The primary objective is to demonstrate that oral semaglutide lowers the risk of major adverse cardiovascular events compared to placebo, both added to standard of care in patients with type 2 diabetes and at high risk of cardiovascular events.The…
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Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is time from randomisation to first occurrence of a major
adverse cardiovascular event, a composite endpoint consisting of:
cardiovascular death, non-fatal myocardial infarction or non-fatal stroke.
Secondary outcome
Time from randomisation to first occurrence of:
• A composite chronic kidney disease endpoint consisting of: cardiovascular
death, renal death, onset of persistent >= 50% reduction in estimated glomerular
filtration rate (CKD-EPI) compared with baseline, onset of persistent eGFR
(CKD-EPI) < 15 mL/min/1.73 m2 or initiation of chronic renal replacement
therapy (dialysis or kidney transplantation)
• cardiovascular death
• Major adverse limb events, a composite endpoint consisting of: acute limb
ischemia hospitalisation or chronic limb ischemia hospitalisation
Background summary
The cardiovascular (CV) effect of oral semaglutide 14 mg once daily (OD) and
s.c. semaglutide 0.5 and 1 mg once weekly were assessed in 2 CV outcomes trials
(NN9924-4221, PIONEER 6 and NN9535-3744, SUSTAIN 6), each designed to rule out
an 80% increased CV risk in patients with type 2 diabetes (T2D) at high risk
for CV disease (CVD) in accordance with FDA guidance. PIONEER 6 demonstrated CV
safety with a favourable point estimate. SUSTAIN 6 however demonstrated a
statistically significant 26% risk reduction with s.c. semaglutide compared
with placebo for the primary endpoint (time from randomisation to first
occurrence of a major adverse cardiovascular event (MACE) consisting of: CV
death, non-fatal myocardial infarction (MI) or non-fatal stroke). Clinical
pharmacology and clinical efficacy data indicate that the action of semaglutide
is the same whether administrated via a subcutaneous injection or orally in a
tablet. Hence, once semaglutide has entered systemic circulation, the
properties and actions of the molecule are similar and independent of the route
of administration. Accordingly it is hypothesised that oral semaglutide in the
dose of 14 mg OD can reduce CV risk.
The current trial serves the purpose of confirming that oral semaglutide
reduces the risk of MACE in patients with T2D and established CVD and/or
chronic kidney disease (CKD).
Study objective
The primary objective is to demonstrate that oral semaglutide lowers the risk
of major adverse cardiovascular events compared to placebo, both added to
standard of care in patients with type 2 diabetes and at high risk of
cardiovascular events.
The key secondary objectives are to compare the effects of oral semaglutide
versus placebo, both added to standard of care in patients with type 2 diabetes
and at high risk of cardiovascular events with regards to chronic kidney
disease, cardiovascular events, peripheral artery disease, glycaemic control
and body weight, and safety
Study design
This is a randomised, double-blind, parallel-group, placebo-controlled trial
comparing oral semaglutide versus placebo both administered once daily and
added to standard of care in patients with type 2 diabetes at high risk of
cardiovascular events. Patients will be randomised 1:1 to receive either oral
semaglutide or placebo
Intervention
Oral semaglutide 3 mg, 7 mg and 14 mg tablets or placebo tablets
Study burden and risks
Data from the clinical development programme for semaglutide has not revealed
any safety issues that would outweigh the benefits. The trial population will
consist of T2D patients with high risk of CV events. Assessment of diabetes and
CV risk factors and appropriate attention to the standard of care treatment
will be ensured throughout the trial. It is therefore concluded that the
potential benefits from the trial will outweigh the potential risks for the
oral semaglutide as well as the placebo treated patients.
Flemingweg 18
Alphen a/d Rijn 2408 AV
NL
Flemingweg 18
Alphen a/d Rijn 2408 AV
NL
Listed location countries
Age
Inclusion criteria
-Male or female, age >=50 years at the time of signing informed consent
-Diagnosed with type 2 diabetes mellitus
-HbA1c 6.5% - 10.0% (47 - 86 mmol/mol) (both inclusive)
-At least one of the below conditions (a-d):
a) Coronary heart disease
b) Cerebrovascular disease
c) Symptomatic peripheral artery disease (PAD)
d) Chronic kidney disease
Exclusion criteria
-Any of the following: myocardial infarction, stroke, hospitalisation for
unstable angina pectoris or transient ischaemic attack within the past 60 days
prior to the day of screening
-Planned coronary, carotid or peripheral artery revascularisation known on the
day of screening
-Heart failure presently classified as being in New York Heart Association
Class IV
-Treatment with any glucagon-like peptide-1 receptor agonist within 30 days
before screening
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
EudraCT | EUCTR2018-003141-42-NL |
ClinicalTrials.gov | NCT03914326 |
CCMO | NL69133.056.19 |