Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Combining Lesinurad With Allopurinol in Inadequate Responders (CLEAR 2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ardea Biosciences, Inc.
ClinicalTrials.gov Identifier:
NCT01493531
First received: December 13, 2011
Last updated: September 3, 2014
Last verified: September 2014
  Purpose

This study will 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.


Condition Intervention Phase
Gout
Drug: Lesinurad
Drug: Placebo
Phase 3

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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Efficacy Month 6 [ Time Frame: 6 months, analysis after all subjects complete 12 months ] [ Designated as safety issue: No ]
    Proportion of subjects with an sUA level that is < 6.0 mg/dL by Month 6


Secondary Outcome Measures:
  • Gout Flares [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Proportion of subjects with ≥ 1 target tophus at Baseline who experience complete resolution of at least 1 target tophus by Month 12


Enrollment: 612
Study Start Date: December 2011
Study Completion Date: July 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: lesinurad 200 mg + allopurinol Drug: Lesinurad
Tablets, 200 mg QD
Experimental: lesinurad 400 mg + allopurinol Drug: Lesinurad
Tablets, 400 mg QD
Placebo Comparator: Placebo + allopurinol Drug: Placebo
Tablets, Placebo QD

Detailed Description:

Allopurinol is the standard of care for the treatment of gout. Nevertheless, most patients treated with allopurinol do not achieve the recommended sUA target of < 6.0 mg/dL and need additional therapy to achieve the target. Probenecid and benzbromarone are 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

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 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.
  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: NCT01493531

  Show 175 Study Locations
Sponsors and Collaborators
Ardea Biosciences, Inc.
Investigators
Study Director: Chris Storgard, MD Ardea Biosciences, Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Ardea Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT01493531     History of Changes
Other Study ID Numbers: RDEA594-302, 2011-003767-29
Study First Received: December 13, 2011
Last Updated: September 3, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
New Zealand: Medsafe
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
South Africa: Department of Health
Spain: Ministry of Health
Switzerland: Swissmedic
United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
Ukraine: Ministry of Health

Keywords provided by Ardea Biosciences, Inc.:
Gout

Additional relevant MeSH terms:
Allopurinol
Antimetabolites
Antioxidants
Antirheumatic Agents
Enzyme Inhibitors
Free Radical Scavengers
Gout Suppressants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014