Study of XL784 in Patients With Albuminuria Due to Diabetic Nephropathy

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Albuminuria; Diabetic Nephropathy	Drug: XL784	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	125 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, 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
Study Start Date :	March 2006
Actual Primary Completion Date :	October 2007
Actual Study Completion Date :	December 2007

Arms and Interventions

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Arm	Intervention/treatment
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)

Outcome Measures

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Primary Outcome Measures :

1. Reduction in albumin excretion relative to creatinine [ Time Frame: 27 weeks ]

Secondary Outcome Measures :

1. Safety and tolerability [ Time Frame: 27 weeks ]
2. Pharmacokinetics and renal elimination [ Time Frame: 27 weeks ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

  Show 45 Study Locations

Sponsors and Collaborators

Symphony Evolution, Inc.

Investigators

Study Director:	Sanjay K Aggarwal, MD, MBA	Exelixis

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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
First Posted:	April 11, 2006
Last Update Posted:	February 23, 2010
Last Verified:	February 2010

Keywords provided by Symphony Evolution, Inc.:

albuminuria; diabetic nephropathy; diabetes

Additional relevant MeSH terms:

Diabetic Nephropathies; Kidney Diseases; Albuminuria; Urologic Diseases; Diabetes Complications; Diabetes Mellitus	Endocrine System Diseases; Proteinuria; Urination Disorders; Urological Manifestations; Signs and Symptoms