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

Primary Purpose

Gout, Moderate Renal Impairment

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Febuxostat IR
Febuxostat XR
Febuxostat placebo
Colchicine
Naproxen
Lansoprazole
Sponsored by
Takeda
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gout focused on measuring Drug therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Benny Green MD PA Family Practice
  • Long Beach Center for Clinical Research
  • Brigid Freyne MD
  • Riverside Clinical Research
  • East West Medical Research Institute
  • Central Kentucy Reseach Associates
  • COR Clinical Research LLC
  • Remesh C Gupta MD
  • 3rd Coast Research Associates
  • Sun Research Institute
  • Briggs Clinical Research LLC

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Active Comparator

Active Comparator

Experimental

Experimental

Placebo Comparator

Arm Label

Febuxostat IR 40 mg

Febuxostat IR 80 mg

Febuxostat XR 40 mg

Febuxostat XR 80 mg

Placebo

Arm Description

Febuxostat Immediate Release (IR) 40 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.

Febuxostat IR 80 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.

Febuxostat Extended Release (XR) 40 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.

Febuxostat XR 80 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.

Febuxostat placebo-matching capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.

Outcomes

Primary Outcome Measures

Percentage of Participants With Serum Urate <5.0 mg/dL at Month 3

Secondary Outcome Measures

Percentage of Participants With at Least One Gout Flare Requiring Treatment
A participant was considered to have a gout flare if the following criteria were met: Participant-reported acute particular pain typical of a gout attack that was deemed by participant and/or investigator to require treatment and was treated with colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs) or steroids, Participant experienced at least 3 or more of: 1) Joint swelling, 2) Redness, 3) Tenderness, 4) Pain, Participant experienced at least one or more of: 1) Rapid onset of pain, 2) Decreased range of motion, 3) Joint warmth, 4) Other symptoms similar to a prior gout flare.
Percentage of Participants With Serum Urate <6.0 mg/dL at Month 3

Full Information

First Posted
April 29, 2014
Last Updated
September 15, 2016
Sponsor
Takeda
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1. Study Identification

Unique Protocol Identification Number
NCT02128490
Brief Title
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

2. Study Status

Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
May 2014 (undefined)
Primary Completion Date
September 2015 (Actual)
Study Completion Date
October 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gout, Moderate Renal Impairment
Keywords
Drug therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
189 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Febuxostat IR 40 mg
Arm Type
Active Comparator
Arm Description
Febuxostat Immediate Release (IR) 40 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
Arm Title
Febuxostat IR 80 mg
Arm Type
Active Comparator
Arm Description
Febuxostat IR 80 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
Arm Title
Febuxostat XR 40 mg
Arm Type
Experimental
Arm Description
Febuxostat Extended Release (XR) 40 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
Arm Title
Febuxostat XR 80 mg
Arm Type
Experimental
Arm Description
Febuxostat XR 80 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Febuxostat placebo-matching capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
Intervention Type
Drug
Intervention Name(s)
Febuxostat IR
Other Intervention Name(s)
Uloric
Intervention Description
Febuxostat IR over-encapsulated tablets
Intervention Type
Drug
Intervention Name(s)
Febuxostat XR
Intervention Description
Febuxostat over-encapsulated capsules
Intervention Type
Drug
Intervention Name(s)
Febuxostat placebo
Intervention Description
Febuxostat IR and XR placebo-matching capsules
Intervention Type
Drug
Intervention Name(s)
Colchicine
Intervention Description
Colchicine tablets
Intervention Type
Drug
Intervention Name(s)
Naproxen
Intervention Description
Naproxen tablets
Intervention Type
Drug
Intervention Name(s)
Lansoprazole
Intervention Description
Lansoprazole capsules
Primary Outcome Measure Information:
Title
Percentage of Participants With Serum Urate <5.0 mg/dL at Month 3
Time Frame
Month 3
Secondary Outcome Measure Information:
Title
Percentage of Participants With at Least One Gout Flare Requiring Treatment
Description
A participant was considered to have a gout flare if the following criteria were met: Participant-reported acute particular pain typical of a gout attack that was deemed by participant and/or investigator to require treatment and was treated with colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs) or steroids, Participant experienced at least 3 or more of: 1) Joint swelling, 2) Redness, 3) Tenderness, 4) Pain, Participant experienced at least one or more of: 1) Rapid onset of pain, 2) Decreased range of motion, 3) Joint warmth, 4) Other symptoms similar to a prior gout flare.
Time Frame
Baseline to Month 3
Title
Percentage of Participants With Serum Urate <6.0 mg/dL at Month 3
Time Frame
Month 3

