Safety and Efficacy Study of PEG-uricase in the Treatment of Hyperuricemic Patients With Symptomatic Gout

Inclusion Criteria

• Outpatients of either gender, age 18 or older ( no upper age limit).
• Patient is hyperuricemic: screening serum uric acid must be ≥8 mg/dL.
• Patient has symptomatic gout (presence of at least 3 gout flares in the 18 months prior to entry, or at least one gout tophus, or gouty arthritis).
• Conventional therapy is contraindicated or has been ineffective in this patient, i.e., patient has a history (either by medical record or patient interview) of hypersensitivity or of failure to normalize SUA with at least 3 months treatment with allopurinol at the maximum labeled dose (800 mg/dL in the U.S.), or at a medically appropriate lower dose based on dose-limiting toxicity or dose-limiting co-morbidity.
• Patient is willing and able to give informed consent and adhere to visit/protocol schedules (informed consent must be given before the first study procedure is performed, including washout).
• If the patient is a woman of childbearing potential, she must have had a negative screening serum pregnancy test and must use a medically approved form of birth control during her participation in the protocol. Such methods include oral, injectable or implantable contraceptives; IUDs and barrier contraceptives in combination with spermicide. (If male or surgically sterile, check N/A.)

Exclusion Criteria

• The patient has unstable angina.
• The patient has uncontrolled arrhythmia.
• The patient has non-compensated congestive heart failure.
• The patient has uncontrolled hypertension (above 150/95).
• The patient has a history of end stage renal disease requiring dialysis.
• The patient has hemoglobin < 8 g/dL (males) or < 7 g/dL (females).
• The patient is an organ transplant recipient
• The patient has had prior treatment with PEG-uricase, or other recombinant uricase, or any concomitant therapy with a PEG-conjugated drug.
• The patient has had a gout flare at screening that is resolved for less than one week prior to first treatment with study drug (exclusive of chronic synovitis/ arthritis).
• The patient has glucose-6-phosphate dehydrogenase (G6PD) deficiency.
• The patient has a history of anaphylactic reaction to a recombinant protein or porcine product, or hypersensitivity to PEG.
• The patient is pregnant or breast feeding.
• The patient has taken an investigational drug within 4 weeks prior to study drug administration or plans to take an investigational agent during the study.
• The patient has a known allergy to urate oxidase or PEGylated products.
• The patient has any other medical or psychological condition which, in the opinion of the investigator, might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements, or to complete the study.