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A Phase 4 Safety and Efficacy Study to Evaluate Lesinurad 200 mg in Participants With Gout and Renal Impairment

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: NCT03226899
Recruitment Status : Terminated (This action was a business decision & not related to any efficacy, safety or clinical concerns with lesinurad.)
First Posted : July 24, 2017
Last Update Posted : March 4, 2019
Sponsor:
Collaborator:
Medpace, Inc.
Information provided by (Responsible Party):
Ironwood Pharmaceuticals, Inc.

Brief Summary:
This study evaluates the safety and efficacy of lesinurad administered with an XOI versus a placebo plus an XOI in gout participants who have moderate renal impairment and who are not at target level of sUA.

Condition or disease Intervention/treatment Phase
Gout Chronic Kidney Disease (CKD) Drug: Lesinurad Drug: XOI Drug: Placebo Phase 4

Detailed Description:
This postmarketing study is a randomized, double-blind, placebo-controlled study to evaluate safety (with particular focus on renal and cardiovascular events) and efficacy of lesinurad 200 mg QD in combination with an XOI for up to 24 months compared with XOI monotherapy, in participants with gout and moderate renal impairment who have not reached target sUA levels (<6.0 mg/dL) on an XOI alone.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 242 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, Double-Blind, Multicenter, Placebo-Controlled
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: active vs placebo visually identical tablets
Primary Purpose: Treatment
Official Title: A Phase 4, Study to Evaluate the Safety and Efficacy of Lesinurad 200 mg in Combination With a Xanthine Oxidase Inhibitor (XOI), Compared With an XOI Alone, in Subjects With Gout and Estimated Creatinine Clearance (eCrCl) 30 to <60 mL/Min Who Have Not Achieved Target Serum Uric Acid Levels (sUA) on an XOI Alone
Actual Study Start Date : July 19, 2017
Actual Primary Completion Date : February 28, 2019
Actual Study Completion Date : February 28, 2019

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Gout
MedlinePlus related topics: Gout
Drug Information available for: Lesinurad

Arm Intervention/treatment
Active Comparator: Lesinurad + XOI
lesinurad 200 mg oral tablet once daily (QD) plus a stable, medically appropriate dose of an XOI
Drug: Lesinurad
200 MG Oral Tablet
Other Name: RDEA594

Drug: XOI
All participants must be on a stable, medically appropriate dose of XOI as their sole urate-lowering therapy (ULT) indicated for the treatment of gout for at least 4 weeks prior to Screening and throughout the Screening Period. This stable dose of XOI will be maintained throughout the study period.

Placebo Comparator: Placebo + XOI
lesinurad placebo matching tablet plus a stable, medically appropriate dose of an XOI
Drug: XOI
All participants must be on a stable, medically appropriate dose of XOI as their sole urate-lowering therapy (ULT) indicated for the treatment of gout for at least 4 weeks prior to Screening and throughout the Screening Period. This stable dose of XOI will be maintained throughout the study period.

Drug: Placebo
matching placebo oral tablet




Primary Outcome Measures :
  1. Absolute Change From Baseline in eCrCl to Month 24 [ Time Frame: Baseline, 24 months ]
  2. Percent Change From Baseline in eCrCl to Month 24 [ Time Frame: Baseline, 24 months ]
  3. Absolute Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment [ Time Frame: Baseline, up to 25 months ]
  4. Percent Change From Baseline in eCrCl Over the Study Period, Including the Last Value On and Off Treatment [ Time Frame: Baseline, up to 25 Months ]
  5. Incidence Of Serum Creatinine (sCr) Elevations (≥1.5 × Baseline) Over the Study Period [ Time Frame: up to 24 months ]
  6. Incidence of Participants Meeting Criteria (eg, Based on sCr or eCrCl Criteria) for Treatment Discontinuations Over the Study Period [ Time Frame: 24 months ]
  7. Incidence of Renal-Related and Kidney Stone Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs). [ Time Frame: 24 months ]
  8. Prevalence of Contributing Factors to Renal SAEs as Adjudicated by the Renal Event Adjudication Committee (REAC) [ Time Frame: 24 months ]
  9. Incidence of Cardiac Event Adjudication Committee (CEAC)-Adjudicated Major Adverse Cardiovascular Events (MACEs) (Cardiovascular Death, Nonfatal Myocardial Infarction, and Nonfatal Stroke) [ Time Frame: 24 months ]
  10. Incidence of CEAC-Adjudicated MACEs or Hospitalization for Unstable Angina (MACE+) [ Time Frame: 24 months ]

