Study of XL784 in Patients With Albuminuria Due to Diabetic Nephropathy

Symphony Evolution

Status and phase

Completed

Phase 2

Conditions

Diabetic Nephropathy

Albuminuria

Treatments

Drug: XL784

Study type

Interventional

Funder types

Industry

Identifiers

NCT00312780

XL784-201

Details and patient eligibility

About

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.

Enrollment

125 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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