Clinical trial NCT02139046: Efficacy and Safety of Extended Release and Immediate Release Febuxostat in Participants With Gout
Official title: A Phase 3, Randomized, Double Blind, Multicenter, Placebo Controlled Study to Evaluate the Efficacy and Safety of Febuxostat 40 mg XR, 80 mg XR, 40 mg IR and 80 mg IR in Subjects With Gout
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gout
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2014-05-15
Enrollment: 1790
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Serum Urate <5.0 mg/dL at Month 3
timeFrame: Month 3
Secondary outcomes:
measure: Percentage of Participants With at Least One Gout Flare Requiring Treatment
timeFrame: Baseline to Month 3
measure: Percentage of Participants With Serum Urate <6.0 mg/dL at Month 3
timeFrame: Month 3
Other outcomes:
Locations:
city: Binghamton
country: United States
state: Alabama
city: Birmingham
country: United States
state: Alabama
city: Huntsville
country: United States
state: Alabama
city: Gilbert
country: United States
state: Arizona
city: Glendale
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Fayetteville
country: United States
state: Arkansas
city: Little Rock
country: United States
state: Arkansas
city: Searcy
country: United States
state: Arkansas
city: Bellflower
country: United States
state: California
city: Carmichael
country: United States
state: California
city: Costa Mesa
country: United States
state: California
city: Covina
country: United States
state: California
city: El Cajon
country: United States
state: California
city: Encinitas
country: United States
state: California
city: Encino
country: United States
state: California
city: Escondido
country: United States
state: California
city: Gold River
country: United States
state: California
city: Irvine
country: United States
state: California
city: Lancaster
country: United States
state: California
city: Lomita
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Monterey Park
country: United States
state: California
city: Murrieta
country: United States
state: California
city: North Hollywood
country: United States
state: California
city: Norwalk
country: United States
state: California
city: Paramount
country: United States
state: California
city: Rancho Cucamonga
country: United States
state: California
city: Riverside
country: United States
state: California
city: Roseville
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Jose
country: United States
state: California
city: San Ramon
country: United States
state: California
city: Santa Clarita
country: United States
state: California
city: Tustin
country: United States
state: California
city: Upland
country: United States
state: California
city: Arvada
country: United States
state: Colorado
city: Westminster
country: United States
state: Colorado
city: Wheat Ridge
country: United States
state: Colorado
city: Lewes
country: United States
state: Delaware
city: Boynton Beach
country: United States
state: Florida
city: Brandon
country: United States
state: Florida
city: Clearwater
country: United States
state: Florida
city: Coral Gables
country: United States
state: Florida
city: Coral Springs
country: United States
state: Florida
city: Daytona Beach
country: United States
state: Florida
city: Deland
country: United States
state: Florida
city: Doral
country: United States
state: Florida
city: Edgewater
country: United States
state: Florida
city: Fort Lauderdale
country: United States
state: Florida
city: Fort Meyers
country: United States
state: Florida
city: Fort Myers
country: United States
state: Florida
city: Hialeah
country: United States
state: Florida
city: Hollywood
country: United States
state: Florida
city: Homestead
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Jupiter
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: North Bay Village
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Pembroke Pines
country: United States
state: Florida
city: Pinellas Park
country: United States
state: Florida
city: Plant City
country: United States
state: Florida
city: Port Charlotte
country: United States
state: Florida
city: Sanford
country: United States
state: Florida
city: Tallahassee
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Winter Haven
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Augusta
country: United States
state: Georgia
city: Columbus
country: United States
state: Georgia
city: Dunwoody
country: United States
state: Georgia
city: Fort Valley
country: United States
state: Georgia
city: Marietta
country: United States
state: Georgia
city: Newnan
country: United States
state: Georgia
city: Norcross
country: United States
state: Georgia
city: Roswell
country: United States
state: Georgia
city: Savannah
country: United States
state: Georgia
city: Suwanee
country: United States
state: Georgia
city: Honolulu
country: United States
state: Hawaii
city: Meridian
country: United States
state: Idaho
city: Gurnee
country: United States
state: Illinois
city: Avon
country: United States
state: Indiana
city: Brownsburg
country: United States
state: Indiana
city: Newburgh
country: United States
state: Indiana
city: Augusta
country: United States
state: Kansas
city: Wichita
country: United States
state: Kansas
city: Crestview Hills
