participants nor the reliability or robustness of the data generated in the study.
Overall rationale for preparing protocol, version 2.0:
Section # and name
Description of change
Brief rationale
Section 4.1 Study design
Section 6.1.1 Lifestyle management
Section 1.1 Synopsis
The “Center for Health Promotion” 
has been changed to “Nutrition 
Research Centre”
The Investigator of the study has 
moved to a new site, the previous 
site “Center for Health Promotion” 
has been replaced with “Nutrition 
Research Centre” throughout the 
document
CONFIDENTIAL

Protocol
Date:
15 September 2022
Novo Nordisk
Study ID: NN9536-4741
Version:
2.0
Semaglutide 2.4 mg s.c.
Status:
Final
Page:
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Table of Contents
Page
Protocol amendment summary of changes table...........................................................................................2 
Table of Contents..............................................................................................................................................3 
1 Protocol summary .......................................................................................................................................6 
1.1 
Synopsis..............................................................................................................................................6 
1.2 
Flowchart ..........................................................................................................................................10 
2 Introduction...............................................................................................................................................11 
2.1 
Study rationale ..................................................................................................................................11 
2.2 
Background.......................................................................................................................................12 
2.3 
Benefit-risk assessment.....................................................................................................................12 
3 Objectives, endpoints and estimands.......................................................................................................13 
4 Study design...............................................................................................................................................16 
4.1 
Overall design...................................................................................................................................16 
4.2 
Scientific rationale for study design..................................................................................................17 
4.2.1 
Patient input into design ....................................................................................................17 
4.3 
Justification for dose.........................................................................................................................17 
4.4 
End of study definition......................................................................................................................17 
5 Study population .......................................................................................................................................19 
5.1 
Inclusion criteria ...............................................................................................................................19 
5.2 
Exclusion criteria ..............................................................................................................................19 
5.3 
Lifestyle considerations ....................................................................................................................20 
5.4 
Screen failures...................................................................................................................................20 
5.5 
Run-in criteria and/or randomisation criteria and/or dosing day criteria..........................................20 
6 Study interventions and concomitant therapy........................................................................................21 
6.1 
Investigational medicinal products (IMP).........................................................................................21 
6.1.1 
Lifestyle management........................................................................................................21 
6.2 
Co-pay assistance..............................................................................................................................22 
6.3 
Measures to minimise bias: Randomisation and blinding.................................................................22 
6.4 
Study intervention compliance..........................................................................................................22 
6.5 
Dose modification.............................................................................................................................22 
6.6 
Continued access to study intervention after end of study................................................................22 
6.7 
Treatment of overdose ......................................................................................................................22 
6.8 
Concomitant therapy.........................................................................................................................23 
7 Discontinuation of study intervention and participant discontinuation/withdrawal..........................24 
7.1 
Discontinuation of study intervention...............................................................................................24 
7.1.1 
Temporary discontinuation of study intervention..............................................................24 
7.2 
Participant discontinuation/withdrawal from the study ....................................................................24 
7.2.1 
Replacement of participants ..............................................................................................25 
7.3 
Lost to follow-up...............................................................................................................................25 
8 Study assessments and procedures ..........................................................................................................26 
8.1 
Efficacy assessments.........................................................................................................................26 
8.1.1 
Body measurements...........................................................................................................26 
8.1.2 
Patient reported outcomes and treatment satisfaction questionnaires ...............................26 
8.1.2.1 
Impact of Weight on Quality of Life-Lite for Clinical Trials (IWQOL-
Lite for CT)....................................................................................................26 
8.1.2.2 
Treatment Satisfaction Questionnaire for Medication (TSQM-9) .................27 
8.1.2.3 
Work Limitations Questionnaire (WLQ-25)..................................................27 
8.2 
Safety assessments............................................................................................................................27 
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Date:
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Study ID: NN9536-4741
Version:
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8.2.1 
Pregnancy testing...............................................................................................................28 
8.3 
Adverse events and other safety reporting........................................................................................28 
8.3.1 
Time period and frequency for collecting AE information ...............................................28 
8.3.2 
Method of detecting AEs...................................................................................................29 
8.3.3 
Follow-up of AEs ..............................................................................................................29 
8.3.4 
Regulatory reporting requirements for SAEs ....................................................................29 
8.3.5 
Pregnancy ..........................................................................................................................29 
8.3.6 
Technical complaints.........................................................................................................29 
8.4 
Pharmacokinetics and pharmacodynamics .......................................................................................30 
8.5 
Genetics ............................................................................................................................................30 
8.6 
Biomarkers........................................................................................................................................30 
8.7 
Immunogenicity assessments............................................................................................................30 
9 Statistical considerations ..........................................................................................................................31 
9.1 
Statistical hypotheses........................................................................................................................31 
9.1.1 
Multiplicity adjustment......................................................................................................31 
9.2 
Analysis sets......................................................................................................................................31 
9.3 
Statistical analyses ............................................................................................................................32 
9.3.1 
General considerations ......................................................................................................32 
9.3.2 
Primary estimand analysis.................................................................................................33 
9.3.3 
Secondary estimands analysis ...........................................................................................33 
9.3.3.1 
Confirmatory secondary estimands................................................................33 
9.3.3.2 
Supportive secondary endpoints ....................................................................34 
9.3.4 
Exploratory endpoints/estimand analysis ..........................................................................34 
9.3.5 
Other safety analyses.........................................................................................................34 
9.3.6 
Other analyses ...................................................................................................................34 
9.4 
Interim analysis.................................................................................................................................34 
9.5 
Sample size determination ................................................................................................................35 
10 Supporting documentation and operational considerations..................................................................38 
10.1 Appendix 1: Regulatory, ethical, and study oversight considerations..............................................38 
10.1.1 
Regulatory and ethical considerations...............................................................................38 
10.1.2 
Financial disclosure...........................................................................................................38 
10.1.3 
Informed consent process..................................................................................................39 
10.1.4 
Information to participants during the study .....................................................................39 
10.1.5 
Data protection ..................................................................................................................39 
10.1.6 
Committee’s structure........................................................................................................40 
10.1.6.1 
Novo Nordisk safety committee.....................................................................40 
10.1.7 
Dissemination of clinical study data..................................................................................40 
10.1.8 
Data quality assurance.......................................................................................................40 
10.1.8.1 
Case report forms...........................................................................................40 
10.1.8.2 
Monitoring .....................................................................................................41 
10.1.8.3 
Protocol compliance.......................................................................................42 
10.1.9 
Source documents..............................................................................................................42 
10.1.10 Retention of clinical study documentation ........................................................................42 
10.1.11 Study and site closure........................................................................................................43 
10.1.12 Responsibilities..................................................................................................................43 
10.1.13 Indemnity statement ..........................................................................................................44 
10.1.14 Publication policy..............................................................................................................44 
10.1.14.1 
Communication of results ..............................................................................44 
10.1.14.2 
Authorship......................................................................................................45 
10.1.14.3 
Site-specific publication(s) by investigator(s)................................................45 
10.1.14.4 
Investigator access to data and review of results ...........................................45 
10.2 Appendix 2: Adverse Events and Serious Adverse Events: Definitions and procedures for 
recording, evaluating, follow-up, and reporting ...............................................................................46 
10.2.1 
Definition of AE................................................................................................................46 
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Study ID: NN9536-4741
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10.2.2 
Definition of an SAE.........................................................................................................46 
10.2.3 
Description of AEs requiring additional data collection ...................................................47 
10.2.4 
Recording and follow-up of AE and/or SAE.....................................................................48 
10.2.4.1 
AE and SAE recording...................................................................................48 
10.2.4.2 
Assessment of severity...................................................................................48 
10.2.4.3 
Assessment of causality .................................................................................49 
10.2.4.4 
Final outcome.................................................................................................49 
10.2.4.5 
Follow-up of AE and SAE.............................................................................50 
10.2.5 
Reporting of SAEs.............................................................................................................50 
10.3 Appendix 3: Contraceptive guidance and collection of pregnancy information...............................51 
10.3.1 
Definitions.........................................................................................................................51 
10.3.2 
Contraceptive guidance .....................................................................................................52 
10.3.3 
Collection of pregnancy information.................................................................................53 
10.4 Appendix 4: Technical complaints: Definition and reporting...........................................................55 
10.4.1 
Definition of technical complaint......................................................................................55 
10.4.2 
Technical complaint reporting...........................................................................................55 
10.4.3 
Collection, storage, and shipment of technical complaint samples ...................................56 
10.5 Appendix 5: Abbreviations...............................................................................................................57 
11 References..................................................................................................................................................59 
CONFIDENTIAL

Protocol
Date:
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Study ID: NN9536-4741
Version:
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Status:
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1
Protocol summary
1.1
Synopsis
This is an interventional, randomized, parallel-group, open-label, active comparator-controlled, 
two-armed, pragmatic study in a multiple employer setting in the US.
Rationale:
The purpose of this post approval pragmatic clinical study is to demonstrate the real-world 
comparative effectiveness of semaglutide 2.4 mg versus existing commercially available Anti-
Obesity Medications, with respect to relative weight reduction, across three US-based employers. 
These employers represent approximately 28,000 employees of diverse demography and job 
functions including hospitality, clerical, administrative, housekeeping, maintenance, and specialised 
employees across a range of socioeconomic and educational backgrounds. 
Pragmatic studies can bridge the gap between randomized clinical studies and clinical practice, 
providing valuable real-world effectiveness data, while maintaining some of the elements of clinical 
study design such as treatment randomization .1, 2 This study will generate important evidence to 
inform health care decision makers such as employers, clinicians, payers, and policy makers about 
comprehensive approaches to obesity care management for employees. This study also 
complements the semaglutide development program by generating novel, ‘real-world’ data on 
semaglutide 2.4 mg compared with other anti-obesity medications, Xenical®, Qsymia®, Contrave®,
and Saxenda® (Other AOMs), within a US-based, multiple employer setting.
Objectives, endpoints and estimand(s):
Primary and secondary confirmatory objectives and endpoints are:
Objectives
Endpoints
Primary
Title
Time frame
Unit
To demonstrate the superiority of 
semaglutide 2.4 mg s.c. once weekly 
versus Other AOMs1, as an adjunct to 
lifestyle management, with respect to 
achieving ≥10.0% body weight reduction 
from baseline, in adults with obesity.
Primary:
Body weight reduction 
≥10.0% (yes/no)
At week 52
Count of 
participants
Secondary Confirmatory
Title
Time frame
Unit
To demonstrate the superiority of 
semaglutide 2.4 mg s.c once weekly versus 
Other AOMs, as an adjunct to lifestyle 
management, with respect to the relative
change in body weight from baseline, in 
adults with obesity
Confirmatory
Change in body weight 
Week 0 to week 52
Percent
To demonstrate the superiority of 
semaglutide 2.4 mg s.c once weekly versus 
Other AOMs, as an adjunct to lifestyle 
management, with respect to the change in 
physical functioning, in adults with obesity
Change in IWQOL-Lite-CT 
physical function domain
Week 0 to week 52
Score 
1 Other AOMs defined as Xenical®, Qsymia®, Contrave®, and Saxenda®
CONFIDENTIAL

Protocol
Date:
15 September 2022
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Study ID: NN9536-4741
Version:
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Semaglutide 2.4 mg s.c.
Status:
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The primary estimand: 
The primary clinical question of interest is: What is the effectiveness of semaglutide 2.4 mg versus 
Other AOMs, as an adjunct to lifestyle management, in adults employed in the US living with 
obesity. This will be measured by the number of participants achieving ≥10% body weight loss at 
week 52, regardless of adherence to randomised treatment, and regardless of initiating other anti-
obesity therapies.
The estimand is described by the following attributes (according to International Council for 
Harmonisation (ICH) E9(R1)3):
Attributes for the primary estimand
Treatment
Semaglutide 2.4 mg versus Other AOMs, as an adjunct to lifestyle management.
Population
Adults employed in the US living with obesity.
Endpoint
Achieving body weight reduction ≥10.0% from baseline to week 52.
Treatment condition
The randomised treatment regardless of discontinuation or dose reduction of 
randomised study product, and regardless of initiating other anti-obesity therapies.
Remaining intercurrent events None, all intercurrent events (discontinuation or dose reduction of randomised study 
product and initiation of other anti-obesity therapies) are captured by the treatment 
condition attribute and handled by the treatment policy strategy.
