Clinical trial NCT02128490: Efficacy and Safety of Extended Release and Immediate Release Febuxostat in Participants With Gout and Moderate Renal Impairment
Official title: A Phase 2, 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 and Moderate Renal Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gout
Moderate Renal Impairment
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2014-05-01
Enrollment: 189
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 gout participants with moderate renal impairment.

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 with moderate renal impairment. 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 200 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the five treatment groups-which will remain undisclosed to the participant 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 other day or naproxen 250 mg twice a day with lansoprazole 15 mg once a day to prevent gout flare ups.

This multi-center 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) \[Modification of Diet in Renal Disease (MDRD)\] ≥30 mL/min and \<60 mL/min at 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 dependant 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 either a myocardial infarction (MI), stroke, hospitalized unstable angina, cardiac or cerebrovascular revascularization procedure or hospitalized transient ischemic attack (TIA).
14. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 5 years prior to the Screening visit. Participant consumes \>14 alcoholic beverages/week.
15. Has participated in another investigational study within the 30 days prior to the Screening Visit.
16. Has a known history of infection with hepatitis B, hepatitis C, or human immunodeficiency virus.
17. 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: Birmingham
country: United States
state: Alabama
city: Muscle Shoals
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Little Rock
country: United States
facility: Benny Green MD PA Family Practice
state: Arkansas
city: Little Rock
country: United States
state: Arkansas
city: Bellflower
country: United States
state: California
city: Escondido
country: United States
state: California
city: Harbor City
country: United States
state: California
city: Huntington Park
country: United States
state: California
city: Irvine
country: United States
state: California
city: Lomita
country: United States
state: California
city: Long Beach
country: United States
facility: Long Beach Center for Clinical Research
state: California
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Murrieta
country: United States
facility: Brigid Freyne MD
state: California
city: Murrieta
country: United States
state: California
city: Orange
country: United States
state: California
city: Rancho Cucamonga
country: United States
state: California
city: Redondo Beach
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Jose
country: United States
state: California
city: San Ramon
country: United States
state: California
city: Clearwater
country: United States
state: Florida
city: Coral Gables
country: United States
state: Florida
city: Coral Springs
country: United States
state: Florida
city: Edgewater
country: United States
facility: Riverside Clinical Research
state: Florida
city: Edgewater
country: United States
state: Florida
city: Hialeah
country: United States
state: Florida
city: Miami Beach
country: United States
state: Florida
city: Miami Lakes
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Pembroke Pines
country: United States
state: Florida
city: Plantation
country: United States
state: Florida
city: Port Charlotte
country: United States
state: Florida
city: Saint Cloud
country: United States
state: Florida
city: Vero Beach
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Dunwoody
country: United States
state: Georgia
city: East Point
country: United States
state: Georgia
city: Suwanee
country: United States
state: Georgia
city: Honolulu
country: United States
facility: East West Medical Research Institute
state: Hawaii
city: Honolulu
country: United States
state: Hawaii
city: Brownsburg
country: United States
state: Indiana
city: Manhattan
country: United States
state: Kansas
city: Wichita
country: United States
state: Kansas
city: Elizabethtown
country: United States
state: Kentucky
city: Lexington
country: United States
facility: Central Kentucy Reseach Associates
state: Kentucky
city: Lexington
country: United States
state: Kentucky
city: Paducah
country: United States
state: Kentucky
city: Mandeville
country: United States
state: Louisiana
city: Metairie
country: United States
state: Louisiana
city: Fall River
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Kalamazoo
country: United States
state: Michigan
city: Hazelwood
country: United States
state: Missouri
city: Washington
country: United States
state: Missouri
city: Las Vegas
country: United States
state: Nevada
city: Albuquerque
country: United States
state: New Mexico
city: Columbiana
country: United States
state: North Carolina
city: Greensboro
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: Franklin
country: United States
state: Ohio
city: Oklahoma City
country: United States
facility: COR Clinical Research LLC
state: Oklahoma
city: Oklahoma City
country: United States
state: Oklahoma
city: Portland
country: United States
state: Oregon
city: Columbia
country: United States
state: South Carolina
city: Greer
country: United States
state: South Carolina
city: Indian Land
country: United States
state: South Carolina
city: Clarksville
country: United States
state: Tennessee
city: Knoxville
country: United States
state: Tennessee
city: Memphis
country: United States
facility: Remesh C Gupta MD
state: Tennessee
city: Memphis
country: United States
state: Tennessee
city: Austin
country: United States
state: Texas
city: Bellaire
country: United States
state: Texas
city: Corpus Christi
country: United States
facility: 3rd Coast Research Associates
state: Texas
city: Corpus Christi
country: United States
state: Texas
city: Nassau Bay
country: United States
state: Texas
city: Plano
country: United States
state: Texas
city: San Antonio
country: United States
facility: Sun Research Institute
state: Texas
city: San Antonio
country: United States
facility: Briggs Clinical Research LLC
state: Texas
city: San Antonio
country: United States
state: Texas
city: Bountiful
country: United States
state: Utah
city: Newport News
country: United States
state: Virginia
city: Norfolk
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Virginia Beach
country: United States
state: Virginia
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
citation: Gunawardhana L, Becker MA, Whelton A, Hunt B, Castillo M, Saag K. Efficacy and safety of febuxostat extended release and immediate release in patients with gout and moderate renal impairment: phase II placebo-controlled study. Arthritis Res Ther. 2018 May 30;20(1):99. doi: 10.1186/s13075-018-1593-0.