To Determine the Effects of Avosentan on Doubling of Serum Creatinine, End Stage Renal Disease and Death in Diabetic Nephropathy

Speedel Pharma

Status and phase

Terminated

Phase 3

Conditions

Diabetic Nephropathy

Treatments

Drug: SPP301

Study type

Interventional

Funder types

Industry

Identifiers

NCT00120328

2005-000604-14

SPP301CRD15

Details and patient eligibility

About

The purpose of this study is to determine whether avosentan (SPP301) is effective in decreasing morbidity and mortality in patients with diabetic nephropathy.

Full description

Diabetic nephropathy has become the leading cause of end stage renal disease (ESRD) in the western world, accounting for approximately 40% of new cases in the US, and up to 20 to 30% in Europe.

Current treatments for diabetic nephropathy usually try to deal with the underlying diabetes or they aim to reduce cardiovascular risk factors such as hypertension, hyperglycemia, smoking and dyslipidemia. A few recently approved drugs such as irbesartan and losartan (for type 2 diabetic nephropathy) have a renoprotective activity beyond their antihypertensive effect. However, morbidity and mortality rates remain high.

Avosentan may have a positive effect on reducing the amount of protein lost in the urine and if this is the case it will help treat patients with diabetic nephropathy.

Sex

All

Ages

21 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Male or female patients 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 >= 2 years;
- Surgically sterile;
- Or, if sexually active and of childbearing potential, using double contraception, with at least one method being barrier contraception. Women of childbearing potential (defined as those who are not surgically sterile, have not had a hysterectomy or are not 2 years' post-menopausal) must have a negative pregnancy test at screening and at randomisation. Pregnancy tests will be repeated monthly during the study
Proteinuria defined as ACR >= 35mg/mmol
Male patients with serum creatinine between 1.3 and 3.0 mg/dL
Female patients with serum creatinine between 1.2 and 3.0 mg/dL
On standard treatment for diabetic nephropathy (such as ACE inhibitors, ARBs or the combination thereof) for at least 6 months before screening. 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

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 >= 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 antiarrhythmic drugs and do not have complete bundle branch block, but who have absolute QT or QTc >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 >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
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.