In This SectionTexas Health Research & Education Institute
Disease or Condition
A Multicenter, Randomized, Active-Control, Phase 3B Study to Evaluate the Cardiovascular Safety of Febuxostat and Allopurinol in Subjects with Gout and Cardiovascular Comorbidities (Cardiology)
The primary objective of this study is to compare the risk of predefined major cardiovascular adverse events (MACE) during treatment with febuxostat and allopurinol in subjects with gout and CV comorbidities.
The subject or the subject’s legally acceptable representative signs and dates a written, informed consent form/Health Insurance Portability and Accountability Act (HIPAA) Authorization prior to the initiation of any study procedures.
The subject is male =50 years of age or female =55 years of age and at least 2-years post-menopausal.
The subject has a history of major CV or cerebrovascular disease including at least one of the following: MI, hospitalized unstable angina, cardiac or cerebrovascular revascularization procedure, stroke, hospitalized TIA, peripheral vascular disease (ankle brachial index =0.6, revascularization and/or well-documented history of claudication), history of diabetes mellitus with evidence of micro- or macrovascular disease (retinopathy, neuropathy, nephropathy, small vessel vascular diseases).
The subject has a history or presence of gout defined as having one or more of the American Rheumatism Association criteria for the diagnosis of gout :
a. a tophus proven to contain urate crystals by chemical or polarized light microscopic means, and/or
b. characteristic urate crystals in the joint fluid, and/or history of at least 6 of the following clinical, laboratory, and x-ray phenomena: more than 1 attack of acute arthritis, maximum inflammation developed within 1 day, monoarticular arthritis, redness observed over joints, first metatarsophalangeal joint painful or swollen, unilateral first metatarsophalangeal joint attack, unilateral tarsal joint attack, tophus (proven or suspected), hyperuricemia, asymmetric swelling within a joint on x-ray, subcortical cysts without erosions on x-ray, joint fluid culture negative for organisms during attack.
The subjects must have either: a sUA level =7.0 mg/dL at the Screening Visit OR a sUA level =6.0 mg/dL at the Screening Visit AND inadequately controlled gout (=1 flare
in the 12 months prior to screening and/or the presence of tophi).
The subject is capable of understanding and complying with protocol requirements.
The subject has secondary hyperuricemia (eg, due to myeloproliferative disorder, or organ transplant).
The subject has a history of xanthinuria.
The subject has received urate-lowering therapy (ie, febuxostat, allopurinol, probenecid, etc.) or excluded medication less than 7 days prior to Study Day 1/Randomization visit.
The subject has a known hypersensitivity to febuxostat or allopurinol or any components of their formulation.
The subject has active peptic ulcer disease.
The subject has a history of cancer (other than basal cell carcinoma of the skin) within 5 years prior to the first dose of study medication.
The subject had MI or stroke within 60 days prior to the Screening Visit.
The subject has ALT and/or AST values greater than 2 times the upper limit of normal (×ULN) during the Screening period.
The subject has a significant medical condition and/or conditions that would interfere with the treatment, safety, or compliance with the protocol.
The subject has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 5 years prior to the Screening Visit or the subject consumes >14 alcoholic beverages per week.
The subject has received any investigational medicinal product within the 30 days prior to the Screening Visit and throughout the study. In addition, the subject has been previously randomized in this study and received at least one dose of double blind study drug treatment.
The subject’s estimated CLcr is <30 mL/min, where CLcr is calculated using the Cockcroft and Gault formula based on ideal body weight (IBW), as provided below:
Estimated CLcr = (140 – age [yr]) × (IBW [kg]) (women multiply by 0.85) 72 × (serum creatinine [mg/dL]) Where IBW is 50 kg for men and 45.5 kg for women, lus 2.3 kg for each inch in height greater than 5 feet (60 inches).
The subject is an immediate family member, study site employee, or is in a dependant relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
The subject is required to take excluded medications listed in Section 7.3.2.
The subject has a known history of infection with hepatitis B, hepatitis C, or human immunodeficiency virus.