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Topiwala National Medical College And B.Y.L.Nair Charitable Hospital,
Department Of Endocrinology,
College Building, 4th Floor,
Department # :419
Topiwala National Medical College And B.Y.L.Nair Charitable Hospital,
Dr.A.L.Nair Road Mumbai MAHARASHTRA
Type 2 Diabetes, (1) ICD-10 Condition: E11||Type 2 diabetes mellitus,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Drug: placebo
For oral use once daily, 19 months
Intervention
Drug: semaglutide
For oral use once daily, 19 months
Inclusion Criteria
Age From
50.00 Year(s)
Age To
90.00 Year(s)
Gender
Both
Details
1. Informed consent obtained before any trial-related activities. Trial-related activities are any
procedures that are carried out as part of the trial, including activities to determine suitability
for the trial.
2. Male or female diagnosed with type 2 diabetes.
3. Age ≥ 50 years at screening and at least one of the below conditions:
a. prior myocardial infarction
b. prior stroke or transient ischaemic attack (TIA)
c. prior coronary, carotid or peripheral arterial revascularisation
d. > 50% stenosis on angiography or imaging of coronary, carotid or lower
extremity arteries
e. history of symptomatic coronary heart disease documented by e.g. positive
exercise stress test or any cardiac imaging or unstable angina pectoris with ECG
changes
f. asymptomatic cardiac ischaemia documented by positive nuclear imaging test or
exercise test or stress echo or any cardiac imaging
g. chronic heart failure New York Heart Association (NYHA) class II-III
h. moderate renal impairment (corresponding to an estimated glomerular filtration
rate (eGFR) between 30-59 mL/min/1.73 m2)
or
Age ≥ 60 years at screening and at least one of the below risk factors:
i. microalbuminuria or proteinuria
j. hypertension and left ventricular hypertrophy by ECG or imaging
k. left ventricular systolic or dysfunction by imaging l. ankle/brachial index < 0.9
ExclusionCriteria
Details
1. Known or suspected hypersensitivity to the trial product or related products.
2. Previous participation in this trial. Participation is defined as signed informed consent. 3. Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing
potential and not using adequate contraceptive methods (adequate contraceptive measures as
required by local regulation or practice. Local country regulations or practices are specified
in section 8 of the protocol).
4. Receipt of any investigational medicinal product within 90 days before screening.
For Brazil only: Participation in other clinical trials within one year prior to screening
unless there is a direct benefit to the research subject at the investigator´s discretion.
5. Participation in another clinical trial of an investigational medicinal product. Participation in
a clinical trial which evaluate stent(s) is allowed.
6. Current or previous (within 90 days prior to screening) treatment with any GLP-1 receptor
agonist, DPP-4 inhibitor or pramlintide.
7. Any disorder, which in the investigator’s opinion might jeopardise subject’s safety or
compliance with the protocol.
8. Family or personal history of multiple endocrine neoplasia type 2 (MEN 2) or medullary
thyroid carcinoma (MTC).
9. History of pancreatitis (acute or chronic).
10. History of major surgical procedures involving the stomach potentially affecting absorption
of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass
surgery).
11. Subjects presently classified as being in New York Heart Association (NYHA) Class IV
heart failure.
12. Planned coronary, carotid or peripheral artery revascularisation known on the day of
screening.
13. Any of the following: myocardial infarction, stroke or hospitalisation for unstable angina or
transient ischaemic attack within the past 60 days prior to screening.
14. Chronic or intermittent hemodialysis or peritoneal dialysis or severe renal impairment
(corresponding to eGFR <30 mL/min/1.73 m2).
15. History or presence of malignant neoplasms within the last 5 years (except basal and
squamous cell skin cancer and carcinoma in situ).
16. History of diabetic ketoacidosis.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator and Outcome Assessor Blinded
Primary Outcome
Outcome
TimePoints
"Time from randomisation to first occurrence of a major adverse cardiovascular event (MACE) composite endpoint consisting of: cardiovascular death, non-fatal myocardial infarction or non-fatal stroke [ Time Frame: From randomisation up to 19 months ] [ Designated as safety issue: No ]
"
1 year 6 months
Secondary Outcome
Outcome
TimePoints
From randomisation to first occurrence of an expanded composite cardiovascular endpoint consisting of: cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, unstable angina requiring hospitalisation or hospitalisation for heart failure [ Time Frame: From randomisation up to 19 months ] [ Designated as safety issue: No ]
Time Frame: From randomisation up to 19 months
Time from randomisation to first occurrence of each of the individual components in the expanded composite cardiovascular endpoint [ Time Frame: From randomisation up to 19 months ] [ Designated as safety issue: No ]
Time Frame: From randomisation up to 19 months
Time from randomisation to first occurrence of a composite endpoint consisting of: all-cause death, non-fatal myocardial infarction or non-fatal stroke [ Time Frame: From randomisation up to 19 months ] [ Designated as safety issue: No ]
Time Frame: From randomisation up to 19 months
Target Sample Size
Total Sample Size="3176" Sample Size from India="200" Final Enrollment numbers achieved (Total)= "3183" Final Enrollment numbers achieved (India)="201"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This trial is conducted globally. The aim of the trial is to
investigate the cardiovascular safety of oral semaglutide in subjects with type
2 diabetes.
ThePrimary Outcome Measures:
Time from randomisation to first occurrence of a major adverse
cardiovascular event (MACE) composite endpoint consisting of: cardiovascular
death, non-fatal myocardial infarction or non-fatal stroke [ Time Frame: From
randomisation up to 19 months ]
Secondary Outcome Measures:
From randomisation to first occurrence of an expanded composite
cardiovascular endpoint consisting of: cardiovascular death, non-fatal
myocardial infarction, non-fatal stroke, unstable angina requiring
hospitalisation or hospitalisation for heart failure [ Time Frame: From
randomisation up to 19 months ]
Time from randomisation to first occurrence of each of the
individual components in the expanded composite cardiovascular endpoint [ Time
Frame: From randomisation up to 19 months ]
Time from randomisation to first occurrence of a composite endpoint
consisting of: all-cause death, non-fatal myocardial infarction or non-fatal
stroke [ Time Frame: From randomisation up to 19 months ]