Study of XL784 in Patients With Albuminuria Due to Diabetic Nephropathy

Diabetic Nephropathy Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled Study of XL784 Administered Orally to Subjects With Albuminuria Due to Diabetic Nephropathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00312780
• Other study ID #: XL784-201
• Status: Completed
• Phase: Phase 2
• First received: April 7, 2006
• Last updated: February 22, 2010
• Start date: March 2006
• Est. completion date: December 2007

Study information

• Verified date: February 2010
• Source: Symphony Evolution, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This clinical study is being conducted at multiple sites to determine the activity, safety and tolerability of XL784 when given daily to patients with albuminuria due to diabetic nephropathy. XL784 is a small molecule reno-protective metalloproteinase inhibitor, inhibiting both ADAMs (including ADAM10, a target of significant interest because of its important role in blood vessel formation and cell proliferation, and ADAM17/TACE, activation of which has been associated with renal deterioration) and MMPs (including MMP-2 and MMP-9). XL784 was specifically optimized to be MMP-1 sparing, which may be clinically significant because inhibition of MMP-1 has been hypothesized to be associated with musculoskeletal toxicity.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 125
• Est. completion date: December 2007
• Est. primary completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Type 1 or Type 2 diabetes mellitus with albuminuria, observed within 3 months of screening

• Prior to randomization, subject has a glomerular filtration rate (GFR) >/= 40 mL/min

• Prior to randomization, the subject has albuminuria defined as ACR >/= 500 mg/g

• Stable seated blood pressure at the screening visit and prior to randomization

• Subject has been on a stable dose and schedule of an angiotension converting enzyme (ACE) inhibitor and/or an angiotension receptor blocker (ARB) for at least 3 months before first dose of study drug

• If on antidiabetic medication, subject has been on a stable dose and schedule for at least 3 months prior to first dose of study drug

• Sexually active subjects must use an accepted method of contraception during the course of the study and for 3 months after

• Signed informed consent

Exclusion Criteria:

• Subject has participated in an investigational study and received an investigational drug within 30 days of the first dose of XL784

• Hemoglobin A1c (HbA1c) value of >10% at screening

• Subject has had either organ transplantation or is currently on immunosuppressive therapy

• Non-steroidal anti-inflammatory drugs (NSAIDs) within 5 days of urine screening assessments

• Current diagnosis of one or more of the following conditions: 1) infection requiring parenteral antibiotics, 2) urinary tract infection, 3) hepatic dysfunction or disease, 4) symptomatic congestive heart failure, 5) unstable angina pectoris, 5) serious cardiac arrhythmia

• Clinically evident diabetic gastroparesis or motility disturbance

• Proteinuria not due to diabetic nephropathy

• Diltiazem or verapamil

• Ongoing condition where treatment with NSAIDs is anticipated (aspirin </= 325 mg/day is allowed)

• Recent history of drug or alcohol abuse

• Pregnant or breastfeeding female subjects

• Known HIV and/or receiving anti-retroviral therapy

• Known allergy or hypersensitivity to any component of XL784 formulation

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Albuminuria
• Diabetic Nephropathies
• Diabetic Nephropathy
• Kidney Diseases

Intervention

Drug:
• XL784
XL784 softgel capsules (100 mg per capsule) orally administered at a dose of 200 mg/day (or placebo softgel capsules)

Locations

Country	Name	City	State
United States	MODEL Clinical Research	Baltimore	Maryland
United States	Renal Associate of Baton Rouge	Baton Rouge	Louisiana
United States	Parkway Medical Center	Birmingham	Alabama
United States	Renal Unit, Joslin Diabetes Center	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	University of Virginia Health System, Nephrology Division	Charlottesville	Virginia
United States	International Clinical Research Network, Inc.	Chula Vista	California
United States	Division of Nephrology/Department of Medicine, Case Western Rserve University, MetroHealth Medical Center Campus	Cleveland	Ohio
United States	The Ohio State University Medical Center, Division of Nephrology	Columbus	Ohio
United States	Clinical Research of South Florida	Coral Gables	Florida
United States	Center for Urban and African American Health	Detroit	Michigan
United States	Duke South	Durham	North Carolina
United States	Mountain View Clinical Research, Inc.	Greer	South Carolina
United States	South Mississippi Nephrology	Gulfport	Mississippi
United States	Winston Technology, Inc.	Haleyville	Alabama
United States	The Center for Diabetes and Endocrine Care	Hollywood	Florida
United States	Rocky Mountain Diabetes and Osteoporosis Center, PA	Idaho Falls	Idaho
United States	Kansas City VA Medical Center	Kansas City	Missouri
United States	FPA Clinical Research	Kissimmee	Florida
United States	Scripps Clinic, Torrey Pines, Division of Nephrology	La Jolla	California
United States	Western Nephrology and Metabolic Bone Disease, PC	Lakewood	Colorado
United States	National Research Institute	Los Angeles	California
United States	UCLA Medical Center, Center for the Health Sciences	Los Angeles	California
United States	West Los Angeles VA Medical Center	Los Angeles	California
United States	Clinical Research Institute of Southern Oregon, PC	Medford	Oregon
United States	Diabetes Center of the Southwest	Midland	Texas
United States	Zablocki Veterans Affairs Medical Center, Nephrology Section	Milwaukee	Wisconsin
United States	Nephrology Associates, PC	Nashville	Tennessee
United States	Heartland Medical, PC	New Tazewell	Tennessee
United States	Soundview Research Associates	Norwalk	Connecticut
United States	COR Clinical Research, LLC	Oklahoma City	Oklahoma
United States	Creighton Dibetes Center	Omaha	Nebraska
United States	University of Nebraska Medical Center - Nephrology	Omaha	Nebraska
United States	Arroyo Research Inc.	Pasadena	California
United States	Pines Clinical Research, Inc.	Pembroke Pines	Florida
United States	Redpoint Research	Phoenix	Arizona
United States	Intermed	Portland	Maine
United States	dgd Research	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Clayton Medical Research	St. Louis	Missouri
United States	Western Nephrology and Metabolic Bone Disease, PC	Thornton	Colorado
United States	MedStar Clinical Research Center	Washington	District of Columbia
United States	Chase Medical Research, LLC	Waterbury	Connecticut
United States	LAND Clinical Studies, LLC	West Caldwell	New Jersey
United States	Fallon Clinic Inc. at Worcester Medical Center, Department of Nephrology	Worchester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Symphony Evolution, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduction in albumin excretion relative to creatinine		27 weeks	No
Secondary	Safety and tolerability		27 weeks	Yes
Secondary	Pharmacokinetics and renal elimination		27 weeks	Yes