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Tophaceous GoutPhase 3CRYSTALNCT01510769

Combination Treatment Study in Subjects With Tophaceous Gout With Lesinurad and Febuxostat

A Phase 3 study testing Lesinurad and Febuxostat in people with Tophaceous Gout, run by Ardea Biosciences, Inc. at 124 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study will compare the serum uric acid lowering effects, clinical benefits, and safety of lesinurad in combination with febuxostat to febuxostat alone in patients with tophaceaous gout. Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Tophaceous Gout
What is being tested?
Lesinurad and Febuxostat
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
330 participants
Where
124 sitesin 6 countries
Study dates
Jan 2012to Jun 2014
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 visit/protocol schedules.
  • Subject meets the diagnosis of gout as per the American Rheumatism Association
  • Criteria for the Classification of Acute Arthritis of Primary Gout.
  • Subject meets one of the following criteria:
  • Subjects who are not currently taking an approved ULT must have an sUA value of ≥ 8 mg/dL (476 µmol/L).
Show all 10Show fewer
  • Subjects entering the study on a medically appropriate dose of febuxostat or allopurinol must have an sUA value of ≥ 6.0 mg/dL (357 µmol/L).
  • Subject must be able to take gout flare prophylaxis with colchicine or non-steroidal anti-inflammatory drug (NSAID) (including Cox-2 selective NSAID) ± PPI.
  • Subject with at least 1 measurable tophus on the hands/wrists and/or feet/ankles ≥ 5 mm and ≤ 20 mm in the longest diameter.
  • Body mass index (BMI) < 45 kg/m2

Who cannot join

  • Subject with known hypersensitivity or allergy to febuxostat.
  • Subject who is taking any approved urate-lowering medication other than allopurinol or febuxostat that is indicated for the treatment of gout within 8 weeks of the Screening Visit.
  • Subject who previously received pegloticase.
  • 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 with a history of myositis/myopathy or rhabdomyolysis.
Show all 20Show fewer
  • 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 thrombosis; or subjects currently receiving anticoagulants.
  • Subject with uncontrolled hypertension.
  • Subject with an estimated creatinine clearance < 30 mL/min.
  • Subjects with a creatine kinase > 2.5 x ULN at any time during the Screening Period.
  • 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 in the opinion of the Investigator and/or Medical Monitor, 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.

Trial locations and contacts

124 sites in 6 countries.

