Efficacy, safety & Modification of Albuminuria in type 2 diabetes subjects with Renal disease with LINAglipti

Conditions: Type 2 diabetes patients receiving treatment with ACEi or ARB with micro- or macroalbuminuria (UACR between 30 and 3000 mg/g creatinine). [ACEi=Angiotensin Converting Enzyme inhibitor
ARB=Angiotensin Receptor Blocker
UACR= Urinary Albumin Creatinine Ratio]
MedDRA version: 18.0Level: SOCClassification code 10027433Term: Metabolism and nutrition disordersSystem Organ Class: 10027433 - Metabolism and nutrition disorders
Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Registration Number: EUCTR2012-002603-17-FI

Lead Sponsor: Boehringer Ingelheim Finland Ky

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 350

Inclusion Criteria

1. Diagnosis of type 2 diabetes mellitus prior to informed consent.
2. Male and female patients on diet and exercise regimen who are:
- drug-naïve, defined as absence of any oral antidiabetic therapy or
- already treated by mono or dual oral andiabetic therapy or
- with basal insulin alone or in combination with one or two oral antidiabetic therapies.
Diet and exercise regime and antidiabetic therapy (and respective dosing) has to be unchanged for 10 weeks prior to informed consent. The following treatments are allowed as background therapy: Metformin, alpha-glucosidase inhibitors (AGI), basal insulin, SU/glinide. Unchanged therapy prior to informed consent is defined as continuous diet and exercise for treatment naive patients and for patients being drug-treated, no dose change in oral antidiabetic treatments and less than 10% dose change in basal insulin.
3. 6,5%= HbA1c = 10% at Visit 1 (screening).
4. Current therapy with either ACEi or ARB (with or without additional background anti-hypertensive therapy). All anti-hypertensive medications at stable dose for 10 weeks prior to informed consent.
5. a) Urinary albumin-to-creatinine ratio (UACR): 30-3000 mg/g creatinine or albuminuria >30 mg/l of urine or >30 µg/min clearly documented in the previous 12 months or detected at Visit 1 (screening).
b) Prior to randomisation albuminuria needs to be confirmed by a geometric mean of UACR samples of 30-3000mg/g creatinine coming from 3 urine samples at Visit 2.
c) If the patients meets UACR criteria at screening, but fail to confirm albuminuria with 3 urine samples at Visit 2 (geometric mean value) this patient is considered as screening failure.
6. Estimated glomerular filtration rate, eGFR = 30 ml/min/1.73m2, based on the MDRD formula, as determined at Visit 1 (screening)
7. Age =18 years but = 80 years at Visit 1 (screening).
8. BMI (body mass index) = 40 kg/m2 at Visit 1 (screening).
9. Signed and dated written informed consent by date of Visit 1 in accordance with GCP and local legislation.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 315
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 35

Exclusion Criteria

1. Dual or triple blockade of the Renin Angiotensin System (RAS) is not allowed (e.g. ACEi + ARB; ACEi + renin inhibitor; or ARB + renin inhibitor: or ACEi + ARB + renin inhibitor).
2. Uncontrolled hyperglycaemia with a glucose level > 240 mg/dl (>13.3 mmol/l) after an overnight fast during screening/run in and confirmed by a second measurement (not on the same day).
3. Mean arterial blood pressure (defined by (SBP+ 2 DBP)/3) > 110 mmHg at Visit 1 (screening) or at Visit 3.
4. Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris), stroke or TIA within 3 months prior to informed consent.
5. History of non diabetic renal disease according investigator’s opinion, renal transplant recipients or signs of acute or chronic urinary tract infection at Visits 1-3.
6. Indication of liver disease, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined during screening and/or the run-in periods.
7. Medical history of pancreatitis.
8. Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption.
9. Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years.
10. Blood dyscrasias or any disorders causing hemolysis or unstable Red Blood Cell (e.g. malaria, babesiosis, haemolytic anemia).
11. Known hypersensitivity or allergy to the investigational product, or their excipients (including matching placebos).
12. Treatment with a glitazone within 6 months prior to informed consent.
13. Treatment with a DPP-4 inhibitor, a GLP-1 agonist, a SGLT2 inhibitor, a dopamin-agonist, a bile-acid sequestrant, a short acting (prandial) insulin or premixed insulin within 10 weeks prior to informed consent.
14. Treatment with anti-obesity drugs 10 weeks prior to informed consent.
15. Alcohol or drug abuse within 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake in the opinion of the investigator.
16. Current treatment with systemic steroids (glucocorticoids) at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent.
17. Participation in another trial with an investigational drug within 2 months prior to informed consent.
18. Pre-menopausal women (last menstruation ?1 year prior to informed consent) who:
- are nursing or pregnant or
- are of child-bearing potential and are not practising an acceptable method of birth control, or do not plan to continue using this method throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include tubal ligation, transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, sexual abstinence (if acceptable by local authorities), double barrier method and vasectomised partner. No exception will be made.
19. Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol or study related procedures according the investigator’s opinion.
20. Any other clinical condition that would jeopardize patients’ safety while participating in this clinical trial in the opinion of the investigator.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The objective of the current study is to investigate the glycemic efficacy and safety of linagliptin 5 mg given orally once daily for 24 weeks to type 2 diabetes patients with albuminuria (urinary albumin-to-creatinine ratio 30-3000 mg/g creatinine) on top of current treatment with ACEi or ARB.<br>;Secondary Objective: The key secondary endpoint is the time weighted average of percentage change from baseline in UACR during the course of 24 weeks of treatment. ;Primary end point(s): The primary endpoint is the change from baseline in HbA1c;Timepoint(s) of evaluation of this end point: 24 weeks

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): The key secondary endpoint is the time weighted average of percentage change from baseline in UACR;Timepoint(s) of evaluation of this end point: 24 weeks