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements. 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. 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: A tophus proven to contain urate crystals by chemical or polarized light microscopic means, AND/OR; Characteristic urate crystals in the joint fluid, AND/OR; 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. Is male or female at least 18 years of age, inclusive. 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. Have a serum urate (sUA) level ≥8.0 mg/dL at the Day -4 Visit or at the retest visit. 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. Has at least one gout flare within 12 months prior to Screening visit. Exclusion Criteria: Has received any investigational compound within 30 days prior to Screening. 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. Is breastfeeding or pregnant. Has secondary hyperuricemia (eg, due to myeloproliferative disorder). Has a history of xanthinuria. Has received ULT (ie, allopurinol, probenecid, etc.) within 20 days prior to Day 1/Randomization Visit. 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. Has active peptic ulcer disease. Has a history of cancer (other than basal cell carcinoma of the skin) within 5 years prior to the Screening Visit. Has alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values >2 x the upper limit of normal (ULN). Has rheumatoid arthritis which requires treatment. Has a significant medical condition and/or conditions that would interfere with the treatment, safety, or compliance with the protocol. Has experienced either a myocardial infarction (MI), stroke, hospitalized unstable angina, cardiac or cerebrovascular revascularization procedure or hospitalized transient ischemic attack (TIA). 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. Has participated in another investigational study within the 30 days prior to the Screening Visit. Has a known history of infection with hepatitis B, hepatitis C, or human immunodeficiency virus. Is required to take excluded medications.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director Clinical Science
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
City
Birmingham
State/Province
Alabama
Country
United States
City
Muscle Shoals
State/Province
Alabama
Country
United States
City
Phoenix
State/Province
Arizona
Country
United States
Facility Name
Benny Green MD PA Family Practice
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72223
Country
United States
City
Little Rock
State/Province
Arkansas
Country
United States
City
Bellflower
State/Province
California
Country
United States
City
Escondido
State/Province
California
Country
United States
City
Harbor City
State/Province
California
Country
United States
City
Huntington Park
State/Province
California
Country
United States
City
Irvine
State/Province
California
Country
United States
City
Lomita
State/Province
California
Country
United States
Facility Name
Long Beach Center for Clinical Research
City
Long Beach
State/Province
California
ZIP/Postal Code
90807
Country
United States
City
Long Beach
State/Province
California
Country
United States
City
Los Angeles
State/Province
California
Country
United States
Facility Name
Brigid Freyne MD
City
Murrieta
State/Province
California
ZIP/Postal Code
92563
Country
United States
City
Murrieta
State/Province
California
Country
United States
City
Orange
State/Province
California
Country
United States
City
Rancho Cucamonga
State/Province
California
Country
United States
City
Redondo Beach
State/Province
California
Country
United States
City
Sacramento
State/Province
California
Country
United States
City
San Jose
State/Province
California
Country
United States
City
San Ramon
State/Province
California
Country
United States
City
Clearwater
State/Province
Florida
Country
United States
City
Coral Gables
State/Province
Florida
Country
United States
City
Coral Springs
State/Province
Florida
Country
United States
Facility Name
Riverside Clinical Research
City
Edgewater
State/Province
Florida
ZIP/Postal Code
32141
Country
United States
City
Edgewater
State/Province
Florida
Country
United States
City
Hialeah
State/Province
Florida
Country
United States
City
Miami Beach
State/Province
Florida
Country
United States
City
Miami Lakes