124 sites in 6 countries

United States99 sites

  • Study site

    Austin, Texas, 78705

  • Study site

    Austin, Texas, 78758

  • Study site

    Belle Vernon, Pennsylvania, 15012

  • Study site

    Birmingham, Alabama, 35211

  • Study site

    Boynton Beach, Florida, 33472

  • Study site

    Brooksville, Florida, 34601

  • Study site

    Calabash, North Carolina, 28467

  • Study site

    Chesapeake, Virginia, 23320

  • Study site

    Chicago, Illinois, 60624

  • Study site

    Chicago, Illinois, 60637

  • Study site

    Clairton, Pennsylvania, 15025

  • Study site

    Columbia, South Carolina, 29204

  • Study site

    Columbus, Ohio, 43203

  • Study site

    Conyers, Georgia, 30013

  • Study site

    Corpus Christi, Texas, 78413

  • Study site

    Dallas, Texas, 75218

  • Study site

    Danville, Virginia, 24541

  • Study site

    Denver, Colorado, 80220

  • Study site

    Denver, Colorado, 80230

  • Study site

    Duncansville, Pennsylvania, 16635

  • Study site

    Durham, North Carolina, 27710

  • Study site

    East Brandenton, Florida, 34208

  • Study site

    Elizabethtown, Kentucky, 42701

  • Study site

    Englewood, Colorado, 80113

  • Study site

    Fargo, North Dakota, 58103

  • Study site

    Fleming Island, Florida, 32003

  • Study site

    Frederick, Maryland, 21702

  • Study site

    Glendale, California, 91204

  • Study site

    Goodyear, Arizona, 85395

  • Study site

    Greenville, North Carolina, 27834

  • Study site

    Greenville, South Carolina, 29615

  • Study site

    Gurnee, Illinois, 60031

  • Study site

    Honolulu, Hawaii, 96814

  • Study site

    Houston, Texas, 77004

  • Study site

    Houston, Texas, 77074

  • Study site

    Huntington Beach, California, 92646

  • Study site

    Irvine, California, 92618

  • Study site

    Jackson, Mississippi, 39202

  • Study site

    Jackson, Tennessee, 38305

  • Study site

    Jefferson City, Missouri, 65109

  • Study site

    Jenkintown, Pennsylvania, 19046

  • Study site

    Johns Creek, Georgia, 30097

  • Study site

    Kalamazoo, Michigan, 49009

  • Study site

    La Jolla, California, 92037

  • Study site

    Lansdale, Pennsylvania, 19446

  • Study site

    Lexington, Kentucky, 40504

  • Study site

    Little Rock, Arkansas, 72204

  • Study site

    Little Rock, Arkansas, 72223

  • Study site

    Los Angeles, California, 90048

  • Study site

    Memphis, Tennessee, 38119

  • Study site

    Meridian, Idaho, 83642

  • Study site

    Meridian, Idaho, 83646

  • Study site

    Miami, Florida, 33135

  • Study site

    Middleburg, Ohio, 44130

  • Study site

    Mineola, New York, 11501

  • Study site

    Missoula, Montana, 59808

  • Study site

    Morgantown, West Virginia, 26505

  • Study site

    Mt. Pleasant, South Carolina, 29464

  • Study site

    Napels, Florida, 34102

  • Study site

    New York, New York, 10016

  • Study site

    Newnan, Georgia, 30265

  • Study site

    Oklahoma City, Oklahoma, 73103

  • Study site

    Oklahoma City, Oklahoma, 73112

  • Study site

    Olive Branch, Mississippi, 38654

  • Study site

    Pembroke Pines, Florida, 33027

  • Study site

    Pembroke Pines, Florida, 33029

  • Study site

    Peoria, Arizona, 85381

  • Study site

    Pheonix, Arizona, 85023

  • Study site

    Pittsburgh, Pennsylvania, 15206

  • Study site

    Port Orange, Florida, 32127

  • Study site

    Rancho Cucamonga, California, 91730

  • Study site

    Richmond, Virginia, 23235

  • Study site

    San Antonio, Texas, 78229

  • Study site

    San Diego, California, 92108

  • Study site

    Savannah, Georgia, 31406

  • Study site

    Scottdale, Pennsylvania, 15683

  • Study site

    Seattle, Washington, 98104

  • Study site

    Sellersville, Pennsylvania, 18960

  • Study site

    Southfield, Michigan, 48034

  • Study site

    Spartanburg, South Carolina, 29303

  • Study site

    Springfield, Illinois, 62704

  • Study site

    Springfield, Illinois, 62711

  • Study site

    St Louis, Missouri, 63117

  • Study site

    Suffolk, Virginia, 23435

  • Study site

    Sugar Land, Texas, 77479

  • Study site

    Tampa, Florida, 33606

  • Study site

    Tampa, Florida, 33607

  • Study site

    Tampa, Florida, 33614

  • Study site

    Trumball, Connecticut, 06611

  • Study site

    Tucson, Arizona, 85724

  • Study site

    Vero Beach, Florida, 32960

  • Study site

    Victoria, Texas, 77901

  • Study site

    Virginia Beach, Virginia, 23462

  • Study site

    Waco, Texas, 76708

  • Study site

    Wadsworth, Ohio, 44281

  • Study site

    Washington D.C., District of Columbia, 20422

  • Study site

    Wilmington, North Carolina, 28401

  • Study site

    Winston-Salem, North Carolina, 27103

  • Study site

    Winter Haven, Florida, 33880

Other trials in United States

Poland9 sites

  • Study site

    Biatystok, 15-430

  • Study site

    Elblag, 82-300

  • Study site

    Gmina Końskie, 26-200

  • Study site

    Katowice, 40-954

  • Study site

    Krakow, 30-510

  • Study site

    Krakow, 31-501

  • Study site

    Kutno, Lodz Province, 99-300

  • Study site

    Poznan, 60-539

  • Study site

    Poznan, 60-773

Other trials in Poland

Canada7 sites

  • Study site

    Halifax, Nova Scotia, B3K 2M5

  • Study site

    Kelowna, British Columbia, V1Y 3G8

  • Study site

    London, Ontario, N6A 5R8

  • Study site

    Mississauga, Ontario, L5M 2V8

  • Study site

    Québec, Quebec, G1V 3M7

  • Study site

    Toronto, Ontario, M9W 4L6

  • Study site

    Victoria, British Columbia, V8V 3N7

Other trials in Canada

Australia4 sites

  • Study site

    Camperdown, New South Wales, 2050

  • Study site

    Hobart, Tasmania, 7000

  • Study site

    Shenton Park, Western Australia, 6008

  • Study site

    Woodville South, South Australia, 5011

Other trials in Australia

New Zealand3 sites

  • Study site

    Grafton, Auckland, 1010

  • Study site

    Hamilton, 3240

  • Study site

    Tauranga, Bay of Plenty, 3143

Other trials in New Zealand

Switzerland2 sites

  • Study site

    Fribourg, 1708

  • Study site

    Lausanne, Vlaud, 1011

Other trials in Switzerland

About this study

Official title: A Phase 3 Randomized, Double-Blind, Multicenter, Placebo- Controlled, Combination Study to Evaluate the Efficacy and Safety of Lesinurad and Febuxostat Compared to Febuxostat Alone at Lowering Serum Uric Acid and Resolving Tophi in Subjects With Tophaceous Gout

This study will compare the serum uric acid lowering effects, clinical benefits, and safety of lesinurad in combination with febuxostat to febuxostat alone in patients with tophaceaous gout.

