Combining Lesinurad With Allopurinol in Inadequate Responders

Gout Clinical Trial

— CLEAR 1  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01510158
• Other study ID #: RDEA594-301
• Status: Completed
• Phase: Phase 3
• First received: January 11, 2012
• Last updated: May 18, 2015
• Start date: January 2012
• Est. completion date: August 2014

Study information

• Verified date: May 2015
• Source: Ardea Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 613
• Est. completion date: August 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Gout

Intervention

Drug:
• Lesinurad
Tablets, 200 mg QD
• Lesinurad
Tablets, 400 mg QD
• Placebo
Tablets, Placebo QD
• Allopurinol

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Ardea Biosciences, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy Month 6	Proportion of subjects with an sUA level that is < 6.0 mg/dL by Month 6	6 Months, analysis after all subjects complete 12 months	No
Secondary	Gout Flares	Mean rate of gout flares requiring treatment for the 6-month period from the end of Month 6 to the end of Month 12	12 Months	No
Secondary	Tophus	Proportion of subjects with = 1 target tophus at Baseline who experience complete resolution of at least 1 target tophus by Month 12	12 Months	No