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

Primary Purpose

Diabetic Nephropathy

Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
SPP301
Sponsored by
Speedel Pharma Ltd.
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional prevention trial for Diabetic Nephropathy focused on measuring serum creatinine, end stage renal disease, cardiovascular mortality, cardiovascular morbidity, non-cardiovascular mortality, non-cardiovascular morbidity

Eligibility Criteria

21 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Dr. Mark Warren

Outcomes

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

Full Information

First Posted
June 30, 2005
Last Updated
October 4, 2007
Sponsor
Speedel Pharma Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT00120328
Brief Title
To Determine the Effects of Avosentan on Doubling of Serum Creatinine, End Stage Renal Disease and Death in Diabetic Nephropathy
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2007
Overall Recruitment Status
Terminated
Study Start Date
July 2005 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
February 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Speedel Pharma Ltd.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Nephropathy
Keywords
serum creatinine, end stage renal disease, cardiovascular mortality, cardiovascular morbidity, non-cardiovascular mortality, non-cardiovascular morbidity

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
2364 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
SPP301
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
To determine the effect of each dose of avosentan on: cardiovascular mortality
Title
non-cardiovascular mortality
Title
coronary or peripheral vascular revascularisations including amputations (except where due to trauma)
Title
non-fatal acute myocardial infarction
Title
stroke
Title
congestive heart failure
Title
unstable angina

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jessica Mann, MD, PhD
Organizational Affiliation
Speedel Pharma Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
Dr. Mark Warren
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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