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

NCT ID: NCT03226899

Last Updated: 2021-11-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 242 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-19
• Study Completion Date: 2019-02-25

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 serum urate (sUA).

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 once daily (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.

Conditions

Gout; Chronic Kidney Disease (CKD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Lesinurad + XOI

lesinurad 200 mg oral tablet QD plus a stable, medically appropriate dose of an XOI

Group Type: ACTIVE_COMPARATOR

Lesinurad

Intervention Type: DRUG

200 mg oral tablet

XOI

Intervention Type: DRUG

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.

colchicine

Intervention Type: DRUG

Gout flare prophylaxis: commercially available colchicine is provided through the Month 6 study visit. Actual colchicine dose (0.5 or 0.6 mg qd) and frequency were adjusted based on the local label, subject medical history, and clinical judgement.

corticosteroids

Intervention Type: DRUG

Gout flare prophylaxis: Participants unable to take colchicine are permitted to take a short course of low-dose oral corticosteroids up to the Month 3 study visit

Placebo + XOI

placebo tablet QD plus a stable, medically appropriate dose of an XOI

Group Type: PLACEBO_COMPARATOR

XOI

Intervention Type: DRUG

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

Intervention Type: DRUG

matching placebo oral tablet

colchicine

Intervention Type: DRUG

Gout flare prophylaxis: commercially available colchicine is provided through the Month 6 study visit. Actual colchicine dose (0.5 or 0.6 mg qd) and frequency were adjusted based on the local label, subject medical history, and clinical judgement.

corticosteroids

Intervention Type: DRUG

Gout flare prophylaxis: Participants unable to take colchicine are permitted to take a short course of low-dose oral corticosteroids up to the Month 3 study visit

Interventions

Lesinurad

200 mg oral tablet

Intervention Type: 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.

Intervention Type: DRUG

Placebo

matching placebo oral tablet

Intervention Type: DRUG

colchicine

Gout flare prophylaxis: commercially available colchicine is provided through the Month 6 study visit. Actual colchicine dose (0.5 or 0.6 mg qd) and frequency were adjusted based on the local label, subject medical history, and clinical judgement.

Intervention Type: DRUG

corticosteroids

Gout flare prophylaxis: Participants unable to take colchicine are permitted to take a short course of low-dose oral corticosteroids up to the Month 3 study visit

Intervention Type: DRUG

Other Intervention Names

RDEA594; allopurinol; febuxostat

Eligibility 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 estimated creatinine clearance (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 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 nonhormonal contraception during the Screening Period and while taking investigation product (IP).

9. Subject has a body mass index < 45 kg/m^2.

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 computerized tomography (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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medpace, Inc.

INDUSTRY

Sponsor Role: collaborator

Ironwood Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ironwood Study Chair

Role: STUDY_CHAIR

Ironwood Pharmaceuticals, Inc.

Locations

Central Alabama Research

Birmingham, Alabama, United States

Southern Arizona VA Health Care System

Tucson, Arizona, United States

Medvin Clinical Research

Covina, California, United States

Northern California Research

Sacramento, California, United States

Capital Nephrology Medical Group

Sacramento, California, United States

Inland Rheumatology Clinical Trials, Inc

Upland, California, United States

Medvin Clinical Research - Whittier

Whittier, California, United States

Western Nephrology-Westminster

Westminster, Colorado, United States

New England Research Associates, Llc

Trumbull, Connecticut, United States

Arthritis, Autoimmune, & Allergy LLC

Daytona Beach, Florida, United States

Riverside Clinical Research

Edgewater, Florida, United States

Florida Medical Research Institute

Gainesville, Florida, United States

Eastern Research

Hialeah, Florida, United States

San Marcus Research Clinic Inc

Miami, Florida, United States

LCC Medical Research Institute, LLC

Miami, Florida, United States

Savin Medical Group

Miami Lakes, Florida, United States

Rheumatology Associates of Central Florida

Orlando, Florida, United States

Omega Research Consultants, LLC

Orlando, Florida, United States

BayCare Medical Group, Inc.

