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

This study has been terminated.
Sponsor:
Information provided by:
Speedel Pharma Ltd.
ClinicalTrials.gov Identifier:
NCT00120328
First received: June 30, 2005
Last updated: October 4, 2007
Last verified: October 2007
  Purpose

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 3

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

Resource links provided by NLM:


Further study details as provided by Speedel Pharma Ltd.:

Primary Outcome Measures:
  • 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 Outcome Measures:
  • 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
  • unstable angina

Estimated Enrollment: 2364
Study Start Date: July 2005
Study Completion Date: February 2007
Detailed 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.

  Eligibility

Ages Eligible for Study:   21 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 >= 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00120328

Locations
United States, North Carolina
Dr. Mark Warren
Greenville, North Carolina, United States, 27834
Sponsors and Collaborators
Speedel Pharma Ltd.
Investigators
Study Director: Jessica Mann, MD, PhD Speedel Pharma Ltd.
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00120328     History of Changes
Other Study ID Numbers: SPP301CRD15, 2005-000604-14
Study First Received: June 30, 2005
Last Updated: October 4, 2007
Health Authority: Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
China: Food and Drug Administration
Columbia: Republica de Colombia, Ministerio de la Proteccion Social
Croatia:Ministry of Health
Czech Republic: State Institute for Drug Control
Estonia: The State Agency of Medicine
Finland: Finnish Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
India: The Drugs Controller General
Indonesia: Badan Pom (NA-DFC)
Italy: Ministry of Health
Israel: The Ministry of Health, Pharmaceutical Department
Korea: Korea Food and Drug Administration
Latvia: State Agency of Medicines
Lithuania: State Medicine Control Agency - Ministry of Health
Malaysia: National Pharmaceutical Bureau Control
Mexico: Federal Commission for Protection against Health Hazards
Peru: Instituto Nacional de Salud
Philippines: Bureau of Food and Drugs
Poland: Ministry of Health
Romania: State Institute for Drug Control
Russia: Federal Services for Supervision in the area of Healthcare and Social Development
Singapore: Health Sciences Authority
Slovakia: State Institute for Drug Control
South Africa: Medicines Control Council
Spain: Agencia del Medicamento y Productos Sanitaros
Sweden: Medical Products Agency
Thailand: Ministry of Publich Health; Head of Thai Drug Control Division
Taiwan: Bureau of Pharmaceutical, Department of Health
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by Speedel Pharma Ltd.:
serum creatinine
end stage renal disease
cardiovascular mortality
cardiovascular morbidity
non-cardiovascular mortality
non-cardiovascular morbidity

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetic Nephropathies
Kidney Diseases
Kidney Failure, Chronic
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Urologic Diseases
Diabetes Complications
Renal Insufficiency, Chronic
Renal Insufficiency

ClinicalTrials.gov processed this record on April 17, 2014