Gout Dose Response Study

NCT ID: NCT00955981

Last Updated: 2014-03-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 123 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31
• Study Completion Date: 2011-09-30

Brief Summary

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

Conditions

Hyperuricemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

RDEA594 200 mg qd for 28 days

Group Type: EXPERIMENTAL

RDEA594

Intervention Type: DRUG

Uricosuric agent for the treatment of gout

RDEA594 200 mg, 400 mg

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

Group Type: EXPERIMENTAL

RDEA594

Intervention Type: DRUG

Uricosuric agent for the treatment of gout

RDEA594 200 mg, 400 mg and 600 mg

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

Group Type: EXPERIMENTAL

RDEA594

Intervention Type: DRUG

Uricosuric agent for the treatment of gout

Matching placebo

RDEA594 matching placebo qd for 28 days

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo

Interventions

RDEA594

Uricosuric agent for the treatment of gout

Intervention Type: DRUG

Placebo

Matching placebo

Intervention Type: DRUG

Eligibility Criteria

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.
• Clinically relevant medical event as determined by the investigator in consultation with medical monitor prior to entering the Extension Period.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ardea Biosciences, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vijay Hingorani, MD, PhD, MBA

Role: STUDY_DIRECTOR

Ardea Biosciences, Inc.

Locations

Los Angeles, California, United States

DeLand, Florida, United States

Winston-Salem, North Carolina, United States

Jackson, Tennessee, United States

Pleven, , Bulgaria

Plovdiv, , Bulgaria

Plovidv, , Bulgaria

Sofia, , Bulgaria

Sofia, , Bulgaria

Varna, , Bulgaria

Coquitlam, British Columbia, Canada

Kelowna, British Columbia, Canada

Thornhill, Ontario, Canada

Toronto, Ontario, Canada

Mirabel, Quebec, Canada

Bruntál, , Czechia

Prague, , Czechia

Prague, , Czechia

Tbilisi, , Georgia

Tbilisi, , Georgia

Goch, , Germany

Hamburg, , Germany

Nuremberg, , Germany

Elblag, , Poland

Lodz, , Poland

Lublin, , Poland

Poznan, , Poland

Radom, , Poland

Wroclaw, , Poland

Countries

United States; Bulgaria; Canada; Czechia; Georgia; Germany; Poland

Other Identifiers

RDEA594-202

Identifier Type: -

Identifier Source: org_study_id