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CONFIRMS: Efficacy and Safety of Oral Febuxostat in Participants With Gout

Sponsor
Takeda (Industry)
Overall Status
Completed
CT.gov ID
NCT00430248
Collaborator
(none)
2,269
Enrollment
258
Locations
3
Arms
12.9
Duration (Months)
8.8
Patients Per Site
0.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the efficacy and safety of febuxostat, once Daily (QD), to allopurinol in subjects with hyperuricemia and gout.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

Renal impairment is common in subjects with gout, with the prevalence ranging from 50% to 70%. This population represents an unmet medical need as uricosuric drugs are contraindicated in these patients, and the only available treatment, allopurinol, may have to be dose reduced to avoid overt side effects.

Febuxostat (TMX-67) is a non-purine selective xanthine oxidase inhibitor being developed as an orally administered agent for management of hyperuricemia in patients with gout.

Treatment duration will be 6 months.

Study Design

Study Type:
Interventional
Actual Enrollment :
2269 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Randomized, Multicenter, Double-Blind, Allopurinol-Controlled Study Assessing the Efficacy and Safety of Oral Febuxostat in Subjects With Gout.
Study Start Date :
Feb 1, 2007
Actual Primary Completion Date :
Mar 1, 2008
Actual Study Completion Date :
Mar 1, 2008

Arms and Interventions

Arm Intervention/Treatment
Experimental: Febuxostat 40 mg QD

Drug: Febuxostat
Febuxostat 40 mg, capsules, orally, once daily for up to 6 months.
Other Names:
  • TMX-67
  • Tei-6720
  • Uloric

    		•
    Experimental: Febuxostat 80 mg QD

    Drug: Febuxostat
    Febuxostat 80 mg, capsules, orally, once daily for up to 6 months.
    Other Names:
  • TMX-67
  • Tei-6720
  • Uloric

    		•
    Active Comparator: Allopurinol 200 mg or 300 mg QD

    (dependent on renal function)

    Drug: Allopurinol
    Allopurinol 200 mg or 300 mg, capsules, orally, once daily for up to 6 months. Dose is dependent on the subject's renal function. Subjects with normal renal function or mild renal impairment received 300 mg once daily; subjects with moderate renal impairment received 200 mg once daily.
    Other Names:
  • Zyloprim

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Subjects Whose Serum Urate Level is <6.0 Milligrams Per Deciliter (mg/dL) at the Final Visit. [Last Visit on treatment (up to 6 months)]

      The percentage of subjects whose serum urate level was <6.0 mg/dL at the Final Visit was summarized. The Final Visit was the last visit at which a serum urate value was collected.

    Secondary Outcome Measures

    1. Percentage of Renal Impairment Subjects Whose Final Visit Serum Urate Level is <6.0 mg/dl [Last Visit on treatment (up to 6 months)]

      The percentage of subjects with mild-to-moderate renal impairment whose serum urate was <6.0 mg/dL at the final visit was summarized. The final visit was the last visit at which a serum urate value was collected.

    2. Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Month 2 Visit. [Month 2]

      Serum urate values were obtained at the Month 2 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 2 visit was summarized.

    3. Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Month 4 Visit. [Month 4]

      Serum urate values were obtained at the Month 4 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 4 visit was summarized.

    4. Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Month 6 Visit. [Month 6]

      Serum urate values were obtained at the Month 6 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 6 visit was summarized.

    5. Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Month 2 Visit. [Month 2]

      Serum urate values were obtained at the Month 2 visit. The percentage of subjects whose serum urate was <5.0 mg/dL at the Month 2 visit was summarized.

    6. Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Month 4 Visit. [Month 4]

      Serum urate values were obtained at the Month 4 visit. The percentage of subjects whose serum urate was <5.0 mg/dL at the Month 4 visit was summarized.

    7. Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Month 6 Visit. [Month 6]

      Serum urate values were obtained at the Month 6 visit. The percentage of subjects whose serum urate was <5.0 mg/dL at the Month 6 visit was summarized.

    8. Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Final Visit. [Last Visit on treatment (up to 6 months)]

      The percentage of subjects whose serum urate level was <5.0 mg/dL at the Final Visit was summarized. The Final Visit was the last visit at which a serum urate values was collected.

    9. Percentage of Subjects Whose Serum Urate Levels Are <4.0 mg/dL at Month 2 Visit [Month 2]

      Serum urate values were obtained at the Month 2 visit. The percentage of subjects whose serum urate was <4.0 mg/dL at the Month 2 visit was summarized.

    10. Percentage of Subjects Whose Serum Urate Levels Are <4.0 mg/dL at Month 4 Visit [Month 4]

      Serum urate values were obtained at the Month 4 visit. The percentage of subjects whose serum urate was <4.0 mg/dL at the Month 4 visit was summarized.

    11. Percentage of Subjects Whose Serum Urate Levels Are <4.0 mg/dL at Month 6 Visit [Month 6]

      Serum urate values were obtained at the Month 6 visit. The percentage of subjects whose serum urate was <4.0 mg/dL at the Month 6 visit was summarized.

    12. Percentage of Subjects Whose Serum Urate Levels Are <4.0 mg/dL at Final Visit [Last Visit on treatment (up to 6 months)]

      The percentage of subjects whose serum urate level was <4.0 mg/dL at the Final Visit was summarized. The Final Visit was the last visit at which a serum urate values was collected.

    13. Mean Percent Change From Baseline in Serum Urate Levels at Month 2 Visit. [Baseline and Month 2]

      Serum urate values were obtained at the Month 2 visit. The percent change in serum urate from baseline to the Month 2 visit was summarized.

    14. Mean Percent Change From Baseline in Serum Urate Levels at Month 4 Visit [Baseline and Month 4]

      Serum urate values were obtained at the Month 4 visit. The percent change in serum urate from baseline to the Month 4 visit was summarized.

    15. Mean Percent Change From Baseline in Serum Urate Levels at Month 6 Visit. [Baseline and Month 6]

      Serum urate values were obtained at the Month 6 visit. The percent change in serum urate from baseline to the Month 6 visit was summarized.

    16. Mean Percent Change From Baseline in Serum Urate Levels at Final Visit. [Baseline and Last Visit on treatment (up to 6 months)]

      The percent change in serum urate from baseline to the Final visit was summarized. The final visit was the last visit at which a serum urate value was collected.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 85 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Has one or more of the American Rheumatism Association criteria for the diagnosis of gout.

    • Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.

