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

Diabetic Nephropathy Clinical Trial

Official title:

ASCEND - A Randomised, Double Blind, Placebo Controlled, Parallel Group Study to Assess the Effect of the Endothelin Receptor Antagonist Avosentan on Time to Doubling of Serum Creatinine, End Stage Renal Disease or Death in Patients With Type 2 Diabetes Mellitus and Diabetic Nephropathy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00120328
• Other study ID #: SPP301CRD15
• Secondary ID: 2005-000604-14
• Status: Terminated
• Phase: Phase 3
• First received: June 30, 2005
• Last updated: October 4, 2007
• Start date: July 2005
• Est. completion date: February 2007

Study information

• Verified date: October 2007
• Source: Speedel Pharma Ltd.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Bulgaria: Bulgarian Drug AgencyCanada: Health CanadaChina: Food and Drug AdministrationColumbia: Republica de Colombia, Ministerio de la Proteccion SocialCroatia:Ministry of HealthCzech Republic: State Institute for Drug ControlEstonia: The State Agency of MedicineFinland: Finnish Medicines AgencyGermany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacyIndia: The Drugs Controller GeneralIndonesia: Badan Pom (NA-DFC)Italy: Ministry of HealthIsrael: The Ministry of Health, Pharmaceutical DepartmentKorea: Korea Food and Drug AdministrationLatvia: State Agency of MedicinesLithuania: State Medicine Control Agency - Ministry of HealthMalaysia: National Pharmaceutical Bureau ControlMexico: Federal Commission for Protection against Health HazardsPeru: Instituto Nacional de SaludPhilippines: Bureau of Food and DrugsPoland: Ministry of HealthRomania: State Institute for Drug ControlRussia: Federal Services for Supervision in the area of Healthcare and Social DevelopmentSingapore: Health Sciences AuthoritySlovakia: State Institute for Drug ControlSouth Africa: Medicines Control CouncilSpain: Agencia del Medicamento y Productos SanitarosSweden: Medical Products AgencyThailand: Ministry of Publich Health; Head of Thai Drug Control DivisionTaiwan: Bureau of Pharmaceutical, Department of HealthTurkey: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2364
• Est. completion date: February 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 80 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Diabetic Nephropathies
• Diabetic Nephropathy
• Kidney Diseases
• Kidney Failure, Chronic

Intervention

Drug:
• SPP301

Locations

Country	Name	City	State
United States	Dr. Mark Warren	Greenville	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Speedel Pharma Ltd.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	To determine the effect of each dose of avosentan on: cardiovascular mortality
Secondary	non-cardiovascular mortality
Secondary	coronary or peripheral vascular revascularisations including amputations (except where due to trauma)
Secondary	non-fatal acute myocardial infarction
Secondary	stroke
Secondary	congestive heart failure
Secondary	unstable angina