Diabetic Nephropathy
Conditions
Sponsors
Speedel Pharma Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male or female patients must be between 21 and 80 years of age, inclusive. • Patients with type 2 diabetes mellitus diagnosed for at least 3 years and receiving oral anti-diabetic treatment and/or insulin. • Female patients will either be: Post menopausal for greater than or equal to 2 years, Surgically sterile Or, if of childbearing potential, using double contraception, with at least one method being barrier contraception. Women of childbearing potential must have a negative pregnancy test at screening and at randomisation. Pregnancy tests will be repeated monthly during the study. • Proteinuria defined as ACR greater than or equal to 50mg/mmol. • Patients with serum creatinine between 1.5 and 3.2 mg/dL. • On standard treatment for diabetic nephropathy (such as angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or the combination thereof) for at least 6 months before study start. Patients who are intolerant to ACE inhibitors or ARBs will be allowed to enter the study. • Able to provide written informed consent prior to study participation. 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Patients with type 1 diabetes mellitus. • Patients with proteinuria of non-diabetic origin. • Patients with a renal transplant. • Patients who have undergone nephrectomy • Patients with an estimated GFR = 15 mL/min • Patients with blood pressure greater than or equal to 160/100 mmHg with or without antihypertensive medication. • Patients with glycosylated haemoglobin (HbA1c) > 12 %. • Patients with normal sinus rhythm who do not have a pacemaker, are not taking anti-arrhythmic drugs and do not have complete bundle branch block, but who have absolute QT or QTc greater than 500 msec. • Patients with recent (60 days) percutaneous transluminal coronary angioplasty (PTCA), percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), or any other major surgical intervention. • Patients with recent (60 days) acute myocardial infarction, unstable angina, stroke or transient ischaemic attack. • Patients with CHF New York Heart Association grade III or IV • Patients with life-threatening arrhythmias including those at high risk for QT/QTc prolongation such as a family history of Long QT Syndrome, severe hypokalaemia, etc • Patients who are positive for hepatitis B surface antigen or hepatitis C antibody at Visit 1 (Screening) and who have abnormal liver function (specifically ALAT/ASAT greater than 1 x ULN). • Patients who have been treated with an endothelin receptor antagonist in the 3 months prior to screening. • Patients being treated with spironolactone or eplerenone at entry into the study • Patients treated with amiodarone in the 4 weeks prior to entry into the study. • Women of child-bearing potential not using adequate contraception as specifies in the inclusion criteria given above. • Pregnant or lactating women. • Patients with a neoplasm who are deemed to live < 12 months. • Patients with history of alcohol and/or drug abuse. • Patients with a known history of a major psychiatric condition that would interfere with the conduct of the trial. • Patients with active endocarditis and/or pericarditis. • Patients allergic to avosentan or any other endothelin receptor antagonist. • Patients who participated in another clinical study or who have donated blood within 60 days of being randomised to this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the effect of each dose of avosentan on time to doubling of serum creatinine, end stage renal disease (ESRD) or death when administered on top of standard treatment in subjects with type 2 diabetes mellitus and diabetic nephropathy.;Secondary Objective: • Effect of each dose of avosentan on glomerular filtration rate (GFR), creatinine clearance and proteinuria [measured as albumin/creatinine ratio (ACR)] • Effect of each dose of avosentan on time to coronary or peripheral vascular revascularisations including amputations (except where due to trauma), non-fatal acute MI, stroke, congestive heart failure, unstable angina, cardiovascular mortality • Effect of each dose of avosentan on non-cardiovascular mortality • Measure avosentan & hydroxymethyl metabolite in a subpopulation of 1000 subjects. •Analysis of avosentan & hydroxymethyl metabolite from any subject who experiences any of: a) LFTs > 3 ULN (liver transaminases) b) secondary endpoint requiring hospitilisation ie. acute MI, CHF, revascularisation, stroke, unstable angina c) withdrawels NOT due to expected events such as any component of the primary endpoint or to any other common event in the patient population d) rare events eg. rhabdomyolysis ;Primary end point(s): The primary efficacy criterion is the time to the composite endpoint of doubling of serum creatinine, ESRD or death. | — |
Countries
Czech Republic, Estonia, Finland, Germany, Hungary, Italy, Latvia, Lithuania, Spain, Sweden, United Kingdom
Outcome results
None listed