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

Condition	Intervention	Phase
Diabetic Nephropathy	Drug: SPP301	Phase III

Further Study Details: 

Primary Outcomes: 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 Outcomes: To determine the effect of each dose of avosentan on: cardiovascular mortality; non-cardiovascular mortality; coronary or peripheral vascular revascularisations including amputations (except where due to trauma); non-fatal acute myocardial infarction; stroke; congestive heart failure
Expected Total Enrollment:  2364

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.

Ages Eligible for Study:  21 Years   -   80 Years,  Genders Eligible for Study:  Both

Criteria

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 >= 50mg/mmol
• Patients with serum creatinine between 1.5 and 4.0 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 with blood pressure >= 160/100 mmHg with or without antihypertensive medication
• Patients with glycosylated haemoglobin (HbA1c) > 11%
• 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 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.

Please refer to this study by ClinicalTrials.gov identifier  NCT00120328

Kenneth Jamerson, M.D.      (734) 998-7991    jamerson@umich.edu

North Carolina
      Dr. Mark Warren, Greenville,  North Carolina,  27834,  United States; Recruiting

Study chairs or principal investigators

Jessica Mann, MD, PhD,  Study Director,  Speedel Pharma Ltd.   

Study ID Numbers:  SPP301CRD15; 2005-000604-14
Record last reviewed:  July 2005
Last Updated:  July 25, 2005
Record first received:  July 15, 2005
ClinicalTrials.gov Identifier:  NCT00120328
Health Authority: United States: Food and Drug Administration; Germany: Federal Institute for Drugs and Medicinal Devices; Sweden: Medical Products Agency; Finland: National Agency for Medicines; United States: Food and Drug Administration; Poland: Ministry of Health; Czech Republic: State Institute for Drug Control; Romania: State Institute for Drug Control; Estonia: The State Agency of Medicine; Lithuania: State Medicine Control Agency - Ministry of Health; Bulgaria: Bulgarian Drug Agency; Croatia:; Hungary: National Institute of Pharmacy; Italy: Ministry of Health; Slovakia: State Institute for Drug Control; Turkey: Ministry of Health; India: India; South Africa: Medicines Control Council
ClinicalTrials.gov processed this record on 2005-07-26