    • Must have a serum urate level greater than or equal to 8.0 milligram per deciliter (mg/dL).

    Exclusion Criteria:

    • Have a severe, unstable, or life threatening medical condition that would likely prevent them from completing this study.

    • Has a known body reaction to febuxostat, allopurinol, naproxen, any other non-steroidal anti-inflammatory drug (NSAID), aspirin, lansoprazole, colchicine, or any components in their formulation.

    • History of xanthinuria.

    • Alcohol consumption greater than 14/week.

    • History of significant concomitant illness.

    • Active liver or peptic ulcer disease.

    • Has rheumatoid arthritis requiring treatment.

    • Has estimated creatinine clearance less than 30 milliliter per minute (mL/min) calculated using the Cockcroft-Gault formula corrected for ideal body weight.

    • Requires therapy with any other urate-lowering drug other than the study drug; long-term use of NSAIDs and COX-2 inhibitors; salicylates; thiazide diuretics; losartan; azathioprine; mercaptopurine; theophylline; intravenous (IV) colchicine; cyclosporine; cyclophosphamide; pyrazinamide; sulfamethoxazole;trimethoprim.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Birmingham Alabama United States
    2 Hoover Alabama United States
    3 Hueytown Alabama United States
    4 Huntsville Alabama United States
    5 Mobile Alabama United States
    6 Montgomery Alabama United States
    7 Northport Alabama United States
    8 Ozark Alabama United States
    9 Tuscaloosa Alabama United States
    10 Chandler Arizona United States
    11 Gilbert Arizona United States
    12 Mesa Arizona United States
    13 Peoria Arizona United States
    14 Phoenix Arizona United States
    15 Scottsdale Arizona United States
    16 Sierra Vista Arizona United States
    17 Tucson Arizona United States
    18 Fort Smith Arkansas United States
    19 Jonesboro Arkansas United States
    20 Little Rock Arkansas United States
    21 Anaheim California United States
    22 Carmichael California United States
    23 Clovis California United States
    24 Concord California United States
    25 El Centro California United States
    26 Fair Oaks California United States
    27 Fullerton California United States
    28 Huntington Beach California United States
    29 Irvine California United States
    30 Laguna Hills California United States
    31 LaJolla California United States
    32 Los Angeles California United States
    33 Pasadena California United States
    34 Rancho Cucamonga California United States
    35 Riverside California United States
    36 Sacramento California United States
    37 San Diego California United States
    38 San Luis Obispo California United States
    39 Santa Barbara California United States
    40 Santa Maria California United States
    41 Torrance California United States
    42 Tustin California United States
    43 Vallejo California United States
    44 Vista California United States
    45 Walnut Creek California United States
    46 West Covina California United States
    47 Westlake Village California United States
    48 Whittier California United States
    49 Boulder Colorado United States
    50 Colorado Springs Colorado United States
    51 Denver Colorado United States
    52 Highlands Ranch Colorado United States
    53 Littleton Colorado United States
    54 Longmont Colorado United States
    55 Wheat Ridge Colorado United States
    56 Danbury Connecticut United States
    57 Trumbull Connecticut United States
    58 Washington District of Columbia United States
    59 Aventura Florida United States
    60 Boynton Beach Florida United States
    61 Brandon Florida United States
    62 Daytona Beach Florida United States
    63 DeLand Florida United States
    64 Delray Beach Florida United States
    65 Fort Lauderdale Florida United States
    66 Fort Myers Florida United States
    67 Gainsville Florida United States
    68 Hallandale Florida United States
    69 Hialeah Florida United States
    70 Holly Hill Florida United States
    71 Jupiter Florida United States
    72 Kissimmee Florida United States
    73 Largo Florida United States
    74 Miami Florida United States
    75 Naples Florida United States
    76 New Port Richey Florida United States
    77 New Smyrna Beach Florida United States
    78 Opa Locka Florida United States
    79 Orlando Florida United States
    80 South Miami Florida United States
    81 St. Petersburg Florida United States
    82 Tallahassee Florida United States
    83 Tampa Florida United States
    84 West Palm Beach Florida United States
    85 Winter Haven Florida United States
    86 Zephyrhills Florida United States
    87 Atlanta Georgia United States
    88 Conyers Georgia United States
    89 Decatur Georgia United States
    90 Dunwoody Georgia United States
    91 Gainesville Georgia United States
    92 Marietta Georgia United States
    93 Stockbridge Georgia United States
    94 Honolulu Hawaii United States
    95 Boise Idaho United States
    96 Coeur d'Alene Idaho United States
    97 Meridian Idaho United States
    98 Nampa Idaho United States
    99 Arlington Heights Illinois United States
    100 Chicago Illinois United States
    101 Evanston Illinois United States
    102 Springfield Illinois United States
    103 Vernon Hills Illinois United States
    104 Elkhart Indiana United States
    105 Evansville Indiana United States
    106 Mishawaka Indiana United States
    107 Clive Iowa United States
    108 Des Moines Iowa United States
    109 Dubuque Iowa United States
    110 Kansas City Kansas United States
    111 Wichita Kansas United States
    112 Elizabethtown Kentucky United States
    113 Lexington Kentucky United States
    114 Louisville Kentucky United States
    115 Baton Rouge Louisiana United States
    116 Metairie Louisiana United States
    117 New Orleans Louisiana United States
    118 Ruston Louisiana United States
    119 Shreveport Louisiana United States
    120 Slidell Louisiana United States
    121 Baltimore Maryland United States
    122 Frederick Maryland United States
    123 Owings Mills Maryland United States
    124 Prince Frederick Maryland United States
    125 Wheaton Maryland United States
    126 Fall River Massachusetts United States
    127 New Bedford Massachusetts United States
    128 Springfield Massachusetts United States
    129 Worcester Massachusetts United States
    130 Ann Arbor Michigan United States
    131 Flint Michigan United States
    132 Kalamazoo Michigan United States
    133 Lansing Michigan United States
    134 Stevensville Michigan United States
    135 Troy Michigan United States
    136 Chaska Minnesota United States
    137 Flowood Mississippi United States
    138 Jackson Mississippi United States
    139 Olive Branch Mississippi United States
    140 Florissant Missouri United States
    141 Jefferson City Missouri United States
    142 Manchester Missouri United States
    143 Mexico Missouri United States
    144 Saint Louis Missouri United States
    145 Billings Montana United States
    146 Butte Montana United States
    147 Grand Island Nebraska United States
    148 Lincoln Nebraska United States
    149 Omaha Nebraska United States
    150 Las Vegas Nevada United States
    151 Reno Nevada United States
    152 Dover New Hampshire United States
    153 Blackwood New Jersey United States
    154 Edison New Jersey United States
    155 Flemington New Jersey United States
    156 Manalapan New Jersey United States
    157 Medford New Jersey United States
    158 Midland Park New Jersey United States
    159 Albuquerque New Mexico United States
    160 Endwell New York United States
    161 Mineola New York United States
    162 New York New York United States
    163 Smithtown New York United States
    164 Syracuse New York United States
    165 Charlotte North Carolina United States
    166 Greensboro North Carolina United States
    167 Greenville North Carolina United States
    168 Harrisburg North Carolina United States
    169 High Point North Carolina United States
    170 Lenoir North Carolina United States
    171 Raleigh North Carolina United States
    172 Winston-Salem North Carolina United States
    173 Austintown Ohio United States
    174 Beachwood Ohio United States
    175 Chardon Ohio United States
    176 Cincinnati Ohio United States
    177 Cleveland Ohio United States
    178 Dayton Ohio United States
    179 Hudson Ohio United States
    180 Kettering Ohio United States
    181 Lyndhurst Ohio United States
    182 Perrysburg Ohio United States
    183 Toledo Ohio United States
    184 Willoughby Hills Ohio United States
    185 Youngstown Ohio United States
    186 Oklahoma City Oklahoma United States
    187 Tulsa Oklahoma United States
    188 Bend Oregon United States
    189 Eugene Oregon United States
    190 Lake Oswego Oregon United States
    191 Medford Oregon United States
    192 Portland Oregon United States
    193 Bethlehem Pennsylvania United States
    194 Duncansville Pennsylvania United States
    195 East Norriton Pennsylvania United States
    196 Feasterville Trevose Pennsylvania United States
    197 Harrisburg Pennsylvania United States
    198 Lansdale Pennsylvania United States
    199 Mechanicsburg Pennsylvania United States
    200 Morrisville Pennsylvania United States
    201 Penndel Pennsylvania United States
    202 Philadelphia Pennsylvania United States
    203 Pittsburgh Pennsylvania United States
    204 Reading Pennsylvania United States
    205 Scotland Pennsylvania United States
    206 West Reading Pennsylvania United States
    207 Cranston Rhode Island United States
    208 East Providence Rhode Island United States
    209 Charleston South Carolina United States
    210 Columbia South Carolina United States
    211 Greenville South Carolina United States
    212 Greer South Carolina United States
    213 Mount Pleasant South Carolina United States
    214 Orangeburg South Carolina United States
    215 Simpsonville South Carolina United States
    216 Spartanburg South Carolina United States
    217 Bristol Tennessee United States
    218 Chattanooga Tennessee United States
    219 Clarksville Tennessee United States
    220 Collierville Tennessee United States
    221 Jackson Tennessee United States
    222 Johnson City Tennessee United States
    223 Memphis Tennessee United States
    224 Nashville Tennessee United States
    225 New Tazewell Tennessee United States
    226 Amarillo Texas United States
    227 Austin Texas United States
    228 Beaumont Texas United States
    229 Bellaire Texas United States
    230 Bryan Texas United States
    231 Dallas Texas United States
    232 El Paso Texas United States
    233 Fort Worth Texas United States
    234 Houston Texas United States
    235 Killeen Texas United States
    236 Lake Jackson Texas United States
    237 Odessa Texas United States
    238 San Antonio Texas United States
    239 Sugar Land Texas United States
    240 Waco Texas United States
    241 Layton Utah United States
    242 Midvale Utah United States
    243 Salt Lake City Utah United States
    244 St. George Utah United States
    245 West Jordan Utah United States
    246 Chesapeake Virginia United States
    247 Newport News Virginia United States
    248 Norfolk Virginia United States
    249 Richmond Virginia United States
    250 Everett Washington United States
    251 Gig Harbor Washington United States
    252 Lakewood Washington United States
    253 Olympia Washington United States
    254 Spokane Washington United States
    255 Tacoma Washington United States
    256 Vancouver Washington United States
    257 Monroe Wisconsin United States
    258 Oregon Wisconsin United States

    Sponsors and Collaborators

    • Takeda

    Investigators

    • Study Chair: Medical Director, Takeda

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Takeda
    ClinicalTrials.gov Identifier:
    NCT00430248
    Other Study ID Numbers:
    • F-GT06-153
    • U1111-1114-0226
    First Posted:
    Feb 1, 2007
    Last Update Posted:
    Feb 2, 2012
    Last Verified:
    Jan 1, 2012
    Keywords provided by Takeda
    tophi
    hyperuricemia
    uric acid
    Drug Therapy
    Additional relevant MeSH terms:
    Gout
    Allopurinol
    Febuxostat

    Study Results

    Participant Flow

    Recruitment Details Subjects were enrolled at 324 sites in the United States from 16 February 2007 to 12 March 2008.
    Pre-assignment Detail Subjects who were currently receiving urate-lowering therapy discontinued those urate-lowering therapies and initiated prophylactic medications before enrollemnt in once daily (QD) treatment groups.
    Arm/Group Title Febuxostat 40 mg QD Febuxostat 80 mg QD Allopurinol 200 mg or 300 mg QD
    Arm/Group Description Febuxostat 40 mg, orally, once daily for up to 6 months. Febuxostat 80 mg, orally, once daily for up to 6 months. Allopurinol, orally, for up to 6 months. Dose of allopurinol received was based on renal status. Subjects with normal renal function or mild renal impairment received 300 mg QD; subjects with moderate renal impairment received 200 mg QD.
    Period Title: Overall Study
    STARTED 757 756 756
    COMPLETED 632 598 621
    NOT COMPLETED 125 158 135

    Baseline Characteristics

    Arm/Group Title Febuxostat 40 mg QD Febuxostat 80 mg QD Allopurinol 200 mg or 300 mg QD Total
    Arm/Group Description Febuxostat 40 mg, orally, once daily for up to 6 months. Febuxostat 80 mg, orally, once daily for up to 6 months. Allopurinol, orally, for up to 6 months. Dose of allopurinol received was based on renal status. Subjects with normal renal function or mild renal impairment received 300 mg QD; subjects with moderate renal impairment received 200 mg QD. Total of all reporting groups
    Overall Participants 757 756 756 2269
    Age, Customized (subjects) [Number]
    <45 years of age
    192
    196
    180
    568
    45 to <65 years of age
    450
    432
    445
    1327
    ≥65 years of age
    115
    128
    131
    374
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    52.5
    (11.68)
    53.0
    (11.79)
    52.9
    (11.73)
    52.8
    (11.73)
    Sex: Female, Male (Count of Participants)
    Female
    35
    4.6%
    46
    6.1%
    47
    6.2%
    128
    5.6%
    Male
    722
    95.4%
    710
    93.9%
    709
    93.8%
    2141
    94.4%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    47
    6.2%
    49
    6.5%
    53
    7%
    149
    6.6%
    Not Hispanic or Latino
    710
    93.8%
    707
    93.5%
    702
    92.9%
    2119
    93.4%
    Unknown or Not Reported
    0
    0%
    0
    0%
    1
    0.1%
    1
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    6
    0.8%
    10
    1.3%
    6
    0.8%
    22
    1%
    Asian
    26
    3.4%
    25
    3.3%
    37
    4.9%
    88
    3.9%
    Native Hawaiian or Other Pacific Islander
    11
    1.5%
    10
    1.3%
    11
    1.5%
    32
    1.4%
    Black or African American
    83
    11%
    78
    10.3%
    67
    8.9%
    228
    10%
    White
    620
    81.9%
    618
    81.7%
    625
    82.7%
    1863
    82.1%
    More than one race
    11
    1.5%
    15
    2%
    8
    1.1%
    34
    1.5%
    Unknown or Not Reported
    0
    0%
    0
    0%
    2
    0.3%
    2
    0.1%
    Body Mass Index (subjects) [Number]
    <18.5 kilograms per meter² (kg/m²)
    0
    1
    1
    2
    18.5 kg/m² to <25 kg/m²
    50
    46
    42
    138
    25 kg/m² to <30 kg/m²
    215
    232
    236
    683
    ≥30 kg/m²
    490
    476
    476
    1442
    Missing
    2
    1
    1
    4
    Cardiovascular Disease (subjects) [Number]
    No
    336
    316
    320
    972
    Yes
    421
    440
    436
    1297
    Renal Function (subjects) [Number]
    Moderate Renal Impairment
    130
    136
    136
    402
    Mild Renal Impairment
    349
    367
    365
    1081
    Normal Renal Function
    278
    253
    255
    786
    Mean Body Mass Index (kg/m²) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m²]
    32.9
    (6.37)
    32.9
    (6.39)
    32.7
    (6.23)
    32.8
    (6.33)
    Serum Urate (milligrams per deciliter (mg/dL)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [milligrams per deciliter (mg/dL)]
    9.6
    (1.15)
    9.6
    (1.20)
    9.5
    (1.19)
    9.6
    (1.18)

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Subjects Whose Serum Urate Level is <6.0 Milligrams Per Deciliter (mg/dL) at the Final Visit.
    Description The percentage of subjects whose serum urate level was <6.0 mg/dL at the Final Visit was summarized. The Final Visit was the last visit at which a serum urate value was collected.
    Time Frame Last Visit on treatment (up to 6 months)

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on intent-to-treat (ITT) subjects, which were defined as all randomized subjects who took at least 1 dose of study drug and who had baseline serum urate ≥8.0 mg/dL. A subject's baseline value was used in the primary analysis if no postbaseline serum urate level was obtained.
    Arm/Group Title Febuxostat 40 mg QD Febuxostat 80 mg QD Allopurinol 200 mg or 300 mg QD
    Arm/Group Description Febuxostat 40 mg, orally, once daily for up to 6 months. Febuxostat 80 mg, orally, once daily for up to 6 months. Allopurinol, orally, for up to 6 months. Dose of allopurinol received was based on renal status. Subjects with normal renal function or mild renal impairment received 300 mg QD; subjects with moderate renal impairment received 200 mg QD.
    Measure Participants 757 756 755
    Number [percentage of subjects]
    45.2
    67.1
    42.1
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments The primary comparison was between febuxostat 40 mg and allopurinol treatment groups.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Noninferiority of febuxostat 40 mg to allopurinol was declared if the value of the lower bound of the 95% confidence interval for the difference was greater than -10%.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 3.1
    Confidence Interval () 95%
    -1.9 to 8.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.233
    Comments The test for superiority was performed using Fisher's exact test (two-tailed 0.05 significance level).
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Comparisons between treatment groups were performed using Fisher's exact test (two-tailed 0.05 significance level).
    Method Fisher Exact
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 24.9
    Confidence Interval () 95%
    20.1 to 29.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Febuxostat 80 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Comparisons between treatment groups were performed using Fisher's exact test (two-tailed 0.05 significance level).
    Method Fisher Exact
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 21.9
    Confidence Interval () 95%
    17.0 to 26.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Percentage of Renal Impairment Subjects Whose Final Visit Serum Urate Level is <6.0 mg/dl
    Description The percentage of subjects with mild-to-moderate renal impairment whose serum urate was <6.0 mg/dL at the final visit was summarized. The final visit was the last visit at which a serum urate value was collected.
    Time Frame Last Visit on treatment (up to 6 months)

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on the ITT subjects with mild-to-moderate renal impairment (estimated creatinine clearance of 30 mL/min to 89 mL/min), with a post-baseline serum urate level.
    Arm/Group Title Febuxostat 40 mg QD Febuxostat 80 mg QD Allopurinol 200 mg or 300 mg QD
    Arm/Group Description Febuxostat 40 mg, orally, once daily for up to 6 months. Febuxostat 80 mg, orally, once daily for up to 6 months. Allopurinol, orally, for up to 6 months. Dose of allopurinol received was based on renal status. Subjects with normal renal function or mild renal impairment received 300 mg QD; subjects with moderate renal impairment received 200 mg QD.
    Measure Participants 479 503 501
    Number [percentage of subjects]
    49.7
    71.6
    42.3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.021
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Febuxostat 80 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    3. Secondary Outcome
    Title Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Month 2 Visit.
    Description Serum urate values were obtained at the Month 2 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 2 visit was summarized.
    Time Frame Month 2

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on the ITT subjects with a serum urate value at Month 2 visit.
    Arm/Group Title Febuxostat 40 mg QD Febuxostat 80 mg QD Allopurinol 200 mg or 300 mg QD
    Arm/Group Description Febuxostat 40 mg, orally, once daily for up to 6 months. Febuxostat 80 mg, orally, once daily for up to 6 months. Allopurinol, orally, for up to 6 months. Dose of allopurinol received was based on renal status. Subjects with normal renal function or mild renal impairment received 300 mg QD; subjects with moderate renal impairment received 200 mg QD.
    Measure Participants 703 691 685
    Number [percentage of subjects]
    49.1
    74.1
    43.2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.031
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Febuxostat 80 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    4. Secondary Outcome
    Title Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Month 4 Visit.
    Description Serum urate values were obtained at the Month 4 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 4 visit was summarized.
    Time Frame Month 4

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on the ITT subjects with a serum urate value at Month 4 visit.
    Arm/Group Title Febuxostat 40 mg QD Febuxostat 80 mg QD Allopurinol 200 mg or 300 mg QD
    Arm/Group Description Febuxostat 40 mg, orally, once daily for up to 6 months. Febuxostat 80 mg, orally, once daily for up to 6 months. Allopurinol, orally, for up to 6 months. Dose of allopurinol received was based on renal status. Subjects with normal renal function or mild renal impairment received 300 mg QD; subjects with moderate renal impairment received 200 mg QD.
    Measure Participants 652 636 646
    Number [percentage of subjects]
    47.1
    75.2
    45.5
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.578
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Febuxostat 80 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    5. Secondary Outcome
    Title Percentage of Subjects Whose Serum Urate Levels Are <6.0 mg/dL at Month 6 Visit.
    Description Serum urate values were obtained at the Month 6 visit. The percentage of subjects whose serum urate was <6.0 mg/dL at the Month 6 visit was summarized.
    Time Frame Month 6

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on the ITT subjects with a serum urate value at Month 6 visit.
    Arm/Group Title Febuxostat 40 mg QD Febuxostat 80 mg QD Allopurinol 200 mg or 300 mg QD
    Arm/Group Description Febuxostat 40 mg, orally, once daily for up to 6 months. Febuxostat 80 mg, orally, once daily for up to 6 months. Allopurinol, orally, for up to 6 months. Dose of allopurinol received was based on renal status. Subjects with normal renal function or mild renal impairment received 300 mg QD; subjects with moderate renal impairment received 200 mg QD.
    Measure Participants 618 596 616
    Number [percentage of participants]
    48.9
    6.5%
    75.3
    10%
    46.6
    6.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.426
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Febuxostat 80 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    6. Secondary Outcome
    Title Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Month 2 Visit.
    Description Serum urate values were obtained at the Month 2 visit. The percentage of subjects whose serum urate was <5.0 mg/dL at the Month 2 visit was summarized.
    Time Frame Month 2

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on the ITT subjects with a serum urate value at Month 2 visit
    Arm/Group Title Febuxostat 40 mg QD Febuxostat 80 mg QD Allopurinol 200 mg or 300 mg QD
    Arm/Group Description Febuxostat 40 mg, orally, once daily for up to 6 months. Febuxostat 80 mg, orally, once daily for up to 6 months. Allopurinol, orally, for up to 6 months. Dose of allopurinol received was based on renal status. Subjects with normal renal function or mild renal impairment received 300 mg QD; subjects with moderate renal impairment received 200 mg QD.
    Measure Participants 703 691 685
    Number [percentage of subjects]
    15.4
    45.9
    11.7
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.050
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Febuxostat 80 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    7. Secondary Outcome
    Title Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Month 4 Visit.
    Description Serum urate values were obtained at the Month 4 visit. The percentage of subjects whose serum urate was <5.0 mg/dL at the Month 4 visit was summarized.
    Time Frame Month 4

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on the ITT subjects with a serum urate value at Month 4 visit.
    Arm/Group Title Febuxostat 40 mg QD Febuxostat 80 mg QD Allopurinol 200 mg or 300 mg QD
    Arm/Group Description Febuxostat 40 mg, orally, once daily for up to 6 months. Febuxostat 80 mg, orally, once daily for up to 6 months. Allopurinol, orally, for up to 6 months. Dose of allopurinol received was based on renal status. Subjects with normal renal function or mild renal impairment received 300 mg QD; subjects with moderate renal impairment received 200 mg QD.
    Measure Participants 652 636 646
    Number [percentage of subjects]
    15.0
    51.6
    13.5
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.428
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Febuxostat 80 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    8. Secondary Outcome
    Title Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Month 6 Visit.
    Description Serum urate values were obtained at the Month 6 visit. The percentage of subjects whose serum urate was <5.0 mg/dL at the Month 6 visit was summarized.
    Time Frame Month 6

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on the ITT subjects with a serum urate value at Month 6 visit.
    Arm/Group Title Febuxostat 40 mg QD Febuxostat 80 mg QD Allopurinol 200 mg or 300 mg QD
    Arm/Group Description Febuxostat 40 mg, orally, once daily for up to 6 months. Febuxostat 80 mg, orally, once daily for up to 6 months. Allopurinol, orally, for up to 6 months. Dose of allopurinol received was based on renal status. Subjects with normal renal function or mild renal impairment received 300 mg QD; subjects with moderate renal impairment received 200 mg QD.
    Measure Participants 618 596 616
    Number [percentage of subjects]
    19.3
    49.7
    14.8
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.041
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Febuxostat 80 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    9. Secondary Outcome
    Title Percentage of Subjects Whose Serum Urate Levels Are <5.0 mg/dL at Final Visit.
    Description The percentage of subjects whose serum urate level was <5.0 mg/dL at the Final Visit was summarized. The Final Visit was the last visit at which a serum urate values was collected.
    Time Frame Last Visit on treatment (up to 6 months)

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on the ITT subjects with a post-baseline serum urate value.
    Arm/Group Title Febuxostat 40 mg QD Febuxostat 80 mg QD Allopurinol 200 mg or 300 mg QD
    Arm/Group Description Febuxostat 40 mg, orally, once daily for up to 6 months. Febuxostat 80 mg, orally, once daily for up to 6 months. Allopurinol, orally, for up to 6 months. Dose of allopurinol received was based on renal status. Subjects with normal renal function or mild renal impairment received 300 mg QD; subjects with moderate renal impairment received 200 mg QD.
    Measure Participants 757 756 755
    Number [percentage of subjects]
    16.5
    44.0
    13.2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.083
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Febuxostat 80 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    10. Secondary Outcome
    Title Percentage of Subjects Whose Serum Urate Levels Are <4.0 mg/dL at Month 2 Visit
    Description Serum urate values were obtained at the Month 2 visit. The percentage of subjects whose serum urate was <4.0 mg/dL at the Month 2 visit was summarized.
    Time Frame Month 2

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on the ITT subjects with a serum urate value at Month 2 visit.
    Arm/Group Title Febuxostat 40 mg QD Febuxostat 80 mg QD Allopurinol 200 mg or 300 mg QD
    Arm/Group Description Febuxostat 40 mg, orally, once daily for up to 6 months. Febuxostat 80 mg, orally, once daily for up to 6 months. Allopurinol, orally, for up to 6 months. Dose of allopurinol received was based on renal status. Subjects with normal renal function or mild renal impairment received 300 mg QD; subjects with moderate renal impairment received 200 mg QD.
    Measure Participants 703 691 685
    Number [percentage of subjects]
    2.1
    17.5
    1.5
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.421
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Febuxostat 80 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    11. Secondary Outcome
    Title Percentage of Subjects Whose Serum Urate Levels Are <4.0 mg/dL at Month 4 Visit
    Description Serum urate values were obtained at the Month 4 visit. The percentage of subjects whose serum urate was <4.0 mg/dL at the Month 4 visit was summarized.
    Time Frame Month 4

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on the ITT subjects with a serum urate value at Month 4 visit.
    Arm/Group Title Febuxostat 40 mg QD Febuxostat 80 mg QD Allopurinol 200 mg or 300 mg QD
    Arm/Group Description Febuxostat 40 mg, orally, once daily for up to 6 months. Febuxostat 80 mg, orally, once daily for up to 6 months. Allopurinol, orally, for up to 6 months. Dose of allopurinol received was based on renal status. Subjects with normal renal function or mild renal impairment received 300 mg QD; subjects with moderate renal impairment received 200 mg QD.
    Measure Participants 652 636 646
    Number [percentage of subjects]
    2.0
    18.6
    1.4
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.520
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Febuxostat 80 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    12. Secondary Outcome
    Title Percentage of Subjects Whose Serum Urate Levels Are <4.0 mg/dL at Month 6 Visit
    Description Serum urate values were obtained at the Month 6 visit. The percentage of subjects whose serum urate was <4.0 mg/dL at the Month 6 visit was summarized.
    Time Frame Month 6

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on the ITT subjects with a serum urate value at Month 6 visit.
    Arm/Group Title Febuxostat 40 mg QD Febuxostat 80 mg QD Allopurinol 200 mg or 300 mg QD
    Arm/Group Description Febuxostat 40 mg, orally, once daily for up to 6 months. Febuxostat 80 mg, orally, once daily for up to 6 months. Allopurinol, orally, for up to 6 months. Dose of allopurinol received was based on renal status. Subjects with normal renal function or mild renal impairment received 300 mg QD; subjects with moderate renal impairment received 200 mg QD.
    Measure Participants 618 596 616
    Number [percentage of subjects]
    3.1
    20.3
    1.8
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.195
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Febuxostat 80 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    13. Secondary Outcome
    Title Percentage of Subjects Whose Serum Urate Levels Are <4.0 mg/dL at Final Visit
    Description The percentage of subjects whose serum urate level was <4.0 mg/dL at the Final Visit was summarized. The Final Visit was the last visit at which a serum urate values was collected.
    Time Frame Last Visit on treatment (up to 6 months)

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on the ITT subjects with a post-baseline serum urate value.
    Arm/Group Title Febuxostat 40 mg QD Febuxostat 80 mg QD Allopurinol 200 mg or 300 mg QD
    Arm/Group Description Febuxostat 40 mg, orally, once daily for up to 6 months. Febuxostat 80 mg, orally, once daily for up to 6 months. Allopurinol, orally, for up to 6 months. Dose of allopurinol received was based on renal status. Subjects with normal renal function or mild renal impairment received 300 mg QD; subjects with moderate renal impairment received 200 mg QD.
    Measure Participants 757 756 755
    Number [percentage of subjects]
    2.5
    17.5
    1.5
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.196
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Febuxostat 80 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments The a priori threshold for statistical significance was 0.05 (two-tailed).
    Method Fisher Exact
    Comments
    14. Secondary Outcome
    Title Mean Percent Change From Baseline in Serum Urate Levels at Month 2 Visit.
    Description Serum urate values were obtained at the Month 2 visit. The percent change in serum urate from baseline to the Month 2 visit was summarized.
    Time Frame Baseline and Month 2

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on the ITT subjects with a serum urate value at Month 2 visit.
    Arm/Group Title Febuxostat 40 mg QD Febuxostat 80 mg QD Allopurinol 200 mg or 300 mg QD
    Arm/Group Description Febuxostat 40 mg, orally, once daily for up to 6 months. Febuxostat 80 mg, orally, once daily for up to 6 months. Allopurinol, orally, for up to 6 months. Dose of allopurinol received was based on renal status. Subjects with normal renal function or mild renal impairment received 300 mg QD; subjects with moderate renal impairment received 200 mg QD.
    Measure Participants 703 691 685
    Mean (Standard Deviation) [percent change from baseline]
    -35.1
    (12.8)
    -44.5
    (15.5)
    -33.8
    (13.2)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.079
    Comments P-value is from contrast within the framework of the ANOVA with significance at the 0.05 level.
    Method ANOVA
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is from contrast within the framework of the ANOVA with significance at the 0.05 level.
    Method ANOVA
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Febuxostat 80 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is from contrast within the framework of the ANOVA with significance at the 0.05 level.
    Method ANOVA
    Comments
    15. Secondary Outcome
    Title Mean Percent Change From Baseline in Serum Urate Levels at Month 4 Visit
    Description Serum urate values were obtained at the Month 4 visit. The percent change in serum urate from baseline to the Month 4 visit was summarized.
    Time Frame Baseline and Month 4

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on the ITT subjects with a serum urate value at Month 4 visit.
    Arm/Group Title Febuxostat 40 mg QD Febuxostat 80 mg QD Allopurinol 200 mg or 300 mg QD
    Arm/Group Description Febuxostat 40 mg, orally, once daily for up to 6 months. Febuxostat 80 mg, orally, once daily for up to 6 months. Allopurinol, orally, for up to 6 months. Dose of allopurinol received was based on renal status. Subjects with normal renal function or mild renal impairment received 300 mg QD; subjects with moderate renal impairment received 200 mg QD.
    Measure Participants 652 636 646
    Mean (Standard Deviation) [percent change from baseline]
    -34.9
    (13.1)
    -45.5
    (15.6)
    -34.5
    (12.8)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.685
    Comments P-value is from contrast within the framework of the ANOVA with significance at the 0.05 level.
    Method ANOVA
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is from contrast within the framework of the ANOVA with significance at the 0.05 level.
    Method ANOVA
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Febuxostat 80 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is from contrast within the framework of the ANOVA with significance at the 0.05 level.
    Method ANOVA
    Comments
    16. Secondary Outcome
    Title Mean Percent Change From Baseline in Serum Urate Levels at Month 6 Visit.
    Description Serum urate values were obtained at the Month 6 visit. The percent change in serum urate from baseline to the Month 6 visit was summarized.
    Time Frame Baseline and Month 6

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on the ITT subjects with a serum urate value at Month 6 visit.
    Arm/Group Title Febuxostat 40 mg QD Febuxostat 80 mg QD Allopurinol 200 mg or 300 mg QD
    Arm/Group Description Febuxostat 40 mg, orally, once daily for up to 6 months. Febuxostat 80 mg, orally, once daily for up to 6 months. Allopurinol, orally, for up to 6 months. Dose of allopurinol received was based on renal status. Subjects with normal renal function or mild renal impairment received 300 mg QD; subjects with moderate renal impairment received 200 mg QD.
    Measure Participants 618 596 616
    Mean (Standard Deviation) [percent change from baseline]
    -35.6
    (13.2)
    -45.1
    (16.0)
    -34.4
    (13.3)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.153
    Comments P-value is from contrast within the framework of the ANOVA with significance at the 0.05 level.
    Method ANOVA
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is from contrast within the framework of the ANOVA with significance at the 0.05 level.
    Method ANOVA
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Febuxostat 80 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is from contrast within the framework of the ANOVA with significance at the 0.05 level.
    Method ANOVA
    Comments
    17. Secondary Outcome
    Title Mean Percent Change From Baseline in Serum Urate Levels at Final Visit.
    Description The percent change in serum urate from baseline to the Final visit was summarized. The final visit was the last visit at which a serum urate value was collected.
    Time Frame Baseline and Last Visit on treatment (up to 6 months)

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on the ITT subjects with a post-baseline serum urate value.
    Arm/Group Title Febuxostat 40 mg QD Febuxostat 80 mg QD Allopurinol 200 mg or 300 mg QD
    Arm/Group Description Febuxostat 40 mg, orally, once daily for up to 6 months. Febuxostat 80 mg, orally, once daily for up to 6 months. Allopurinol, orally, for up to 6 months. Dose of allopurinol received was based on renal status. Subjects with normal renal function or mild renal impairment received 300 mg QD; subjects with moderate renal impairment received 200 mg QD.
    Measure Participants 757 756 755
    Mean (Standard Deviation) [percent change from baseline]
    -33.1
    (15.5)
    -40.6
    (19.9)
    -31.3
    (16.2)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.050
    Comments P-value is from contrast within the framework of the ANOVA with significance at the 0.05 level.
    Method ANOVA
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Febuxostat 80 mg QD, Allopurinol 200 mg or 300 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is from contrast within the framework of the ANOVA with significance at the 0.05 level.
    Method ANOVA
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Febuxostat 40 mg QD, Febuxostat 80 mg QD
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments P-value is from contrast within the framework of the ANOVA with significance at the 0.05 level.
    Method ANOVA
    Comments

