Clinical trial NCT00312780: Study of XL784 in Patients With Albuminuria Due to Diabetic Nephropathy
Official title: A Randomized, Double-Blind, Placebo-Controlled Study of XL784 Administered Orally to Subjects With Albuminuria Due to Diabetic Nephropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Albuminuria
Diabetic Nephropathy
Keywords: albuminuria
diabetic nephropathy
diabetes
Lead sponsor: Symphony Evolution, Inc.
Sponsor class: INDUSTRY
First posted: 2006-04-11
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Reduction in albumin excretion relative to creatinine
timeFrame: 27 weeks
Secondary outcomes:
measure: Safety and tolerability
timeFrame: 27 weeks
measure: Pharmacokinetics and renal elimination
timeFrame: 27 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Parkway Medical Center
state: Alabama
city: Haleyville
country: United States
facility: Winston Technology, Inc.
state: Alabama
city: Phoenix
country: United States
facility: Redpoint Research
state: Arizona
city: Chula Vista
country: United States
facility: International Clinical Research Network, Inc.
state: California
city: La Jolla
country: United States
facility: Scripps Clinic, Torrey Pines, Division of Nephrology
state: California
city: Los Angeles
country: United States
facility: National Research Institute
state: California
city: Los Angeles
country: United States
facility: West Los Angeles VA Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center, Center for the Health Sciences
state: California
city: Pasadena
country: United States
facility: Arroyo Research Inc.
state: California
city: Lakewood
country: United States
facility: Western Nephrology and Metabolic Bone Disease, PC
state: Colorado
city: Thornton
country: United States
facility: Western Nephrology and Metabolic Bone Disease, PC
state: Colorado
city: Norwalk
country: United States
facility: Soundview Research Associates
state: Connecticut
city: Waterbury
country: United States
facility: Chase Medical Research, LLC
state: Connecticut
city: Washington
country: United States
facility: MedStar Clinical Research Center
state: District of Columbia
city: Coral Gables
country: United States
facility: Clinical Research of South Florida
state: Florida
city: Hollywood
country: United States
facility: The Center for Diabetes and Endocrine Care
state: Florida
city: Kissimmee
country: United States
facility: FPA Clinical Research
state: Florida
city: Pembroke Pines
country: United States
facility: Pines Clinical Research, Inc.
state: Florida
city: Idaho Falls
country: United States
facility: Rocky Mountain Diabetes and Osteoporosis Center, PA
state: Idaho
city: Baton Rouge
country: United States
facility: Renal Associate of Baton Rouge
state: Louisiana
city: Portland
country: United States
facility: Intermed
state: Maine
city: Baltimore
country: United States
facility: MODEL Clinical Research
state: Maryland
city: Boston
country: United States
facility: Renal Unit, Joslin Diabetes Center
state: Massachusetts
city: Worchester
country: United States
facility: Fallon Clinic Inc. at Worcester Medical Center, Department of Nephrology
state: Massachusetts
city: Detroit
country: United States
facility: Center for Urban and African American Health
state: Michigan
city: Gulfport
country: United States
facility: South Mississippi Nephrology
state: Mississippi
city: Kansas City
country: United States
facility: Kansas City VA Medical Center
state: Missouri
city: St. Louis
country: United States
facility: Clayton Medical Research
state: Missouri
city: Omaha
country: United States
facility: Creighton Dibetes Center
state: Nebraska
city: Omaha
country: United States
facility: University of Nebraska Medical Center - Nephrology
state: Nebraska
city: West Caldwell
country: United States
facility: LAND Clinical Studies, LLC
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Durham
country: United States
facility: Duke South
state: North Carolina
city: Cleveland
country: United States
facility: Division of Nephrology/Department of Medicine, Case Western Rserve University, MetroHealth Medical Center Campus
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Medical Center, Division of Nephrology
state: Ohio
city: Oklahoma City
country: United States
facility: COR Clinical Research, LLC
state: Oklahoma
city: Medford
country: United States
facility: Clinical Research Institute of Southern Oregon, PC
state: Oregon
city: Greer
country: United States
facility: Mountain View Clinical Research, Inc.
state: South Carolina
city: Nashville
country: United States
facility: Nephrology Associates, PC
state: Tennessee
city: New Tazewell
country: United States
facility: Heartland Medical, PC
state: Tennessee
city: Midland
country: United States
facility: Diabetes Center of the Southwest
state: Texas
city: San Antonio
country: United States
facility: dgd Research
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Health System, Nephrology Division
state: Virginia
city: Milwaukee
country: United States
facility: Zablocki Veterans Affairs Medical Center, Nephrology Section
state: Wisconsin
Study officials:
affiliation: Exelixis
name: Sanjay K Aggarwal, MD, MBA
role: STUDY_DIRECTOR
References: