A long-term, randomised, double-blind, placebo-controlled, multinational, multi-centre trial to evaluate cardiovascular and other long-term outcomes with semaglutide in subjects with type 2 diabetes

Study ID
STU 112012-028

Cancer Related
No

Healthy Volunteers
No

Study Sites

  • UT Southwestern-Other
  • Parkland Health & Hospital System

Contact
Madhuri Poduri
214-648-2321
madhuri.poduri@utsouthwestern.edu

Principal Investigator
Ildiko Lingvay

Summary

This trial is a long-term randomised, double-blind, placebo-controlled, four-armed parallel-group, multinational, multi-centre trial to evaluate cardiovascular and other long-term outcomes.
if the subject decides to participate in this study, they will be treated with either:
* Semaglutide (either a dose of 0.5 mg or 1.0 mg) administered by subcutaneous (under the skin) injection once weekly or
* Placebo (contains no active drug) administered by subcutaneous (under the skin) injection once weekly

Primary endpoint:
Time from randomisation to first occurrence of a MaCe, defined as cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke.

Secondary endpoints
- Time from randomisation to first occurrence of an expanded composite cardiovascular outcome, defined as either MaCe, revascularization (coronary and peripheral), unstable angina requiring hospitalisation or hospitalisation for chronic heart failure.
- Time from randomisation to each individual component of the expanded composite cardiovascular outcome.
- Time from randomisation to first occurrence of either a need for retinal photocoagulation, or treatment with intravitreal agents, or vitreous haemorrhage, or diabetes-related blindness (defined as Snellen visual acuity of 20/200 [6/60] or less, or visual field of less than 20 degrees, in the better eye with best correction possible).
- Time from randomisation to first occurrence of new or worsening nephropathy, defined as new onset of persistent macro albuminuria ([Greater Than]300 mg/g), or persistent doubling of serum creatinine level and creatinine clearance per modification of diet in renal disease (MDRD) [LessThanorequalTo]45 mL/min/1.73m2, or the need for continuous renal-replacement therapy (in the absence of an acute reversible cause), or death due to renal disease).
- incidence of hospitalisation for cardiac arrhythmia and conduction disturbances.
- Change from baseline to last assessment during the treatment period in:
o body weight and waist circumference
o Hba1c, FPG, fasting plasma insulin, homeostasis model assessment of beta-cell function (HoMa-B), and pro-insulin to insulin ratio
o lipid profile, including total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides and free fatty acids
o systolic and diastolic blood pressure and pulse
o urinary albumin to creatinine ratio (uaCR).
- Proportion of subjects achieving [GreaterThanorequalTo]5% and [GreaterThanorequalTo]10% body weight loss.
- Proportion of subjects requiring addition of glucose-lowering medication to achieve/maintain glycaemic target.
- incidence of hypoglycaemia.
- incidence of aes and the following MeSis:
o neoplasm (malignant and benign)
o pancreatitis, or clinical suspicion of pancreatitis
o acute gallstone disease (biliary colic or acute cholecystitis)
o thyroid disease
o cardiac arrhythmia (specifically, atrial fibrillation, atrial flutter, ventricular tachycardia, ventricular fibrillation, torsade de pointes, second degree heart block type 2, third degree heart block, and symptomatic bradycardia requiring pacemaker placement)
o acute renal failure
o severe hypoglycaemic episode
o immunogenicity event (allergic reactions, immune-complex disease and lack of efficacy)
o medication errors concerning trial products
o suspected transmission of an infectious agent via a trial product
o aes leading to treatment discontinuation
- Laboratory parameters: haematology and biochemistry (including amylase and lipase), hormone (calcitonin) and urinalysis.
- anti-semaglutide antibodies.
- Changes from baseline in electrocardiogram (eCG).
- Semaglutide plasma concentration in a subset of the population (n[?] approximately 60 subjects with severe renal impairment (GFR value 15-29 mL/min/1.73m2), n[?] approximately 180 subjects without severe renal impairment).
- Change from baseline to last assessment during the treatment period in SF-36v2TM patient reported outcome (PRo) scores.

Participant Eligibility

1. Men and women with type 2 diabetes mellitus.
2. Age >=50 years at screening and clinical evidence of cardiovascular disease defined as meeting
at least one of the below criteria (a - h). All applicable categories included in this criterion must be ticked off in the eCRF
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 eg positive exercise stress test or any cardiac imaging or unstable angina with ECG changes
f) asymptomatic cardiac ischemia 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) chronic renal impairment, documented (prior to screening) by estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 per MDRD
or:
Age >=60 years at screening and subclinical evidence of cardiovascular disease defined as meeting at least one of the below criteria (i - l). All applicable categories included in this criterion must be ticked off in the eCRF
i) persistent microalbuminuria (30-299 mg/g) or proteinuria
j) hypertension and left ventricular hypertrophy by ECG or imaging
k) left ventricular systolic or diastolic dysfunction by imaging
l) ankle/brachial index <0.9
4. Anti-diabetic drug naive, or treated with one or two OAD(s), or treated with human NPH insulin
or long-acting insulin analogue or pre-mixed insulin, alone or in combination with one or two
OAD(s).
5. HbA1c >= 7.0% at screening.