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

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

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.

Study Overview

• Status: Completed
• Conditions: Gout; Moderate Renal Impairment
• Intervention / Treatment: Drug: Lansoprazole; Drug: Febuxostat IR; Drug: Colchicine; Drug: Naproxen; Drug: Febuxostat XR; Drug: Febuxostat placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 189
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States
    • Muscle Shoals, Alabama, United States
  • Arizona
    • Phoenix, Arizona, United States
  • Arkansas
    • Little Rock, Arkansas, United States
    • Little Rock, Arkansas, United States, 72223
      • Benny Green MD PA Family Practice
  • California
    • Bellflower, California, United States
    • Escondido, California, United States
    • Harbor City, California, United States
    • Huntington Park, California, United States
    • Irvine, California, United States
    • Lomita, California, United States
    • Long Beach, California, United States, 90807
      • Long Beach Center For Clinical Research
    • Long Beach, California, United States
    • Los Angeles, California, United States
    • Murrieta, California, United States
    • Murrieta, California, United States, 92563
      • Brigid Freyne MD
    • Orange, California, United States
    • Rancho Cucamonga, California, United States
    • Redondo Beach, California, United States
    • Sacramento, California, United States
    • San Jose, California, United States
    • San Ramon, California, United States
  • Florida
    • Clearwater, Florida, United States
    • Coral Gables, Florida, United States
    • Coral Springs, Florida, United States
    • Edgewater, Florida, United States
    • Edgewater, Florida, United States, 32141
      • Riverside Clinical Research
    • Hialeah, Florida, United States
    • Miami, Florida, United States
    • Miami Beach, Florida, United States
    • Miami Lakes, Florida, United States
    • Orlando, Florida, United States
    • Pembroke Pines, Florida, United States
    • Plantation, Florida, United States
    • Port Charlotte, Florida, United States
    • Saint Cloud, Florida, United States
    • Vero Beach, Florida, United States
  • Georgia
    • Atlanta, Georgia, United States
    • Dunwoody, Georgia, United States
    • East Point, Georgia, United States
    • Suwanee, Georgia, United States
  • Hawaii
    • Honolulu, Hawaii, United States
    • Honolulu, Hawaii, United States, 96814
      • East West Medical Research Institute
  • Indiana
    • Brownsburg, Indiana, United States
  • Kansas
    • Manhattan, Kansas, United States
    • Wichita, Kansas, United States
  • Kentucky
    • Elizabethtown, Kentucky, United States
    • Lexington, Kentucky, United States
    • Lexington, Kentucky, United States, 40509
      • Central Kentucy Reseach Associates
    • Paducah, Kentucky, United States
  • Louisiana
    • Mandeville, Louisiana, United States
    • Metairie, Louisiana, United States
  • Massachusetts
    • Fall River, Massachusetts, United States
  • Michigan
    • Detroit, Michigan, United States
    • Kalamazoo, Michigan, United States
  • Missouri
    • Hazelwood, Missouri, United States
    • Washington, Missouri, United States
  • Nevada
    • Las Vegas, Nevada, United States
  • New Mexico
    • Albuquerque, New Mexico, United States
  • North Carolina
    • Columbiana, North Carolina, United States
    • Greensboro, North Carolina, United States
    • Salisbury, North Carolina, United States
    • Wilmington, North Carolina, United States
  • North Dakota
    • Fargo, North Dakota, United States
  • Ohio
    • Franklin, Ohio, United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
    • Oklahoma City, Oklahoma, United States, 73103
      • COR Clinical Research LLC
  • Oregon
    • Portland, Oregon, United States
  • South Carolina
    • Columbia, South Carolina, United States
    • Greer, South Carolina, United States
    • Indian Land, South Carolina, United States
  • Tennessee
    • Clarksville, Tennessee, United States
    • Knoxville, Tennessee, United States
    • Memphis, Tennessee, United States
    • Memphis, Tennessee, United States, 38119
      • Remesh C Gupta MD
  • Texas
    • Austin, Texas, United States
    • Bellaire, Texas, United States
    • Corpus Christi, Texas, United States
    • Corpus Christi, Texas, United States, 78413
      • 3rd Coast Research Associates
    • Nassau Bay, Texas, United States
    • Plano, Texas, United States
    • San Antonio, Texas, United States
    • San Antonio, Texas, United States, 78215
      • Sun Research Institute
    • San Antonio, Texas, United States, 78224
      • Briggs Clinical Research LLC
  • Utah
    • Bountiful, Utah, United States
  • Virginia
    • Newport News, Virginia, United States
    • Norfolk, Virginia, United States
    • Richmond, Virginia, United States
    • Virginia Beach, Virginia, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Febuxostat IR 40 mg; 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.	Drug: Lansoprazole; Lansoprazole capsules; Drug: Febuxostat IR; Febuxostat IR over-encapsulated tablets; Other Names: Uloric; Drug: Colchicine; Colchicine tablets; Drug: Naproxen; Naproxen tablets
Active Comparator: Febuxostat IR 80 mg; 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.	Drug: Lansoprazole; Lansoprazole capsules; Drug: Febuxostat IR; Febuxostat IR over-encapsulated tablets; Other Names: Uloric; Drug: Colchicine; Colchicine tablets; Drug: Naproxen; Naproxen tablets
Experimental: Febuxostat XR 40 mg; 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.	Drug: Lansoprazole; Lansoprazole capsules; Drug: Colchicine; Colchicine tablets; Drug: Naproxen; Naproxen tablets; Drug: Febuxostat XR; Febuxostat over-encapsulated capsules
Experimental: Febuxostat XR 80 mg; 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.	Drug: Lansoprazole; Lansoprazole capsules; Drug: Colchicine; Colchicine tablets; Drug: Naproxen; Naproxen tablets; Drug: Febuxostat XR; Febuxostat over-encapsulated capsules
Placebo Comparator: Placebo; 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.	Drug: Lansoprazole; Lansoprazole capsules; Drug: Colchicine; Colchicine tablets; Drug: Naproxen; Naproxen tablets; Drug: Febuxostat placebo; Febuxostat IR and XR placebo-matching capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants With Serum Urate <5.0 mg/dL at Month 3	Month 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline to Month 3
Percentage of Participants With Serum Urate <6.0 mg/dL at Month 3		Month 3

Collaborators and Investigators

• Sponsor: Takeda

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: April 29, 2014
• First Submitted That Met QC Criteria: April 29, 2014
• First Posted (Estimate): May 1, 2014

Study Record Updates

• Last Update Posted (Estimate): November 3, 2016
• Last Update Submitted That Met QC Criteria: September 15, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Drug therapy
• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Genetic Diseases, Inborn; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Metabolism, Inborn Errors; Crystal Arthropathies; Purine-Pyrimidine Metabolism, Inborn Errors; Renal Insufficiency; Gout; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Gout Suppressants; Dexlansoprazole; Lansoprazole; Colchicine; Naproxen; Febuxostat
• Other Study ID Numbers: FEB-XR_201; U1111-1152-3942 (Other Identifier: World Health Organization)