A Randomised, Double-blind, Placebo-Controlled, Dose-ranging, Parallel Design Study to Evaluate the Efficacy and Safety of the Endothelin Antagonist Avosentan in Patients With Diabetic Kidney Disease

Conditions: Diabetic kidney disease
MedDRA version: 9.1Level: LLTClassification code 10012687Term: Diabetic renal disease

Registration Number: EUCTR2008-000786-32-HU

Lead Sponsor: Speedel Pharma Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 265

Inclusion Criteria

Main inclusion criteria:
Diagnosis and main criteria for inclusion at beginning of Screening Phase:
•Male or female patient; 21 to 80 years of age.
•Type 2 diabetes mellitus.
•Glycosylated haemoglobin (HbA1c) = 6.5% and = 10%.
•Diabetic kidney disease evidenced by:
oEstimated glomerular filtration rate (eGFR) (by Modification of Diet in Renal Disease [MDRD] Study formula) = 45 mL/min/1.73 m2 (i.e., Kidney Disease Outcomes Quality Initiative-chronic kidney disease [KDOQI-CKD] Stage I, II and high-end III); and
oAlbuminuria = 34 mg/mmol and = 350 mg/mmol ACR or = 300 mg/24h and = 3.5 g/24h.
•Systolic BP = 150 mm Hg and diastolic BP = 100 mm Hg, after sitting quietly for 10 minutes.
•Body mass index = 35 kg/m2.
Qualification criteria:
Diagnosis and main criteria for inclusion at qualification visit (Study Visit 4):
•Diabetic kidney disease evidenced by:
oeGFR (by MDRD study formula) = 45 mL/min/1.73 m2 (i.e., KDOQI-CKD stage I, II and high-end III); and
oAlbuminuria = 34 mg/mmol and = 350 mg/mmol ACR or
= 300 mg/24h and = 3.5 g/24h.
•Systolic BP = 150 mm Hg and diastolic BP = 100 mm Hg, after sitting quietly for 10 minutes.

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

Main exclusion criteria:
•Type 1 diabetes mellitus.
•Albuminuria of non-diabetic origin.
•Renal transplant or nephrectomy.
•Congestive heart failure (CHF) New York Heart Association Grade II to IV.
•Any evidence of CHF on physical examination.
•History of pulmonary oedema, liver cirrhosis, pleural effusion or ascites.
•Any massive peripheral oedema (above 5 mm indentation).
•Concomitant treatment with insulin sensitisers (glitazones) or dihydropyridines (L-type Ca+ antagonist) at Visit 4 in patients who also have peripheral oedema.
•Unwillingness of either patient or investigator to discontinue concomitant use of ACE inhibitors or ARBs other than irbesartan at Week -8.
•History of arrhythmia, known pacemaker, on anti-arrhythmic drugs, complete bundle branch block, or an absolute QT or QTc interval > 500 msec as measured by 12 lead electrocardiogram (ECG).
•Recent (within 60 days) percutaneous transluminal coronary angioplasty (PTCA), percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) or any other major surgical intervention.
•Recent (within 60 days) acute myocardial infarction, unstable angina, stroke or transient ischaemic attack.
•Any history of life-threatening arrhythmias, or any patient at high risk for QT/QTc prolongation such as those with a family history of Long QT Syndrome, severe hypokalaemia, etc.
•Haemoglobin =10 g/dL