country: United States
state: Kentucky
city: Elizabethtown
country: United States
state: Kentucky
city: Lexington
country: United States
state: Kentucky
city: Louisville
country: United States
state: Kentucky
city: Owensboro
country: United States
state: Kentucky
city: Paducah
country: United States
state: Kentucky
city: Baker
country: United States
state: Louisiana
city: Lafayette
country: United States
state: Louisiana
city: Mandeville
country: United States
state: Louisiana
city: Metairie
country: United States
state: Louisiana
city: Biddeford
country: United States
state: Maine
city: Columbia
country: United States
state: Maryland
city: Frederick
country: United States
state: Maryland
city: Oxon Hill
country: United States
state: Maryland
city: Brockton
country: United States
state: Massachusetts
city: Fall River
country: United States
state: Massachusetts
city: Buckley
country: United States
state: Michigan
city: Detroit
country: United States
state: Michigan
city: Kalamazoo
country: United States
state: Michigan
city: Biloxi
country: United States
state: Mississippi
city: Olive Branch
country: United States
state: Mississippi
city: Hazelwood
country: United States
state: Missouri
city: Washington
country: United States
state: Missouri
city: Billings
country: United States
state: Montana
city: Missoula
country: United States
state: Montana
city: Bellevue
country: United States
state: Nebraska
city: Lincoln
country: United States
state: Nebraska
city: Omaha
country: United States
state: Nebraska
city: Las Vegas
country: United States
state: Nevada
city: Reno
country: United States
state: Nevada
city: Lodi
country: United States
state: New Jersey
city: Teaneck
country: United States
state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: Brooklyn
country: United States
state: New York
city: Endwell
country: United States
state: New York
city: Manhasset
country: United States
state: New York
city: Columbiana
country: United States
state: North Carolina
city: Greensboro
country: United States
state: North Carolina
city: Greenville
country: United States
state: North Carolina
city: Hickory
country: United States
state: North Carolina
city: Raleigh
country: United States
state: North Carolina
city: Salisbury
country: United States
state: North Carolina
city: Wilmington
country: United States
state: North Carolina
city: Fargo
country: United States
state: North Dakota
city: Chagrin Falls
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Lyndhurst
country: United States
state: Ohio
city: Mentor
country: United States
state: Ohio
city: Perrysburg
country: United States
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Wadsworth
country: United States
state: Ohio
city: Willoughby Hills
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Tulsa
country: United States
state: Oklahoma
city: Portland
country: United States
state: Oregon
city: Altoona
country: United States
state: Pennsylvania
city: Duncansville
country: United States
state: Pennsylvania
city: Harleysville
country: United States
state: Pennsylvania
city: Lansdale
country: United States
state: Pennsylvania
city: McMurray
country: United States
state: Pennsylvania
city: Media
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Uniontown
country: United States
state: Pennsylvania
city: Wyomissing
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Columbia
country: United States
state: South Carolina
city: Greer
country: United States
state: South Carolina
city: Mount Pleasant
country: United States
state: South Carolina
city: Rapid City
country: United States
state: South Dakota
city: Bristol
country: United States
state: Tennessee
city: Collierville
country: United States
state: Tennessee
city: Jackson
country: United States
state: Tennessee
city: Memphis
country: United States
state: Tennessee
city: Arlington
country: United States
state: Texas
city: Austin
country: United States
state: Texas
city: Bellaire
country: United States
state: Texas
city: Carrollton
country: United States
state: Texas
city: Corpus Christi
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Humble
country: United States
state: Texas
city: Plano
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Sugar Land
country: United States
state: Texas
city: The Woodlands
country: United States
state: Texas
city: Bountiful
country: United States
state: Utah
city: Salt Lake City City
country: United States
state: Utah
city: West Jordan
country: United States
state: Utah
city: Alexandria
country: United States
state: Virginia
city: Arlington
country: United States
state: Virginia
city: Burke
country: United States
state: Virginia
city: Charlottesville
country: United States
state: Virginia
city: Danville
country: United States
state: Virginia
city: Midlothian
country: United States
state: Virginia
city: Newport News
country: United States
state: Virginia
city: Norfolk
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Sterling
country: United States
state: Virginia
city: Spokane
country: United States
state: Washington
city: Clarksburg
country: United States
state: West Virginia
city: Milwaukee
country: United States
state: Wisconsin
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
citation: 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.