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

Condition(s) targeted: Gout; Moderate Renal Impairment

Intervention: Febuxostat IR (Drug); Febuxostat XR (Drug); Febuxostat placebo (Drug); Colchicine (Drug); Naproxen (Drug); Lansoprazole (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Takeda

Official(s) and/or principal investigator(s):
Medical Director Clinical Science, Study Director, Affiliation: Takeda

Overall contact:
Takeda Study Registration Call Center, Phone: 800-778-2860, Email: medicalinformation@tpna.com

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.

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 design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Percentage of Participants with Serum Urate <5.0 mg/dL at Month 3

Secondary outcome:

Percentage of Participants with at Least One Gout Flare Requiring Treatment

Percentage of Participants with Serum Urate <6.0 mg/dL at month 3

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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 that 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 know 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 know history of infection with hepatitis B, hepatitis C, or human immunodeficiency virus. 17. Is required to take excluded medications.

Takeda Study Registration Call Center, Phone: 800-778-2860, Email: medicalinformation@tpna.com

Birmingham, Alabama, United States; Recruiting

Muscle Shoals, Alabama, United States; Completed

Phoenix, Arizona, United States; Recruiting

Little Rock, Arkansas, United States; Recruiting

Benny Green MD PA Family Practice, Little Rock, Arkansas 72223, United States; Recruiting

Bellflower, California, United States; Active, not recruiting

Harbor City, California, United States; Recruiting

Huntington Park, California, United States; Not yet recruiting

Irvine, California, United States; Recruiting

Lomita, California, United States; Recruiting

Long Beach, California, United States; Recruiting

Long Beach Center for Clinical Research, Long Beach, California 90807, United States; Recruiting

Los Angeles, California, United States; Recruiting

Murrieta, California, United States; Completed

Brigid Freyne MD, Murrieta, California 92563, United States; Recruiting

Orange, California, United States; Active, not recruiting

Rancho Cucamonga, California, United States; Active, not recruiting

Redondo Beach, California, United States; Active, not recruiting

Sacramento, California, United States; Recruiting

San Jose, California, United States; Recruiting

San Ramon, California, United States; Recruiting

Clearwater, Florida, United States; Recruiting

Coral Gables, Florida, United States; Recruiting

Coral Springs, Florida, United States; Recruiting

Edgewater, Florida, United States; Recruiting

Riverside Clinical Research, Edgewater, Florida 32141, United States; Recruiting

Hialeah, Florida, United States; Recruiting

Miami Beach, Florida, United States; Recruiting

Miami Lakes, Florida, United States; Recruiting

Miami, Florida, United States; Recruiting

Orlando, Florida, United States; Recruiting

Pembroke Pines, Florida, United States; Recruiting

Plantation, Florida, United States; Recruiting

Port Charlotte, Florida, United States; Recruiting

Saint Cloud, Florida, United States; Completed

Vero Beach, Florida, United States; Recruiting

Atlanta, Georgia, United States; Recruiting

Dunwoody, Georgia, United States; Recruiting

East Point, Georgia, United States; Completed

Norcross, Georgia, United States; Recruiting

Suwanee, Georgia, United States; Recruiting

Honolulu, Hawaii, United States; Recruiting

East West Medical Research Institute, Honolulu, Hawaii 96814, United States; Recruiting

Chicago, Illinois, United States; Active, not recruiting

Chicago, Illinois, United States; Recruiting

Gurnee, Illinois, United States; Recruiting

Brownsburg, Indiana, United States; Recruiting

Manhattan, Kansas, United States; Recruiting

Wichita, Kansas, United States; Recruiting

Elizabethtown, Kentucky, United States; Recruiting

Lexington, Kentucky, United States; Recruiting

Central Kentucy Reseach Associates, Lexington, Kentucky 40509, United States; Recruiting

Paducah, Kentucky, United States; Recruiting

Mandeville, Louisiana, United States; Recruiting

Metairie, Louisiana, United States; Recruiting

Fall River, Massachusetts, United States; Recruiting

Detroit, Michigan, United States; Recruiting

Kalamazoo, Michigan, United States; Recruiting

Hazelwood, Missouri, United States; Recruiting

Washington, Missouri, United States; Recruiting

Las Vegas, Nevada, United States; Recruiting

Albuquerque, New Mexico, United States; Recruiting

Columbiana, North Carolina, United States; Recruiting

Greensboro, North Carolina, United States; Recruiting

Salisbury, North Carolina, United States; Active, not recruiting

Wilmington, North Carolina, United States; Recruiting

Fargo, North Dakota, United States; Recruiting

Franklin, Ohio, United States; Active, not recruiting

Oklahoma City, Oklahoma, United States; Recruiting

COR Clinical Research LLC, Oklahoma City, Oklahoma 73103, United States; Recruiting

Portland, Oregon, United States; Recruiting

Duncansville, Pennsylvania, United States; Recruiting

Harleysville, Pennsylvania, United States; Active, not recruiting

McMurray, Pennsylvania, United States; Recruiting

Media, Pennsylvania, United States; Recruiting

Philadelphia, Pennsylvania, United States; Completed

Eastwick Primary Care, PC, Philadelphia, Pennsylvania 19153, United States; Completed

Pittsburgh, Pennsylvania, United States; Recruiting

Upper Saint Clair, Pennsylvania, United States; Not yet recruiting

Columbia, South Carolina, United States; Recruiting

Fort Mill, South Carolina, United States; Recruiting

Greer, South Carolina, United States; Recruiting

Indian Land, South Carolina, United States; Recruiting

Clarksville, Tennessee, United States; Not yet recruiting

Knoxville, Tennessee, United States; Recruiting

Memphis, Tennessee, United States; Completed

Remesh C Gupta MD, Memphis, Tennessee 38119, United States; Recruiting

Austin, Texas, United States; Recruiting

Bellaire, Texas, United States; Recruiting

Corpus Christi, Texas, United States; Recruiting

3rd Coast Research Associates, Corpus Christi, Texas 78413, United States; Not yet recruiting

Nassau Bay, Texas, United States; Recruiting

Plano, Texas, United States; Recruiting

San Antonio, Texas, United States; Recruiting

Briggs Clinical Research LLC, San Antonio, Texas 78224, United States; Recruiting

Sun Research Institute, San Antonio, Texas 78215, United States; Completed

Bountiful, Utah, United States; Recruiting

Newport News, Virginia, United States; Recruiting

Norfolk, Virginia, United States; Recruiting

Richmond, Virginia, United States; Recruiting

Virginia Beach, Virginia, United States; Recruiting

Clarksburg, West Virginia, United States; Completed

Starting date: May 2014
Last updated: August 21, 2015