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Febuxostat 40 mg QD Febuxostat 80 mg QD Allopurinol 200 mg or 300 mg QD
    Arm/Group Description Febuxostat 40 mg, orally, once daily for up to 6 months. Febuxostat 80 mg, orally, once daily for up to 6 months. Allopurinol, orally, for up to 6 months. Dose of allopurinol received was based on renal status. Subjects with normal renal function or mild renal impairment received 300 mg QD; subjects with moderate renal impairment received 200 mg QD.
    All Cause Mortality
    Febuxostat 40 mg QD Febuxostat 80 mg QD Allopurinol 200 mg or 300 mg QD
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Febuxostat 40 mg QD Febuxostat 80 mg QD Allopurinol 200 mg or 300 mg QD
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 19/ (NaN) 28/ (NaN) 31/ (NaN)
    Blood and lymphatic system disorders
    Leukocytoses not elsewhere classified (NEC) 0/757 (0%) 1/756 (0.1%) 0/756 (0%)
    Thrombocytopenias 0/757 (0%) 1/756 (0.1%) 0/756 (0%)
    Cardiac disorders
    Cardiac Conduction Disorders 0/757 (0%) 2/756 (0.3%) 0/756 (0%)
    Cardiac Hypertensive Complications 0/757 (0%) 0/756 (0%) 1/756 (0.1%)
    Coronary Artery Disorders NEC 2/757 (0.3%) 0/756 (0%) 2/756 (0.3%)
    Heart Failures NEC 2/757 (0.3%) 0/756 (0%) 1/756 (0.1%)
    Ischaemic Coronary Artery Disorders 1/757 (0.1%) 2/756 (0.3%) 1/756 (0.1%)
    Supraventricular Arrhythmias 0/757 (0%) 1/756 (0.1%) 0/756 (0%)
    Ear and labyrinth disorders
    Inner Ear Signs and Symptoms 0/757 (0%) 1/756 (0.1%) 0/756 (0%)
    Gastrointestinal disorders
    Acute and Chronic Pancreatitis 0/757 (0%) 1/756 (0.1%) 0/756 (0%)
    Benign Neoplasms GastrointestinaI (Excluding Oral Cavity) 1/757 (0.1%) 0/756 (0%) 0/756 (0%)
    Dyspeptic Signs and Symptoms 0/757 (0%) 0/756 (0%) 1/756 (0.1%)
    Gastrointestinal & Abdominal Pains (Excluding Oral and Throat) 0/757 (0%) 0/756 (0%) 1/756 (0.1%)
    Gastrointestinal Ulcers and Perforation, Site Unspecified 0/757 (0%) 0/756 (0%) 1/756 (0.1%)
    Intestinal Haemorrhages 0/757 (0%) 0/756 (0%) 1/756 (0.1%)
    Intestinal Ulcers and Perforation NEC 2/757 (0.3%) 1/756 (0.1%) 0/756 (0%)
    Nausea and Vomiting Symptoms 0/757 (0%) 0/756 (0%) 1/756 (0.1%)
    Non-Site Specific Gastrointestinal Haemorrhages 0/757 (0%) 1/756 (0.1%) 0/756 (0%)
    General disorders
    General Signs and Symptoms NEC 1/757 (0.1%) 0/756 (0%) 0/756 (0%)
    Pain and Discomfort NEC 1/757 (0.1%) 2/756 (0.3%) 1/756 (0.1%)
    Hepatobiliary disorders
    Cholecystitis and Cholelithiasis 0/757 (0%) 0/756 (0%) 3/756 (0.4%)
    Immune system disorders
    Allergies to Food, Food Additives, Drugs and Other Chemicals 0/757 (0%) 0/756 (0%) 1/756 (0.1%)
    Anaphylactic Responses 1/757 (0.1%) 0/756 (0%) 0/756 (0%)
    Infections and infestations
    Abdominal and Gastrointestinal Infections 2/757 (0.3%) 0/756 (0%) 1/756 (0.1%)
    Bacterial Infections NEC 1/757 (0.1%) 1/756 (0.1%) 2/756 (0.3%)
    Lower Respiratory Tract and Lung Infections 1/757 (0.1%) 1/756 (0.1%) 3/756 (0.4%)
    Sepsis, Bacteraemia, Viraemia, and Infections 0/757 (0%) 1/756 (0.1%) 1/756 (0.1%)
    Injury, poisoning and procedural complications
    Fractures and Dislocations NEC 0/757 (0%) 1/756 (0.1%) 0/756 (0%)
    Muscle, Tendon and Ligament Injuries 0/757 (0%) 1/756 (0.1%) 0/756 (0%)
    Non-Site Specific Injuries NEC 0/757 (0%) 2/756 (0.3%) 0/756 (0%)
    Non-Site Specific Procedural Complications 1/757 (0.1%) 0/756 (0%) 1/756 (0.1%)
    Upper limb Fractures and Dislocations 0/757 (0%) 1/756 (0.1%) 1/756 (0.1%)
    Metabolism and nutrition disorders
    Purine Metabolism Disorders NEC 0/757 (0%) 1/756 (0.1%) 1/756 (0.1%)
    Musculoskeletal and connective tissue disorders
    Joint Related Disorders NEC 0/757 (0%) 1/756 (0.1%) 0/756 (0%)
    Joint Related Signs and Symptoms 0/757 (0%) 1/756 (0.1%) 0/756 (0%)
    Osteoarthropathies 0/757 (0%) 1/756 (0.1%) 0/756 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bladder Neoplasms Malignant 0/757 (0%) 1/756 (0.1%) 0/756 (0%)
    Breast and Nipple Neoplasms Malignant 1/757 (0.1%) 0/756 (0%) 0/756 (0%)
    Colonic Neoplasms Malignant 0/757 (0%) 0/756 (0%) 1/756 (0.1%)
    Nervous System Neoplasms Unpecified Malignancy NEC 0/757 (0%) 0/756 (0%) 1/756 (0.1%)
    Nonsmall Cell Neoplasm Malignant/Respiratory Type Specified 0/757 (0%) 0/756 (0%) 1/756 (0.1%)
    Prostatic Neoplasms Benign 0/757 (0%) 1/756 (0.1%) 0/756 (0%)
    Prostatic Neoplasms Malignant 0/757 (0%) 1/756 (0.1%) 3/756 (0.4%)
    Nervous system disorders
    Central Nervous System Hemorrhages & Cerebrovascular Accidents 0/757 (0%) 1/756 (0.1%) 1/756 (0.1%)
    Disturbances in Consciousness NEC 0/757 (0%) 0/756 (0%) 3/756 (0.4%)
    Increased Intracranial Pressure Disorders 0/757 (0%) 1/756 (0.1%) 0/756 (0%)
    Neurological Signs and Symptoms NEC 1/757 (0.1%) 0/756 (0%) 0/756 (0%)
    Transient Cerebrovascular Events 1/757 (0.1%) 1/756 (0.1%) 1/756 (0.1%)
    Renal and urinary disorders
    Renal Failure and Impairment 0/757 (0%) 1/756 (0.1%) 0/756 (0%)
    Renal Vascular and Ischaemic Conditions 0/757 (0%) 1/756 (0.1%) 0/756 (0%)
    Reproductive system and breast disorders
    Prostatic Signs, Symptoms and Disorders NEC 0/757 (0%) 1/756 (0.1%) 0/756 (0%)
    Respiratory, thoracic and mediastinal disorders
    Bronchospasms and Obstruction 0/757 (0%) 1/756 (0.1%) 1/756 (0.1%)
    Pulmonary Thrombotic and Embolic Conditions 0/757 (0%) 1/756 (0.1%) 0/756 (0%)
    Vascular disorders
    Aortic Aneurysms and Dissections 1/757 (0.1%) 0/756 (0%) 1/756 (0.1%)
    Other (Not Including Serious) Adverse Events
    Febuxostat 40 mg QD Febuxostat 80 mg QD Allopurinol 200 mg or 300 mg QD
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 193/ (NaN) 167/ (NaN) 166/ (NaN)
    Gastrointestinal disorders
    Diarrhoea (Excluding Infective) 45/757 (5.9%) 47/756 (6.2%) 57/756 (7.5%)
    Infections and infestations
    Upper Respiratory Tract Infections 71/757 (9.4%) 53/756 (7%) 57/756 (7.5%)
    Investigations
    Liver Function Analyses 63/757 (8.3%) 52/756 (6.9%) 50/756 (6.6%)
    Musculoskeletal and connective tissue disorders
    Musculoskeletal and Connective Tissues Signs and Symptoms NEC 43/757 (5.7%) 38/756 (5%) 32/756 (4.2%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    No publication related to study results will be published prior to publication of a multi-center report submitted for publication within 18 months after conclusion or termination of a study. Results publications will be submitted to sponsor for review 60 days in advance of publication. Sponsor can require removal of confidential information unrelated to study results. Sponsor can embargo a proposed publication for another 60 days to preserve intellectual property.

    Results Point of Contact

    Name/Title Sr. VP, Clinical Sciences
    Organization Takeda Global Research and Development Center, Inc.
    Phone 800-778-2860
    Email clinicaltrialregistry@tpna.com
    Responsible Party:
    Takeda
    ClinicalTrials.gov Identifier:
    NCT00430248
    Other Study ID Numbers:
    • F-GT06-153
    • U1111-1114-0226
    First Posted:
    Feb 1, 2007
    Last Update Posted:
    Feb 2, 2012
    Last Verified:
    Jan 1, 2012