Overview

This trial is active, not recruiting.

Condition diabetes mellitus, type 2
Treatments linagliptin, empagliflozin placebo + linagliptin placebo, empagliflozin + linagliptin low dose, linagliptin lacebo, empagliflozin + linagliptin high dose
Phase phase 3
Sponsor Boehringer Ingelheim
Collaborator Eli Lilly and Company
Start date May 2015
End date January 2017
Trial size 273 participants
Trial identifier NCT02453555, 1275.19

Summary

This trial will compare the use of fiixed dose conbination of empagliflozin and linagliptin to linagliptine alone in patient with type 2 diabetes mellitus

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
(Active Comparator)
patient to receive 5 mg linagliptin once daily
linagliptin tablet
empagliflozin placebo + linagliptin placebo
Matching placebo empagliflozin + linagliptin
(Experimental)
patient to receive one tablet once daily
empagliflozin + linagliptin low dose
tablet
linagliptin lacebo
Matching placebo linagliptin
(Experimental)
patient to receive one tablet once daily
linagliptin lacebo
Matching placebo linagliptin
empagliflozin + linagliptin high dose
tablet

Primary Outcomes

Measure
Change of glycosylated haemoglobin A1c (glycosylated haemoglobin A1c after 24 weeks of doubleblind treatment from baseline)
time frame: 24 weeks

Secondary Outcomes

Measure
Change in HbA1c from Week 28 at Week 52 (empagliflozin high dose/linagliptin FDC only)
time frame: 52 weeks
Change in HbA1c from baseline at Week 52 (empagliflozin1/linagliptin FDC versus linagliptin plus placebo)
time frame: 52 weeks
Change in HbA1c from baseline at Week 52 (empagliflozin high dose/linagliptin FDC versus placebo for empagliflozin high dose/linagliptin FDC)
time frame: 52 weeks
Change in HbA1c from baseline at Week 52 (empagliflozin high ose/linagliptin FDC versus linagliptin plus placebo)
time frame: 52 weeks

Eligibility Criteria

Male or female participants at least 20 years old.

Inclusion criteria: 1. Diagnosis of T2DM prior to informed consent 2. Male and female patients on diet and exercise regimen for at least 12 weeks prior to informed consent who are: - 1 drug-naïve, defined as no antidiabetic drugs for at least 12 weeks prior to informed consent, or - 2 pre-treated with one oral antidiabetic drug (for sulfonylurea, with up to half of the maximum approved dose) on stable dosage for at least 12 weeks prior to informed consent (for thiazolidinedione, therapy has to be unchanged for at least 18 weeks prior to the informed consent, for linagliptin 5 mg at least 16 weeks prior to Visit 1). Individual antidiabetic drug (except linagliptin) will have to be discontinued at Visit 1. 3. HbA1c at Visit 1 - 1 HbA1c =8.0% and =10.5% for patients who are drug-naïve, or - 2 HbA1c =7.5% and =10.5% for patients with one oral antidiabetic drug (except linagliptin), or - 3 HbA1c =7.5% and =10.0% for patients with linagliptin 5 mg 4. HbA1c =7.5% and =10.0% at Visit 4 for randomisation into the double-blind treatment period. Patient who are pre-treated with linagliptin 5 mg for 16 weeks or more prior to Visit 1 and meet the criteria of HbA1c can directly move on to the run-in (Visit 4). 5. Age =20 years at informed consent 6. BMI =40.0 kg/m2 at Visit 1 (screening) 7. Signed and dated written informed consent by date of Visit 1 in accordance with Good Clinical Practice (GCP) and local legislation Exclusion criteria: 1. Uncontrolled hyperglycemia with a glucose level >270 mg/dL (>15.0 mmol/L) after an overnight fast during the open-label stabilisation period (from Visit 2 to Visit 4) and run-in period (from Visit 4 to Visit 5) , confirmed by a second measurement (not on the same day and done either at the central or at local laboratory). 2. Acute coronary syndrome (ST-elevation myocardial infarction [STEMI], non-STEMI, and unstable angina pectoris), stroke or transient ischemic attack within 12 weeks prior to informed consent 3. Indication of liver disease, defined by serum levels of either alanine aminotransferase (ALT [SGPT]), aspartate aminotransferase (AST [SGOT]), or alkaline phosphatase (ALP) above 3 x upper limit of normal (ULN) as determined during screening, open-label stabilisation period and/or run-in period 4. Impaired renal function, defined as estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2 (MDRD formula) as determined during screening, open-label stabilisation period and/or run-in period 5. Known hereditary galactose intolerance 6. Known contraindications to linagliptin and empagliflozin according to the Japanese label 7. Any previous (within 2 years prior to informed consent) or planned bariatric surgery (or any other weight loss surgery) or other gastrointestinal surgery that induce chronic malabsorption 8. Medical history of cancer (except for resected non-invasive basal cell or squamous carcinoma) and/or treatment for cancer within the last 5 years 9. Known blood dyscrasias or any disorders causing haemolysis or unstable red blood cell (RBC) count (e.g. malaria, babesiosis, haemolytic anaemia). 10. Treatment with insulin, GLP-1 agonists, within 12 weeks prior to informed consent 11. Treatment with anti-obesity drugs within 12 weeks prior to informed consent or any other treatment at the time of screening (i.e., surgery, aggressive diet regimen, etc.) leading to unstable body weight 12. Current treatment with systemic steroids (other than inhaled or topical steroids) at informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except T2DM 13. Pre-menopausal women (last menstruation =1 year prior to informed consent) who: - 1 are nursing or pregnant or - 2 are of child-bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the trial and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include tubal ligation, intra uterine devices/systems, oral contraceptives, complete sexual abstinence, double barrier method and vasectomised partner 14. Known or suspected allergy or hypersensitivity to trial products or related products (e.g., DPP-4 inhibitors or SGLT-2 inhibitors) 15. Alcohol or drug abuse within the 12 weeks prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to trial procedures or trial drug intake, by the judgment of the investigator 16. Intake of an investigational drug in another trial within 30 days prior to Visit 1 or participation in the follow-up period of another trial (participation in observational studies is permitted) 17. Any other clinical condition that, in the opinion of the investigator, would jeopardize patient¿s safety while participating in this clinical trial

Additional Information

Official title A Phase III, Randomised, Double-blind, Parallel Group, 52 Week Study to Evaluate Efficacy and Safety of Once Daily Empagliflozin and Linagliptin Fixed Dose Combination Compared With Linagliptin Plus Placebo in Japanese Type 2 Diabetes Mellitus Patients With Insufficient Glycaemic Control After 16 Weeks Treatment With Once Daily Linagliptin 5 mg.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Boehringer Ingelheim.