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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04707469




Registration number
NCT04707469
Ethics application status
Date submitted
12/01/2021
Date registered
13/01/2021

Titles & IDs
Public title
Research Study to Compare Three Doses of Semaglutide Tablets Taken Once Daily in People With Type 2 Diabetes
Scientific title
Efficacy and Safety of Once-daily Oral Semaglutide 25 mg and 50 mg Compared With 14 mg in Subjects With Type 2 Diabetes
Secondary ID [1] 0 0
U1111-1247-0210
Secondary ID [2] 0 0
NN9924-4635
Universal Trial Number (UTN)
Trial acronym
PIONEER PLUS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes Mellitus, Type 2 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Oral semaglutide

Experimental: Oral semaglutide 50 mg - Participants will receive once daily semaglutide tablets in a dose escalating manner for 68 weeks: 3 mg (week 1-4), 7 mg (week 5-8), 14 mg (week 9-12), 25 mg (week 13-16) and 50 mg (week 17-68).

Experimental: Oral semaglutide 25 mg - Participants will receive once daily semaglutide tablets in a dose escalating manner for 68 weeks: 3 mg (week 1-4), 7 mg (week 5-8), 14 mg (week 9-12) and 25 mg (week 13-68).

Active comparator: Oral semaglutide 14 mg - Participants will receive once daily semaglutide tablets in a dose escalating manner for 68 weeks: 3 mg (week 1-4), 7 mg (week 5-8) and 14 mg (week 9-68).


