Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Combining Lesinurad With Allopurinol in Inadequate Responders (CLEAR 1)

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: NCT01510158
Recruitment Status : Completed
First Posted : January 13, 2012
Results First Posted : August 18, 2016
Last Update Posted : August 18, 2016
Sponsor:
Information provided by (Responsible Party):
Ardea Biosciences, Inc.

Tracking Information
First Submitted Date  ICMJE January 11, 2012
First Posted Date  ICMJE January 13, 2012
Results First Submitted Date  ICMJE January 21, 2016
Results First Posted Date  ICMJE August 18, 2016
Last Update Posted Date August 18, 2016
Study Start Date  ICMJE January 2012
Actual Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 11, 2016)
Proportion of Subjects With an sUA Level That is < 6.0 mg/dL [ Time Frame: 6 Months, analysis after all subjects complete 12 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 11, 2012)
Efficacy Month 6 [ Time Frame: 6 Months ]
Proportion of subjects with an sUA level that is < 6.0 mg/dL by Month 6
Change History Complete list of historical versions of study NCT01510158 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 14, 2013)
  • Gout Flares [ Time Frame: 12 Months ]
    Mean rate of gout flares requiring treatment for the 6-month period from the end of Month 6 to the end of Month 12
  • Tophus [ Time Frame: 12 Months ]
    Proportion of subjects with ≥ 1 target tophus at Baseline who experience complete resolution of at least 1 target tophus by Month 12
Original Secondary Outcome Measures  ICMJE
 (submitted: January 11, 2012)
  • Treatment [ Time Frame: 12 Months ]
    Proportion of subjects requiring treatment for a gout flare during Month 12
  • Tohpus [ Time Frame: 12 Months ]
    Proportion of subjects with ≥ 1 target tophus at Baseline who experience complete resolution of at least 1 target tophus by Month 12
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combining Lesinurad With Allopurinol in Inadequate Responders
Official Title  ICMJE A Phase 3 Randomized, Double-Blind, Multicenter, Placebo-Controlled, Combination Study to Evaluate the Efficacy and Safety of Lesinurad and Allopurinol Compared to Allopurinol Alone in Subjects With Gout Who Have Had an Inadequate Hypouricemic Response to Standard of Care Allopurinol.
Brief Summary This study that compare the serum uric acid lowering effects, clinical benefits, and safety of lesinurad in combination with allopurinol to allopurinol alone in subjects with gout who have had an inadequate response to allopurinol.
Detailed Description Allopurinol is the standard of care for the treatment of gout. Nevertheless, most patients treated with allopurinol do not achieve the recommended serum urate (sUA) target of < 6.0 mg/dL and need additional therapy to achieve the target. Probenecid and benzbromarone are uric acid transporter 1 (URAT1) inhibitors, generally recommended as second-line agents for patients who are either resistant to or intolerant of allopurinol. However, benzbromarone is not available in the US and probenecid is rarely used. Consequently, there is a clear unmet medical need for a new safe and effective therapy for gout, such as lesinurad, a potent URAT1 inhibitor, that can be used in combination with allopurinol in patients not responding adequately to allopurinol monotherapy so that very high rates of response can be achieved by nearly all gout patients, rather than a minority.The subjects selected for this study will have moderate to severe gout with an inadequate response to allopurinol
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Condition  ICMJE Gout
Intervention  ICMJE
  • Drug: Lesinurad
    Tablets, 200 mg once daily (qd)
  • Drug: Lesinurad
    Tablets, 400 mg qd
  • Drug: Placebo
    Tablets, Placebo qd
  • Drug: Allopurinol
    Tablets, ≥ 300 mg QD (≥ 200 mg qd for subjects with moderate renal impairment)
Study Arms  ICMJE
  • Experimental: lesinurad 200 mg + allopurinol
    Interventions:
    • Drug: Lesinurad
    • Drug: Allopurinol
  • Experimental: lesinurad 400 mg + allopurinol
    Interventions:
    • Drug: Lesinurad
    • Drug: Allopurinol
  • Placebo Comparator: Placebo + allopurinol
    Interventions:
    • Drug: Placebo
    • Drug: Allopurinol
Publications * Saag KG, Fitz-Patrick D, Kopicko J, Fung M, Bhakta N, Adler S, Storgard C, Baumgartner S, Becker MA. Lesinurad Combined With Allopurinol: A Randomized, Double-Blind, Placebo-Controlled Study in Gout Patients With an Inadequate Response to Standard-of-Care Allopurinol (a US-Based Study). Arthritis Rheumatol. 2017 Jan;69(1):203-212. doi: 10.1002/art.39840. Erratum in: Arthritis Rheumatol. 2018 Aug;70(8):1318.

