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

NCT03226899 | Terminated Phase 4 Results DMC FDA Drug

• 1 other identifier: RDEA594-401
• Study Type: interventional
• Target: 242
• Locations: 4 countries
• Sites: 116

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).

Conditions

Gout; Chronic Kidney Disease (CKD)

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Achieve Serum Urate (sUA) < 6.0 mg/dL at Month 6

  Month 6

Secondary Outcomes (13)

• Percentage of Participants Who Achieve sUA < 6.0 mg/dL Over Time

  Baseline, Months 1, 3, 6, 9, 12, 15, 18

• Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment

  Baseline, Months 1, 3, 6, 9, 12, 15, 18

• Percent Change From Baseline in sUA Over Time, Including the Last Value On and Off Treatment

  Baseline, Months 1, 3, 6, 9, 12, 15, 18

• Change From Baseline in Estimated Creatinine Clearance (eCrCl) at Month 24

  Baseline, 24 months

• Percent Change From Baseline in eCrCl at Month 24

  Baseline, 24 months

Study Arms (2)

Lesinurad + XOI

ACTIVE COMPARATOR

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

Drug: Lesinurad; Drug: XOI; Drug: colchicine; Drug: corticosteroids

Placebo + XOI

PLACEBO COMPARATOR

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

Drug: XOI; Drug: Placebo; Drug: colchicine; Drug: corticosteroids

Interventions

Lesinurad DRUG

200 mg oral tablet

Also known as: RDEA594

Lesinurad + XOI

XOI 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.

Also known as: allopurinol, febuxostat

Lesinurad + XOI; Placebo + XOI

Placebo DRUG

matching placebo oral tablet

Placebo + XOI

colchicine 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.

Lesinurad + XOI; Placebo + XOI

corticosteroids 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

Lesinurad + XOI; Placebo + XOI

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 is willing to adhere to the protocol schedule.
• Subject is ≥ 18 years and ≤ 85 years of age.
• Subject has a diagnosis of gout.
• 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.
• 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.
• Subject has a serum uric acid level ≥ 6.0 mg/dL (357 µmol/L) at Screening Visits 1 and 2.
• 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).
• Subject has a body mass index \< 45 kg/m\^2.

You may not qualify if:

• 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.
• Subject has uncontrolled hypertension (defined as systolic pressure above 160 or diastolic pressure above 95 mm Hg at either Screening Visits 1 or 2).
• Subject has severe hepatic impairment (defined as Child-Pugh Class C) or is known human immunodeficiency virus (HIV) positive.
• Subject is a solid organ transplant recipient.
• Subject has a urine protein of 3+ or higher by dipstick by the central laboratory at Screening Visit 2.
• Subject has a history of glomerulonephritis.
• Subject is taking valpromide, progabide, valproic acid, or other known inhibitors of epoxide hydrolase, or subject is taking ranolazine, cyclosporine, azathioprine or mercaptopurine.
• Subject is receiving chronic treatment with more than 325 mg of salicylates per day.
• Subject is unable to initiate gout flare prophylaxis with colchicine or low-dose oral corticosteroids at Baseline.
• 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.
• 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).
• 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.
• Subject has a gout flare during the Screening Period.
• Subject is pregnant or breastfeeding.
• 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).

Sponsors & Collaborators

• Ironwood Pharmaceuticals, Inc.: lead
• Medpace, Inc.: collaborator

Study Sites (116)

Central Alabama Research

Birmingham, Alabama, 35209, United States

Location

Southern Arizona VA Health Care System

Tucson, Arizona, 85723, United States

Location

Medvin Clinical Research

Covina, California, 91722, United States

Location

Northern California Research

Sacramento, California, 95821, United States

Location

Capital Nephrology Medical Group

Sacramento, California, 95825, United States

Location

Inland Rheumatology Clinical Trials, Inc

Upland, California, 91786, United States

Location

Medvin Clinical Research - Whittier

Whittier, California, 90602, United States

Location

Western Nephrology-Westminster

Westminster, Colorado, 80031, United States

Location

New England Research Associates, Llc

Trumbull, Connecticut, 06611, United States

Location

Arthritis, Autoimmune, & Allergy LLC

Daytona Beach, Florida, 32117, United States

Location

Riverside Clinical Research

Edgewater, Florida, 32132, United States

Location

Florida Medical Research Institute

Gainesville, Florida, 32607, United States

Location

Eastern Research

Hialeah, Florida, 33013, United States

Location

San Marcus Research Clinic Inc

Miami, Florida, 33015, United States

Location

LCC Medical Research Institute, LLC

Miami, Florida, 33126, United States

Location

Savin Medical Group

Miami Lakes, Florida, 33014, United States

Location

Rheumatology Associates of Central Florida

Orlando, Florida, 32806, United States

Location

Omega Research Consultants, LLC

Orlando, Florida, 32810, United States

Location

BayCare Medical Group, Inc.

