Clinical trial NCT00955981: Gout Dose Response Study
Official title: Randomized, Double-Blind, Multicenter, Placebo-Controlled, Safety and Efficacy Study of RDEA594 Versus Placebo in the Treatment of Hyperuricemia in Patients With Gout
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hyperuricemia
Lead sponsor: Ardea Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2009-08-10
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.
* 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.

Primary outcomes:
measure: To compare the proportion of subjects whose serum urate (sUA) level is < 6.0 mg/dL after 28 days of dosing by treatment group.
timeFrame: 28 Days
Secondary outcomes:
measure: 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.
timeFrame: 28 Days
measure: To evaluate the absolute and percent reduction from baseline in sUA levels at each weekly study visit.
timeFrame: 28 Days and through extension
measure: To evaluate the percentage change in 24-hour urine urate level (excretion) from baseline to Day 28.
timeFrame: 28 Days and through extension
measure: To evaluate the incidence of gout flares.
timeFrame: 28 Days and through extension
measure: To evaluate the safety and tolerability of RDEA594 in subjects with gout.
timeFrame: 28 Days and through extension
measure: 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.
timeFrame: 18 Months
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: DeLand
country: United States
state: Florida
city: Winston-Salem
country: United States
state: North Carolina
city: Jackson
country: United States
state: Tennessee
city: Pleven
country: Bulgaria
city: Plovdiv
country: Bulgaria
city: Plovidv
country: Bulgaria
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Varna
country: Bulgaria
city: Coquitlam
country: Canada
state: British Columbia
city: Kelowna
country: Canada
state: British Columbia
city: Thornhill
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Mirabel
country: Canada
state: Quebec
city: Bruntal
country: Czech Republic
city: Prague
country: Czech Republic
city: Prague
country: Czech Republic
city: Tbilisi
country: Georgia
city: Tbilisi
country: Georgia
city: Goch
country: Germany
city: Hamburg
country: Germany
city: Nuremberg
country: Germany
city: Elblag
country: Poland
city: Lodz
country: Poland
city: Lublin
country: Poland
city: Poznan
country: Poland
city: Radom
country: Poland
city: Wroclaw
country: Poland
Study officials:
affiliation: Ardea Biosciences, Inc.
name: Vijay Hingorani, MD, PhD, MBA
role: STUDY_DIRECTOR
References: