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

NCT02139046 | Completed Phase 3 Results DMC

• 2 other identifiers: FEB-XR_301U1111-1152-4040
• Study Type: interventional
• Target: 1,790
• Locations: 1 country
• Sites: 192

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.

Conditions

Gout

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

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

  Month 3

Secondary Outcomes (2)

• Percentage of Participants With at Least One Gout Flare Requiring Treatment

  Baseline to Month 3

• Percentage of Participants With Serum Urate <6.0 mg/dL at Month 3

  Month 3

Study Arms (5)

Febuxostat IR 40 mg

ACTIVE COMPARATOR

Febuxostat Immediate Release (IR) 40 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day (for participants with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min) or every other day (if eGFR ≥ 15 - ≤ 59 mL/min), or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.

Drug: Febuxostat IR; Drug: Colchicine; Drug: Naproxen; Drug: Lansoprazole

Febuxostat IR 80 mg

ACTIVE COMPARATOR

Febuxostat IR 80 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.

Drug: Febuxostat IR; Drug: Colchicine; Drug: Naproxen; Drug: Lansoprazole

Febuxostat XR 40 mg

EXPERIMENTAL

Febuxostat Extended Release (XR) 40 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.

Drug: Febuxostat XR; Drug: Colchicine; Drug: Naproxen; Drug: Lansoprazole

Febuxostat XR 80 mg

EXPERIMENTAL

Febuxostat XR 80 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.

Drug: Febuxostat XR; Drug: Colchicine; Drug: Naproxen; Drug: Lansoprazole

Placebo

PLACEBO COMPARATOR

Febuxostat placebo-matching capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every day or every other day, or, alternatively, if colchicine is not tolerated and the subject's eGFR is ≥ 50 mL/min, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.

Drug: Febuxostat placebo; Drug: Colchicine; Drug: Naproxen; Drug: Lansoprazole

Interventions

Febuxostat IR DRUG

Febuxostat IR over-encapsulated tablets

Also known as: Uloric

Febuxostat IR 40 mg; Febuxostat IR 80 mg

Febuxostat XR DRUG

Febuxostat XR over-encapsulated capsules

Also known as: Uloric

Febuxostat XR 40 mg; Febuxostat XR 80 mg

Febuxostat placebo DRUG

Febuxostat placebo-matching capsules

Placebo

Colchicine DRUG

Colchicine tablets

Febuxostat IR 40 mg; Febuxostat IR 80 mg; Febuxostat XR 40 mg; Febuxostat XR 80 mg; Placebo

Naproxen DRUG

Naproxen tablets

Febuxostat IR 40 mg; Febuxostat IR 80 mg; Febuxostat XR 40 mg; Febuxostat XR 80 mg; Placebo

Lansoprazole DRUG

Lansoprazole capsules

Febuxostat IR 40 mg; Febuxostat IR 80 mg; Febuxostat XR 40 mg; Febuxostat XR 80 mg; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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) ≥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.
• Has at least one gout flare within 12 months prior to Screening visit.

You may not qualify if:

• Has received any investigational compound within 30 days prior to Screening.
• 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.
• 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 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.
• 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.
• Participant consumes \>14 alcoholic beverages/week. Has a history of alcoholism or illicit drug abuse within 5 years.

Sponsors & Collaborators

• Takeda: lead

Study Sites (192)

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Binghamton, Alabama, United States

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Birmingham, Alabama, United States

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Huntsville, Alabama, United States

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Gilbert, Arizona, United States

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Glendale, Arizona, United States

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Phoenix, Arizona, United States

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Tucson, Arizona, United States

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Fayetteville, Arkansas, United States

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Little Rock, Arkansas, United States

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Searcy, Arkansas, United States

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Bellflower, California, United States

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Carmichael, California, United States

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Costa Mesa, California, United States

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Covina, California, United States

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El Cajon, California, United States

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Encinitas, California, United States

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Encino, California, United States

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Escondido, California, United States

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Gold River, California, United States

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Irvine, California, United States

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Lancaster, California, United States

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Lomita, California, United States

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Long Beach, California, United States

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Los Angeles, California, United States

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Monterey Park, California, United States

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Murrieta, California, United States

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North Hollywood, California, United States

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Norwalk, California, United States

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Paramount, California, United States

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Rancho Cucamonga, California, United States

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Riverside, California, United States

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Roseville, California, United States

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Sacramento, California, United States

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San Diego, California, United States

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San Jose, California, United States

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San Ramon, California, United States

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Santa Clarita, California, United States

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Tustin, California, United States

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Upland, California, United States

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Arvada, Colorado, United States

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Westminster, Colorado, United States

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Wheat Ridge, Colorado, United States

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Lewes, Delaware, United States

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Boynton Beach, Florida, United States

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Brandon, Florida, United States

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Clearwater, Florida, United States

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Coral Gables, Florida, United States

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Coral Springs, Florida, United States

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Daytona Beach, Florida, United States

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DeLand, Florida, United States

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Doral, Florida, United States

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Edgewater, Florida, United States

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Fort Lauderdale, Florida, United States

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Fort Meyers, Florida, United States

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Fort Myers, Florida, United States

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Hialeah, Florida, United States

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Hollywood, Florida, United States

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Homestead, Florida, United States

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Jacksonville, Florida, United States

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Jupiter, Florida, United States

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Miami, Florida, United States

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North Bay Village, Florida, United States

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Orlando, Florida, United States

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Pembroke Pines, Florida, United States

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Pinellas Park, Florida, United States

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Plant City, Florida, United States

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Port Charlotte, Florida, United States

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Sanford, Florida, United States

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Tallahassee, Florida, United States

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Tampa, Florida, United States

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Winter Haven, Florida, United States

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Atlanta, Georgia, United States

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Augusta, Georgia, United States

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Columbus, Georgia, United States

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Dunwoody, Georgia, United States

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Fort Valley, Georgia, United States

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Marietta, Georgia, United States

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Newnan, Georgia, United States

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Norcross, Georgia, United States

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Roswell, Georgia, United States

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Savannah, Georgia, United States

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Suwanee, Georgia, United States

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Honolulu, Hawaii, United States

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Meridian, Idaho, United States

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Gurnee, Illinois, United States

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Avon, Indiana, United States

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Brownsburg, Indiana, United States

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Newburgh, Indiana, United States

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Augusta, Kansas, United States

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Wichita, Kansas, United States

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Crestview Hills, Kentucky, United States

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Elizabethtown, Kentucky, United States

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Lexington, Kentucky, United States

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Louisville, Kentucky, United States

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Owensboro, Kentucky, United States

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Paducah, Kentucky, United States

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Baker, Louisiana, United States

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Lafayette, Louisiana, United States

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Mandeville, Louisiana, United States

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Metairie, Louisiana, United States

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Biddeford, Maine, United States

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Columbia, Maryland, United States

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Frederick, Maryland, United States

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Oxon Hill, Maryland, United States

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Brockton, Massachusetts, United States

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Fall River, Massachusetts, United States

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Buckley, Michigan, United States

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Detroit, Michigan, United States

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Kalamazoo, Michigan, United States

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Biloxi, Mississippi, United States

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Olive Branch, Mississippi, United States

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Hazelwood, Missouri, United States

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Washington, Missouri, United States

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Billings, Montana, United States

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Missoula, Montana, United States

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Bellevue, Nebraska, United States

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Lincoln, Nebraska, United States

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Omaha, Nebraska, United States

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Las Vegas, Nevada, United States

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Reno, Nevada, United States

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Lodi, New Jersey, United States

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Teaneck, New Jersey, United States

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Albuquerque, New Mexico, United States

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Brooklyn, New York, United States

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Endwell, New York, United States

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Manhasset, New York, United States

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Columbiana, North Carolina, United States

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Greensboro, North Carolina, United States

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Greenville, North Carolina, United States

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Hickory, North Carolina, United States

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Raleigh, North Carolina, United States

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Salisbury, North Carolina, United States

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Wilmington, North Carolina, United States

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Fargo, North Dakota, United States

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Chagrin Falls, Ohio, United States

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Cincinnati, Ohio, United States

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Cleveland, Ohio, United States

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Lyndhurst, Ohio, United States

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Mentor, Ohio, United States

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Perrysburg, Ohio, United States

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Toledo, Ohio, United States

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Wadsworth, Ohio, United States

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Willoughby Hills, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Tulsa, Oklahoma, United States

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Portland, Oregon, United States

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Altoona, Pennsylvania, United States

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Duncansville, Pennsylvania, United States

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Harleysville, Pennsylvania, United States

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Lansdale, Pennsylvania, United States

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McMurray, Pennsylvania, United States

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Media, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Uniontown, Pennsylvania, United States

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Wyomissing, Pennsylvania, United States

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Charleston, South Carolina, United States

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Columbia, South Carolina, United States

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Greer, South Carolina, United States

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Mt. Pleasant, South Carolina, United States

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Rapid City, South Dakota, United States

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Bristol, Tennessee, United States

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Collierville, Tennessee, United States

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Jackson, Tennessee, United States

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Memphis, Tennessee, United States

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Arlington, Texas, United States

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Austin, Texas, United States

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Bellaire, Texas, United States

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Carrollton, Texas, United States

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Corpus Christi, Texas, United States

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Houston, Texas, United States

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Humble, Texas, United States

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Plano, Texas, United States

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San Antonio, Texas, United States

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Sugar Land, Texas, United States

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The Woodlands, Texas, United States

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Bountiful, Utah, United States

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Salt Lake City, Utah, United States

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West Jordan, Utah, United States

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Alexandria, Virginia, United States

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Arlington, Virginia, United States

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Burke, Virginia, United States

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Charlottesville, Virginia, United States

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Danville, Virginia, United States

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Midlothian, Virginia, United States

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Newport News, Virginia, United States

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Norfolk, Virginia, United States

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Richmond, Virginia, United States

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Sterling, Virginia, United States

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Spokane, Washington, United States

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Clarksburg, West Virginia, United States

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Milwaukee, Wisconsin, United States

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Related Publications (1)

• 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.

  PMID: 30073793 DERIVED

MeSH Terms

Conditions

Gout

Interventions

Febuxostat; Colchicine; Naproxen; Lansoprazole

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Alkaloids; Naphthaleneacetic Acids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Pyridines; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2014
• First Posted: May 15, 2014
• Study Start: April 1, 2014
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: November 3, 2016
• Results First Posted: November 3, 2016

Record last verified: 2016-09

Locations

US (192)