Treatment: Drugs: Oral semaglutide
Participants will receive once daily semaglutide tablets (oral administration) in a dose escalating manner for 68 weeks.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Glycated Haemoglobin (HbA1c) (Week 52)
Timepoint [1] 0 0
Baseline (week 0), week 52
Secondary outcome [1] 0 0
Change From Baseline in Body Weight (Week 52)
Timepoint [1] 0 0
Baseline (week 0), week 52
Secondary outcome [2] 0 0
Change From Baseline in HbA1c (Week 68)
Timepoint [2] 0 0
Baseline (week 0), week 68
Secondary outcome [3] 0 0
Change From Week 12 in HbA1c (Week 52)
Timepoint [3] 0 0
Week 12, Week 52
Secondary outcome [4] 0 0
Change From Baseline in Fasting Plasma Glucose (FPG) (Week 52)
Timepoint [4] 0 0
Baseline (week 0), week 52
Secondary outcome [5] 0 0
Change From Baseline in FPG (Week 68)
Timepoint [5] 0 0
Baseline (week 0), week 68
Secondary outcome [6] 0 0
Percentage of Participants Who Achieved HbA1c Less Than (<) 7.0 (Percent [%]) (Week 52)
Timepoint [6] 0 0
At week 52
Secondary outcome [7] 0 0
Percentage of Participants Who Achieved HbA1c < 7.0 % (Week 68)
Timepoint [7] 0 0
At week 68
Secondary outcome [8] 0 0
Percentage of Participants Who Achieved HbA1c Less Than or Equal to (<=) 6.5 % (Week 52)
Timepoint [8] 0 0
At week 52
Secondary outcome [9] 0 0
Percentage of Participants Who Achieved HbA1c <= 6.5 % (Week 68)
Timepoint [9] 0 0
At week 68
Secondary outcome [10] 0 0
Time to Event Analyses of Rescue Medication
Timepoint [10] 0 0
Baseline (week 0), week 68
Secondary outcome [11] 0 0
Change From Baseline in Body Weight (Week 68)
Timepoint [11] 0 0
Baseline (week 0), week 68
Secondary outcome [12] 0 0
Percentage Change From Baseline in Body Weight (Week 52)
Timepoint [12] 0 0
Baseline (week 0), week 52
Secondary outcome [13] 0 0
Percentage Change From Baseline in Body Weight (Week 68)
Timepoint [13] 0 0
Baseline (week 0), week 68
Secondary outcome [14] 0 0
Percentage Change From Week 12 in Body Weight (Week 52)
Timepoint [14] 0 0
Week 12, Week 52
Secondary outcome [15] 0 0
Change From Baseline in Body Mass Index (BMI) (Week 52)
Timepoint [15] 0 0
Baseline (week 0), week 52
Secondary outcome [16] 0 0
Change From Baseline in BMI (Week 68)
Timepoint [16] 0 0
Baseline (week 0), week 68
Secondary outcome [17] 0 0
Change From Baseline in Waist Circumference (Week 52)
Timepoint [17] 0 0
Baseline (week 0), week 52
Secondary outcome [18] 0 0
Change From Baseline in Waist Circumference (Week 68)
Timepoint [18] 0 0
Baseline (week 0), week 68
Secondary outcome [19] 0 0
Percentage of Participants Who Achieved Weight Loss Greater Than or Equal to (>=) 5 % (Week 52)
Timepoint [19] 0 0
At week 52
Secondary outcome [20] 0 0
Percentage of Participants Who Achieved Weight Loss >= 5 % (Week 68)
Timepoint [20] 0 0
At week 68
Secondary outcome [21] 0 0
Percentage of Participants Who Achieved Weight Loss >= 10 % (Week 52)
Timepoint [21] 0 0
At week 52
Secondary outcome [22] 0 0
Percentage of Participants Who Achieved Weight Loss >= 10 % (Week 68)
Timepoint [22] 0 0
At week 68
Secondary outcome [23] 0 0
Change From Baseline in Total Cholesterol (Week 52)
Timepoint [23] 0 0
Baseline, Week 52
Secondary outcome [24] 0 0
Change From Baseline in Total Cholesterol (Week 68)
Timepoint [24] 0 0
Baseline, Week 68
Secondary outcome [25] 0 0
Change From Baseline in Low Density Lipoproteins (LDL) (Week 52)
Timepoint [25] 0 0
Baseline, Week 52
Secondary outcome [26] 0 0
Change From Baseline in LDL (Week 68)
Timepoint [26] 0 0
Baseline, Week 68
Secondary outcome [27] 0 0
Change From Baseline in High Density Lipoproteins (HDL) (Week 52)
Timepoint [27] 0 0
Baseline, Week 52
Secondary outcome [28] 0 0
Change From Baseline in HDL (Week 68)
Timepoint [28] 0 0
Baseline, Week 68
Secondary outcome [29] 0 0
Change From Baseline in Triglycerides (Week 52)
Timepoint [29] 0 0
Baseline, Week 52
Secondary outcome [30] 0 0
Change From Baseline in Triglycerides (Week 68)
Timepoint [30] 0 0
Baseline, Week 68
Secondary outcome [31] 0 0
Number of Adverse Events
Timepoint [31] 0 0
From baseline (week 0) up to week 73
Secondary outcome [32] 0 0
Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 Milligram Per Decilitre [mg/dL]) or Severe Hypoglycaemic Episodes (Level 3)
Timepoint [32] 0 0
From baseline (week 0) up to week 68
Secondary outcome [33] 0 0
Change From Baseline in Systolic Blood Pressure (Week 52)
Timepoint [33] 0 0
Baseline (week 0), week 52
Secondary outcome [34] 0 0
Change From Baseline in Systolic Blood Pressure (Week 68)
Timepoint [34] 0 0
Baseline (week 0), week 68
Secondary outcome [35] 0 0
Change From Baseline in Diastolic Blood Pressure (Week 52)
Timepoint [35] 0 0
Baseline (week 0), week 52
Secondary outcome [36] 0 0
Change From Baseline in Diastolic Blood Pressure (Week 68)
Timepoint [36] 0 0
Baseline (week 0), week 68
Secondary outcome [37] 0 0
Change From Baseline in Pulse (Week 52)
Timepoint [37] 0 0
Baseline (week 0), week 52
Secondary outcome [38] 0 0
Change From Baseline in Pulse (Week 68)
Timepoint [38] 0 0
Baseline (week 0), week 68

Eligibility
Key inclusion criteria
* Male or female, age above or equal to 18 years at the time of signing informed consent.
* Diagnosed with type 2 diabetes mellitus at least 180 days prior to the day of screening.
* HbA1c of 8.0-10.5% (64-91 mmol/mol) (both inclusive).
* BMI equal to or above 25 kg/m^2
* Stable daily dose(s) for 90 days prior to the day of screening of any of the following treatment regimens:
* No more than 3 of the following oral anti-diabetic drugs and at least 1 marked with a *:

