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

NCT ID: NCT01510769

Last Updated: 2016-05-26

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

330 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-01-31

Study Completion Date

2014-06-30

Brief Summary

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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.

Detailed Description

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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

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Tophaceous Gout

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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lesinurad 400 mg + febuxostat 80 mg

Group Type EXPERIMENTAL

Lesinurad

Intervention Type DRUG

Tablets, 400 mg once daily (QD)

Febuxostat

Intervention Type DRUG

80 mg

lesinurad 200 mg + febuxostat 80 mg

Group Type EXPERIMENTAL

Lesinurad

Intervention Type DRUG

Tablets, 200 mg QD

Febuxostat

Intervention Type DRUG

80 mg

placebo + febuxostat 80 mg

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Tablets, Placebo QD

Febuxostat

Intervention Type DRUG

80 mg

Interventions

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Lesinurad

Tablets, 400 mg once daily (QD)

Intervention Type DRUG

Lesinurad

Tablets, 200 mg QD

Intervention Type DRUG

Placebo

Tablets, Placebo QD

Intervention Type DRUG

Febuxostat

80 mg

Intervention Type DRUG

Eligibility Criteria

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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 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).
* 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

Exclusion Criteria

* 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.
* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ardea Biosciences, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Chris Storgard, MD

Role: STUDY_DIRECTOR

Ardea Biosciences, Inc.

Locations

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Birmingham, Alabama, United States

Site Status

Goodyear, Arizona, United States

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Peoria, Arizona, United States

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Pheonix, Arizona, United States

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Tucson, Arizona, United States

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Little Rock, Arkansas, United States

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Little Rock, Arkansas, United States

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Glendale, California, United States

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Huntington Beach, California, United States

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Irvine, California, United States

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La Jolla, California, United States

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Los Angeles, California, United States

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Rancho Cucamonga, California, United States

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San Diego, California, United States

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Denver, Colorado, United States

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Denver, Colorado, United States

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Englewood, Colorado, United States

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Trumball, Connecticut, United States

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Washington D.C., District of Columbia, United States

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Boynton Beach, Florida, United States

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Brooksville, Florida, United States

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East Brandenton, Florida, United States

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Fleming Island, Florida, United States

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Miami, Florida, United States

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Napels, Florida, United States

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Pembroke Pines, Florida, United States

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Pembroke Pines, Florida, United States

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Port Orange, Florida, United States

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Tampa, Florida, United States

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Tampa, Florida, United States

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Tampa, Florida, United States

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Vero Beach, Florida, United States

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Winter Haven, Florida, United States

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Conyers, Georgia, United States

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Johns Creek, Georgia, United States

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Newnan, Georgia, United States

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Savannah, Georgia, United States

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Honolulu, Hawaii, United States

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Meridian, Idaho, United States

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Meridian, Idaho, United States

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Chicago, Illinois, United States

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Chicago, Illinois, United States

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Gurnee, Illinois, United States

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Springfield, Illinois, United States

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Springfield, Illinois, United States

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Elizabethtown, Kentucky, United States

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Lexington, Kentucky, United States

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Frederick, Maryland, United States

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Kalamazoo, Michigan, United States

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Southfield, Michigan, United States

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Jackson, Mississippi, United States

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Olive Branch, Mississippi, United States

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Jefferson City, Missouri, United States

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St Louis, Missouri, United States

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Missoula, Montana, United States

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Mineola, New York, United States

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New York, New York, United States

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Calabash, North Carolina, United States

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Durham, North Carolina, United States

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Greenville, North Carolina, United States

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Wilmington, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Fargo, North Dakota, United States

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Columbus, Ohio, United States

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Middleburg, Ohio, United States

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Wadsworth, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Oklahoma City, Oklahoma, United States

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Belle Vernon, Pennsylvania, United States

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Clairton, Pennsylvania, United States

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Duncansville, Pennsylvania, United States

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Jenkintown, Pennsylvania, United States

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Lansdale, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Scottdale, Pennsylvania, United States

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Sellersville, Pennsylvania, United States

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Columbia, South Carolina, United States

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Greenville, South Carolina, United States

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Mt. Pleasant, South Carolina, United States

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Spartanburg, South Carolina, United States

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Jackson, Tennessee, United States

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Memphis, Tennessee, United States

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Austin, Texas, United States

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Austin, Texas, United States

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Corpus Christi, Texas, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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San Antonio, Texas, United States

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Sugar Land, Texas, United States

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Victoria, Texas, United States

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Waco, Texas, United States

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Chesapeake, Virginia, United States

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Danville, Virginia, United States

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Richmond, Virginia, United States

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Suffolk, Virginia, United States

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Virginia Beach, Virginia, United States

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Seattle, Washington, United States

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Morgantown, West Virginia, United States

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Camperdown, New South Wales, Australia

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Woodville South, South Australia, Australia

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Hobart, Tasmania, Australia

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Shenton Park, Western Australia, Australia

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Kelowna, British Columbia, Canada

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Victoria, British Columbia, Canada

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Halifax, Nova Scotia, Canada

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London, Ontario, Canada

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Mississauga, Ontario, Canada

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Toronto, Ontario, Canada

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Québec, Quebec, Canada

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Grafton, Auckland, New Zealand

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Tauranga, Bay of Plenty, New Zealand

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Hamilton, , New Zealand

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Kutno, Lodz Province, Poland

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Biatystok, , Poland

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Elblag, , Poland

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Gmina Końskie, , Poland

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Katowice, , Poland

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Krakow, , Poland

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Krakow, , Poland

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Poznan, , Poland

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Poznan, , Poland

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Lausanne, Vlaud, Switzerland

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Fribourg, , Switzerland

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Countries

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United States Australia Canada New Zealand Poland Switzerland

References

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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.

Reference Type DERIVED
PMID: 35835008 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30616614 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28597604 (View on PubMed)

Related Links

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Other Identifiers

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2011-003768-55

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RDEA594-304

Identifier Type: -

Identifier Source: org_study_id

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