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

NCT00120328 | Terminated Phase 3 DMC

• 2 other identifiers: SPP301CRD152005-000604-14
• Study Type: interventional
• Target: 2,364
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetic Nephropathy

Keywords

serum creatinine; end stage renal disease; cardiovascular mortality; cardiovascular morbidity; non-cardiovascular mortality; non-cardiovascular morbidity

Outcome Measures

Primary Outcomes (1)

• 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 (7)

• 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

Interventions

SPP301 DRUG

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Speedel Pharma Ltd.: lead

Study Sites (1)

Dr. Mark Warren

Greenville, North Carolina, 27834, United States

Location

MeSH Terms

Conditions

Diabetic Nephropathies; Kidney Failure, Chronic

Interventions

Avosentan

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jessica Mann, MD, PhD

  Speedel Pharma Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: June 30, 2005
• First Posted: July 15, 2005
• Study Start: July 1, 2005
• Study Completion: February 1, 2007
• Last Updated: October 5, 2007

Record last verified: 2007-10

Locations

US (1)