Secondary Outcome Measures :
  1. Proportion of Participants Who Achieve sUA <6.0 mg/dL at Month 6 [ Time Frame: 6 months ]
  2. Absolute Change From Baseline in sUA at Each Visit [ Time Frame: Baseline, up to 24 months ]
  3. Percent Change From Baseline in sUA at Each Visit [ Time Frame: Baseline, up to 24 months ]
  4. Proportion of Participants Who Achieve sUA <6.0 mg/dL at Each Visit [ Time Frame: up to 24 months ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject is able to understand the study procedures, the risks involved, and willing to provide written informed consent before the first study related activity.
  2. Subject is willing to adhere to the protocol schedule.
  3. Subject is ≥18 years and ≤85 years of age.
  4. Subject has a diagnosis of gout.
  5. Subject has moderate renal impairment with eCrCl (calculated by the Cockcroft-Gault formula using ideal body weight) 25.0 to ≤65.0 mL/min at Screening Visits 1 and 2 and an average eCrCl for both screening visits of 30.0 to <60.0 mL/min.
  6. Subject has been taking an XOI as urate-lowering therapy (ULT) indicated for the treatment of gout for at least 4 weeks prior to Screening at a stable, medically appropriate dose, as determined by the Investigator. The minimum dose of allopurinol is 200 mg daily, and the minimum dose of febuxostat is the lowest approved dose per the local product label.
  7. Subject has a serum uric acid level ≥6.0 mg/dL (357 µmol/L) at Screening Visits 1 and 2.
  8. Subject is male or female; females must not be pregnant or breastfeeding and females of childbearing potential must agree to use non hormonal contraception during the Screening Period and while taking investigation product (IP).
  9. Subject has a body mass index <45 kg/m2.

Exclusion Criteria:

  1. Subject had unstable angina, New York Heart Association class III or IV heart failure, myocardial infarction, or stroke within the last 6 months prior to randomization; or had a deep venous thrombosis within the previous 3 months prior to randomization.
  2. Subject has uncontrolled hypertension (defined as systolic pressure above 160 or diastolic pressure above 95 mm Hg at either Screening Visits 1 or 2).
  3. Subject has severe hepatic impairment (defined as Child-Pugh Class C) or is known human immunodeficiency virus (HIV) positive.
  4. Subject is a solid organ transplant recipient.
  5. Subject has a urine protein of 3+ or higher by dipstick by the central laboratory at Screening Visit 2.
  6. Subject has a history of glomerulonephritis.
  7. Subject is taking valpromide, progabide, valproic acid, or other known inhibitors of epoxide hydrolase, or subject is taking ranolazine, cyclosporine, azathioprine or mercaptopurine.
  8. Subject is receiving chronic treatment with more than 325 mg of salicylates per day.
  9. Subject is unable to initiate gout flare prophylaxis with colchicine or low-dose oral corticosteroids at Baseline.
  10. Subject is taking any other drug approved for use as a urate-lowering medication other than allopurinol or febuxostat (eg, pegloticase, probenecid, benzbromarone) within 4 weeks prior to Screening or during Screening.
  11. For subjects who will be taking colchicine for gout flare prophylaxis: Subject is taking, or anticipated to take during the first 6 months on study, moderate or strong Cytochrome P450 3A4 (CYP3A4) inhibitors (ie, verapamil or diltiazem, clarithromycin, and fluconazole; or grapefruit or grapefruit juice).
  12. Subject previously participated in a clinical study involving lesinurad (RDEA594) or verinurad (RDEA3170) and received active treatment or placebo, or has taken commercially-available lesinurad.
  13. Subject has a gout flare during the Screening Period.
  14. Subject is pregnant or breastfeeding.
  15. Subject 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).
  16. Subject has a history of malignancy and has been on active treatment within the previous 5 years prior to randomization with the exception of non-melanoma skin cancer, treated in situ Grade 1 cervical cancer, or treated ductal carcinoma in situ of the breast.
  17. Subject has been hospitalized (other than for elective surgery) or received intravenous contrast (eg, for CT scan or any angiography) within 1 month prior to Screening or during Screening.
  18. Subject has participated in a clinical trial within 8 weeks prior to Screening.
  19. Subject has any other medical or psychological condition, which in the opinion of the Investigator 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.
  20. The maximum number of subjects in the eCrCl stratification subgroup has been reached.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03226899


Locations
Show Show 116 study locations
Sponsors and Collaborators
Ironwood Pharmaceuticals, Inc.
Medpace, Inc.
Investigators
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Study Chair: Niels Borgstein, MD Ironwood Pharmaceuticals, Inc.

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Responsible Party: Ironwood Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03226899    
Other Study ID Numbers: RDEA594-401
First Posted: July 24, 2017    Key Record Dates
Last Update Posted: March 4, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Gout
Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Renal Insufficiency
Arthritis
Joint Diseases
Musculoskeletal Diseases
Crystal Arthropathies
Rheumatic Diseases
Purine-Pyrimidine Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Lesinurad
Gout Suppressants
Antirheumatic Agents
Uricosuric Agents
Renal Agents