*   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: July 11, 2016)
607
Original Estimated Enrollment  ICMJE
 (submitted: January 11, 2012)
750
Actual Study Completion Date  ICMJE August 2014
Actual Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subject is able to understand the study procedures, the risks involved and willing to provide written informed consent before the first study related activity.
  • Subject meets the diagnosis of gout as per the American Rheumatism Association Criteria for the Classification of Acute Arthritis of Primary Gout.
  • Subject has been taking allopurinol as the sole urate-lowering therapy indicated for the treatment of gout for at least 8 weeks prior to the Screening Visit at a stable, medically appropriate dose, as determined by the investigator, of at least 300 mg per day (at least 200 mg for subjects with moderate renal impairment).
  • Subject must be able to take gout flare prophylaxis with colchicine or an Nonsteroidal anti-inflammatory drug (NSAID) (including Cox-2 selective NSAID) ± PPI.
  • Subject has an sUA level ≥ 6.5 mg/dL at the Screening Visit and ≥ 6.0 mg/dL at Day -7 Visit.
  • Subject has reported at least 2 gout flares in the prior 12 months.
  • Body mass index (BMI) < 45 kg/m2

Exclusion Criteria:

  • Subject with known hypersensitivity or allergy to allopurinol.
  • Subject who is taking any other approved urate-lowering medication that is indicated for the treatment of gout other than allopurinol within 8 weeks of the Screening Visit.
  • Subject who is pregnant or breastfeeding.
  • Subject who consumes more than 14 drinks of alcohol per week (eg, 1 drink = 5 oz [150 mL] of wine, 12 oz [360 mL] of beer, or 1.5 oz [45 mL] of hard liquor).
  • Subject with a history or suspicion of drug abuse within the past 5 years.
  • Subject that requires or may require systemic immunosuppressive or immunomodulatory treatment.
  • Subject with known or suspected human immunodeficiency virus (HIV) infection.
  • Subject with a positive test for active hepatitis B or hepatitis C infection.
  • Subject with a history of malignancy within the previous 5 years with the exception of non-melanoma skin cancer that has been treated with no evidence of recurrence, treated cervical dysplasia or treated in situ Grade 1 cervical cancer.
  • Subject within the last 12 months with: unstable angina, New York Heart Association class III or IV heart failure, myocardial infarction, stroke, or deep venous thrombosis; or subjects currently receiving anticoagulants.
  • Subject with uncontrolled hypertension.
  • Subject with an estimated creatinine clearance < 30 mL/min.
  • Subject with active peptic ulcer disease requiring treatment.
  • Subject with a history of xanthinuria, active liver disease, or hepatic dysfunction.
  • Subject receiving chronic treatment with more than 325 mg of salicylates per day.
  • Subject taking valpromide, progabide, or valproic acid.
  • Subject who has received an investigational therapy within 8 weeks or 5 half-lives (whichever is longer) prior to the Screening Visit.
  • Subject with any other medical or psychological condition, which 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 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 United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01510158
Other Study ID Numbers  ICMJE RDEA594-301
Has Data Monitoring Committee Yes
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: Chris Storgard, MD Ardea Biosciences, Inc.
PRS Account Ardea Biosciences, Inc.
Verification Date July 2016

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