Population-level summary
For achieving body weight reduction ≥10.0%, the treatment effect will be quantified 
by the difference in proportions (calculated from odds) between treatment conditions.
Rationale for estimand
The primary estimand takes into account both safety and efficacy and reflects clinical 
practice in an employer setting. The primary estimand is thus relevant when evaluating 
treatment effect in an employer setting.
Overall design:
This is a 52-week, interventional, randomized, open-label, parallel-group, active comparator-
controlled, two-armed pragmatic study in a multiple employer setting in the US. See Figure 4-1 for 
an overview of the study design.
The clinical investigators participating in this study are part of the coordinating healthcare system, 
Loma Linda University Health, Nutrition Research Center.
The investigators will manage/facilitate the identification and consenting of potential participants
who are employees at employers enrolled in this study based on evaluation of participants’ meeting 
eligibility criteria. Throughout the study period the investigators will provide obesity care and treat 
the participants based on their clinical judgement and routine practice and document decisions and 
assessment results into the eCRF.
Following the investigators decision to initiate therapy with a commercially available anti-obesity 
medication for chronic weight management, participants will be randomized 1:1 to receive either 
semaglutide 2.4 mg (Wegovy®) or one of the Other AOMs.Other than the randomization to study
treatment, the investigators will follow their routine care and medical judgement to treat the 
participants. 
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Protocol
Date:
15 September 2022
Novo Nordisk
Study ID: NN9536-4741
Version:
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Semaglutide 2.4 mg s.c.
Status:
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To ensure treatment is as close to real world practice as possible, the commercially available anti-
obesity medications currently approved for chronic weight management (Xenical®, Qsymia®,
Contrave®, and Saxenda®) are allowed as randomized treatment in the Other AOMs treatment 
group. 
Total study duration for the individual participant will be approximately one year. The study 
consists of the following visits:
x
screening and informed consent
x
randomization and treatment initiation 
x
intermediate visits depending on the local clinical practice
x
a mid-point visit
x
end of IMP treatment/end of study
If deemed appropriate by the investigator, screening and randomization can occur at the same visit. 
All intermediate visits can be converted to phone/virtual visits at the discretion of the investigator
and preference of the patient and in accordance with local clinical practice.
The investigator will be responsible for reporting of safety information within reporting timelines, 
and for contacting the participant for any required follow-up.
Study intervention groups and duration:
The medications used in this study are:
x
Wegovy® used in accordance with US approved prescribing information
x
Other AOMs, used in accordance with approved US prescribing information
The investigators may make treatment adjustments according to their clinical judgement, and the
prescribing information provided on the labels. 
The participants will be randomized equally (1:1) to either Wegovy® or one of the Other AOMs.
Participants randomized to Wegovy® are to remain on that treatment throughout the course of the 
study. For participants randomized to the Other AOMs arm, the choice of treatment, Xenical®,
Qsymia®, Contrave®, or Saxenda®, is at the discretion of the investigator in dialogue with the 
participant and based on prescribing information.
The randomized treatments will be dispensed by a pharmacy. Novo Nordisk A/S will be providing 
partial payment of the randomized treatment prescription cost via a prescription card to ensure an 
out-of-pocket maximum for all participants regardless of treatment arm as part of the study for the 
duration of the study.
The duration of intervention for each participant is 52 weeks.
Number of participants:
Approximately 600 participants will be screened to achieve 500 participants randomized to 
semaglutide 2.4 mg or Other AOMs.
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Date:
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Study ID: NN9536-4741
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Status:
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Participant characteristics:
The participants will be aged ≥18 years at inclusion who meet the following key inclusion criteria, 
and none of the following key exclusion criteria. 
Key inclusion criteria:
x
BMI ≥30.0 kg/m2.
x
Employed at randomisation by one of the selected employers and expecting to be so for the 
duration of the study.
Key exclusion criteria:
x
Known or suspected hypersensitivity or contraindications to Wegovy® or related products 
according to the label.
x
Known or suspected hypersensitivity or contraindications to all of the Other AOMs for 
chronic weight management (Xenical®, Qsymia®, Contrave®, and Saxenda®) or related 
products according to the labels.
x
Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing 
potential and not using highly effective contraceptive method, as defined in Appendix 3
(Section 10.3).
x
History of type 1 or type 2 diabetes mellitus.
x
Any disorder, unwillingness, or inability, not covered by any of the other exclusion criteria, 
which in the investigator’s opinion might jeopardise participant’s safety or compliance with 
the protocol.
Data monitoring committee: No
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Study ID: NN9536-4741
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2
Introduction
Semaglutide is a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA). GLP-1 is an 
incretin hormone with multiple physiological actions, including stimulation of insulin secretion and 
inhibition of glucagon secretion in a glucose-dependent manner.4, 5 GLP-1 RAs induce feelings of 
satiety and fullness and reduce the feeling of hunger6-8 via GLP-1 receptors in the brain.9-11 The 
effect is reduced energy intake that results in weight loss.
Semaglutide 2.4 mg s.c. once-weekly has been approved by the Food and Drug Administration 
(FDA) as an adjunct to a reduced calorie diet and increased physical activity for chronic weight 
management in adult patients with a BMI of ≥30 kg/m2 or ≥27 kg/m2 in the presence of at least one 
weight-related comorbidity (Wegovy®). Clinical12-17 and non-clinical data18 indicate that the body 
weight-reducing effect of semaglutide is mainly mediated by a reduced energy intake. 
The phase 3a clinical development program with semaglutide 2.4 mg enrolled approximately 4,500 
adults with overweight or obesity. The program consisted of four phase 3a studies (NN9536-4373,
NN9536-4374, NN9536-4375 and NN9536-4376). Analysis of the pooled data from the studies 
indicates that the safety and tolerability of semaglutide 2.4 mg is similar to that of other approved 
GLP-1 RAs.  No new or unexpected safety findings were identified. Across all four studies, 
clinically significant weight loss was observed for semaglutide 2.4 mg versus placebo. Additionally, 
significant improvements in glycaemic status and cardiovascular parameters were observed.
2.1
Study rationale
The prevalence of obesity has been increasing globally.19 In the United States (US), 42% of adults 
have obesity, with varying prevalence among the different states.20, 21 Obesity is associated with 
serious health risks.22-25 Severe obesity further increases the risk of obesity-related complications, 
such as pre-diabetes and cardiovascular disease.26, 27
Lifestyle interventions in the form of improving diet and increasing physical activity is first-line 
treatment for obesity and overweight.28 However, the majority of people with obesity and 
overweight struggle to achieve and maintain weight loss.29 Medications approved for chronic 
weight management can be useful adjuncts to lifestyle change for patients who have been 
unsuccessful with diet and exercise alone.30
In the US, employers are the ultimate purchasers of health care for the majority (56%) of 
Americans.31 The prevalence of obesity in the US is increasing,32 and employer health care 
expenditures associated with obesity complications are rising.33 In addition to increased health risks,
and reduced quality of life, employees with obesity are more likely to experience increased 
absenteeism, premature disability, and reduced productivity. 33
Results from the pragmatic Cleveland Clinic study, comparing the effectiveness of a single 
employer-based Weight Management Program (WMP) with anti-obesity medications versus WMP 
without anti-obesity medications on weight loss, have been recently published.34 Among
200 participants who were members of the Cleveland Clinic Employee health plan, 62% of those 
randomized to WMP with anti-obesity medications lost at least 5% of their baseline body weight 
(mean weight loss of 7.7%) compared to 44.8% of those randomized to the WMP without anti-
obesity medications (mean weight loss of 4.2%). In addition, more participants in the WMP with 
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Protocol
Date:
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Study ID: NN9536-4741
Version:
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Status:
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anti-obesity medications group (34.3%) than in the WMP without anti-obesity medications group 
(16.7%) lost at least 10% of their baseline body weight.
Currently, in order for anti-obesity medications to be included in the health care offered to 
employees, employers must “opt-in,” or deliberately decide to pay for these medications for 
employees, even when payers have added them to their formulary. The purpose of this post 
approval pragmatic clinical study is to demonstrate the real-world comparative effectiveness of 
semaglutide 2.4 mg versus existing commercially available anti-obesity medications, with respect to 
relative weight reduction, across three US-based employers. These employers represent 
approximately 28,000 employees of diverse demography and job functions including hospitality, 
clerical, administrative, housekeeping, maintenance, and specialised employees across a range of 
socioeconomic and educational backgrounds.
Pragmatic studies can bridge the gap between clinical studies and clinical practice, providing 
valuable real-world effectiveness data, while maintaining some of the elements of clinical study
design, such as treatment randomization.1, 2 This study will generate important evidence to inform 
health care decision makers such as employers, clinicians, payers, and policy makers about 
comprehensive approaches to obesity care management for employees. This study also 
complements the semaglutide development program by generating novel, ‘real-world’ data on 
semaglutide 2.4 mg compared with Other AOMs, within a US-based, multiple employer setting.
2.2
Background
A comprehensive review of results from the non-clinical and clinical studies of semaglutide can be 
found in the current edition of the investigator’s brochure (IB)35 and any updates hereof, and in the 
US FDA approved prescribing information.
The study population will consist of employees with obesity (BMI ≥30.0 kg/m2), a population that 
is likely to benefit from intervention with weight loss medications and has been shown to be 
associated with high costs in major US industries. Few eligibility criteria are included to keep the 
study as close to real-world as possible.
2.3
Benefit-risk assessment
A summary of the known and potential risks and benefits for semaglutide 2.4 mg (Wegovy®) and 
Other AOMs to which the participant can be randomized are described in the respective prescribing 
information. For each participant a benefit risk assessment is done according to regular clinical 
practice and current approved prescribing information by the investigator as part of the inclusion in 
the study.
Other than mandatory visits, study participation and visits will follow regular clinical practice and 
include participants deemed appropriate to start on weight management medication by the 
investigator. Participants randomized to Wegovy® are to remain on the treatment throughout the
course of the study. For participants randomized to the Other AOM arm, the choice of treatment,
Xenical®, Qsymia®, Contrave®, or Saxenda®, is at the discretion of the investigator in dialogue with 
the participant and based on prescribing information.
CONFIDENTIAL

Protocol
Date:
15 September 2022
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Study ID: NN9536-4741
Version:
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Status:
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3
Objectives, endpoints and estimands
Table 3-1
Objectives and endpoints
Objectives
Endpoints
Primary
Title
Time frame
Unit
To demonstrate the superiority of 
semaglutide 2.4 mg s.c once weekly versus 
Other AOMs1, as an adjunct to lifestyle 
management, with respect to achieving 
≥10.0% body weight reduction from 
baseline, in adults with obesity.
Primary:
Body weight reduction 
≥10.0% (yes/no)
At week 52
Count of 
participants
Secondary Confirmatory
Title
Time frame
Unit
To demonstrate the superiority of 
semaglutide 2.4 mg s.c once weekly versus 
Other AOMs, as an adjunct to lifestyle 
management, with respect to the relative 
change in body weight from baseline, in 
adults with obesity
Confirmatory
Change in body weight 
Week 0 to week 52
Percent
To demonstrate the superiority of 
semaglutide 2.4 mg s.c once weekly versus 
Other AOMs, as an adjunct to lifestyle 
management, with respect to the change in 
physical functioning, in adults with obesity
Change in IWQOL-Lite-CT 
physical function domain2
Week 0 to week 52
Score 
Secondary Supportive
Title
Time frame
Unit
To compare the effect of semaglutide 2.4 
mg s.c once weekly versus Other AOMs, 
as an adjunct to lifestyle management, with 
respect to additional body weight 
parameters, in adults with obesity
Supportive 
Body weight reduction 
≥15.0% (yes/no)
At week 52
Count of 
participants
Body weight reduction 
≥20.0% (yes/no)
At week 52
Count of 
participants
To compare the effect of semaglutide 2.4 
mg s.c once weekly versus Other AOMs, 
as an adjunct to lifestyle management, with 
respect to achieving responder threshold
for physical functioning, in adults with 
obesity
Change in IWQOL-Lite for 
CT physical function domain 
score > 14.6(yes/no)2,3 
At week 52
Count of 
participants
To compare the effect of semaglutide 2.4 
mg s.c once weekly versus Other AOMs, 
as an adjunct to lifestyle management, 
with respect to adherence to medication 
for chronic weight management and work 
limitations, in adults with obesity
Proportion of days covered 
(PDC) by study product
Week 0 to week 52
Percent
Covered by study product 
≥80% of days (yes/no)
At week 52
Count of 
participants
Change in Work Limitations 
Questionnaire 25-item version 
(WLQ-25), total score2
Week 0 to week 52
Score
Exploratory
Title
Time frame
Unit
To compare the effect of semaglutide 2.4 
mg s.c once weekly versus Other AOMs, 
as an adjunct to lifestyle management, with 
respect to absence from work, in adults 
with obesity
Exploratory:
Proportion of days missed 
from work due to participant 
illness or not feeling well
Week 0 to week 52
Percent
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Objectives
Endpoints
To compare the effect of semaglutide 2.4 
mg s.c once weekly versus Other AOMs, 
as an adjunct to lifestyle management, with 
respect to treatment satisfaction, in adults 
with obesity
Treatment satisfaction 
assessed by Abbreviated 
Treatment Satisfaction 
Questionnaire for Medication 
(TSQM-9), Global 
Satisfaction, total score2
End of treatment at 
week 52
Score points
1 Other AOMs are defined as one of the following medications approved for chronic weight management: Xenical®,
Qsymia®, Contrave®, and Saxenda®.
