Gout Dose Response Study

Ardea Biosciences

Status and phase: Completed; Phase 2

Conditions: Hyperuricemia

Treatments: Drug: Placebo; Drug: RDEA594

Study type: Interventional

Funder types: Industry

Identifiers

NCT00955981

RDEA594-202

Details and patient eligibility

About

To compare the proportion of subjects whose serum urate (sUA) level is < 6.0 mg/dL after 28 days of dosing by treatment group.

Enrollment: 123 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or post-menopausal or surgically sterile female.
• 18 - 75 years of age.
• Hyperuricemic (i.e., screening sUA ≥8 mg/dL).
• Meets criteria for the diagnosis of gout as per the American Rheumatism Association (ARA) Criteria for the Classification of Acute Arthritis of Primary Gout.
• 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).
• Subjects entering the optional Extension Period must have successfully completed the Double-Blind Treatment Period and Follow-up Period within approximately 4 months and must not have experienced any serious adverse events considered possibly related to study drug.

Exclusion criteria

• Classified as an overproducer of urine urate (Cur > 6.0 ml/min/1.73 m2 24- hour urine).
• Consumes more than 14 drinks of alcohol per week (e.g., 1 drink = 5 oz [150 ml] of wine, 12 oz [360 ml] of beer, or 1.5 oz [45 ml] of hard liquor).
• History or suspicion of drug abuse.
• Documented history of or suspicion of kidney stones.
• History of rheumatoid arthritis or other autoimmune disease.
• Confirmed (positive serology to HIV1 and HIV 2) or suspected HIV infection.
• Positive serology to HCV antibodies (Abs), and/or hepatitis B surface antigen (HBsAg).
• History of malignancy, except treated non-melanomatous skin cancer or cervical dysplasia.
• History of cardiac abnormalities, including abnormal and clinically relevant ECG changes such as bradycardia (sinus rate <45 bpm), complete left bundle branch block (LBBB), second or third degree heart block, intraventricular conduction delay with QRS duration >120 msec, symptomatic or asymptomatic arrhythmias with the exception of sinus arrhythmia, evidence of ventricular pre-excitation, frequent palpitations or syncopal episodes, heart failure, hypokalemia, family history of Long QT Syndrome, and/or family history of sudden death in an otherwise healthy individual between the ages of 1 and 30 years.
• Any condition predisposing them to QT prolongation including pathological Q-wave (defined as Q-wave >40 msec or depth > 0.4-0.5 mV).
• Any use of a concomitant medication that prolong the QT/QTc interval within the 14 days prior to Baseline (Day 0)
• QT interval corrected for heart rate according to Fridericia (QTcF) > 450 msec at Screening or pre-dose at Baseline (Day 0)
• Uncontrolled hypertension (above 150/95)
• Inadequate renal function
• Hemoglobin < 10 g/dL (males) or < 9 g/dL (females)
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 x upper limit of normal (ULN)
• Gamma glutamyl transferase (GGT) > 3 x ULN
• Active peptic ulcer disease requiring treatment
• History of xanthinuria, active liver disease, or hepatic dysfunction.
• Requires therapy with any other urate-lowering medication, other than the study medication.
• Requires long-term use of salicylates; diuretics; azathioprine; mercaptopurine; theophylline; intravenous colchicine; cyclosporine; cyclophosphamide; pyrazinamide; sulfamethoxazole; or trimethoprim
• Taking medications known as enzyme inducers
• Receiving a strong or moderate inhibitor of CYP3A4 or a P-gp inhibitor within 1 month prior to study drug dosing
• Gout flare at screening that is resolved for less than one week prior to the first treatment with study medication (exclusive of chronic synovitis/ arthritis)
• Female of childbearing potential
• Received an investigational medication within 4 weeks prior to study medication administration
• Previously participated in a clinical study involving RDEA806 or RDEA594.
• Known hypersensitivity or allergy to RDEA594 or colchicine or any components in their formulations.
• Body mass index (BMI) >40 kg/m2.
• Taking greater than 1000 mg/day of Vitamin C.
• Any other medical or psychological condition, which in the opinion of the Investigator and/or Medical Monitor, 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.
• Inadequate renal function after completing the Double-Blind Treatment period prior to entering Extension Period.
• Requiring treatment with prohibited medications noted in exclusion criteria numbers 20-23 after completing the Double-Blind Treatment Period prior to entering the Extension Period.
• Clinically relevant medical event as determined by the investigator in consultation with medical monitor prior to entering the Extension Period.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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123 participants in 4 patient groups, including a placebo group

RDEA594 200 mg qd for 28 days

Experimental group

Treatment:

Drug: RDEA594

RDEA594 200 mg, 400 mg

Experimental group

Description:

RDEA594 200 mg qd for 7 days followed by 400 mg qd for 21 days

Treatment:

Drug: RDEA594

RDEA594 200 mg, 400 mg and 600 mg

Experimental group

Description:

RDEA594 200 mg qd for 7 days followed by 400 mg qd for 7 days followed by 600 mg qd for 14 days

Treatment:

Drug: RDEA594

Matching placebo

Placebo Comparator group

Description:

RDEA594 matching placebo qd for 28 days

Treatment:

Drug: Placebo