State/Province
Florida
Country
United States
City
Miami
State/Province
Florida
Country
United States
City
Orlando
State/Province
Florida
Country
United States
City
Pembroke Pines
State/Province
Florida
Country
United States
City
Plantation
State/Province
Florida
Country
United States
City
Port Charlotte
State/Province
Florida
Country
United States
City
Saint Cloud
State/Province
Florida
Country
United States
City
Vero Beach
State/Province
Florida
Country
United States
City
Atlanta
State/Province
Georgia
Country
United States
City
Dunwoody
State/Province
Georgia
Country
United States
City
East Point
State/Province
Georgia
Country
United States
City
Suwanee
State/Province
Georgia
Country
United States
Facility Name
East West Medical Research Institute
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96814
Country
United States
City
Honolulu
State/Province
Hawaii
Country
United States
City
Brownsburg
State/Province
Indiana
Country
United States
City
Manhattan
State/Province
Kansas
Country
United States
City
Wichita
State/Province
Kansas
Country
United States
City
Elizabethtown
State/Province
Kentucky
Country
United States
Facility Name
Central Kentucy Reseach Associates
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40509
Country
United States
City
Lexington
State/Province
Kentucky
Country
United States
City
Paducah
State/Province
Kentucky
Country
United States
City
Mandeville
State/Province
Louisiana
Country
United States
City
Metairie
State/Province
Louisiana
Country
United States
City
Fall River
State/Province
Massachusetts
Country
United States
City
Detroit
State/Province
Michigan
Country
United States
City
Kalamazoo
State/Province
Michigan
Country
United States
City
Hazelwood
State/Province
Missouri
Country
United States
City
Washington
State/Province
Missouri
Country
United States
City
Las Vegas
State/Province
Nevada
Country
United States
City
Albuquerque
State/Province
New Mexico
Country
United States
City
Columbiana
State/Province
North Carolina
Country
United States
City
Greensboro
State/Province
North Carolina
Country
United States
City
Salisbury
State/Province
North Carolina
Country
United States
City
Wilmington
State/Province
North Carolina
Country
United States
City
Fargo
State/Province
North Dakota
Country
United States
City
Franklin
State/Province
Ohio
Country
United States
Facility Name
COR Clinical Research LLC
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73103
Country
United States
City
Oklahoma City
State/Province
Oklahoma
Country
United States
City
Portland
State/Province
Oregon
Country
United States
City
Columbia
State/Province
South Carolina
Country
United States
City
Greer
State/Province
South Carolina
Country
United States
City
Indian Land
State/Province
South Carolina
Country
United States
City
Clarksville
State/Province
Tennessee
Country
United States
City
Knoxville
State/Province
Tennessee
Country
United States
Facility Name
Remesh C Gupta MD
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38119
Country
United States
City
Memphis
State/Province
Tennessee
Country
United States
City
Austin
State/Province
Texas
Country
United States
City
Bellaire
State/Province
Texas
Country
United States
Facility Name
3rd Coast Research Associates
City
Corpus Christi
State/Province
Texas
ZIP/Postal Code
78413
Country
United States
City
Corpus Christi
State/Province
Texas
Country
United States
City
Nassau Bay
State/Province
Texas
Country
United States
City
Plano
State/Province
Texas
Country
United States
Facility Name
Sun Research Institute
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Facility Name
Briggs Clinical Research LLC
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78224
Country
United States
City
San Antonio
State/Province
Texas
Country
United States
City
Bountiful
State/Province
Utah
Country
United States
City
Newport News
State/Province
Virginia
Country
United States
City
Norfolk
State/Province
Virginia
Country
United States
City
Richmond
State/Province
Virginia
Country
United States
City
Virginia Beach
State/Province
Virginia
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
29848361
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.
Results Reference
derived

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

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