2Please refer to Section 8.1 for detailed information on scales and scoring of patient reported outcomes forms
3Responder threshold is the threshold for meaningful within participant change. The threshold is anchor based using the 
Patient Global Impression of Status, PGI-S.
Primary estimand
The primary clinical question of interest is: What is the effectiveness of semaglutide 2.4 mg versus 
Other AOMs, as an adjunct to lifestyle management, in adults employed in the US living with 
obesity. This will be measured by the number of participants achieving ≥10% body weight loss at 
week 52, regardless of adherence to randomised treatment, and regardless of initiating other anti-
obesity therapies (weight management drugs not included in the randomized treatment arm, see 
Table 6-1, or bariatric surgery).
The estimand is described by the following attributes (according to International Council for 
Harmonisation (ICH) E9(R1)3):
x
Population: Adults employed in the US living with obesity
x
Endpoint: Body weight reduction ≥10.0% (yes/no) from baseline to week 52
x
Treatment condition: The randomised treatment regardless of discontinuation or dose 
reduction of randomised study product, and regardless of initiating other anti-obesity 
therapies (as defined above).
x
Remaining intercurrent events: None, all intercurrent events (discontinuation or dose 
reduction of randomised study product and initiation of other anti-obesity therapies) are 
captured by the treatment condition attribute and handled by the treatment policy strategy.
x
Population-level summary: The treatment effect will be quantified by the difference in 
proportions (calculated from odds) between treatment conditions.
x
Rationale for estimand: The primary estimand takes into account both safety and efficacy 
and reflect clinical practice in an employer setting. The primary estimand is thus relevant 
when evaluating treatment effect in an employer setting.
Secondary estimand
For secondary objectives assessed by binary endpoints, the estimands are similar to the primary 
estimand except for the endpoint attribute. For secondary objectives assessed by continuous 
endpoints, the estimands are similar to the primary estimand except for the endpoint and the 
population level summary, which is the difference between treatment conditions for means in
change from baseline to week 52.
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Additional estimand
An additional clinical question of interest for the primary objective is: What is the effectiveness of 
semaglutide 2.4 mg, as an adjunct to usual employer-offered lifestyle management, in adults 
employed in the US living with obesity had they remained on their randomised treatment (possibly 
on reduced dose) for the entire planned duration of the study, and not initiated other anti-obesity 
therapies (weight management drugs not included in the randomized treatment arm, see Table 6-1,
or bariatric surgery). This will be measured by the number of participants achieving ≥10% body 
weight loss at week 52
The estimand is described by the following attributes (according to ICH E9(R1)3):
x
Population: Adults employed in the US living with obesity
x
Endpoint: Body weight reduction ≥10.0% (yes/no) from baseline to week 52
x
Treatment condition: randomised treatment if participants had remained on randomized 
treatment (regardless of dose reductions) for the entire duration of the study and not initiated 
any other anti-obesity therapies (as defined above).
x
Remaining intercurrent events: None, all intercurrent events (discontinuation or initiation 
of other anti-obesity therapies and dose reduction) are captured by the treatment condition 
attribute. Discontinuation or initiation of other anti-obesity therapies are handled by the 
hypothetical strategy. Dose reduction of randomised study product is captured by the 
treatment policy strategy.
x
Population-level summary: The treatment effect will be quantified by the difference in 
proportions (calculated from odds) between treatment conditions.
x
Rationale for estimand: The additional estimand aims at reflecting the treatment effect 
without the confounding effects of other anti-obesity therapies or treatment discontinuation.
Similar additional estimands apply to secondary objectives assessed by binary endpoints, except for
the endpoint attribute. For secondary objectives assessed by continuous endpoints, the estimands are 
similar except for the endpoint attribute and the population level summary, which is the difference 
between treatment conditions for means in change from baseline to week 52.
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4
Study design
4.1
Overall design
This is a 52-week, interventional, randomized, open-label, parallel-group, active comparator-
controlled, two-armed pragmatic study in a multiple employer setting in the US. See Figure 4-1 for 
an overview of the study design.
The conduct and operations of the study will be managed by the investigators within the 
coordinating healthcare system, Loma Linda University Health, Nutrition Research Center. The 
investigators will manage/facilitate the identification and consenting of potential participants who 
are employees at employers enrolled in this study based on evaluation of participants’ meeting 
eligibility criteria defined in Section 5.1 and 5.2. Throughout the study period the investigators will 
provide obesity care and treat the participants based on their clinical judgement and routine practice 
and document decisions and assessment results into the eCRF.
Following the investigators’ decision to initiate therapy with a commercially available anti-obesity 
medication for chronic weight management, participants will be randomized 1:1 to receive either 
semaglutide 2.4 mg (Wegovy®) or Other AOMs.To ensure treatment practice is as close to real 
world as possible, the commercially available anti-obesity medications currently approved for 
chronic weight management (Xenical®, Qsymia®, Contrave®, and Saxenda®) are allowed as 
randomized treatment in the Other AOMs treatment group. Total study duration for the individual 
participant will be approximately one year. The study consists of the following visits:
x
screening and informed consent
x
randomization and treatment initiation 
x
intermediate visits depending on the local clinical practice
x
a mid-point visit
x
end of treatment/end of study
If deemed appropriate, screening and randomization can occur at the same visit. All intermediate 
visits can be converted to virtual visits at the discretion of the investigator and preference of the 
participant and in accordance with local clinical practice. Participants who terminate employment 
with participating employers during the study will be permitted to continue in the study.
The investigator will be responsible for reporting of safety information within reporting timelines, 
and for contacting the participant for any required follow-up.
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Figure 4-1
Study design
4.2
Scientific rationale for study design
Based on the clinical development program of semaglutide 2.4 mg, and the clinical data provided in 
the Other AOMs labels, the study treatment duration of 52 weeks is considered sufficient to 
evaluate the weight loss potential of the interventions.
Randomization is included to reduce selection bias and ensure comparable patient populations in 
the two treatment arms (semaglutide 2.4 mg versus the Other AOMs). 
The study population will consist of employees with obesity (BMI ≥30.0 kg/m2), a population likely 
to benefit from intervention with weight loss medications.36-39
There are three mandatory visits to ensure adequate data collection: the randomization visit; a study 
mid-point visit; and an end of study visit.
4.2.1
Patient input into design
Patient input to the design of the current study has not been provided. However, relevant experience 
and feedback from sites of previous obesity studies has been implemented to the extent possible.
4.3
Justification for dose
All the medications included in this study are approved by the FDA as adjuncts to a reduced-calorie 
diet and increased physical activity for chronic weight management. The investigators will 
prescribe the randomized treatment, and instruct the participant on dosing, based on the US 
prescribing information and their clinical judgment.
4.4
End of study definition
The end of the study is defined as the date of the last visit of the last participant in the study.
A participant is considered to have completed the study if he/she has completed all periods of the 
study including the last visit shown in the flowchart.
The primary completion date (PCD) is defined as the date of visit 7 (week 52) on which the last 
participant in the clinical study has an assessment for the primary endpoint. If the last participant is 
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withdrawn early, the PCD is considered the date when the last participant would have completed 
visit 7. 
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5
Study population
Prospective approval of protocol deviations to recruitment and enrolment criteria, also known as 
protocol waivers or exemptions, is not permitted.
Pre-screening is defined as review of the patient medical records, including handing out participant 
information, as well as database review. Any pre-screening activities must be documented on site 
by the investigator.
5.1
Inclusion criteria
Participants are eligible to be included in the study only if all the following criteria apply:
1. 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.
2. Age ≥18 years at the time of signing informed consent.
3. BMI ≥30.0 kg/m2.
4. Employed at randomization by one of the selected employers and expecting to be so for the 
duration of the study.
5.2
Exclusion criteria
Participants are excluded from the study if any of the following criteria apply:
1. Known or suspected hypersensitivity or contraindications to Wegovy® or related products 
according to the label.
2. Known or suspected hypersensitivity or contraindications to all of the Other AOMs for chronic 
weight management (Xenical®, Qsymia®, Contrave®, and Saxenda®) or related products 
according to the labels.
3. Previous randomization in this study
4. More than one rescreening for this study
5. Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing 
potential and not using highly effective contraceptive method, as defined in Appendix 3
(Section 10.3).
6. Participation (i.e., signed informed consent) in any interventional, clinical study within 30 days 
before screening.
7. Treatment with any medication prescribed for the indication of obesity or weight management 
within 90 days before screening.
8. A self-reported change in body weight >5 kg (11 lbs) within 90 days before screening 
irrespective of medical records.
9. History of type 1 or type 2 diabetes mellitusa.
10. HbA1c ≥6.5% (48 mmol/mol) at screening or within the last 90 days prior to the day of 
screening.
11. 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 >1 year before screening, (2) adjustable gastric banding, if the band has been 
removed >1 year before screening, (3) intragastric balloon, if the balloon has been removed >1 
year before screening or (4) duodenal-jejunal bypass liner (e.g., Endobarrier), if the sleeve has 
been removed >1 year before screening.
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12. Any disorder, unwillingness, or inability, not covered by any of the other exclusion criteria, 
which in the investigator’s opinion might jeopardise participant’s safety or compliance with the 
protocol.
aAs declared by the participant or reported in the medical records.
5.3
Lifestyle considerations
Lifestyle considerations will follow standard of care (see Section 6.1.1).
5.4
Screen failures
A screen failure occurs when a participant who consents to participate in the clinical study is not 
subsequently eligible for participation according to inclusion/exclusion criteria. A minimal set of 
screen failure information is required to ensure transparent reporting of screen failure participants to 
meet requirements from regulatory authorities. Minimal information includes informed consent 
date, demography, screen failure details, and eligibility criteria. 
A screen failure session must be made in the Randomization and Trial Supply Management system
(RTSM). 
Individuals who do not meet the criteria for participation in this study may be rescreened once.
Individuals who are rescreened are required to sign a new informed consent form and provided with 
a new patient ID. A new screening session must be made in the RTSM.
5.5
Run-in criteria and/or randomisation criteria and/or dosing day criteria
Not applicable.
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6
Study interventions and concomitant therapy
Study intervention is defined as any investigational interventions, marketed products, placebo, or 
medical devices intended to be administered to a study participant according to the study protocol.
Study product comprises the approved medicinal products prescribed in the study.
6.1
Investigational medicinal products (IMP)
Table 6-1 provides an overview of the study products.
Table 6-1
Study products
Study group 
API (route of administration) 
Brand name 
Semaglutide
Semaglutide 2.4 mg (s.c.)
Wegovy®
Other AOMs
Orlistat (p.o.) 
Xenical®
Phentermine/Topiramate extended release 
(p.o.) 
Qsymia®
Naltrexone/Bupropion extended release (p.o.) 
Contrave®
Liraglutide 3.0 mg (s.c.) 
Saxenda®
Abbreviation: API: active pharmaceutical ingredient; p.o.: per os (by mouth);
s.c.: subcutaneous.
All study products should be used in accordance with clinical practice and prescribing information. 
The participant will be provided instructions per routine practice.
For participants randomized to the Other AOMs group, switch of treatment between the Other 
AOMs listed in Table 6-1 can be done at the discretion of the investigator. Participants must only be 
treated with one anti-obesity medication at a time, in accordance with labels. For participants 
randomized to the semaglutide group, switch of treatment to Other AOMs during the study must not 
be done.
6.1.1
Lifestyle management
All participants should be instructed in how to follow recommended lifestyle management as per 
standard local clinical practice and in accordance with label instructions, at the discretion of the 
investigator.
The standard of care for obesity diagnosis and management at Loma Linda University Nutrition 
Research Center follow the AACE/ACE obesity guidelines40 and may involve laboratory testing. 
Blood samples may be taken as part of routine procedures.
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6.2
Co-pay assistance
The randomized treatment will be handled and dispensed by a pharmacy to remain as close to real 
world as possible. Novo Nordisk A/S will ensure partial reimbursement by providing an out-of-
pocket maximum for all randomized treatments. Co-pay assistance will only apply to the 
randomized treatment as defined above (i.e., not to any subsequent add-on treatment or treatment 
changes outside the randomized treatment definition). Prescription cards will be issued to 
participant to ensure co-pay assistance . Data regarding study product use registered on the card will 
be provided to Novo Nordisk A/S by an external vendor.
6.3
Measures to minimise bias: Randomisation and blinding
This is an open-label study. Randomization will be included to reduce selection bias and ensure 
comparable patient populations in the two treatment groups.
All participants will be screened and centrally randomized using an RTSM system and assigned to
treatment according to the randomization schedule. 
Participants randomized to Wegovy® are expected to remain on that treatment throughout the 
course of the study.
For participants randomized to the Other AOMs arm, the choice of treatment (Xenical®, Qsymia®,
Contrave®, or Saxenda) is at the discretion of the investigator in dialogue with the participant and
based on prescribing information.
The amount of co-payment required by the participant will be the same for all of the prescribing 
options, to remove cost bias in treatment selection.
6.4
Study intervention compliance
Participants’ adherence to randomized treatment will be captured via the participant's prescription 
card. The investigator should support compliance to randomized treatment as for all other 
treatments as part of regular clinical practice.
6.5
Dose modification
See section 4.3 on dose justification.
6.6
Continued access to study intervention after end of study
At the end of the study participants can continue their randomized treatments at the discretion of the 
investigator but co-pay assistance will be discontinued.
6.7
Treatment of overdose
In the event of overdose, appropriate supportive treatment should be initiated according to the 
participants’ clinical signs and symptoms and the investigator should closely monitor the participant 
for overdose-related AEs/SAEs.
Accidental overdose must be reported as a medication error. Intentional overdose must be reported 
as misuse and abuse, please refer to Section 8.3 and Appendix 2 (Section 10.2) for further details.
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Decisions regarding dose interruptions or modifications will be made by the investigator based on 
the clinical evaluation of the participant.
For more information on overdose, also consult the current version of the prescribing information 
provided in the labels of all the anti-obesity medications included in the study.
6.8
Concomitant therapy
Any medication related to the treatment of diabetes (developed during the study),
hypercholesterolemia, hypertension, and obesity (that are not included as randomized treatments) 
that the participant is receiving at the time of the first visit, or receives until end of study, must be 
recorded along with:
x
Trade name or generic name
x
Primary indication
x
Dose and frequency
x
Dates of administration including start and stop dates
Collection of specific concomitant medication reflects the pragmatic approach of this study by
focusing on the co-morbidities associated with obesity that directly impact cardiovascular status, as 
this presents the greatest risk of morbidity and mortality in the target population.41, 42
Initiating anti-obesity medications that are not part of the randomized treatments in the study is not 
permitted. If such treatment is initiated, the participant should be instructed to discontinue the 
additional therapy immediately, and the information on the medication must be recorded in the 
eCRF.
Changes in concomitant therapy must be recorded according to the flowchart. If a change is due to 
an AE, then this must be reported according to Section 8.3.
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7
Discontinuation of study intervention and participant 
discontinuation/withdrawal
Discontinuation of specific sites or of the study as a whole is detailed in Appendix 1
(Section 10.1.11).
7.1
Discontinuation of study intervention
Study intervention may be discontinued at any time during the study at the discretion of the 
participant or at the discretion of the investigator for safety, behavioural, compliance or 
administrative reasons.
Efforts must be made to have the participants who discontinue study intervention attend visit V7 
(end of study/end of treatment visit) to collect the required data for the analysis of the primary and 
confirmatory secondary estimands/endpoint. Only participants who withdraw consent will be 
considered as withdrawn from the study. Participants must be informed about the continued 
scientific importance of their data, even if they discontinue study intervention.
The study intervention must be discontinued if any of the following applies for the participant:
1. Pregnancy
2. Intention of becoming pregnant
3. Simultaneous use of an approved or non-approved investigational medicinal product in another 
clinical study
4. Other reasons according to prescribing information 
The primary reason for discontinuation of study intervention must be specified in the CRF. A 
discontinuation session must be made in the RTSM system.
Participants should be reminded that use of a highly effective method of contraception is needed for 
two months after end of study treatment.
7.1.1
Temporary discontinuation of study intervention
If a participant has discontinued study intervention due to temporary safety concern not related to 
the study intervention and is allowed to resume, or if a participant discontinues study intervention 
on their own initiative, he/she should be encouraged to resume the study intervention.
7.2
Participant discontinuation/withdrawal from the study
A participant may withdraw consent at any time at his/her own request.
If a participant withdraws consent, or is withdrawn by the investigator, prior to receipt of study 
intervention, he/she will not be asked to have any follow-up assessments performed. The following 
data must be collected: Demography, eligibility criteria, date of informed consent, and the date 
when participant’s participation ended. The end of study form must be completed.
If a participant withdraws consent or is withdrawn by the investigator after receipt of study 
intervention, the investigator must ask the participant if he/she is willing, as soon as possible, to 
have assessments performed according to V7. See the flowchart for data to be collected.
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If the participant withdraws consent, Novo Nordisk may retain and continue to use any data 
collected before such a withdrawal of consent for the purpose of the study or scientific research.
Although a participant is not obliged to give his/her reason(s) for withdrawing, the investigator 
must make a reasonable effort to ascertain the reason(s), while fully respecting the participant’s 
rights. Where the reasons are obtained, the primary reason for withdrawal must be specified in the 
CRF.
7.2.1
Replacement of participants
If a participant discontinues study intervention, withdraws consent or is withdrawn by the 
investigator, he/she will not be replaced.
7.3
Lost to follow-up
A participant will be considered lost to follow-up if he/she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the site.
The following actions must be taken if a participant fails to return to the site for a required visit:
x
The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether the participant wishes to and/or should continue in the study.
x
Before a participant is deemed lost to follow-up, the investigator or designee must make every 
effort to regain contact with the participant. These contact attempts should be documented in the 
participant’s source document.
x
Should the participant continue to be unreachable, he/she will be considered to have withdrawn 
from the study with a primary reason of ‘lost to follow-up’.
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8
Study assessments and procedures
The following sections describe the assessments and procedures, while their timing is summarised 
in the flowchart.
Informed consent must be obtained before any study-related activity, see Appendix 1
(Section 10.1.3).
All screening evaluations must be completed and reviewed to confirm that potential participants 
meet all inclusion criteria and none of the exclusion criteria.
The investigator will maintain a screening log to record details of all participants screened and 
rescreened and to confirm eligibility or record reason for screen failure, as applicable.
At randomisation, participants will be provided with a prescription card they will use to buy the 
prescribed medication at the pharmacy.
Adherence to the study design requirements, including those specified in the flowchart, is essential 
and required for study conduct.
8.1
Efficacy assessments
Planned time points for all efficacy assessments are provided in the flowchart.
8.1.1
Body measurements
Body weight should be measured without shoes, on an empty bladder and only wearing light 
clothing. It should be measured on a digital scale and recorded in the eCRF in pounds (lb.) (with 
one decimal point) using the same scale throughout the study.
Height is measured without shoes in inches (with one decimal point).
Initial BMI will be calculated by the site from screening data and must be in agreement with 
inclusion criterion no. 3.
8.1.2
Patient reported outcomes and treatment satisfaction questionnaires
All questionnaires will be administered electronically directly to the participant or by the 
investigators. Investigators will ensure all questionnaires are completed for the mandatory 
assessments noted in the flowchart.
8.1.2.1
Impact of Weight on Quality of Life-Lite for Clinical Trials (IWQOL-Lite for 
CT)
IWQOL-Lite-CT is a 20-item patient reported outcome instrument used to assess the impact of 
body weight changes on patients’ physical and psychosocial functioning in three composite scores 
(physical function, physical and psychosocial) and a total score. The possible score range for each 
composite score and for the total score is 0 to 100. Higher values on composite scores as well as 
total score of the IWQOL-Lite-CT indicate improved patient functioning.
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8.1.2.2
Treatment Satisfaction Questionnaire for Medication (TSQM-9)
The TSQM-9 (version 9) is a generic questionnaire to measure patients’ satisfaction with 
medication using yes/no answers, and 5- or 7-point Likert scale response options. It is a self-
administered patient reported outcome instrument designed for adults aged 18 years or older with a 
recall period of two to three weeks, or since the last medication use. Version TSQM-9 includes 
three domains: effectiveness (three items), convenience (three items), and global satisfaction scale
(three items). It takes approximately five minutes to complete. Scores range from 0 to 100. Higher 
scores indicate better treatment satisfaction.
8.1.2.3
Work Limitations Questionnaire (WLQ-25)
The Work Limitations Questionnaire (WLQ-25), version 2.1, is a 25-item questionnaire that 
measures the degree to which health problems interfere with specific aspects of job performance 
and the productivity impact of these work limitations during the past 2 weeks using a 5-point Likert
scale response option. It is a self-administrated questionnaire consisting of 4 domains of work 
limitation: Time Management (5), Physical Demands (6), Mental/Interpersonal (9), Output 
Demands (5). The responses are used to calculate a total WLQ index score. Lower scores indicate 
less work limitation.
8.2
Safety assessments
There are no safety assessments in this study.
Medical history is a medical event that the participant experienced prior to the time point from 
which AEs are collected. Only relevant and significant medical history, as judged by the 
investigator, on comorbidities related to obesity should be recorded, specifically a history of:
x
Cardiovascular disorder and procedure
x
Heart failure
x
Dyslipidaemia
x
Gallbladder disease and procedure
x
Gastrointestinal disorder
x
Genitourinary tract disorder
x
Kidney disease
x
Liver disease
x
Musculoskeletal system disorder
x
Psychiatric disorder
x
Respiratory disorder
x
Glucose metabolism disorder
A concomitant illness is any illness that is already present at the time point from which AEs are 
collected or found as a result of a screening procedure or other study procedures performed before 
exposure to study intervention under clinical investigation.
In case of an abnormal and clinically significant finding fulfilling the definition of medical history 
or concomitant illness, the investigator must record the finding on the medical history/concomitant 
illness form. The information collected should include diagnosis, date of onset and date of 
resolution or continuation.
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been discontinued from/completed the study, and the investigator considers the event to be related 
to the IMPs or related to study participation, the investigator must promptly notify Novo Nordisk.
8.3.2
Method of detecting AEs 
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures for 
completing and transmitting SAE reports are provided in Appendix 2 (Section 10.2)
Care should be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and non-
leading verbal questioning of the participant is the preferred method to inquire about events.
8.3.3
Follow-up of AEs 
After the initial AE/SAE report, the investigator is required to proactively follow each participant at 
subsequent visits/contacts. All SAEs should be followed until final outcome of the event or until the 
participant is lost to follow-up as described in Section 7.3. Further information on follow-up and 
final outcome of events is given in Appendix 2 (Section 10.2).
8.3.4
Regulatory reporting requirements for SAEs
Prompt notification by the investigator to Novo Nordisk of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a study 
intervention under clinical investigation are met.
Novo Nordisk has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. Novo 
Nordisk will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, IRB/IEC, and investigators. This also includes suspected unexpected 
serious adverse reactions (SUSAR).
An investigator who receives an investigator safety report describing an SAE or other specific 
safety information (e.g., summary or listing of SAEs) from Novo Nordisk will review and then file 
it, and will notify the IRB/IEC, if appropriate according to local requirements.
8.3.5
Pregnancy 
Details of pregnancies in female participants will be collected after first exposure to IMP and until
end of study visit. For details regarding collection and reporting of pregnancy information, please 
refer to Appendix 3 (Section 10.3).
Participants should be reminded that use of a highly effective method of contraception is needed for 
two months after end of study treatment.
8.3.6
Technical complaints 
Technical complaints will be collected for all products listed on the technical complaint form.
Instructions for reporting technical complaints can be found in Appendix 4 (Section 10.4).
In order for Novo Nordisk to perform a complete investigation of reported SAEs, Novo Nordisk 
might ask the investigator to complete a technical complaint form.
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8.4
Pharmacokinetics and pharmacodynamics
Not applicable for this study.
8.5
Genetics
Not applicable for this study.
8.6
Biomarkers
Not applicable for this study.
8.7
Immunogenicity assessments
Not applicable for this study.
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9
Statistical considerations
The statistical analysis plan (SAP) will be finalized prior to first participant first visit (FPFV) and it 
will include a more technical and detailed description of the statistical analyses described in this 
section. This section is a summary of the planned statistical analyses of the most important
endpoints including primary and key secondary endpoints.
9.1
Statistical hypotheses
The tests of superiority of semaglutide 2.4 mg to the group of other commercially available 
medication for chronic weight management (Other AOMs) for the primary and confirmatory 
secondary endpoints will be based only on analyses addressing the primary and secondary 
estimands.  
For the primary estimand, the following confirmatory 1-sided hypothesis is planned to be tested for 
semaglutide 2.4 mg versus Other AOMs. Let the odds ratio be defined as OR = (odds[semaglutide 
2.4 mg] divided by odds[Other AOMs]):
Superiority: H01 : OR ≤1 against Ha1 : OR >1
For the two confirmatory secondary estimands, the following confirmatory 1-sided hypotheses are
planned to be tested for semaglutide 2.4 mg versus Other AOMs. Let the mean difference be 
defined as μ = ([semaglutide 2.4 mg] minus [Other AOMs]):
Superiority for change in body weight: H02 : μ ≥0.0 against Ha2 : μ <0.0
Superiority for change in IWQOL-Lite-CT phys. func. domain: H02 : μ ≤0.0 against Ha2 : μ >0.0
Operationally, the hypotheses will be evaluated by 2-sided tests.
9.1.1
Multiplicity adjustment
The type I error will be controlled in the strong sense using a hierarchical (fixed sequence) testing 
procedure. This is based on priority ordering of the null hypotheses and testing them in this order 
using the 2-sided 95% confidence interval approach until an insignificant result appears. For 
example, the second null hypothesis will only be tested if the first null hypothesis has been rejected 
in favour of semaglutide 2.4 mg. 
The steps in the hierarchical testing procedure are as follows:
x
Step 1: ≥10% body weight reduction (yes/no) from baseline (week 0) to end of treatment 
(week 52) superiority of semaglutide 2.4 mg versus Other AOMs.
x
Step 2: Change in body weight (%) from baseline (week 0) to end of treatment (week 52) 
superiority of semaglutide 2.4 mg versus Other AOMs. 
x
Step 3: change in IWQOL-Lite-CT physical function domain from baseline (week 0) to end 
of treatment (week 52) superiority of semaglutide 2.4 mg versus Other AOMs
9.2
Analysis sets
The following analysis sets and data point sets are defined:
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Table 9-1
Analysis sets
Participant Analysis Set
Description
Full analysis set (FAS)
Consists of all randomized participants. Participants will be included in the 
analyses according to the planned intervention.
Safety analysis set (SAS)
All participants who are exposed to study intervention. Participants will be 
included in the analyses according to the intervention they actually received.
Table 9-2
Defined data point sets
Defined data point sets (DPS)
Description
In-study (DPS1)
The time period where the participant is assessed in the study. The in-study 
observation period for a participant begins on the date of randomization and ends 
at the first of the following dates (both inclusive):
x
End of study visit
x
Withdrawal of consent
x
Last contact with participant (for participants lost to follow-up)
x
Death
Adherent (DPS2)
The consecutive time period where the participant is adherent to treatment 
(possibly on a lower than intended dose) and has not initiated other anti-obesity 
therapies (weight management drugs not included in randomised treatment arm 
(see Table 6-1) or bariatric surgery). End of the adherent period is defined as:
x
End of study visit
x
Treatment discontinuation1
x
Initiation of other anti-obesity therapies2
1 Treatment discontinuation is defined as when the period with no coverage of prescription claims exceeds 20%.
2 Other anti-obesity therapies are defined as weight management drugs not included in the randomized treatment arm, 
see Table 6-1, or bariatric surgery.
FAS and DPS1 are used to estimate the primary estimand and the secondary estimands.
FAS and DPS2 are used to estimate the additional estimands.
SAS and DPS1 are used to present safety data.
9.3
Statistical analyses
9.3.1
General considerations
This section is a summary of the planned statistical analyses of the most important estimands
including primary and confirmatory secondary estimands.
The last available observation at or before randomization is used as the baseline value. If no 
assessments are available, the mean value at randomization across all participants is used as the 
baseline value.
All tests are tests of superiority of semaglutide s.c. 2.4 mg once weekly to Other AOMs. All 
estimated treatment contrasts between semaglutide 2.4 mg and Other AOMs will be reported 
together with the associated two-sided 95% confidence interval (CI) and corresponding p-value.
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9.3.2
Primary estimand analysis
The primary estimand will be estimated by logistic regression (LR) with randomised treatment as 
factor and baseline body weight (kg) as covariate.
All available weight measurements (kg) at week 52 are used, and missing values at week 52 will be 
imputed. The imputation method for the primary analysis is a multiple imputation approach similar 
to the one described by McEvoy et al.43 Imputation is done separately for each treatment group and 
also separately for participants being on and off treatment at week 52. The imputation model will 
include sex, baseline BMI-group, baseline body weight, last available observation on treatment 
(LAO-OT) and timing (as covariate) of last available observation on treatment. Details of the 
multiple imputation approach are provided in the SAP.
Sensitivity analyses
A tipping point multiple imputation analysis (TP-MI) will be performed as sensitivity analysis.
First, missing weight measurements (kg) at week 52 will be imputed as described for the primary 
estimand. Second, for the semaglutide 2.4 mg arm, a penalty (a weight change) is added to the 
imputed values and then the logistic regression described for the primary estimand will be 
performed. The penalty will be increased until the conclusion from the primary estimand analysis is 
reversed. A max penalty of 30 kg will be added. This maximum is imposed since it may not be 
possible to reverse the conclusion for a binary endpoint and since systematic weight gains greater 
than 30 kg on top of the imputed values are highly unrealistic.
Supplementary analyses
The statistical model used to estimate the additional estimand is the same as the one used for the 
primary estimand.
All available weight measurements (kg) at week 52 for participants that are adherent (see 
Section 9.2) until and including the week 52 assessment will be used. Measurements for participants
that are not adherent at week 52 will be predicted. Prediction of missing values will be done by 
modelling all available body weight (kg) data from the adherent period for all participants using a 
mixed model for repeated measurements (MMRM) approach. The MMRM will be fitted using the 
same factors and covariate as for the primary analysis all nested within visit. An unstructured 
covariance matrix for measurements within the same participant will be employed, assuming that 
measurements for different participants are independent.
9.3.3
Secondary estimands analysis
9.3.3.1
Confirmatory secondary estimands
The primary estimand will be analysed by a linear regression model (ANCOVA) with randomised 
treatment as factor and baseline body weight (kg) as covariate. 
All available weight measurements (kg) at week 52 are used and missing values at week 52 will be 
imputed. The imputation method is identical to the imputation method for the primary estimand.
The analysis model for change in physical function assessed using IWQOL-Lite-CT is identical to 
the linear regression model for the estimation of the secondary estimand related to change in body 
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weight (%) except that baseline physical function score is included as covariate instead of baseline 
body weight. Imputation of missing values will be done using the same approach as for the primary 
estimand. 
Sensitivity analyses
A tipping point multiple imputation analysis (TP-MI) will be performed as sensitivity analysis for 
each of the two endpoints. This will be done as for the sensitivity analysis for the primary estimand 
analysis, except that 
1. The penalty for physical function will be in score points and with a maximum penalty of 100. A
maximum penalty of 100 is set since this corresponds to the range of the score scale. 
2. The statistical model used for analysis of change since baseline will be as described for the 
confirmatory secondary estimands analyses.
Supplementary analyses
The additional estimand for change in body weight (%) will be estimated using an MMRM 
approach. The MMRM will use the adherent data point set for all participants. The MMRM will be 
fitted using change in body weight (%) and the same factor and covariate as for the primary analysis 
all nested within visit. An unstructured covariance matrix for measurements within the same 
participant will be employed, assuming that measurements for different participants are 
independent. 
Change in physical function assessed using IWQOL-Lite-CT is estimated as for change in body 
weight (%) except that baseline physical function score is included as covariate instead of baseline 
body weight.
9.3.3.2
Supportive secondary endpoints
Supportive secondary endpoints are described in Section 3, and the statistical analyses are detailed 
in the SAP.
9.3.4
Exploratory endpoints/estimand analysis
Exploratory endpoints are described in Section 3, and the statistical analyses are detailed in the 
SAP.
9.3.5
Other safety analyses
No formal safety analyses are planned.
The reported safety assessments (AEs) will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA) and descriptively summarised by System Organ Class (SOC) and preferred 
term. No AE-rates will be calculated. 
9.3.6
Other analyses
For other analyse(s), please refer to the SAP. 
9.4
Interim analysis
There is no interim analysis planned for this study.
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9.5
Sample size determination
The study is designed with an effective power of >80% to demonstrate superiority of semaglutide 
2.4 mg to the group of Other AOMs with respect to all three endpoints in the test hierarchy. The 
calculated powers are for the primary and confirmatory secondary estimands. The effective power is 
calculated under the assumption of independence of hypotheses by multiplying the respective 
marginal powers successively which is a conservative approach. The power calculations for 
continuous endpoints are based on a t-test on the mean difference assuming equal variances, 
whereas the power calculation for the categorical endpoint is based on the Pearson chi-square test 
for two independent proportions.
Assumptions used for the power calculations are presented in Table 9-3. Assumptions for the power 
calculations are based on study NN8022-4432 (Cleveland Clinic obesity pragmatic study) and study
NN9536-4373 (STEP 1). Additional important assumptions and assumptions with effect on 
assumed treatment effects and SDs in Table 9-3 are:
x
1:1 randomization
x
25% of the participants are expected to permanently stop study product in each treatment arm 
prior to the end of study.
x
50% of the participants that stop study product administration prior to week 52 are expected to 
have the end of study assessments performed.
x
Participants that do not have end of study assessments performed are assumed to have a 
treatment effect corresponding to other participants in the respective treatment arm and 
according to treatment status (i.e., on/off allowed obesity medication in relevant treatment arm) 
at week 52.
x
Dose reductions are assumed to have negligible impact on treatment effect in each arm, since 
dose reductions happening in this study are not likely to differ significantly from dose 
reductions happening in NN8022-4432 and NN9536-4373 wherefrom effect estimates originate.
x
Based on NN8022-4432 and NN9536-4373, the number of participants undergoing bariatric 
surgery is expected to be low and the impact on treatment effect in each arm is expected to be 
negligible. 
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Figure 9-2
Marginal power curves for IWQOL-Lite-CT Physical Function change where 
two standard deviations differing from 21.5 are included to evaluate robustness 
of sample size calculations
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10 Supporting documentation and operational considerations
10.1
Appendix 1: Regulatory, ethical, and study oversight considerations
10.1.1
Regulatory and ethical considerations
This study will be conducted in accordance with the protocol and with the following:
x
Consensus ethical principles derived from international guidelines including the Declaration of 
Helsinki44 and applicable ICH Good Clinical Practice (GCP) Guideline45
x
Applicable laws and regulations
The protocol, informed consent form, investigator’s brochure (as applicable) and other relevant 
documents (e.g., advertisements) must be submitted to an IRB/IEC and reviewed and approved by 
the IRB/IEC before the study is initiated.
Regulatory authorities will receive the clinical study application, protocol amendments, reports on 
SAEs, and the CSR according to national requirements.
Any amendments to the protocol will require IRB/IEC approval before implementation of changes 
made to the study design, except for changes necessary to eliminate an immediate safety hazard to 
study participants.
Before a site is allowed to start screening participants, written notification from Novo Nordisk must 
be received.
The investigator will be responsible for:
x
providing written summaries of the status of the study annually or more frequently in 
accordance with the requirements, policies, and procedures established by the IRB/IEC and/or 
regulatory authorities
x
notifying the IRB/IEC of SAEs or other significant safety findings as required by IRB/IEC 
procedures
x
providing oversight of the conduct of the study at the site and adherence to requirements of ICH 
guidelines, the IRB/IEC, and all other applicable local regulations
x
ensuring submission of the CSR synopsis to the IRB/IEC
x
reporting any potential serious breaches to the sponsor immediately after discovery
10.1.2
Financial disclosure
Investigators and sub-investigators will provide Novo Nordisk with sufficient, accurate financial 
information as requested to allow Novo Nordisk to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and one 
year after completion of the study. Verification under disclosures per Code of Federal Regulations 
(CFR) of Financial Conflict of Interest.
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10.1.3
Informed consent process
The investigator or his/her representative will explain the nature of the study, including the risks 
and benefits, to the participant and answer all questions regarding the study. This includes the use of 
an impartial witness where required according to local requirements.
The investigator must ensure the participant ample time to come to a decision whether or not to 
participate in the study.
Participants must be informed that their participation is voluntary. Participants will be required to 
sign and date a statement of informed consent that meets the requirements of local regulations, ICH 
GCP45 guidelines, Declaration of Helsinki,44 privacy and data protection requirements, where 
applicable, and the IRB/IEC or site.
The medical record must include a statement that written informed consent was obtained before any 
study-related activity and the date when the written consent was obtained. The authorised person 
obtaining the informed consent must also sign and date the informed consent form before any 
study-related activity.
The responsibility of seeking informed consent must remain with the investigator, but the 
investigator may delegate the task to a medically qualified person, in accordance with local 
requirements.
Participants must be re-consented to the most current version of the informed consent form(s)
during their participation in the study.
A copy of the informed consent form(s) must be provided to the participant.
10.1.4
Information to participants during the study
All written information to participants must be sent to IRB/IEC for approval/favourable opinion and 
to regulatory authorities for approval or notification according to local regulations.
10.1.5
Data protection
Participants will be assigned a 6-digit unique identifier, a subject ID. Any participant records or 
datasets that are transferred to Novo Nordisk will contain the identifier only. No direct identifiers 
from the participant are transferred to Novo Nordisk.
The participant and any biological material obtained from the participant will be identified by 
subject ID, visit number and study ID. Appropriate measures such as encryption or leaving out 
certain identifiers will be enforced to protect the identity of participants as required by local, 
regional, and national requirements.
The participant must be informed about his/her privacy rights, including that his/her personal study-
related data will be used by Novo Nordisk in accordance with local data protection law. The 
disclosure of the data must also be explained to the participant.
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The participant must be informed that his/her medical records may be examined by auditors or other 
authorised personnel appointed by Novo Nordisk, by appropriate IRB/IEC members, and by 
inspectors from regulatory authorities.
Personal data may be collected from participants due to process requirements from Novo Nordisk’s 
suppliers. This data is needed to ensure that the relevant data analysis for the study can be 
performed but will not be part of the data transferred to Novo Nordisk, the assessment of the study 
endpoints or the clinical study report. A list of any such data values must be kept as part of the 
study documentation along with an explanation of why it was required.
10.1.6
Committee’s structure
10.1.6.1
Novo Nordisk safety committee
Novo Nordisk will perform ongoing safety surveillance. If new safety signals are identified, these 
will be evaluated by an internal safety committee.
10.1.7
Dissemination of clinical study data
Study information will be disclosed at clinicaltrials.gov and novonordisk-trials.com and, if 
applicable, also on other national or regional study registries. It will be disclosed according to 
applicable requirements, relevant recommendations or regulations, such as the Declaration of 
Helsinki,44 the International Committee of Medical Journal Editors (ICMJE),46 the Food and Drug 
Administration Amendment Act (FDAAA),47 European Commission Requirements48-50 and in 
accordance with Novo Nordisk commitment to clinical transparency. If a participant requests to be 
included in the study via the Novo Nordisk e-mail contact at these web sites, Novo Nordisk may 
disclose the investigator’s contact details to the participant. As a result of increasing requirements 
for transparency, some countries require public disclosure of investigator names and their 
affiliations.
The PCD determines the deadline for results disclosure at clinicaltrials.gov according to FDAAA, 
see Section 4.4 for definition of PCD.
10.1.8
Data quality assurance
10.1.8.1
Case report forms
Novo Nordisk or designee is responsible for the data management of this study including quality 
checking of the data.
To demonstrate his/her oversight of the collected data, the investigator should sign the CRF on a 
regular basis during the conduct of the study as well as at the end of the study.
All participant data relating to the study will be recorded on CRFs unless transmitted electronically 
to Novo Nordisk or designee (e.g., patient reported outcome, prescription card data). The 
investigator is responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
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The following will be provided as paper CRFs: 
x
Pregnancy forms
x
Technical complaint forms
The following will be provided as paper CRFs to be used when access to the CRF is revoked or the 
CRF is temporarily unavailable: 
x
AE forms
x
Safety information forms
Corrections to the CRF data may be made by the investigator or the investigator’s delegated staff. 
An audit trail will be maintained in the CRF application containing as a minimum: the old and the 
new data, identification of the person entering the data, date and time of the entry and reason for the 
correction. If corrections are made by the investigator’s delegated staff after the date when the 
investigator signed the CRF, the CRF must be signed and dated again by the investigator.
The investigator must ensure that data is recorded in the CRF as soon as possible, preferably within 
5 working days after the visit. Once data has been entered, it will be available to Novo Nordisk for 
data verification and validation purposes.
10.1.8.2
Monitoring
The investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents (original documents, data, 
and records). Direct access includes permission to examine, analyse, verify, and reproduce any 
record(s) and report(s) that are important to the evaluation of the study. If the electronic source data 
does not have a visible audit trail, the investigator must provide the monitor with signed and dated 
printouts. In addition, the relevant site staff should be available for discussions at monitoring visits 
and between monitoring visits (e.g., by telephone).
Study monitors will perform ongoing source data verification of critical data points to confirm that 
data entered into the CRF by authorised site personnel are accurate, complete, and verifiable from 
source documents. Study monitors will perform ongoing source data review to ensure that the study 
is being conducted in accordance with the current approved protocol and any other study 
agreements, ICH GCP45 and all applicable regulatory requirements, evaluating the adequacy of 
critical processes at site for the execution of the protocol, collection of study data, to ensure that the 
safety and rights of participants are being protected.
Monitoring will be conducted using a risk-based approach including risk assessment, monitoring 
plans, centralised monitoring (remote assessment of data by Novo Nordisk) and, if necessary, visits 
to sites.
Monitors will review the patient’s medical records and other source data, to ensure consistency 
and/or identify omissions compared to the eCRF.
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10.1.8.3
Protocol compliance
Deviations from the protocol should be avoided. If deviations do occur, the investigator must 
inform the monitor without delay and the implications of the deviation must be reviewed and 
discussed.
Deviations must be documented and explained in a protocol deviation by stating the reason, date, 
and the action(s) taken.
10.1.9
Source documents
All data entered in the CRF must be verifiable in source documentation other than the CRF.
For ePROs, data in the service providers database is considered source data.
If source data is entered directly in a paper CRF, each data entry or clear series of data entries must 
be signed and dated separately by the study staff making the entry.
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the site. Any source data generated by 
investigator’s subcontractors must be archived and accessible by the site.
Data that is transcribed into the CRF from source documents must be consistent with the source 
documents, or the discrepancies must be explained. The investigator may need to request previous 
medical records or transfer records. Also, current medical records must be available.
It must be possible to verify participant’s medical history in source documents, such as participant’s 
medical record.
The investigator must document any attempt to obtain external medical information by noting the 
date(s) when information was requested, and who was contacted.
Definition of what constitutes source data can be found in a source document agreement at each site 
There will only be one source document defined at any time for any data element.
10.1.10
Retention of clinical study documentation
Records and documents, including signed informed consent forms, pertaining to the conduct of this 
study must be retained by the investigator for 25 years after end of study unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during the 
retention period without the written approval of Novo Nordisk. No records may be transferred to 
another location or party without written notification to Novo Nordisk.
The investigator must be able to access his/her study documents without involving Novo Nordisk in 
any way. If applicable, electronic CRF (eCRF) and other participant data will be provided in an 
electronic readable format to the investigator before access is revoked to the systems supplied by 
Novo Nordisk. Site-specific CRFs and other participant data (in an electronic readable format or as 
paper copies or prints) must be retained by the site. A copy of all data will be stored by Novo 
Nordisk.
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Participant’s medical records must be kept for the maximum period permitted by the hospital, 
institution, or private practice.
10.1.11
Study and site closure
Novo Nordisk reserves the right to close the site or terminate the study at any time for any reason at 
the sole discretion of Novo Nordisk. If the study is suspended or terminated, the investigator must 
inform the participants promptly and ensure appropriate therapy and follow-up. The investigator 
and/or Novo Nordisk must also promptly inform the regulatory authorities and IRBs/IECs and 
provide a detailed written explanation.
Sites will be closed upon study completion. A site is considered closed when all required documents 
and study supplies have been collected and a site closure visit has been performed.
The investigator may initiate site closure at any time, provided there is reasonable cause and 
sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a site by Novo Nordisk or investigator may include but are not 
limited to:
x
failure of the investigator to comply with the protocol, the requirements of the IRB/IEC or local 
health authorities, Novo Nordisk procedures or GCP guidelines
x
inadequate recruitment of participants by the investigator
x
discontinuation of further study intervention development.
10.1.12
Responsibilities
The investigator is accountable for the conduct of the study at his/her site and must ensure adequate 
supervision of the conduct of the study at the site. If any tasks are delegated, the investigator must 
maintain a log of appropriately qualified persons to whom he/she has delegated specified study-
related duties. The investigator must ensure that there is adequate and documented training for all 
staff participating in the conduct of the study. It is the investigator’s responsibility to supervise the 
conduct of the study and to protect the rights, safety, and well-being of the participants.
A qualified physician, who is an investigator or a sub investigator for the study, must be responsible 
for all study-related medical decisions.
The investigator is responsible for filing essential documents (i.e., those documents which 
individually and collectively permit evaluation of the conduct of a study and the quality of the data 
produced) in the investigator trial master file. The documents, including the participant 
identification code list must be kept in a secure locked facility so that no unauthorised persons can 
get access to the data.
The investigator will take all necessary technical and organisational safety measures to prevent 
accidental or wrongful destruction, loss, or deterioration of data. The investigator will prevent any 
unauthorised access to data or any other processing of data against applicable law. This also 
includes ensuring that no indirect sharing of user credentials for IT systems used in this study takes 
place (e.g., by not sharing IT equipment with others in a way where user credentials have the 
possibility of being shared). The investigator must be able to provide the necessary information or 
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otherwise demonstrate to Novo Nordisk that such technical and organisational safety measures have 
been taken.
During any period of unavailability, the investigator must delegate responsibility for medical care of 
participants to a specific qualified physician who will be readily available to participants during that 
time.
If the investigator is no longer able to fulfil the role as investigator (e.g., if he/she moves or retires), 
a new investigator will be appointed in consultation with Novo Nordisk.
The investigator and other site personnel must have sufficient English skills according to their 
assigned task(s).
10.1.13
Indemnity statement
Novo Nordisk carries product liability for its products, and liability as assumed under the special 
laws, acts and/or guidelines for conducting clinical studies in any country, unless others have shown 
negligence.
Novo Nordisk assumes no liability in the event of negligence or any other liability of the sites or 
investigators conducting the study or by persons for whom the said site or investigator are 
responsible.
10.1.14
Publication policy
The information obtained during the conduct of this study is considered confidential and may be 
used by or on behalf of Novo Nordisk for regulatory purposes as well as for the general 
development of the study intervention. All information supplied by Novo Nordisk in connection 
with this study shall remain the sole property of Novo Nordisk and is to be considered confidential 
information.
No confidential information shall be disclosed to others without prior written consent from Novo 
Nordisk. Such information shall not be used except in the performance of this study.
The information obtained during this study may be made available to other investigators who are 
conducting other clinical studies with the study intervention, if deemed necessary by Novo Nordisk. 