* Metformin (equal to or above1500 mg or maximum tolerated or effective dose).
* Sulfonylureas (SU) (equal to or above half of the maximum approved dose according to local label or maximum tolerated or effective dose).
* Sodium/glucose cotransporter 2 (SGLT2) inhibitors (maximum tolerated dose).
* Dipeptidyl peptidase-4 (DPP-4) inhibitors (maximally indicated dose as per local label).
* Subjects, on treatment with stable dose of DPP-4 inhibitors at inclusion, must be willing to discontinue DPP-4 inhibitor treatment at randomisation (with no wash-out).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Treatment with any medication indicated for the treatment of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed.
* Renal impairment measured as estimated glomerular filtration rate (eGFR) value of below 30 mL/min/1.73 m^2 according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation as defined by kidney disease improving global outcomes (KDIGO 2012) classification.
* Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/01/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
8/03/2023
Sample size
Target
Accrual to date
Final
1606
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [3] 0 0
Core Research Centre - Milton
Recruitment hospital [4] 0 0
South Australian Endocrine Research - Keswick
Recruitment hospital [5] 0 0
Southern Adelaide Diabetes & Endocrine Services - Oaklands Park
Recruitment hospital [6] 0 0
Barwon Health (The Geelong Hospital) - Geelong
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
4064 - Milton
Recruitment postcode(s) [4] 0 0
5035 - Keswick
Recruitment postcode(s) [5] 0 0
5046 - Oaklands Park
Recruitment postcode(s) [6] 0 0
3220 - Geelong
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Hawaii
Country [7] 0 0
United States of America
State/province [7] 0 0
Idaho
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Indiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Iowa
Country [11] 0 0
United States of America
State/province [11] 0 0
Kansas
Country [12] 0 0
United States of America
State/province [12] 0 0
Kentucky
Country [13] 0 0
United States of America
State/province [13] 0 0
Maryland
Country [14] 0 0
United States of America
State/province [14] 0 0
Massachusetts
Country [15] 0 0
United States of America
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Michigan
Country [16] 0 0
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Montana
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New Jersey
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North Carolina
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North Dakota
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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Tennessee
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Texas
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Virginia
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Washington
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Bulgaria
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Blagoevgrad
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Bulgaria
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Lom
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Bulgaria
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Pazardzhik
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Bulgaria
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Pleven
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Bulgaria
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Plovdiv
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Bulgaria
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Sliven
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Bulgaria
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Smolyan
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Sofia
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Varna
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Vratsa
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Bulgaria
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Yambol
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Canada
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Alberta
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Canada
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New Brunswick
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Ontario
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Quebec
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Grad Zagreb
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Primorsko - Goranska Županija
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Osijek
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Tartu
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Essen
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Falkensee
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Hamburg
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Münster
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Germany
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Oldenburg in Holstein
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Rehlingen-Siersburg
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Komárom-Esztergom
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Budapest
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Pécs
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Szombathely
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Kerala
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Punjab
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India
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Tamil Nadu
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India
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Telengana
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India
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Uttar Pradesh
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India
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West Bengal
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Lubelski
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Lubuskie
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Wielkopolskie Voivodeship
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Bialystok
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Elblag
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Gdansk
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Krakow
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Lodz
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Poznan
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Radom
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Warszawa
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Wroclaw
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Zabrze
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Puerto Rico
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Manati
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Slovakia
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Bardejov
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Slovakia
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Hnusta
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Slovakia
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Kezmarok
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Slovakia
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Kralovsky Chlmec
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Lucenec
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Slovakia
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Presov
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Slovakia
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Rimavska Sobota
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Slovakia
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Sabinov
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Slovakia
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Spisska Nova Ves
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Slovenia
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Celje
Country [108] 0 0
Slovenia
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Koper
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Slovenia
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Ljubljana
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Slovenia
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Maribor
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Slovenia
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Nova Gorica
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Taiwan
State/province [112] 0 0
Taichung City
Country [113] 0 0
Taiwan
State/province [113] 0 0
Tainan

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novo Nordisk A/S
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Transparency (dept. 1452)
Address 0 0
Novo Nordisk A/S
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://novonordisk-trials.com


What supporting documents are/will be available?




Results publications and other study-related documents

TypeCitations or Other Details
Journal Aroda VR, Aberle J, Bardtrum L, Christiansen E, Kn... [More Details]


Results are available at https://clinicaltrials.gov/study/NCT04707469