Diabetes mellitus type 2 MedDRA version: 17.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 100000004861
Conditions
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men or women at least 40 years old with a diagnosis of type 2 diabetes. 2. Established cardiovascular disease, including at least 1 of the following: a.Coronary artery disease with EITHER of the following: •Documented history of spontaneous myocardial infarction, at least 30 days prior to screening. •Documented coronary artery disease (CAD) = 50% stenosis in 1 or more major epicardial coronary arteries, determined by invasive angiography, or history of surgical or percutaneous (balloon and/or stent) coronary revascularization procedure (at least 30 days prior to screening for percutaneous procedures and at least 5 years prior to study entry for coronary artery bypass graft (CABG)). b.Cerebrovascular disease – ANY of the following: •Documented history of ischaemic stroke, at least 90 days prior to study entry. •Carotid arterial disease with = 50% stenosis documented by carotid ultrasound, magnetic resonance imaging or angiography, with or without symptoms of neurologic deficit. •Carotid vascular procedure (e.g. stenting or surgical revascularisation), at least 30 days prior to screening. c.Peripheral arterial disease (PAD) with EITHER of the following: •intermittent claudication and ankle:brachial index 7.0% (53 mmol/mol) based on the most recent documented laboratory assessment measured no more than 6 months prior to randomization. Local laboratory HbA1c values taken as part of usual care are permitted. 4. Female: subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin (hCG) test for females of reproductive potential only), not breastfeeding, and at least one of the following conditions applies: a. Reproductive potential and agrees to follow one of the options listed in the GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) (e.g, combined oral contraceptive pill; see Appendix 2) from 30 days prior to the first dose of study medication and until after the last dose of study medication and completion of the follow-up visit. This does not apply to FRP with same sex partners, when this is their preferred and usual lifestyle or for subjects who are and will continue to be abstinent. Other situations in which contraception in FRP may not need to be mandated should be discussed with the Medical Monitor. b. Non-reproductive potential defined as either: ? Pre-menopausal with one of the following: (i) documented tubal ligation; (ii) documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; (iii) hysterectomy; or (iv) documented bilateral oophorectomy, or; Postmenopausal defined as 12 months of spontaneous amenorrhea and age appropriate (i.e. >50 years). In questionable cases, a blood sample with simultaneous follicle stimulating hormone (FSH) >40 mIU/mL and oestradiol <40 pg/mL (<140 pmol/L) is confirmatory, depending on local laboratory ranges. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status prior to study enrolment. 5
Exclusion criteria
Exclusion criteria: 1. eGFR calculated using MDRD formula 40MU/ml and oestrodiol <40 pg/mL (<140 pmol/L) are simultaneously measured will be considered confirmatory. 8.Known allergy to any GLP-1 receptor agonist or excipients of albiglutide. 9.Use of another investigational product within 30 days or according to local regulations, or currently enrolled in a study of an investigational device. 10.Any other reason the investigator deems the subject to be unsuitable for the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether albiglutide is non-inferior with respect to MACE when added to glycaemic standard of care versus standard of care alone.;Secondary Objective: 1. To supplement the primary objective by further characterization of the effects of albiglutide on cardiovascular outcomes. 2. To evaluate the effects of albiglutide on metabolic management of type 2 diabetes. 3. To evaluate the safety of albiglutide.;Primary end point(s): Time to first occurrence of MACE (cardiovascular death, myocardial infarction, or stroke) [Non-inferiority];Timepoint(s) of evaluation of this end point: The study will be event driven, i.e. follow up will continue until it is projected that approximately 611 adjudicated MACE events will have occurred. Consequently, the maximum duration of the study for an individual participant is dependent both on the time taken for recruitment and the MACE event rate, and is estimated to be between 3 and 5 years. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Time to first occurrence of MACE [Superiority] •Time to first occurrence of the following: -MACE or urgent revascularisation for unstable angina -The individual components of the primary endpoint -Cardiovascular death or hospitalization due to heart failure 2. Time to initiation of insulin of more than 3 months duration for those subjects not treated with insulin at study start. •Time to initiation of prandial insulin in those subjects on basal insulin at study start •The proportion of subjects achieving glycaemic control (HbA1c = 7.0% at final assessment) with no severe hypoglycaemic incidents and weight gain <5% of body weight. •The time to first occurrence of a clinically important microvascular event (see Section 6.2.4 of the protocol) •Change in HbA1c •Change in body weight •Patient reported outcomes from TRIM-D/EQ5D 3. •All cause mortality •Non-fatal SAEs •AEs leading to discontinuation of investigational product •AE of special interest (see Section 6.2.3 of the protocol) •Change in eGFR calculated using Modification of Diet in Renal Disease (MDRD) formula •Change in blood pressure and heart rate ;Timepoint(s) of evaluation of this end point: The study will be event driven, i.e. follow up will continue until it is projected that approximately 611 adjudicated MACE events will have occurred. Consequently, the maximum duration of the study for an individual participant is dependent both on the time taken for recruitment and the MACE event rate, and is estimated to be between 3 and 5 years. | — |
Countries
Argentina, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Czech Republic, Denmark, France, Germany, Greece, Hong Kong, Hungary, Italy, Korea, Republic of, Mexico, Netherlands, Norway, Peru, Philippines, Poland, Puerto Rico, Russian Federation, South Africa, Spain, Sweden, Taiwan, Thailand, Ukraine, United Kingdom, United States
Contacts
Public ContactAlexandra H West
GlaxoSmithKline Research & Development Limited
Outcome results
None listed