Provided that certain conditions are fulfilled, Novo Nordisk may grant access to information 
obtained during this study to researchers who require access for research projects studying the same 
or related diseases and/or study intervention studied in this study.
Novo Nordisk may publish on its clinical studies website a redacted CSR for this study.
One investigator will be appointed by Novo Nordisk to review and sign the CSR (signatory 
investigator) on behalf of all participating investigators.
10.1.14.1
Communication of results
Novo Nordisk commits to communicate and disclose results of studies regardless of outcome. 
Disclosure includes publication of a manuscript in a peer-reviewed scientific journal, abstract 
submission with a poster or oral presentation at a scientific meeting or disclosure by other means.
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The results of this study will be subject to public disclosure on external web sites according to 
international and national regulations. Novo Nordisk reserves the right to defer the release of data 
until specified milestones are reached, for example when the CSR is available. This includes the 
right not to release the results of interim analyses, because the release of such information may 
influence the results of the entire study.
At the end of the study, one or more scientific publications may be prepared collaboratively by the 
investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or 
communication for up to 60 days to protect intellectual property.
In all cases, the study results will be reported in an objective, accurate, balanced, and complete 
manner, with a discussion of the strengths and limitations. In the event of any disagreement on the 
content of any publication, both the investigators’ and Novo Nordisk’s opinions will be fairly and 
sufficiently represented in the publication.
10.1.14.2
Authorship
Novo Nordisk will work with one or more investigator(s) and other experts who have contributed to 
the study concept or design, acquisition, analysis, or interpretation of data to report the results in 
one or more publications. 
Authorship of publications should be in accordance with the Recommendations for the Conduct, 
Reporting, Editing and Publication of Scholarly Work in Medical Journals by the International 
Committee of Medical Journal Editors.51
All authors will be provided with the relevant statistical tables, figures, and reports needed to 
evaluate the planned publication.
Where required by the journal, the investigator from each site will be named in an 
acknowledgement or in the supplementary material, as specified by the journal.
10.1.14.3
Site-specific publication(s) by investigator(s)
For a multicentre clinical study, analyses based on single-site data usually have significant 
statistical limitations and frequently do not provide meaningful information for healthcare 
professionals or participants, and therefore may not be supported by Novo Nordisk. Thus, Novo 
Nordisk may deny a request or ask for deferment of the publication of individual site results until 
the primary manuscript is accepted for publication. In line with Good Publication Practice, such 
individual reports should not precede the primary manuscript and should always reference the 
primary manuscript of the study.
10.1.14.4
Investigator access to data and review of results
As owner of the study database, Novo Nordisk has the discretion to determine who will have access 
to the database.
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10.2
Appendix 2: Adverse Events and Serious Adverse Events: Definitions and procedures 
for recording, evaluating, follow-up, and reporting
10.2.1
Definition of AE
An AE is any untoward medical occurrence in a clinical study participant that is temporally 
associated with the use of IMP, whether or not considered related to the IMP. An AE can therefore 
be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or 
disease (new or exacerbated) temporally associated with the use of an IMP.
Events to be reported as AEs:
x
Any abnormal laboratory test results or safety assessments considered clinically significant in 
the medical and scientific judgment of the investigator, including events that have worsened 
from prior to the time point from which AEs are collected
x
Conditions detected or diagnosed after IMP administration even though it may have been 
present prior to the time point from which AEs are collected
x
Exacerbation/worsening of a chronic or intermittent condition including either an increase in 
frequency and/or intensity of the condition
x
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction
x
Signs, symptoms, or the clinical sequelae of a suspected overdose of IMP regardless of intent
A ‘lack of efficacy’ or ‘failure of expected pharmacological action’ per se will not be reported as an 
AE or SAE. Such instances will be captured in the efficacy assessments. However, the signs, 
symptoms and/or clinical sequelae resulting from lack of efficacy will be reported as AE or SAE if 
they fulfil the definition.
Events NOT to be reported as AEs:
x
Conditions present prior to the time point from which AEs are collected and anticipated day-to-
day fluctuations of these conditions. This includes those conditions identified during screening 
or identified during other study procedures performed before exposure to IMP. 
Note: Conditions present or occurring prior to the time point from which AEs are collected 
should be recorded as concomitant illness/medical history.
x
Medical or surgical procedures (e.g., endoscopy, appendectomy). The condition that leads to the 
procedure is the AE.
x
Medical or surgical procedures not preceded by an AE or worsening of a known condition.
10.2.2
Definition of an SAE
An SAE is any untoward medical occurrence that fulfils at least one of the following criteria:
x
Results in death
x
Is life-threatening
x
The term ‘life-threatening’ refers to an event in which the participant was at risk of death at 
the time of the event. It does not refer to an event which hypothetically might have caused 
death if it were more severe.
x
Requires inpatient hospitalisation or prolongation of existing hospitalisation
x
Hospitalisation signifies that the participant has been admitted at the hospital or emergency 
ward for observation and/or treatment that would not have been appropriate in the 
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physician’s office or outpatient setting. Complications that occur during hospitalisation are 
AEs. If a complication prolongs hospitalisation or fulfils any other seriousness criteria, the 
event is serious. When in doubt as to whether ‘hospitalisation’ occurred or was necessary, 
the AE should be considered serious.
x
Hospitalisation for elective treatment (e.g., elective medical or surgical procedures) of a 
condition that was present prior to the time point from which AEs are collected, and that did 
not worsen, is not considered an AE.
Note: Hospitalisations for administrative, study-related, social and convenience reasons do 
not constitute AEs and should therefore not be reported as AEs or SAEs. Hospital 
admissions for medical or surgical procedures, planned before study inclusion, are not
considered AEs or SAEs
x
Results in persistent or significant disability/incapacity
x
The term ‘disability’ means a substantial disruption of a person’s ability to conduct normal 
life functions. This definition is not intended to include experience of relatively minor 
medical significance, such as uncomplicated headache, nausea, vomiting, diarrhoea, 
influenza, and accidental trauma (e.g., sprained ankle), that may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption.
x
Is a congenital anomaly/birth defect
x
Important medical event:
x
Medical or scientific judgment should be exercised by the investigator in deciding whether 
SAE reporting is appropriate in other situations. This includes important medical events that 
may not be immediately life-threatening or result in death or hospitalisation but may 
jeopardise the participant or may require medical or surgical intervention to prevent one of 
the other outcomes listed in the above definition. These events should usually be considered 
serious and reported as SAEs using the important medical event criterion.
x
The following must be reported as an SAE using the important medical event criterion if no 
other seriousness criteria are applicable:
o
Suspicion of transmission of infectious agents via IMP
o
Risk of liver injury defined as alanine aminotransferase (ALT) or asparate 
aminotransferase (AST) >3x UNL and total bilirubin >2x UNL where no alternative 
aetiology exists (Hy’s law)
10.2.3
Description of AEs requiring additional data collection
Adverse events requiring additional data collection
An AE requiring additional data collection is an AE where Novo Nordisk has evaluated that 
additional data is needed in the evaluation of safety.
Medication error:
x
A medication error is an unintended failure in the IMP treatment process that leads to, or has the 
potential to lead to, harm to the participant, such as:
x
administration of wrong drug
x
wrong route of administration, such as intramuscular instead of subcutaneous
x
accidental administration of a higher dose than intended. The administered dose must 
deviate from the intended dose to an extent where clinical consequences for the study 
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participant were likely to happen as judged by the investigator, although they did not 
necessarily occur.
Misuse and abuse:
x
Situations where the IMP is intentionally and inappropriately used not in accordance with the 
protocol (e.g., overdose to maximize effect)
x
Persistent or sporadic, intentional excessive use of an IMP which is accompanied by harmful 
physical or psychological effects (e.g., overdose with the intention to cause harm)
Note: Medication error, misuse and abuse must always be reported on an AE form and a specific 
event form must be completed. The AE diagnosis on the AE form must reflect what occurred (e.g., 
accidental overdose, intentional overdose or other). If the medication error and/or misuse and abuse 
resulted in a clinical consequence, this must be reported on an additional AE form.
10.2.4
Recording and follow-up of AE and/or SAE
10.2.4.1
AE and SAE recording
SAEs and AEs listed in Section 8.3 and AEs/SAEs in connection with pregnancies, must be 
recorded by the investigator in the CRF. The investigator will attempt to establish a diagnosis of the 
event based on signs, symptoms, and/or other clinical information. In such cases, the diagnosis (not
the individual signs/symptoms) will be documented as the AE/SAE.
When an AE/SAE occurs, it is the responsibility of the investigator to review all documentation 
(e.g., hospital progress notes, laboratory, and diagnostics reports) related to the event.
There may be instances when copies of source documents (e.g., medical records) for certain cases 
are requested by Novo Nordisk. In such cases, all participant identifiers, with the exception of the 
subject ID, must be redacted on the copies of the source documents before submission to Novo 
Nordisk.
For all non-serious AEs, the applicable forms should be signed when the event is resolved or at the 
end of the study at the latest. For sign-off of SAE-related forms, refer to “AE and SAE reporting via 
paper CRF” later in this section.
Novo Nordisk products used as concomitant medication: if an AE is considered to have a causal 
relationship with a Novo Nordisk marketed product used as concomitant medication in the study, it 
is important that the suspected relationship is reported to Novo Nordisk, e.g., in the alternative 
aetiology section on the safety information form. Novo Nordisk may need to report this adverse 
event to relevant regulatory authorities
10.2.4.2
Assessment of severity
The investigator will assess severity for each event reported during the study and assign it to one of 
the following categories:
x
Mild: An event that is easily tolerated by the participant, causing minimal discomfort, and not 
interfering with everyday activities.
x
Moderate: An event that causes sufficient discomfort and interferes with normal everyday 
activities.
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x
Severe: An event that prevents normal everyday activities. 
Note: An AE that is assessed as severe should not be confused with an SAE. Both AEs and 
SAEs can be assessed as severe.
10.2.4.3
Assessment of causality
The investigator is obligated to assess the relationship between IMP and the occurrence of each 
AE/SAE. The investigator will use clinical judgment to determine the relationship. 
Relationship between an AE/SAE and the relevant IMP should be assessed as: 
x
Probable - Good reason and sufficient documentation to assume a causal relationship.
x
Possible - A causal relationship is conceivable and cannot be dismissed.
x
Unlikely - The event is most likely related to etiology other than the IMP.
Alternative aetiology, such as underlying disease(s), concomitant medication, and other risk factors, 
as well as the temporal relationship of the event to IMP administration, should be considered and 
investigated.
The investigator should use the product information, for marketed products, for the assessment. For 
each AE/SAE, the investigator must document in the medical records that he/she has reviewed the 
AE/SAE and has provided an assessment of causality.
There may be situations in which an SAE has occurred, and the investigator has minimal 
information to include in the initial report. However, it is important that the investigator always 
makes an assessment of causality for every event before the initial transmission of the SAE 
data.
The investigator may change his/her opinion of causality, in light of follow-up information, and 
update the causality assessment in the CRF.
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements
10.2.4.4
Final outcome
The investigator will select the most appropriate outcome:
x
Recovered/resolved: The participant has fully recovered, or by medical or surgical treatment 
the condition has returned to the level observed when first documented
x
Recovering/resolving: The condition is improving, and the participant is expected to recover 
from the event.  This term may also be applicable for AEs ongoing at the time of death (where 
death was due to another AE).
Note: For SAEs, this term is only applicable if the participant has completed the follow-up
period and is expected to recover.
x
Recovered/resolved with sequelae: The participant has recovered from the condition but with 
lasting effect due to a disease, injury, treatment, or procedure. If a sequela meets an SAE 
criterion, the AE must be reported as an SAE.
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x
Not recovered/not resolved: The condition of the participant has not improved, and the 
symptoms are unchanged, or the outcome is not known. This term may be applicable in cases of 
chronic conditions, cancer, or AEs ongoing at time of death (where death is due to another AE).
x
Fatal: This term is only applicable if the participant died from a condition related to the 
reported AE. Outcomes of other reported AEs in a participant before he/she died should be 
assessed as ‘recovered/resolved’, ‘recovering/resolving’, ‘recovered/resolved with sequelae’ or 
‘not recovered/not resolved’. An AE with a fatal outcome must be reported as an SAE.
x
Unknown: This term is only applicable if the participant is lost to follow-up
10.2.4.5
Follow-up of AE and SAE
The investigator is obligated to perform or arrange for the conduct of supplemental measurements 
and/or evaluations as medically indicated or as requested by Novo Nordisk to elucidate the nature 
and/or causality of the AE or SAE as fully as possible (e.g., severe hypersensitivity reactions, Hy’s 
law). This may include additional laboratory tests or investigations, histopathological examinations, 
or consultation with other health care professionals.
