A trial to Investigate the cardiovascular Safety of Oral Semaglutide in the Subjects with Type 2 Diabetes.

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2017/02/007841
• Date of registration: 13-02-2017
• Prospective Registration: Yes
• Primary sponsor: Novo Nordisk India Private Ltd
• Public title: A trial to Investigate the cardiovascular Safety of Oral Semaglutide in the Subjects with Type 2 Diabetes.
• Scientific title: Cardiovascular outcomes A trial investigating the cardiovascular safety of oral semaglutide in subjects with type 2 diabetes
• Date of first enrolment: 15-03-2017
• Target sample size: 3176
• Recruitment status: Completed
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=15364
• Study type: Interventional
• Study design: Randomized, Parallel Group, Placebo Controlled Trial; Method of generating randomization sequence:Computer generated randomization Method of allocation concealment:Centralized Blinding and masking:Participant, Investigator and Outcome Assessor Blinded
• Phase: Phase 3

Countries of recruitment

Algeria, Argentina, Brazil, Canada, Denmark, Germany, India, Israel, Italy, Malaysia, Mexico, Netherlands, Poland, Romania, South Africa, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States of America

Contacts

• Name: Dr Anil N Shinde
• Affiliation: Novo Nordisk India Private Ltd.

• Name: Dr Anil N Shinde
• Affiliation: Novo Nordisk India Private Ltd.

Key inclusion & exclusion criteria

Inclusion criteria: 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
Exclusion criteria: 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 investigatorâ??s opinion might jeopardise subjectâ??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.

Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: null- Type 2 Diabetes Health Condition 2: E11- Type 2 diabetes mellitus

Intervention(s)

Intervention1: Drug: semaglutide
: For oral use once daily, 19 months

Control Intervention1: Drug: placebo
: For oral use once daily, 19 months

Primary Outcome(s)

"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 ]

"

Timepoint: 1 year 6 months

Secondary Outcome(s)

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 ]Timepoint: 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 ]Timepoint: 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 ]Timepoint: Time Frame: From randomisation up to 19 months

Secondary ID(s)

NN9924-4221 ver 3.0 dated 12 February 2016

U1111-1173-0750

Source(s) of Monetary Support

Novo Nordisk India Private Ltd. Plot No.32, 47 - 50, EPIP Area, Whitefield, Bangalore - 560 066 India

Ethics review

Status: Approved
Approval date: 16/07/2016
Contact:

Sterling Hospital Ethics Committee

Status: Approved
Approval date: 27/07/2016
Contact:

Institutional Ethics Committee ,Max Super Speciality Hospital

Status: Approved
Approval date: 24/08/2016
Contact:

Ethics Committee for Research on Human Subjects, GS medical college & KEM Hospital

Status: Approved
Approval date: 07/10/2016
Contact:

Institutional Ethics Committee,Poona Medical Research Foundation

Status: Approved
Approval date: 15/10/2016
Contact:

Institutional Ethics Committee, Care Hospital

Status: Approved
Approval date: 03/12/2016
Contact:

Institutional Ethics Committee Apollo Gleneagles Hospitals

Status: Approved
Approval date: 23/01/2017
Contact:

Ethics Committee Govt Medical College

Status: Approved
Approval date: 02/02/2017
Contact:

Institutional Ethics Committee (TNBYL)

Status: Approved
Approval date: 07/02/2017
Contact:

Institutional Ethics Committee ,Department of Endocrinology & Daibetes, Amrita Institute of medical Sciences & Research Centre

Status: Approved
Approval date: 10/02/2017
Contact:

Institute ethics committee , AIIMS, New Delhi

Status: Approved
Approval date: 11/02/2017
Contact:

INSTITUTIONAL ETHICS COMMITTEE , Indian Institute of Diabetes

Status: Approved
Approval date: 15/02/2017
Contact:

Ethics committee for Human Research

Status: Approved
Approval date: 18/03/2017
Contact:

Institutional Ethics Committee, Goa Medical College

Status: Approved
Approval date: 29/03/2017
Contact:

Institutional Ethics Committee, Christian Medical College & Hospital

Status: Approved
Approval date: 31/03/2017
Contact:

IPGME&R Research Oversight Committee

Status: Approved
Approval date: 07/04/2017
Contact:

Institutional Ethics Committee of Madras Diabetes Research Foundation

Status: Approved
Approval date: 08/04/2017
Contact:

Institutional Ethics Committee Deenanath Mangeshkar Hospital & Research Center

Status: Not Applicable
Approval date:
Contact:

Ethics Committee Osmania Medical college & Osmania General Hospital

Status: Not Applicable
Approval date:
Contact:

Ethics Committee,Apollo Hospital,

Status: Not Applicable
Approval date:
Contact:

Institutional Ethics Committee (NHLIEC)

Status: Not Applicable
Approval date:
Contact:

Institutional Ethics Committee, Sri Ramachandra University

Results

• Date Completed: 21/09/2018