Efficacy and Safety of Extended Release and Immediate Release Febuxostat in Participants With Gout

NCT ID: NCT02139046

Last Updated: 2016-11-03

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1790 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-04-30

Study Completion Date

2015-11-30

Brief Summary

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The purpose of this study is to evaluate the efficacy and safety of febuxostat 40 mg extended release (XR) and 80 mg XR in comparison with febuxostat 40 mg immediate release (IR) and 80 mg IR, respectively, in participants with gout.

Detailed Description

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The drug being tested in this study is called febuxostat. Febuxostat is being tested to decrease and maintain serum urate in people who have gout. This study will look at serum urate levels in people who take febuxostat extended release (XR) capsules compared to febuxostat immediate release (IR) capsules and placebo.

The study will enroll approximately 1750 patients. Participants will be randomly assigned (by chance) to one of the five treatment groups-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):

* Febuxostat 40 mg XR
* Febuxostat 80 mg XR
* Febuxostat 40 mg IR
* Febuxostat 80 mg IR
* Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient.

All participants will be asked to take one capsule at the same time each day throughout the study, and will be asked to call an interactive voice response system any time they are having a gout flare up. In addition to study medication, participants will also take 0.6 mg of colchicine every day or every other day, or naproxen 250 mg twice a day and lansoprazole 15 mg once a day to prevent gout flare ups.

This multi-centre trial will be conducted in the United States. The overall time to participate in this study is up to approximately 4 months and participants will make up to 7 visits to the clinic.

Conditions

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Gout

Keywords

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Drug therapy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Febuxostat IR 40 mg

Febuxostat Immediate Release (IR) 40 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day (for participants with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min) or every other day (if eGFR ≥ 15 - ≤ 59 mL/min), or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.

Group Type ACTIVE_COMPARATOR

Febuxostat IR

Intervention Type DRUG

Febuxostat IR over-encapsulated tablets

Colchicine

Intervention Type DRUG

Colchicine tablets

Naproxen

Intervention Type DRUG

Naproxen tablets

Lansoprazole

Intervention Type DRUG

Lansoprazole capsules

Febuxostat IR 80 mg

Febuxostat IR 80 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.

Group Type ACTIVE_COMPARATOR

Febuxostat IR

Intervention Type DRUG

Febuxostat IR over-encapsulated tablets

Colchicine

Intervention Type DRUG

Colchicine tablets

Naproxen

Intervention Type DRUG

Naproxen tablets

Lansoprazole

Intervention Type DRUG

Lansoprazole capsules

Febuxostat XR 40 mg

Febuxostat Extended Release (XR) 40 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.

Group Type EXPERIMENTAL

Febuxostat XR

Intervention Type DRUG

Febuxostat XR over-encapsulated capsules

Colchicine

Intervention Type DRUG

Colchicine tablets

Naproxen

Intervention Type DRUG

Naproxen tablets

Lansoprazole

Intervention Type DRUG

Lansoprazole capsules

Febuxostat XR 80 mg

Febuxostat XR 80 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.

Group Type EXPERIMENTAL

Febuxostat XR

Intervention Type DRUG

Febuxostat XR over-encapsulated capsules

Colchicine

Intervention Type DRUG

Colchicine tablets

Naproxen

Intervention Type DRUG

Naproxen tablets

Lansoprazole

Intervention Type DRUG

Lansoprazole capsules

Placebo

Febuxostat placebo-matching capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.

Group Type PLACEBO_COMPARATOR

Febuxostat placebo

Intervention Type DRUG

Febuxostat placebo-matching capsules

Colchicine

Intervention Type DRUG

Colchicine tablets

Naproxen

Intervention Type DRUG

Naproxen tablets

Lansoprazole

Intervention Type DRUG

Lansoprazole capsules

Interventions

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Febuxostat IR

Febuxostat IR over-encapsulated tablets

Intervention Type DRUG

Febuxostat XR

Febuxostat XR over-encapsulated capsules

Intervention Type DRUG

Febuxostat placebo

Febuxostat placebo-matching capsules

Intervention Type DRUG

Colchicine

Colchicine tablets

Intervention Type DRUG

Naproxen

Naproxen tablets

Intervention Type DRUG

Lansoprazole

Lansoprazole capsules

Intervention Type DRUG

Other Intervention Names

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Uloric Uloric

Eligibility Criteria

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Inclusion Criteria

1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
2. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedure.
3. Has a history or presence of gout defined as having one or more of the American Rheumatism Association (ARA) criteria for the diagnosis of gout:

1. A tophus proven to contain urate crystals by chemical or polarized light microscopic means, AND/OR;
2. Characteristic urate crystals in the joint fluid, AND/OR;
3. History of at least 6 of the following clinical, laboratory, and x-ray phenomena:

i. more than one attack of acute arthritis, ii. maximum inflammation developed within 1 day, iii. monoarticular arthritis, iv. redness observed over joints, v. first metatarsophalangeal joint painful or swollen, vi. unilateral first metatarsophalangeal joint attack, vii. unilateral tarsal joint attack, viii. tophus (proven or suspected), ix. Hyperuricemia, x. asymmetric swelling within a joint on x-ray, xi. subcortical cysts without erosions on x-ray; xii. joint fluid culture negative for organisms during attack.
4. Is male or female at least 18 years of age, inclusive.
5. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study.
6. Have a serum urate (sUA) level ≥8.0 mg/dL at the Day -4 Visit or at the retest visit.
7. Has an estimated Glomerular Filtration Rate (eGRF) ≥15 mL/min using the Modification of Diet in Renal Disease (MDRD) formula at the Screening visit (Day -21 for participants on urate lowering therapy (ULT) and Day -4 for participants not on ULT) or at the retest visit.
8. Has at least one gout flare within 12 months prior to Screening visit.

Exclusion Criteria

1. Has received any investigational compound within 30 days prior to Screening.
2. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
3. Is breastfeeding or pregnant.
4. Has secondary hyperuricemia (eg, due to myeloproliferative disorder).
5. Has a history of xanthinuria.
6. Has received ULT (ie, allopurinol, probenecid, etc.) within 20 days prior to Day 1/Randomization Visit.
7. Has a known hypersensitivity to febuxostat or any components of their formulation; has a known hypersensitivity to naproxen, any other nonsteroidal anti-inflammatory drug (NSAID), aspirin, lansoprazole, colchicine or any components in their formulation.
8. Has active peptic ulcer disease.
9. Has a history of cancer (other than basal cell carcinoma of the skin) within 5 years prior to the Screening Visit.
10. Has alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values \>2 x the upper limit of normal (ULN).
11. Has rheumatoid arthritis which requires treatment.
12. Has a significant medical condition and/or conditions that would interfere with the treatment, safety, or compliance with the protocol.
13. Has experienced a myocardial infarction (MI), stroke, hospitalized unstable angina, cardiac or cerebrovascular revascularization procedure or hospitalized transient ischemic attack (TIA) - except in participants who have severe renal impairment.
14. Participants with severe renal impairment had a MI or stroke within 90 days prior to initial screening visit or has a MI or stroke during the screening period prior to Day 1/Randomization Visit.
15. Participant consumes \>14 alcoholic beverages/week. Has a history of alcoholism or illicit drug abuse within 5 years.
16. Has participated in another investigational study within the 30 days prior to the Screening Visit.
17. Has a known history of infection with hepatitis B, hepatitis C, or human immunodeficiency virus.
18. Is required to take excluded medications.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Takeda

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director Clinical Science

Role: STUDY_DIRECTOR

Takeda

Locations

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San Ramon, California, United States

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Santa Clarita, California, United States

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Tustin, California, United States

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Upland, California, United States

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Binghamton, Alabama, United States

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Birmingham, Alabama, United States

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Huntsville, Alabama, United States

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Gilbert, Arizona, United States

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Glendale, Arizona, United States

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Phoenix, Arizona, United States

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Tucson, Arizona, United States

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Fayetteville, Arkansas, United States

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Little Rock, Arkansas, United States

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Searcy, Arkansas, United States

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Bellflower, California, United States

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Carmichael, California, United States

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Costa Mesa, California, United States

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Covina, California, United States

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El Cajon, California, United States

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Encinitas, California, United States

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Encino, California, United States

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Escondido, California, United States

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Gold River, California, United States

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Irvine, California, United States

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Lancaster, California, United States

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Lomita, California, United States

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Long Beach, California, United States

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Los Angeles, California, United States

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Monterey Park, California, United States

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Murrieta, California, United States

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North Hollywood, California, United States

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Norwalk, California, United States

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Paramount, California, United States

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Rancho Cucamonga, California, United States

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Riverside, California, United States

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Roseville, California, United States

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Sacramento, California, United States

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San Diego, California, United States

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San Jose, California, United States

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Arvada, Colorado, United States

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Westminster, Colorado, United States

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Wheat Ridge, Colorado, United States

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Lewes, Delaware, United States

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Boynton Beach, Florida, United States

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Brandon, Florida, United States

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Clearwater, Florida, United States

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Coral Gables, Florida, United States

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Coral Springs, Florida, United States

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Daytona Beach, Florida, United States

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DeLand, Florida, United States

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Doral, Florida, United States

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Edgewater, Florida, United States

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Fort Lauderdale, Florida, United States

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Fort Meyers, Florida, United States

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Fort Myers, Florida, United States

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Hialeah, Florida, United States

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Hollywood, Florida, United States

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Homestead, Florida, United States

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Jacksonville, Florida, United States

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Jupiter, Florida, United States

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Miami, Florida, United States

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North Bay Village, Florida, United States

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Orlando, Florida, United States

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Pembroke Pines, Florida, United States

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Pinellas Park, Florida, United States

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Plant City, Florida, United States

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Port Charlotte, Florida, United States

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Sanford, Florida, United States

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Tallahassee, Florida, United States

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Tampa, Florida, United States

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Winter Haven, Florida, United States

