Gout Dose Response Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ardea Biosciences, Inc.
ClinicalTrials.gov Identifier:
NCT00955981
First received: August 7, 2009
Last updated: February 5, 2014
Last verified: February 2014
  Purpose

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


Condition Intervention Phase
Hyperuricemia
Drug: RDEA594
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Ardea Biosciences, Inc.:

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. [ Time Frame: 28 Days ] [ Designated as safety issue: No ]

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. [ Time Frame: 28 Days ] [ Designated as safety issue: No ]
  • To evaluate the absolute and percent reduction from baseline in sUA levels at each weekly study visit. [ Time Frame: 28 Days and through extension ] [ Designated as safety issue: No ]
  • To evaluate the percentage change in 24-hour urine urate level (excretion) from baseline to Day 28. [ Time Frame: 28 Days and through extension ] [ Designated as safety issue: No ]
  • To evaluate the incidence of gout flares. [ Time Frame: 28 Days and through extension ] [ Designated as safety issue: No ]
  • To evaluate the safety and tolerability of RDEA594 in subjects with gout. [ Time Frame: 28 Days and through extension ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 123
Study Start Date: July 2009
Study Completion Date: September 2011
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00955981

  Show 29 Study Locations
Sponsors and Collaborators
Ardea Biosciences, Inc.
Investigators
Study Director: Vijay Hingorani, MD, PhD, MBA Ardea Biosciences, Inc.
  More Information

No publications provided

Responsible Party: Ardea Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT00955981     History of Changes
Other Study ID Numbers: RDEA594-202
Study First Received: August 7, 2009
Last Updated: February 5, 2014
Health Authority: Canada: Health Canada
Czech Republic: State Institute for Drug Control
Georgia: Ministry of Health
Poland: Ministry of Health
United States: Food and Drug Administration
Bulgaria: Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Hyperuricemia
Pathologic Processes

ClinicalTrials.gov processed this record on October 19, 2014