Tampa, Florida, 33614, United States

Location

Meridien Research - Tampa

Tampa, Florida, 33634, United States

Location

The Kaufmann Clinic, Inc

Atlanta, Georgia, 30308, United States

Location

Ellipsis Group

Atlanta, Georgia, 30342, United States

Location

Rocky Mountain Diabetes and Osteoporosis Center PA

Idaho Falls, Idaho, 83404, United States

Location

Clinical Investigation Specialists, Inc. - Gurnee

Gurnee, Illinois, 60031, United States

Location

Nephrology Specialists

Merrillville, Indiana, 46410, United States

Location

Kansas Nephrology Research Institute

Wichita, Kansas, 67214, United States

Location

Center for Arthritis & Osteoporosis

Elizabethtown, Kentucky, 42701, United States

Location

Four Rivers Clinical Research

Paducah, Kentucky, 42003, United States

Location

Ochsner Clinic Foundation

Baton Rouge, Louisiana, 70809, United States

Location

Clinical Trials Management, LLC - Northshore

Covington, Louisiana, 70433, United States

Location

Clinical Trials Management LLC - Southshore

Metairie, Louisiana, 70006, United States

Location

Arthritis and Diabetes Clinic

Monroe, Louisiana, 71203, United States

Location

Northwest Louisiana Nephrology

Shreveport, Louisiana, 71101, United States

Location

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, 01605, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Michigan Kidney Consultants

Pontiac, Michigan, 48341, United States

Location

St. Clair Nephrology Research

Roseville, Michigan, 48066, United States

Location

CRC of Jackson, LLC

Jackson, Mississippi, 39202, United States

Location

VA Medical Center - Kansas City

Kansas City, Missouri, 64128, United States

Location

Meridian Clinical Research - Norfolk, NE

Norfolk, Nebraska, 68701, United States

Location

New Mexico Clinical Research & Osteoporosis Center Inc.

Albuquerque, New Mexico, 87106, United States

Location

Ellipsis Research Group, LLC

Brooklyn, New York, 11215, United States

Location

Buffalo VA Medical Center

Buffalo, New York, 14215, United States

Location

Winthrop University Hospital

Mineola, New York, 11501, United States

Location

DJL Clinical Research PLLC

Charlotte, North Carolina, 28210, United States

Location

PhysiqueMed Clinical Trials

Greensboro, North Carolina, 27405, United States

Location

Burke Primary Care

Morganton, North Carolina, 28655, United States

Location

Trial Management Associates, LLC

Wilmington, North Carolina, 28403, United States

Location

Sterling Research Group, Ltd. - Auburn

Cincinnati, Ohio, 45219, United States

Location

Sterling Research Group, Ltd. - Cincinnati

Cincinnati, Ohio, 45246, United States

Location

Prestige Clinical Research

Franklin, Ohio, 45005, United States

Location

Columbia Research Group, Inc.

Portland, Oregon, 97239, United States

Location

Northeast Clinical Research Center

Bethlehem, Pennsylvania, 18017, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Rhode Island Hospital

East Providence, Rhode Island, 02914, United States

Location

Low Country Rheumatology

Charleston, South Carolina, 29406, United States

Location

Piedmont Research Partners, LLC

Fort Mill, South Carolina, 29707, United States

Location

Mountain View Clinical Research - Greer

Greer, South Carolina, 29651, United States

Location

Knoxville Kidney Center, PLLC

Knoxville, Tennessee, 37923, United States

Location

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

Nashville, Tennessee, 37203, United States

Location

Nephrology Associates, P.C.

Nashville, Tennessee, 37205, United States

Location

FMC Science

Lampasas, Texas, 76550, United States

Location

P&I Clinical Research

Lufkin, Texas, 75904, United States

Location

Clinical Advancement Center, PLLC

San Antonio, Texas, 78215, United States

Location

Briggs Clinical Research, Inc.

San Antonio, Texas, 78224, United States

Location

3rd Coast Research Associates

Victoria, Texas, 77901, United States

Location

Spectrum Medical, Inc.

Danville, Virginia, 24541, United States

Location

Manassas Clinical Research Center

Manassas, Virginia, 20110, United States

Location

Clinical Research Partners, LLC

Richmond, Virginia, 23235, United States

Location

CCBR Czech Brno, s. r. o

Brno, 60200, Czechia

Location

REVMACLINIC s.r.o. - Revmatologicka ambulance

Brno, 611 41, Czechia

Location

DTTO Faculty Hospital Brno

Brno, 62500, Czechia

Location

Revmatologie MUDr. Bilkova s.r.o.

Olomouc, 779 00, Czechia

Location

CCBR Ostrava s.r.o.

