Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Allopurinol Combination Study (RDEA594-203)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01001338
Recruitment Status : Completed
First Posted : October 26, 2009
Last Update Posted : January 24, 2017
Sponsor:
Information provided by (Responsible Party):
Ardea Biosciences, Inc.

Tracking Information
First Submitted Date  ICMJE October 22, 2009
First Posted Date  ICMJE October 26, 2009
Last Update Posted Date January 24, 2017
Study Start Date  ICMJE October 2009
Actual Primary Completion Date January 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 28, 2010)
To compare the percent reduction from baseline in serum urate levels following 4 wks of continuous treatment of RDEA594 in combination with allopurinol to allopurinol alone in subjects with documented inadequate hypouricemic response. [ Time Frame: 28 days ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 23, 2009)
To compare the proportion of subjects whose serum urate (sUA) levels are < 6.0 mg/dL following 4 weeks of continuous treatment of RDEA594 in combination with allopurinol to allopurinol alone in subjects with documented inadequate hypouricemic response wi [ Time Frame: 28 days ]
Change History Complete list of historical versions of study NCT01001338 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 3, 2011)
  • 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 study visit by treatment group in all subjects and in subjects who have an sUA ≥6 mg/dL at the baseline visit. [ Time Frame: 28 days and through extension ]
  • To evaluate the absolute and percent reduction from baseline in sUA levels at each visit. [ Time Frame: 28 days and through extension ]
  • To evaluate the percentage change in 24-hour urine urate level (excretion) from baseline to Day 28. [ Time Frame: 28 days and through extension ]
  • To evaluate the incidence of gout flares. [ Time Frame: 28 days and through extension ]
  • To evaluate the safety and tolerability of RDEA594 in combination with allopurinol in subjects with gout. [ Time Frame: 28 days and through extension ]
  • To compare the multiple-dose pharmacokinetics (PK) of allopurinol and oxypurinol in the absence versus presence of RDEA594 co-administration. [ Time Frame: 28 days ]
  • To evaluate the proportion of subjects whose sUA level decreases to or is maintained at <6.0 mg/dL and <5.0 mg/dL in the Double-Blind and Open-Label Extension Period. [ Time Frame: 3 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 23, 2009)
  • 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 study visit by treatment group. [ Time Frame: 28 days ]
  • To evaluate the absolute and percent reduction from baseline in sUA levels at each visit. [ Time Frame: 28 days ]
  • To evaluate the percentage change in 24-hour urine urate level (excretion) from baseline to Day 28. [ Time Frame: 28 days ]
  • To evaluate the incidence of gout flares. [ Time Frame: 28 days ]
  • To evaluate the safety and tolerability of RDEA594 in combination with allopurinol in subjects with gout. [ Time Frame: 28 days ]
  • To compare the multiple-dose pharmacokinetics (PK) of allopurinol and oxypurinol in the absence versus presence of RDEA594 co-administration. [ Time Frame: 28 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Allopurinol Combination Study
Official Title  ICMJE Randomized, Double-Blind, Multicenter, Placebo-Controlled, Combination Study to Evaluate the Safety, Efficacy and Potential Pharmacokinetic Interaction of RDEA594 and Allopurinol in Gout Patients With an Inadequate Hypouricemic Response With Standard Doses of Allopurinol
Brief Summary To compare the proportion of subjects whose serum urate (sUA) levels are < 6.0 mg/dL following 4 weeks of continuous treatment of RDEA594 in combination with allopurinol to allopurinol alone in subjects with documented inadequate hypouricemic response with standard doses of allopurinol.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Gout
Intervention  ICMJE
  • Drug: RDEA594
    Uricosuric agent for the treatment of gout.
  • Drug: Placebo
    Matching Placebo
  • Drug: Allopurinol
    Allopurinol
Study Arms  ICMJE
  • Experimental: RDEA594 200 mg qd
    RDEA594 200 mg qd plus allopurinol qd
    Interventions:
    • Drug: RDEA594
    • Drug: Allopurinol
  • Experimental: RDEA594 200 mg, 400 mg qd

    RDEA594 200 mg then 400 mg qd plus allopurinol qd.

    Patients on lesinurad 400 mg had their dose changed to lesinurad 200 mg after protocol amendment 16 dated 07 October 2015.

    Interventions:
    • Drug: RDEA594
    • Drug: Allopurinol
  • Placebo Comparator: Matching Placebo

    RDEA594 matching placebo qd plus allopurinol qd, then allopurinol qd alone in open label period.

    Patients on allopurinol qd alone were discontinued after protocol amendment 16 dated 07 October 2015.

    Interventions:
    • Drug: Placebo
    • Drug: Allopurinol
  • Experimental: RDEA594 600 mg qd

    RDEA594 200 mg then 400 mg then 600 mg plus allopurinol qd

    Patients on lesinurad 600 mg had their dose changed to lesinurad 200 mg after protocol amendment 16 dated 07 October 2015.

