Study of XL784 in Patients With Albuminuria Due to Diabetic Nephropathy - Full Text View

Sponsor:	Symphony Evolution, Inc.
Information provided by:	Symphony Evolution, Inc.
ClinicalTrials.gov Identifier:	NCT00312780

Purpose

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.

Condition	Intervention	Phase
Albuminuria Diabetic Nephropathy	Drug: XL784	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Randomized, Double-Blind, Placebo-Controlled Study of XL784 Administered Orally to Subjects With Albuminuria Due to Diabetic Nephropathy

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetic Kidney Problems

U.S. FDA Resources

Further study details as provided by Symphony Evolution, Inc.:

Primary Outcome Measures:

Reduction in albumin excretion relative to creatinine [ Time Frame: 27 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Safety and tolerability [ Time Frame: 27 weeks ] [ Designated as safety issue: Yes ]
Pharmacokinetics and renal elimination [ Time Frame: 27 weeks ] [ Designated as safety issue: Yes ]

Enrollment:	125
Study Start Date:	March 2006
Study Completion Date:	December 2007
Primary Completion Date:	October 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm 1: XL784	Drug: XL784 XL784 softgel capsules (100 mg per capsule) orally administered at a dose of 200 mg/day (or placebo softgel capsules)
Placebo Comparator: Arm 2: Placebo Gel capsules	Drug: XL784 XL784 softgel capsules (100 mg per capsule) orally administered at a dose of 200 mg/day (or placebo softgel capsules)

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00312780

Show 45 Study Locations

Sponsors and Collaborators

Symphony Evolution, Inc.

Investigators

Study Director:

Sanjay K Aggarwal, MD, MBA

Exelixis, Inc.

More Information

No publications provided

Responsible Party:	Charles W. Finn, PhD, President and CEO, Symphony Evolution, Inc.
ClinicalTrials.gov Identifier:	NCT00312780 History of Changes
Other Study ID Numbers:	XL784-201
Study First Received:	April 7, 2006
Last Updated:	February 22, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by Symphony Evolution, Inc.:

albuminuria
diabetic nephropathy
diabetes

Additional relevant MeSH terms:

Albuminuria
Diabetic Nephropathies
Kidney Diseases
Proteinuria
Urination Disorders
Urologic Diseases

Urological Manifestations
Signs and Symptoms
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases

ClinicalTrials.gov processed this record on February 12, 2012