Ostrava, 70200, Czechia

Location

CCBR Clinical Research, Pardubice

Pardubice, 53002, Czechia

Location

CCBR Czech Prague s.r.o.

Prague, 130 00, Czechia

Location

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

Uherské Hradiště, 686 01, Czechia

Location

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

Ústí nad Labem, 40113, Czechia

Location

PV - MEDICAL, s.r.o.

Zlín, 760 01, Czechia

Location

Nemocnice Znojmo p.o - Interni oddeleni

Znojmo, 66902, Czechia

Location

Bajai Szent Rokus Korhaz

Baja, 6500, Hungary

Location

DRC Gyogyszervizsgalo Kozpont Kft

Balatonfüred, 8230, Hungary

Location

Dr Lakatos Ferenc Belgyogyaszati-Kardiologiai Maganrendelo

Békéscsaba, 5600, Hungary

Location

Clinexpert Kft.

Budapest, 1033, Hungary

Location

Vaszary Kolos Korhaz Esztergom - Reumatologiai osztaly

Esztergom, 2500, Hungary

Location

BKS Research Kft.

Hatvan, 3000, Hungary

Location

Kalocsai Szent Kereszt Korhaz

Kalocsa, 6300, Hungary

Location

Selye Janos Hospital - Rheumatology Department

Komárom, 2921, Hungary

Location

CRU Hungary Kft.

Miskolc, 3529, Hungary

Location

Clinfan Ltd SMO

Szekszárd, 7100, Hungary

Location

Mentahaz Maganorvosi Kozpont (SMO)

Székesfehérvár, 8000, Hungary

Location

Allergo-Derm Bakos Kft.

Szolnok, 5000, Hungary

Location

Medical Expert Kft.

Veszprém, 8200, Hungary

Location

Stacja Dializ Zyrardow

Żyrardów, Zyrardo, 96-300, Poland

Location

B_Serwis Popenda Sp. J.

Chorzów, 41-500, Poland

Location

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

Elblag, 82-300, Poland

Location

MCBK s.c.

Grodzisk Mazowiecki, 05-825, Poland

Location

NZOZ Praktyka Lekarza Rodzinnego Elzbieta Kelm

Katowice, 40-040, Poland

Location

Centrum Medyczne Pratia Krakow

Krakow, 30-002, Poland

Location

Malopolskie Centrum Medyczne

Krakow, 30-510, Poland

Location

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

Lodz, 90-153, Poland

Location

Centrum Terapii Wspolczesnej J. M. Jasnorzewska Spolka Komandytowo Akcyjna

Lodz, 90-242, Poland

Location

AppleTreeClinics Sp. z o.o.

Lodz, 90-349, Poland

Location

Centrum Medyczne AMED Oddzial w Lodzi

Lodz, 91-363, Poland

Location

NZOZ All - Med Centrum Medyczne Specjalistyczne Gabinety Lekarskie Marcin Ogorek

Lodz, 94-048, Poland

Location

Centrum Medyczne Chodzki

Lublin, 20-093, Poland

Location

Alfa Specjalistyczne Gabinety Lekarskie Ewa Moroz

Nowy Sącz, 33-300, Poland

Location

Centrum Zdrowia Metabolicznego Pawel Bogdanski

Poznan, 60-589, Poland

Location

Centrum Badan Klinicznych s.c.

Poznan, 60-773, Poland

Location

Praktyka Lekarska Ewa Krzyzagorska

Poznan, 61-655, Poland

Location

Prywatny Gabinet Lekarski NZOZ Centrum Medyczne Aeskulap

Radom, 26-610, Poland

Location

Centrum Medyczne Pratia Warszawa

Warsaw, 01-868, Poland

Location

Centrum Medyczne K2J2

Wołomin, 05-200, Poland

Location

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

Zamość, 22-400, Poland

Location

Centrum Dializa Sp. z o.o. - Zyrardow

Żyrardów, 96-300, Poland

Location

MeSH Terms

Conditions

Gout; Renal Insufficiency, Chronic

Interventions

lesinurad; Allopurinol; Febuxostat; Colchicine; Adrenal Cortex Hormones

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Alkaloids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Ironwood Study Chair
• Organization: Ironwood Pharmaceuticals, Inc.

Info@ironwoodpharma.com

(617) 621-7722

Study Officials

• Ironwood Study Chair

  Ironwood Pharmaceuticals, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: active vs placebo visually identical tablets
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, Double-Blind, Multicenter, Placebo-Controlled

Study Record Dates

• First Submitted: July 20, 2017
• First Posted: July 24, 2017
• Study Start: July 19, 2017
• Primary Completion: February 25, 2019
• Study Completion: February 25, 2019
• Last Updated: November 4, 2021
• Results First Posted: November 4, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (70); PL (22); HU (13); CZ (11)