Gout Dose Response Study

Randomized, Double-Blind, Multicenter, Placebo-Controlled, Safety and Efficacy Study of RDEA594 Versus Placebo in the Treatment of Hyperuricemia in Patients With Gout

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

Study Overview

• Status: Completed
• Conditions: Hyperuricemia
• Intervention / Treatment: Drug: Placebo; Drug: RDEA594

• Study Type: Interventional
• Enrollment (Actual): 123
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Pleven, Bulgaria, 5800
  • Plovdiv, Bulgaria, 4002
  • Plovidv, Bulgaria, 4002
  • Sofia, Bulgaria, 1233
  • Sofia, Bulgaria, 1709
  • Varna, Bulgaria, 9010
• Canada
  • British Columbia
    • Coquitlam, British Columbia, Canada, V3K 3P4
    • Kelowna, British Columbia, Canada, V1Y8E7
  • Ontario
    • Thornhill, Ontario, Canada, L4J6W6
    • Toronto, Ontario, Canada, M9W 4L6
  • Quebec
    • Mirabel, Quebec, Canada, J7J 2K8
• Czech Republic
  • Bruntal, Czech Republic, 792 01
  • Prague, Czech Republic, 140 00
  • Prague, Czech Republic, 148 00
• Georgia
  • Tbilisi, Georgia, 0186
  • Tbilisi, Georgia, 0102
• Germany
  • Goch, Germany, 47574
  • Hamburg, Germany, 22143
  • Nuremberg, Germany, 90402
• Poland
  • Elblag, Poland, 82-300
  • Lodz, Poland, 90-153
  • Lublin, Poland, 20-607
  • Poznan, Poland, 61-289
  • Radom, Poland, 26-610
  • Wroclaw, Poland, 53-025
• United States
  • California
    • Los Angeles, California, United States, 90017
  • Florida
    • DeLand, Florida, United States, 32720
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
  • Tennessee
    • Jackson, Tennessee, United States, 38305

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RDEA594 200 mg qd for 28 days	Drug: RDEA594; Uricosuric agent for the treatment of gout
Experimental: RDEA594 200 mg, 400 mg; RDEA594 200 mg qd for 7 days followed by 400 mg qd for 21 days	Drug: RDEA594; Uricosuric agent for the treatment of gout
Experimental: 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	Drug: RDEA594; Uricosuric agent for the treatment of gout
Placebo Comparator: Matching placebo; RDEA594 matching placebo qd for 28 days	Drug: Placebo; Matching placebo

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate the proportion of subjects whose sUA levels are <6.0 mg/dL, <5.0 mg/dL and <4.0 mg/dL at each weekly study visit during the Double-Blind Period.	28 Days
To evaluate the absolute and percent reduction from baseline in sUA levels at each weekly study visit.	28 Days and through extension
To evaluate the percentage change in 24-hour urine urate level (excretion) from baseline to Day 28.	28 Days and through extension
To evaluate the incidence of gout flares.	28 Days and through extension
To evaluate the safety and tolerability of RDEA594 in subjects with gout.	28 Days and through extension
To evaluate the proportion of subjects whose sUA level decreases to or is maintained at <6.0 mg/dL in the Open-Label Extension Period.	18 Months

Collaborators and Investigators

• Sponsor: Ardea Biosciences, Inc.
• Investigators: Study Director: Vijay Hingorani, MD, PhD, MBA, Ardea Biosciences, Inc.

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: August 7, 2009
• First Submitted That Met QC Criteria: August 7, 2009
• First Posted (Estimate): August 10, 2009

Study Record Updates

• Last Update Posted (Estimate): March 7, 2014
• Last Update Submitted That Met QC Criteria: February 5, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Hyperuricemia; Antirheumatic Agents; Gout Suppressants; Renal Agents; Uricosuric Agents; Lesinurad
• Other Study ID Numbers: RDEA594-202