Overview

This trial is active, not recruiting.

Condition diabetes mellitus, type 2
Treatments linagliptin, glimepiride, linagliptin placebo, glimepride placebo
Phase phase 3
Sponsor Boehringer Ingelheim
Collaborator Eli Lilly and Company
Start date October 2010
End date February 2019
Trial size 6115 participants
Trial identifier NCT01243424, 1218.74, 2009-013157-15

Summary

The aim of the study is to investigate the longterm impact on cardiovascular morbidity and mortality, relevant efficacy parameters (e.g., glycaemic parameters) and safety (e.g., weight and hypoglycaemia) of treatment with linagliptin in patients with type 2 diabetes at elevated cardiovascular risk receiving usual care, and compare outcome against glimepiride.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double-blind
Primary purpose treatment
Arm
(Experimental)
patient to receive linagliptin or glimepiride placebo overencapsulated tablet QD
linagliptin
linagliptin tablets 5mg QD
glimepride placebo
glimepiride placebo
(Active Comparator)
patient to receive glimepiride 1-4 mg or linagliptin placebo tablet QD
glimepiride
glimepiride over-encapsulated tablet 1-4 mg QD
linagliptin placebo
linagliptin placebo

Primary Outcomes

Measure
Time to first occurence of any of the following adjudicated components of the primary composite endpoint: CV death, non-fatal MI (excluding silent MI), non-fatal stroke and hospitalisation for unstable angina pectoris
time frame: 400 weeks

Secondary Outcomes

Measure
Time to first occurrence of any of the following adjudicated components of the composite endpoint: CV death (including fatal stroke and fatal MI), non-fatal stroke, non-fatal MI (excluding silent MI)
time frame: 400 weeks
Proportion of patients on study treatment at study end, that at Final Visit maintain glycemic control (HbA1c <= 7.0%) without need for rescue medication, without any moderate/severe hypoglycaemic episodes and without > 2% weight gain (from V6 on)
time frame: 400 weeks
Occurence of any of the adjudicated components of the composite primary and composite first key secondary endpoint.
time frame: 400 weeks
Transitions in albuminuria classes between baseline and Final visit.
time frame: 400 weeks
Proportion of patients on study treatment at study end, that at Final Visit maintain glycaemic control (HbA1c <= 7.0%) without need for rescue medication and without > 2% weight gain (from V6 on)
time frame: 400 weeks
Occurence of and time to composite endpoint of all CEC confirmed adjudicated events
time frame: 400 weeks
Change from baseline to Final Visit in diabetes related laboratory parameters: HbA1c, fasting plasma glucose, Total cholesterol, LDL cholesterol, HDL cholesterol, Triglycerides, Creatinine, eGFR (MDRD formula), Albumin
time frame: 400 weeks

Eligibility Criteria

Male or female participants from 40 years up to 85 years old.

Inclusion criteria: 1. Type 2 diabetes 2. Elevated glycosylated haemoglobin (HbA1c): 6.5 - 8.5%, inclusive, if treatment naïve or mono-/dual therapy with metformin and/or an alpha-glucosidase inhibitor; 6.5 - 7.5%, inclusive, if treatment with sulphonylurea/glinide in mono- or dual (with metformin OR an alpha-glucosidase inhibitor) therapy) 3. Pre-existing cardiovascular disease OR specified diabetes end-organ damage OR age => 70 years OR two or more specified cardiovascular risk factor 4. BMI =< 45kg/m² 5. age between >= 40 and =< 85 years 6. signed and dated written ICF 7. stable anti-diabetic background for at least 8 wks before study start Exclusion criteria: 1. Type 1 diabetes 2. Treatment with other antidiabetic drugs (e.g. rosiglitazone, pioglitazone, Glucagon-like peptide 1 (GLP-1) analogue/agonists, Dipeptidyl-peptidase IV (DPP-IV) inhibitors or any insulin) prior to informed consent (previous short term use of insulin (up to two weeks) is allowed if taken at least 8 weeks prior informed consent) 3. treatment with any anti-obesity drug less than 3 months before ICF 4. uncontrolled hyperglycemia 5. previous or planned bariatric surgery or intervention 6. current or planned system corticoid treatment 7. change in thyroid hormones treatment 8. acute liver disease or impaired hepatic function 9. pre-planned coronary artery revascularization within 6 months of ICF 10. known hypersensitivity to any of the components 11. Inappropriateness of glimepiride treatment for renal safety issues according to local prescribing information 12. congestive heart failure class III or IV 13. acute or chronic metabolic acidosis 14. hereditary galactose intolerance 15. alcohol or drug abuse 16. participation in another trail with IMP given 2 months before IMP start 17. pre-menopausal women who are nursing or pregnant or of child-bearing potential and not willing to use acceptable method of birth control 18. patients considered reliable by the investigator 19. acute coronary syndrome =< 6 wks before ICF 20. stroke or TIA =< 3 months prior to ICF

Additional Information

Official title A Multicentre, International, Randomised, Parallel Group, Double Blind Study to Evaluate Cardiovascular Safety of Linagliptin Versus Glimepiride in Patients With Type 2 Diabetes Mellitus at High Cardiovascular Risk.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Boehringer Ingelheim.