    Interventions:
    • Drug: RDEA594
    • Drug: Allopurinol
Publications * Perez-Ruiz F, Sundy JS, Miner JN, Cravets M, Storgard C; RDEA594-203 Study Group. Lesinurad in combination with allopurinol: results of a phase 2, randomised, double-blind study in patients with gout with an inadequate response to allopurinol. Ann Rheum Dis. 2016 Jun;75(6):1074-80. doi: 10.1136/annrheumdis-2015-207919. Epub 2016 Jan 7.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 23, 2017)
227
Original Estimated Enrollment  ICMJE
 (submitted: October 23, 2009)
108
Actual Study Completion Date  ICMJE August 2016
Actual Primary Completion Date January 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or a post-menopausal or surgically sterile female.
  2. 18 - 80 years of age.
  3. Has been taking allopurinol as the sole urate lowering therapy for hyperuricemia for at least 6 weeks at a dose between 200 mg and 600 mg per day without an adequate response.
  4. Has a sUA level ≥ 6 mg/dL at screening.
  5. Meets criteria for the diagnosis of gout as per the American Rheumatism Association (ARA) Criteria for the Classification of Acute Arthritis of Primary Gout.
  6. 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).
  7. Subjects entering the optional Extension Period must have completed 28 days of dosing in the Double-Blind Treatment Period and the Day 42 Visit in the Follow-up Period within 4 months and must not have experienced any serious adverse events considered possibly related to study drug.
  8. Subjects entering the optional Open-Label Extension Period must continue to be compliant with the protocol through Week 44 of the Double-Blind Extension Period and must not have experienced any serious adverse events considered possibly related to study drug.

Exclusion Criteria:

  1. 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).
  2. History or suspicion of drug abuse.
  3. History of documented or suspected kidney stones.
  4. Has rheumatoid arthritis or other autoimmune disease requiring treatment.
  5. Documented or suspicion of HIV infection.
  6. Positive serology to HCV antibodies (Abs), and/or hepatitis B surface antigen (HBsAg).
  7. History of malignancy within 5 years prior to the first dose of study medication, other than non-melanomatous skin cancer or cervical dysplasia.
  8. History of cardiac abnormalities, including abnormal and clinically relevant ECG changes
  9. Any condition predisposing to QT prolongation including pathological Q-wave (defined as Q-wave >40 msec or depth > 0.4-0.5 mV).
  10. Any use of concomitant medications that prolong the QT/QTc interval within the 14 days prior to Baseline (Day 1).
  11. QT interval corrected for heart rate according to Fridericia (QTcF) > 450 msec at Screening or pre-dose at Baseline (Day 1).
  12. Uncontrolled hypertension (above 150/95).
  13. Inadequate renal function [serum creatinine >1.5 mg/dL or creatinine clearance < 60 mL/min (by Cockroft-Gault formula)].
  14. Hemoglobin < 10 g/dL (males) or < 9 g/dL (females).
  15. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 x upper limit of normal (ULN).
  16. Gamma glutamyl transferase (GGT) > 3 x ULN.
  17. Active peptic ulcer disease requiring treatment.
  18. History of xanthinuria, active liver disease, or hepatic dysfunction.
  19. Requires therapy with any other urate-lowering medication, other than the study medications.
  20. Requires long-term use of salicylates; diuretics; losartan; azathioprine; mercaptopurine; theophylline; intravenous colchicine; cyclosporine; cyclophosphamide; pyrazinamide; sulfamethoxazole; or trimethoprim.
  21. Taking medications known as enzyme inducers (see section 3.7 for listing).
  22. Reports receiving a strong or moderate inhibitor of CYP3A4 or a P-gp inhibitor within 1 month prior to study drug dosing, due to potential interactions with colchicine.
  23. Acute gout flare (exclusive of chronic synovitis/ arthritis) during the Screening-Period that has not resolved one week prior to the Baseline Visit (Day 0).
  24. Pregnant or breast feeding.
  25. Has received an investigational medication within 4 weeks prior to the screening visit for this study.
  26. Previously participated in a clinical study involving RDEA806 or RDEA594.
  27. Known hypersensitivity or allergy to RDEA594, allopurinol or colchicine or any components in their formulations.
  28. Body mass index (BMI) >48 kg/m2.
  29. Taking greater than 1000 mg/day of Vitamin C.
  30. 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.
  31. Inadequate renal function after completing the Double-Blind Treatment period prior to entering Double-Blind Extension Period.
  32. 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.
  33. Clinically relevant medical event as determined by the investigator in consultation with medical monitor prior to entering the Extension Period.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Poland,   Spain,   Ukraine,   United Kingdom,   United States
Removed Location Countries Georgia
 
Administrative Information
NCT Number  ICMJE NCT01001338
Other Study ID Numbers  ICMJE RDEA594-203
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ardea Biosciences, Inc.
Study Sponsor  ICMJE Ardea Biosciences, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Nihar Bhakta, MD Ardea Biosciences, Inc.
PRS Account Ardea Biosciences, Inc.
Verification Date January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP