The primary objective is to confirm that treatment with oral semaglutide does not result in an unacceptable increase in cardiovascular risk compared to placebo (rule out 80% excess risk) in subjects with T2D at high risk of cardiovascular events.The…
ID
Source
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 MACE
composite endpoint consisting of: cardiovascular death, non-fatal myocardial
infarction or non-fatal stroke.
Secondary outcome
Key secondary endpoints:
* Time 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 from randomisation to first occurrence of each of the individual
components in the
expanded composite cardiovascular endpoint
* Time from randomisation to first occurrence of a composite endpoint
consisting of: all-cause
death, non-fatal myocardial infarction or non-fatal stroke
Background summary
Semaglutide is in development for once-weekly subcutaneous injection and for
oral once-daily treatment of T2D. This trial investigates the oral once-daily
use (tablets). Semaglutide is a long-acting GLP-1 structurally similar to
liraglutide (Victoza®), which is an once-daily GLP-1 receptor agonist developed
by Novo Nordisk and approved worldwide for the treatment of T2D.
The purpose of this trial is to assess the cardiovascular safety of oral
semaglutide in subjects with T2D at high risk of cardiovascular events. This
trial has been designed to address the requirements contained in the US Food
and Drug Administration (FDA) and European Medicines Agency (EMA) guidance
documents which specify how to demonstrate that a new antidiabetic therapy is
not associated with an unacceptable increase in cardiovascular risk.
Study objective
The primary objective is to confirm that treatment with oral semaglutide does
not result in an unacceptable increase in cardiovascular risk compared to
placebo (rule out 80% excess risk) in subjects with T2D at high risk of
cardiovascular events.
The secondary objectives are to compare the efficacy and safety of oral
semaglutide versus placebo in subjects with T2D at high risk of cardiovascular
events.
Study design
This trial is a randomised, double-blind, placebo-controlled trial to assess
the cardiovascular safety of oral semaglutide versus placebo when added to
standard of care in subjects with type 2 diabetes at high risk of
cardiovascular events. Subjects will be randomised 1:1 to receive either oral
semaglutide or placebo. The trial will be event-driven and will be continued
until at least 122 first major adverse cardiovascular events (MACEs) confirmed
by adjudication have accrued. The treatment period for each subject is
estimated to be between 12 and 19 months, depending on the time-point of
recruitment and the accrual of first MACEs confirmed by adjudication.
Intervention
Daily administration of 3, 7 or 14 mg oral semaglutide/placebo tablets.
Study burden and risks
The safety profile for the investigational medicinal product generated from the
clinical and nonclinical development programme has not revealed any safety
issues that would prohibit administration of oral semaglutide in accordance
with the planned clinical trial.
Patients are requested to visit the trial site and to attend phone calls more
often than during regular treatment. Several trial assessments are part of
standard diabetes care, but the frequency in the trial is higher. Hypoglycaemia
and (gastrointestinal) adverse events could occur. Therefor the subject is
closely followed. As in the case with all protein based pharmaceuticals
treatment with oral semaglutide may evoke allergic reactions. See section 18.1
of the protocol.
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 diagnosed with type 2 diabetes (T2D)
-Age * 50 years at screening and presence of cardiovascular disease, or age * 60 years at screening and presence of at least one cardiovascular risk factor
Exclusion criteria
-Current or previous (within 90 days prior to screening) treatment with any GLP-1 receptor agonist, DPP-4 inhibitor or pramlintide
-Family or personal history of multiple endocrine neoplasia type 2 (MEN 2) or medullary thyroid carcinoma (MTC)
-History of pancreatitis (acute or chronic)
-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)
-Subjects presently classified as being in New York Heart Association (NYHA) Class IV heart failure
-Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
-Any of the following: myocardial infarction, stroke or hospitalisation for unstable angina or transient ischaemic attack within the past 60 days prior to screening
-Chronic or intermittent hemodialysis or peritoneal dialysis or severe renal impairment (corresponding to eGFR <30 mL/min/1.73 m2)
-History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and carcinoma in situ)
-Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus
photography or dilated fundoscopy performed within 90 days prior to screening or within the
period between screening and randomisation.
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 | EUCTR2015-003563-10-NL |
| ClinicalTrials.gov | NCT02863419 |
| CCMO | NL56580.091.16 |