Gout Dose Response Study
Primary Purpose
Hyperuricemia
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
RDEA594
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hyperuricemia
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
RDEA594 200 mg qd for 28 days
RDEA594 200 mg, 400 mg
RDEA594 200 mg, 400 mg and 600 mg
Matching placebo
Arm Description
RDEA594 200 mg qd for 7 days followed by 400 mg qd for 21 days
RDEA594 200 mg qd for 7 days followed by 400 mg qd for 7 days followed by 600 mg qd for 14 days
RDEA594 matching placebo qd for 28 days
Outcomes
Primary Outcome Measures
To compare the proportion of subjects whose serum urate (sUA) level is < 6.0 mg/dL after 28 days of dosing by treatment group.
Secondary Outcome Measures
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.
To evaluate the absolute and percent reduction from baseline in sUA levels at each weekly study visit.
To evaluate the percentage change in 24-hour urine urate level (excretion) from baseline to Day 28.
To evaluate the incidence of gout flares.
To evaluate the safety and tolerability of RDEA594 in subjects with gout.
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.
Full Information
NCT ID
NCT00955981
First Posted
August 7, 2009
Last Updated
February 5, 2014
Sponsor
Ardea Biosciences, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT00955981
Brief Title
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
2. Study Status
Record Verification Date
February 2014
Overall Recruitment Status
Completed
Study Start Date
July 2009 (undefined)
Primary Completion Date
March 2010 (Actual)
Study Completion Date
September 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ardea Biosciences, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperuricemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
123 (Actual)
8. Arms, Groups, and Interventions
Arm Title
RDEA594 200 mg qd for 28 days
Arm Type
Experimental
Arm Title
RDEA594 200 mg, 400 mg
Arm Type
Experimental
Arm Description
RDEA594 200 mg qd for 7 days followed by 400 mg qd for 21 days
Arm Title
RDEA594 200 mg, 400 mg and 600 mg
Arm Type
Experimental
Arm Description
RDEA594 200 mg qd for 7 days followed by 400 mg qd for 7 days followed by 600 mg qd for 14 days
Arm Title
Matching placebo
Arm Type
Placebo Comparator
Arm Description
RDEA594 matching placebo qd for 28 days
Intervention Type
Drug
Intervention Name(s)
RDEA594
Intervention Description
Uricosuric agent for the treatment of gout
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo
Primary Outcome Measure Information:
Title
To compare the proportion of subjects whose serum urate (sUA) level is < 6.0 mg/dL after 28 days of dosing by treatment group.
Time Frame
28 Days
Secondary Outcome Measure Information:
Title
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.
Time Frame
28 Days
Title
To evaluate the absolute and percent reduction from baseline in sUA levels at each weekly study visit.
Time Frame
28 Days and through extension
Title
To evaluate the percentage change in 24-hour urine urate level (excretion) from baseline to Day 28.
Time Frame
28 Days and through extension
Title
To evaluate the incidence of gout flares.
Time Frame
28 Days and through extension
Title
To evaluate the safety and tolerability of RDEA594 in subjects with gout.
Time Frame
28 Days and through extension
Title
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.
Time Frame
18 Months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vijay Hingorani, MD, PhD, MBA
Organizational Affiliation
Ardea Biosciences, Inc.
Official's Role
Study Director
Facility Information:
City
Los Angeles
State/Province
California
ZIP/Postal Code
90017
Country
United States
City
DeLand
State/Province
Florida
ZIP/Postal Code
32720
Country
United States
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27103
Country
United States
City
Jackson
State/Province
Tennessee
ZIP/Postal Code
38305
Country
United States
City
Pleven
ZIP/Postal Code
5800
Country
Bulgaria
City
Plovdiv
ZIP/Postal Code
4002
Country
Bulgaria
City
Plovidv
ZIP/Postal Code
4002
Country
Bulgaria
City
Sofia
ZIP/Postal Code
1233
Country
Bulgaria
City
Sofia
ZIP/Postal Code
1709
Country
Bulgaria
City
Varna
ZIP/Postal Code
9010
Country
Bulgaria
City
Coquitlam
State/Province
British Columbia
ZIP/Postal Code
V3K 3P4
Country
Canada
City
Kelowna
State/Province
British Columbia
ZIP/Postal Code
V1Y8E7
Country
Canada
City
Thornhill
State/Province
Ontario
ZIP/Postal Code
L4J6W6
Country
Canada
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M9W 4L6
Country
Canada
City
Mirabel
State/Province
Quebec
ZIP/Postal Code
J7J 2K8
Country
Canada
City
Bruntal
ZIP/Postal Code
792 01
Country
Czech Republic
City
Prague
ZIP/Postal Code
140 00
Country
Czech Republic
City
Prague
ZIP/Postal Code
148 00
Country
Czech Republic
City
Tbilisi
ZIP/Postal Code
0102
Country
Georgia
City
Tbilisi
ZIP/Postal Code
0186
Country
Georgia
City
Goch
ZIP/Postal Code
47574
Country
Germany
City
Hamburg
ZIP/Postal Code
22143
Country
Germany
City
Nuremberg
ZIP/Postal Code
90402
Country
Germany
City
Elblag
ZIP/Postal Code
82-300
Country
Poland
City
Lodz
ZIP/Postal Code
90-153
Country
Poland
City
Lublin
ZIP/Postal Code
20-607
Country
Poland
City
Poznan
ZIP/Postal Code
61-289
Country
Poland
City
Radom
ZIP/Postal Code
26-610
Country
Poland
City
Wroclaw
ZIP/Postal Code
53-025
Country
Poland
12. IPD Sharing Statement
Learn more about this trial
Gout Dose Response Study
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