Tampa, Florida, United States

Meridien Research - Tampa

Tampa, Florida, United States

The Kaufmann Clinic, Inc

Atlanta, Georgia, United States

Ellipsis Group

Atlanta, Georgia, United States

Rocky Mountain Diabetes and Osteoporosis Center PA

Idaho Falls, Idaho, United States

Clinical Investigation Specialists, Inc. - Gurnee

Gurnee, Illinois, United States

Nephrology Specialists

Merrillville, Indiana, United States

Kansas Nephrology Research Institute

Wichita, Kansas, United States

Center for Arthritis & Osteoporosis

Elizabethtown, Kentucky, United States

Four Rivers Clinical Research

Paducah, Kentucky, United States

Ochsner Clinic Foundation

Baton Rouge, Louisiana, United States

Clinical Trials Management, LLC - Northshore

Covington, Louisiana, United States

Clinical Trials Management LLC - Southshore

Metairie, Louisiana, United States

Arthritis and Diabetes Clinic

Monroe, Louisiana, United States

Northwest Louisiana Nephrology

Shreveport, Louisiana, United States

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Michigan Kidney Consultants

Pontiac, Michigan, United States

St. Clair Nephrology Research

Roseville, Michigan, United States

CRC of Jackson, LLC

Jackson, Mississippi, United States

VA Medical Center - Kansas City

Kansas City, Missouri, United States

Meridian Clinical Research - Norfolk, NE

Norfolk, Nebraska, United States

New Mexico Clinical Research & Osteoporosis Center Inc.

Albuquerque, New Mexico, United States

Ellipsis Research Group, LLC

Brooklyn, New York, United States

Buffalo VA Medical Center

Buffalo, New York, United States

Winthrop University Hospital

Mineola, New York, United States

DJL Clinical Research PLLC

Charlotte, North Carolina, United States

PhysiqueMed Clinical Trials

Greensboro, North Carolina, United States

Burke Primary Care

Morganton, North Carolina, United States

Trial Management Associates, LLC

Wilmington, North Carolina, United States

Sterling Research Group, Ltd. - Auburn

Cincinnati, Ohio, United States

Sterling Research Group, Ltd. - Cincinnati

Cincinnati, Ohio, United States

Prestige Clinical Research

Franklin, Ohio, United States

Columbia Research Group, Inc.

Portland, Oregon, United States

Northeast Clinical Research Center

Bethlehem, Pennsylvania, United States

Altoona Center for Clinical Research

Duncansville, Pennsylvania, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Rhode Island Hospital

East Providence, Rhode Island, United States

Low Country Rheumatology

Charleston, South Carolina, United States

Piedmont Research Partners, LLC

Fort Mill, South Carolina, United States

Mountain View Clinical Research - Greer

Greer, South Carolina, United States

Knoxville Kidney Center, PLLC

Knoxville, Tennessee, United States

Discovery Alliance International Inc. d/b/a Tennessee Health Research Alliance LLC

Nashville, Tennessee, United States

Nephrology Associates, P.C.

Nashville, Tennessee, United States

FMC Science

Lampasas, Texas, United States

P&I Clinical Research

Lufkin, Texas, United States

Clinical Advancement Center, PLLC

San Antonio, Texas, United States

Briggs Clinical Research, Inc.

San Antonio, Texas, United States

3rd Coast Research Associates

Victoria, Texas, United States

Spectrum Medical, Inc.

Danville, Virginia, United States

Manassas Clinical Research Center

Manassas, Virginia, United States

Clinical Research Partners, LLC

Richmond, Virginia, United States

CCBR Czech Brno, s. r. o

Brno, , Czechia

REVMACLINIC s.r.o. - Revmatologicka ambulance

Brno, , Czechia

DTTO Faculty Hospital Brno

Brno, , Czechia

Revmatologie MUDr. Bilkova s.r.o.

Olomouc, , Czechia

CCBR Ostrava s.r.o.

Ostrava, , Czechia

CCBR Clinical Research, Pardubice

Pardubice, , Czechia

CCBR Czech Prague s.r.o.

Prague, , Czechia

MEDICAL PLUS, s.r.o. - Revmatologicka ambulance

Uherské Hradiště, , Czechia

Krajska zdravotni, a.s. - Masarykova nemocnice v Usti nad Labem, o.z.

Ústí nad Labem, , Czechia

PV - MEDICAL, s.r.o.

Zlín, , Czechia

Nemocnice Znojmo p.o - Interni oddeleni

Znojmo, , Czechia

Bajai Szent Rokus Korhaz

Baja, , Hungary

DRC Gyogyszervizsgalo Kozpont Kft

Balatonfüred, , Hungary

Dr Lakatos Ferenc Belgyogyaszati-Kardiologiai Maganrendelo

Békéscsaba, , Hungary

Clinexpert Kft.

Budapest, , Hungary

Vaszary Kolos Korhaz Esztergom - Reumatologiai osztaly

Esztergom, , Hungary

BKS Research Kft.

Hatvan, , Hungary

Kalocsai Szent Kereszt Korhaz

Kalocsa, , Hungary

Selye Janos Hospital - Rheumatology Department

Komárom, , Hungary

CRU Hungary Kft.

Miskolc, , Hungary

Clinfan Ltd SMO

Szekszárd, , Hungary

Mentahaz Maganorvosi Kozpont (SMO)

Székesfehérvár, , Hungary

Allergo-Derm Bakos Kft.

Szolnok, , Hungary

Medical Expert Kft.

Veszprém, , Hungary

Stacja Dializ Zyrardow

Żyrardów, Zyrardo, Poland

B_Serwis Popenda Sp. J.

Chorzów, , Poland

Centrum Kliniczno Badawcze J. Brzezicki B. Gornikiewicz - Brzezicka Lekarze Sp. p.

Elblag, , Poland

MCBK s.c.

Grodzisk Mazowiecki, , Poland

NZOZ Praktyka Lekarza Rodzinnego Elzbieta Kelm

Katowice, , Poland

Centrum Medyczne Pratia Krakow

Krakow, , Poland

Malopolskie Centrum Medyczne

Krakow, , Poland

Samodzielny Publiczny ZOZ Uniwersytecki Szpital Kliniczny nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Lodzi, Oddzial Kliniczny Nefrologii, Hipertensjologii i Transplantologii Nerek

Lodz, , Poland

Centrum Terapii Wspolczesnej J. M. Jasnorzewska Spolka Komandytowo Akcyjna

Lodz, , Poland

AppleTreeClinics Sp. z o.o.

Lodz, , Poland

Centrum Medyczne AMED Oddzial w Lodzi

Lodz, , Poland

NZOZ All - Med Centrum Medyczne Specjalistyczne Gabinety Lekarskie Marcin Ogorek

Lodz, , Poland

Centrum Medyczne Chodzki

Lublin, , Poland

Alfa Specjalistyczne Gabinety Lekarskie Ewa Moroz

Nowy Sącz, , Poland

Centrum Zdrowia Metabolicznego Pawel Bogdanski

Poznan, , Poland

Centrum Badan Klinicznych s.c.

Poznan, , Poland

Praktyka Lekarska Ewa Krzyzagorska

Poznan, , Poland

Prywatny Gabinet Lekarski NZOZ Centrum Medyczne Aeskulap

Radom, , Poland

Centrum Medyczne Pratia Warszawa

Warsaw, , Poland

Centrum Medyczne K2J2

Wołomin, , Poland

KO - MED Centra Kliniczne Sp. z o.o., Osrodek Badan Klinicznych w Zamosciu

Zamość, , Poland

Centrum Dializa Sp. z o.o. - Zyrardow

Żyrardów, , Poland

Countries

United States; Czechia; Hungary; Poland

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

RDEA594-401

Identifier Type: -

Identifier Source: org_study_id