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Atlanta, Georgia, United States

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Augusta, Georgia, United States

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Columbus, Georgia, United States

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Dunwoody, Georgia, United States

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Fort Valley, Georgia, United States

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Marietta, Georgia, United States

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Newnan, Georgia, United States

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Norcross, Georgia, United States

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Roswell, Georgia, United States

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Savannah, Georgia, United States

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Suwanee, Georgia, United States

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Honolulu, Hawaii, United States

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Meridian, Idaho, United States

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Gurnee, Illinois, United States

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Avon, Indiana, United States

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Brownsburg, Indiana, United States

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Newburgh, Indiana, United States

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Augusta, Kansas, United States

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Wichita, Kansas, United States

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Crestview Hills, Kentucky, United States

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Elizabethtown, Kentucky, United States

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Lexington, Kentucky, United States

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Louisville, Kentucky, United States

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Owensboro, Kentucky, United States

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Paducah, Kentucky, United States

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Baker, Louisiana, United States

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Lafayette, Louisiana, United States

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Mandeville, Louisiana, United States

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Metairie, Louisiana, United States

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Biddeford, Maine, United States

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Columbia, Maryland, United States

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Frederick, Maryland, United States

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Oxon Hill, Maryland, United States

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Brockton, Massachusetts, United States

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Fall River, Massachusetts, United States

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Buckley, Michigan, United States

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Detroit, Michigan, United States

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Kalamazoo, Michigan, United States

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Biloxi, Mississippi, United States

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Olive Branch, Mississippi, United States

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Hazelwood, Missouri, United States

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Washington, Missouri, United States

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Billings, Montana, United States

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Missoula, Montana, United States

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Bellevue, Nebraska, United States

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Lincoln, Nebraska, United States

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Omaha, Nebraska, United States

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Las Vegas, Nevada, United States

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Reno, Nevada, United States

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Lodi, New Jersey, United States

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Teaneck, New Jersey, United States

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Albuquerque, New Mexico, United States

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Brooklyn, New York, United States

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Endwell, New York, United States

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Manhasset, New York, United States

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Columbiana, North Carolina, United States

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Greensboro, North Carolina, United States

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Greenville, North Carolina, United States

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Hickory, North Carolina, United States

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Raleigh, North Carolina, United States

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Salisbury, North Carolina, United States

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Wilmington, North Carolina, United States

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Fargo, North Dakota, United States

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Chagrin Falls, Ohio, United States

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Cincinnati, Ohio, United States

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Cleveland, Ohio, United States

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Lyndhurst, Ohio, United States

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Mentor, Ohio, United States

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Perrysburg, Ohio, United States

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Toledo, Ohio, United States

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Wadsworth, Ohio, United States

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Willoughby Hills, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Tulsa, Oklahoma, United States

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Portland, Oregon, United States

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Altoona, Pennsylvania, United States

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Duncansville, Pennsylvania, United States

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Harleysville, Pennsylvania, United States

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Lansdale, Pennsylvania, United States

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McMurray, Pennsylvania, United States

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Media, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Uniontown, Pennsylvania, United States

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Wyomissing, Pennsylvania, United States

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Charleston, South Carolina, United States

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Columbia, South Carolina, United States

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Greer, South Carolina, United States

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Mt. Pleasant, South Carolina, United States

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Rapid City, South Dakota, United States

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Bristol, Tennessee, United States

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Collierville, Tennessee, United States

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Jackson, Tennessee, United States

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Memphis, Tennessee, United States

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Arlington, Texas, United States

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Austin, Texas, United States

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Bellaire, Texas, United States

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Carrollton, Texas, United States

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Corpus Christi, Texas, United States

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Houston, Texas, United States

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Humble, Texas, United States

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Plano, 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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The Woodlands, Texas, United States

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Bountiful, Utah, United States

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Salt Lake City, Utah, United States

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West Jordan, Utah, United States

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Alexandria, Virginia, United States

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Arlington, Virginia, United States

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Burke, Virginia, United States

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Charlottesville, Virginia, United States

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Danville, Virginia, United States

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Midlothian, Virginia, United States

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Newport News, Virginia, United States

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Norfolk, Virginia, United States

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Richmond, Virginia, United States

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Sterling, Virginia, United States

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Spokane, Washington, United States

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Clarksburg, West Virginia, United States

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Milwaukee, Wisconsin, United States

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Countries

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United States

References

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Saag KG, Becker MA, Whelton A, Hunt B, Castillo M, Kisfalvi K, Gunawardhana L. Efficacy and Safety of Febuxostat Extended and Immediate Release in Patients With Gout and Renal Impairment: A Phase III Placebo-Controlled Study. Arthritis Rheumatol. 2019 Jan;71(1):143-153. doi: 10.1002/art.40685.

Reference Type DERIVED
PMID: 30073793 (View on PubMed)

Other Identifiers

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U1111-1152-4040

Identifier Type: OTHER

Identifier Source: secondary_id

FEB-XR_301

Identifier Type: -

Identifier Source: org_study_id