If a participant dies during participation in the study or during a recognised follow-up period, the 
investigator should, upon request, provide Novo Nordisk with a copy of the autopsy report 
including histopathology.
New or updated information should be recorded in the CRF.
10.2.5
Reporting of SAEs 
AE and SAE reporting via CRF
Relevant forms must be completed in the CRF.
For SAEs, initial notification via telephone is acceptable, although it does not replace the need for 
the investigator to complete the AE and safety information forms within the designated reporting 
timelines:
x
AE form within 24 hours
x
Safety information form within 5 calendar days
x
Both forms must be signed within 7 calendar days after first knowledge by the investigator.
x
Specific event form within 14 calendar days.
If the eCRF is unavailable for more than 24 hours, then the sites will use the paper AE form, and if 
the eCRF is unavailable for more than 5 calendar days, then the site will use the paper safety 
information form. The site should enter the SAE data in the eCRF as soon as it becomes available.
The relevant CRF forms (AE and safety information forms) must be forwarded to Novo Nordisk in 
accordance with Section 10.1.5.
After the study is completed, the study database will be locked, and the CRF will be 
decommissioned to prevent the entry of new data or changes to existing data.  If a site receives a 
report of a new SAE from a participant or receives updated information on a previously reported 
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SAE after CRF decommission, the site can report this information on a paper AE and safety 
information form (see below) or to Novo Nordisk by telephone.
Figure 10-1 Decision tree for determining the event type and the respective forms to 
complete with associated timelines
Contact details for SAE reporting can be found in the investigator trial master file
10.3
Appendix 3: Contraceptive guidance and collection of pregnancy information
10.3.1
Definitions
Woman of childbearing potential (WOCBP)
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile.
If fertility is unclear (e.g., amenorrhea in adolescents or athletes), and a menstrual cycle cannot be 
confirmed before first dose of study intervention, additional evaluation should be considered.
Females in the following categories are not considered WOCBP
1. Premenarcheal
2. Females with one or more of the following:
x
Documented total hysterectomy
x
Documented bilateral salpingectomy
x
Documented bilateral oophorectomy
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For females with permanent infertility due to an alternate medical cause other than the above 
(e.g., Müllerian agenesis, androgen insensitivity), investigator discretion should be applied in 
determining study enrolment.
3. Postmenopausal female:
x
A postmenopausal state is defined as amenorrhoea for at least 12 months without an 
alternative medical cause in a female > 45 years of age.  Alternative medical causes for 
amenorrhoea include, but are not limited to, hormonal contraception or hormonal 
replacement therapy. 
x
Females ≥ 60 years of age can be considered postmenopausal.
Females on HRT and whose menopausal status is in doubt are considered of childbearing potential 
and will be required to use one of the highly effective contraception methods. 
Note: Documentation regarding categories 1-3 can come from the site staff’s review of participant’s 
medical records, medical examination, or medical history interview.
10.3.2
Contraceptive guidance
Male participants
No contraception measures are needed for male participants.
Female participants
Female participants of childbearing potential are eligible to participate if they agree to use methods 
of contraception consistently and correctly. Table 10-1 lists the highly effective methods of 
contraception allowed. 
Highly effective contraception should be utilised until the end of treatment.
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Table 10-1
Highly effective contraceptive methods allowed52
Highly effective methodsa (Failure rate of <1% per year when used consistently and correctly):
x Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulationb
x oral
x intravaginal
x transdermal
x Progestogen-only hormone contraception associated with inhibition of ovulation
x oral
x injectable
x implantable
x Intrauterine device (IUD)
x Intrauterine hormone-releasing system (IUS)
x Bilateral tubal occlusion
x Vasectomized partner
Vasectomized partner is a highly effective contraceptive method provided that the partner is the sole sexual partner 
of the woman of childbearing potential, and the absence of sperm has been confirmed. If not, an additional highly 
effective method of contraception should be used. Spermatogenesis cycle is approximately 90 days.
x Sexual abstinence
Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of risk associated with the study intervention. The reliability of sexual 
abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the 
participant.
NOTES
a. Contraceptive use by men or women should comply with local regulations regarding the use of contraceptive 
methods for those participating in clinical studies.
b. If locally required, in accordance with Clinical Trial Facilitation Group (CTFG) guidelines, acceptable 
contraceptive methods are limited to those which inhibit ovulation as the primary mode of action.
c. Male condom and female condom should not be used together (due to risk of failure from friction).
The following methods are not acceptable methods of contraception: Periodic abstinence (calendar, 
symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and 
lactational amenorrhea method (LAM).
10.3.3
Collection of pregnancy information
Female participants who become pregnant
Investigator will collect pregnancy information on any female participant who becomes pregnant 
while participating in this study.
Information will be recorded on the appropriate form and submitted to Novo Nordisk within 14 
calendar days of learning of a participant’s pregnancy.
The participant will be followed to determine the outcome of the pregnancy. The investigator will 
collect follow-up information on participant and neonate which will be forwarded to Novo Nordisk 
within 14 calendar days. Generally, follow-up will not be required for longer than 1 month beyond 
the delivery date.
Any termination of pregnancy will be reported, regardless of foetal status (presence or absence of 
anomalies) or indication for procedure.
While pregnancy itself is not considered to be an AE or SAE, any adverse event in connection with 
pregnancy or elective termination of a pregnancy for medical reasons will be reported as an AE or
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SAE. If relevant, consider adding ‘gestational’, ‘pregnancy-related’ or a similar term when 
reporting the AE/SAE.
Pregnancy outcome should be documented in the participant’s medical record. Abnormal pregnancy 
outcome (e.g., spontaneous abortion, foetal death, stillbirth, congenital anomalies, and ectopic 
pregnancy) is considered an SAE. In case of abnormal pregnancy outcome, paternal information 
should be recorded in the appropriate form after obtaining the necessary signed paternal informed 
consent.
If the investigator learns of an SAE occurring as a result of a post-study pregnancy which is 
considered related to the IMP by the investigator, the SAE should be reported to Novo Nordisk as 
described in Appendix 2(Section 10.2.)
Figure 10-2 Decision tree for determining the forms to complete for collection of pregnancy 
information and timelines for reporting – For female participants
Any female participant who becomes pregnant while participating in the study will discontinue 
study intervention.
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10.4
Appendix 4: Technical complaints: Definition and reporting
Technical complaints on Wegovy® and Saxenda® which occur from the first time of usage of the 
product until the last time of usage of the product and which is considered related to:
x
- an adverse event leading to product discontinuation
x
- an SAE
must be reported to Novo Nordisk via study specific technical complaint form and according to the 
instructions found in Appendix 4 (Section 10.4.2).
In order for Novo Nordisk to perform a complete investigation of a reported SAE which is not 
linked to a technical complaint, Novo Nordisk might ask the investigator to complete a technical 
complaint form for Wegovy® and Saxenda®.
Technical complaints on Wegovy® and Saxenda® NOT related to an adverse event, or related to an 
adverse event which is not systematically collected according to protocol, may be reported to Novo 
Nordisk affiliate via the spontaneous reporting system.
Technical complaint on non Novo Nordisk products may be reported to the manufacturing 
authorization holder of the given product. Still any adverse events or SAEs for the non-Novo
Nordisk product must be reported according to Appendix 3 (Section 10.3.2).
10.4.1
Definition of technical complaint
A technical complaint is any written, electronic, or oral communication that alleges product 
(medicine or device) defects. The technical complaint may be associated with an AE but does not 
concern the AE itself. 
Examples of technical complaints:
x
Problems with the physical or chemical appearance of study interventions (e.g., 
discoloration, particles, or contamination)
x
Problems with packaging material including labelling
x
Problems related to devices (e.g., to the injection mechanism, dose setting mechanism, push 
button or interface between the pen-injector and the needle
10.4.2
Technical complaint reporting
Recording and follow-up of technical complaints to Novo Nordisk
The investigator must complete and forward the technical complaint form to Customer Complaint 
Center, Novo Nordisk, within:
x
24 hours if related to an SAE
x
5 calendar days if related to an adverse event leading to product discontinuation
For contact details for Customer Complaint Center, please refer to instruction page for technical 
complaint form.
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Follow-up of technical complaints
The investigator is responsible for ensuring that new or updated information will be recorded on the 
originally completed form.
10.4.3
Collection, storage, and shipment of technical complaint samples 
Technical complaints on Wegovy® and Saxenda® reported on the study specific technical 
complaint form:
The investigator must collect the technical complaint sample and all associated parts and notify the 
monitor within 5 calendar days of obtaining the sample at site. The sample and all associated parts 
must be sent as soon as possible to Customer Complaint Center, Novo Nordisk, together with a 
copy of the completed technical complaint form. The technical complaint sample should contain the 
batch, code, or lot number. If the technical complaint sample is unobtainable, the reason must be 
stated on the technical complaint form. If several samples are shipped in one shipment, the sample 
and the corresponding technical complaint form should be kept together.
Storage of the technical complaint sample must be done in accordance with the conditions 
prescribed for the study intervention.
Other technical complaints:
Instructions will be provided by Novo Nordisk affiliate or the relevant manufacturing authorization 
holder.
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10.5
Appendix 5: Abbreviations
AE
adverse event
ALT
Alanine aminotransferase
AOM
anti-obesity medication
API
active pharmaceutical ingredient
AST
Aspartate aminotransferase
BMI
body mass index
CI
confidence interval
CRF
case report form
CSR
clinical study report
eCRF
electronic case report form
DPS
data point set
FAS
full analysis set
FDA
U.S. Food and Drug Administration
FPFV
first patient first visit
GCP
Good Clinical Practice
GLP-1 (RA)
glucagon-like peptide 1 (receptor agonist)
HbA1c
glycated haemoglobin
IB
investigator’s brochure
ICH
International Council for Harmonisation
IEC
independent ethics committee
IMP
investigational medicinal product
IRB
institutional review board
IWQOL
Impact of Weight on Quality of Life (questionnaire)
LR
logistic regression
MedDRA
Medical Dictionary for Regulatory Activities
MMRM
mixed model repeated measures
Other AOMs
Xenical®, Qsymia®, Contrave®, and Saxenda®
PCD
primary completion date
PDC
proportion of days covered (by medication)
p.o.
per os (by mouth)
RTSM
Randomisation and trial supply management (system)
SAE
serious adverse event
SAP
statistical analysis plan
SAS
safety analysis set
s.c.
sub-cutaneous
CONFIDENTIAL

Protocol
Date:
15 September 2022
Novo Nordisk
Study ID: NN9536-4741
Version:
2.0
Semaglutide 2.4 mg s.c.
Status:
Final
Page:
58 of 62
SD
standard deviation
SOC
system organ class
SUSAR
suspected unexpected serious adverse reaction
TP-MI
tipping point, multiple imputation analysis
TSQM
Treatment Satisfaction for Medication (questionnaire)
UNL
upper normal limit
WLQ
Work Limitations Questionnaire
WMP
weight management program
WOCBP
woman of childbearing potential
CONFIDENTIAL

Protocol
Date:
15 September 2022
Novo Nordisk
Study ID: NN9536-4741
Version:
2.0
Semaglutide 2.4 mg s.c.
Status:
Final
Page:
59 of 62
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CONFIDENTIAL

Protocol
Date:
15 September 2022
Novo Nordisk
Study ID: NN9536-4741
Version:
2.0
Semaglutide 2.4 mg s.c.
Status:
Final
Page:
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CONFIDENTIAL

Protocol
Date:
15 September 2022
Novo Nordisk
Study ID: NN9536-4741
Version:
2.0
Semaglutide 2.4 mg s.c.
Status:
Final
Page:
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CONFIDENTIAL

Protocol
Date:
15 September 2022
Novo Nordisk
Study ID: NN9536-4741
Version:
2.0
Semaglutide 2.4 mg s.c.
Status:
Final
Page:
62 of 62
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