Read the detailed description

Febuxostat is an XO (Xanthine Oxidase) Inhibitor approved Urate Lowering Therapy (ULT) for patients with gout. Although febuxostat has been demonstrated to be superior to allopurinol in lowering serum urate (sUA) to < 6mg/dL in 3 randomized, controlled clinical trials, proportions of subjects experiencing a reduction in tophus area and gout flares were not significantly different compared to allopurinol. Although this study will allow subjects who are naïve to ULT to enroll, it is anticipated that the majority of subjects will currently be taking or have previously experienced XO Inhibitor therapy. This trial will enroll a population of subjects with high uric acid body burden, as all must demonstrate the presence of tophi.

Conditions
Tophaceous Gout
Being tested
Lesinurad, Placebo, Febuxostat

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LesinuradDrug

    Tablets, 400 mg once daily (QD)

  • LesinuradDrug

    Tablets, 200 mg QD

  • PlaceboDrug

    Tablets, Placebo QD

  • FebuxostatDrug

    80 mg

Study groups in NCT01510769
Study groupRoleWhat they receive
lesinurad 400 mg + febuxostat 80 mgExperimentalNot described
Receives: Drug: Lesinurad; Drug: Febuxostat
lesinurad 200 mg + febuxostat 80 mgExperimentalNot described
Receives: Drug: Lesinurad; Drug: Febuxostat
placebo + febuxostat 80 mgPlacebo comparatorNot described
Receives: Drug: Placebo; Drug: Febuxostat

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Subjects With a Serum Urate (sUA) Level That is < 5.0 mg/dL by Month 6

    Proportion of subjects with an sUA level that is < 5.0 mg/dL by Month 6

    Measured: 6 months, analysis after all subjects complete 12 months

Secondary outcomes (3)

  1. Complete Resolution of at Least One Target Tophus

    Proportion of subjects who experience complete resolution of at least 1 target tophus by Month 12

    Measured: 12 Months

  2. Complete or Partial Response of at Least One Tophus

    Proportion of subjects with a best tophus response on at least 1 target tophus of complete (disappearance of at least 1 target tophus) or partial (≥ 50% decrease in the area of at least 1 target tophus) resolution by Month 12

    Measured: 12 Months

  3. Quality of Life

    Proportion of subjects with an improvement from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) of at least 0.25 at Month 12. The HAQ-DI assesses a patient's level of functional ability with items scores ranging from 0-3 with 0 being the least disability.

    Measured: 12 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jan 2012 (estimated)
  2. Study startJan 2012
  3. Primary completionJun 2014
  4. Study completionJun 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
330 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01510769
Sponsor's protocol ID
RDEA594-304
Other IDs
2011-003768-55
Acronym
CRYSTAL
Status last verified
Apr 2016
First submitted
12 Jan 2012
Last updated
26 May 2016
Data monitoring committee
Yes

Publications

  • Topless R, Noorbaloochi S, Merriman TR, Singh JA. Change in serum urate level with urate-lowering therapy initiation associates in the immediate term with patient-reported outcomes in people with gout. Semin Arthritis Rheum. 2022 Oct;56:152057. doi: 10.1016/j.semarthrit.2022.152057. Epub 2022 Jun 29.

    PubMed 35835008

  • Dalbeth N, Jones G, Terkeltaub R, Khanna D, Fung M, Baumgartner S, Perez-Ruiz F. Efficacy and safety during extended treatment of lesinurad in combination with febuxostat in patients with tophaceous gout: CRYSTAL extension study. Arthritis Res Ther. 2019 Jan 7;21(1):8. doi: 10.1186/s13075-018-1788-4.

    PubMed 30616614

  • Dalbeth N, Jones G, Terkeltaub R, Khanna D, Kopicko J, Bhakta N, Adler S, Fung M, Storgard C, Baumgartner S, Perez-Ruiz F. Lesinurad, a Selective Uric Acid Reabsorption Inhibitor, in Combination With Febuxostat in Patients With Tophaceous Gout: Findings of a Phase III Clinical Trial. Arthritis Rheumatol. 2017 Sep;69(9):1903-1913. doi: 10.1002/art.40159. Epub 2017 Aug 4.

    PubMed 28597604

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Lesinurad and Febuxostat in people with Tophaceous Gout, run by Ardea Biosciences, Inc. at 124 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 May 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 124 sites in United States, Poland, Canada, Australia, New Zealand and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Subjects With a Serum Urate (sUA) Level That is < 5.0 mg/dL by Month 6 (time frame: 6 months, analysis after all subjects complete 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01510769, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 May 2016.

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