Trial Outcomes & Findings for Dose-Response, Safety and Efficacy of Febuxostat in Subjects With Gout (NCT NCT00174967)
NCT ID: NCT00174967
Last Updated: 2011-07-29
Results Overview
Serum urate values were obtained at the Day 28 visit. The percentage of subjects whose serum urate decreased to \<6.0 mg/dL at the Day 28 visit was summarized.
COMPLETED
PHASE2
153 participants
Day 28.
2011-07-29
Participant Flow
Subjects were enrolled at 24 investigative sites from 31 January 2001 to 9 July 2001
Participants currently receiving urate-lowering therapy discontinued those urate-lowering therapies and initiated prophylactic medications before enrollemnt in once daily (QD) treatment groups. All other subjects also initiated prophylactic medications.
Participant milestones
| Measure |
Febuxostat 40 mg QD
Febuxostat 40 mg, orally, once daily.
|
Febuxostat 80 mg QD
Febuxostat 80 mg, orally, once daily.
|
Febuxostat 120 mg QD
Febuxostat 120 mg, orally, once daily.
|
Placebo QD
Placebo, orally, once daily
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
37
|
40
|
38
|
38
|
|
Overall Study
COMPLETED
|
36
|
37
|
36
|
36
|
|
Overall Study
NOT COMPLETED
|
1
|
3
|
2
|
2
|
Reasons for withdrawal
| Measure |
Febuxostat 40 mg QD
Febuxostat 40 mg, orally, once daily.
|
Febuxostat 80 mg QD
Febuxostat 80 mg, orally, once daily.
|
Febuxostat 120 mg QD
Febuxostat 120 mg, orally, once daily.
|
Placebo QD
Placebo, orally, once daily
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
1
|
2
|
2
|
1
|
|
Overall Study
Gout Flare
|
0
|
0
|
0
|
1
|
|
Overall Study
Other
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Dose-Response, Safety and Efficacy of Febuxostat in Subjects With Gout
Baseline characteristics by cohort
| Measure |
Febuxostat 40 mg QD
n=37 Participants
Febuxostat 40 mg, orally, once daily.
|
Febuxostat 80 mg QD
n=40 Participants
Febuxostat 80 mg, orally, once daily.
|
Febuxostat 120 mg QD
n=38 Participants
Febuxostat 120 mg, orally, once daily.
|
Placebo QD
n=38 Participants
Placebo, orally, once daily
|
Total
n=153 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age Continuous
|
52.2 years
STANDARD_DEVIATION 14.04 • n=5 Participants
|
55.2 years
STANDARD_DEVIATION 13.09 • n=7 Participants
|
56.2 years
STANDARD_DEVIATION 10.83 • n=5 Participants
|
52.4 years
STANDARD_DEVIATION 12.63 • n=4 Participants
|
54.0 years
STANDARD_DEVIATION 12.69 • n=21 Participants
|
|
Age, Customized
<45 years
|
8 participants
n=5 Participants
|
10 participants
n=7 Participants
|
7 participants
n=5 Participants
|
12 participants
n=4 Participants
|
37 participants
n=21 Participants
|
|
Age, Customized
45 years to <65 years
|
21 participants
n=5 Participants
|
19 participants
n=7 Participants
|
23 participants
n=5 Participants
|
17 participants
n=4 Participants
|
80 participants
n=21 Participants
|
|
Age, Customized
≥65 years
|
8 participants
n=5 Participants
|
11 participants
n=7 Participants
|
8 participants
n=5 Participants
|
9 participants
n=4 Participants
|
36 participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
17 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
33 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
32 Participants
n=4 Participants
|
136 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
White
|
32 participants
n=5 Participants
|
35 participants
n=7 Participants
|
34 participants
n=5 Participants
|
32 participants
n=4 Participants
|
133 participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
3 participants
n=5 Participants
|
3 participants
n=7 Participants
|
2 participants
n=5 Participants
|
3 participants
n=4 Participants
|
11 participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
1 participants
n=4 Participants
|
4 participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
0 participants
n=4 Participants
|
2 participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
2 participants
n=4 Participants
|
3 participants
n=21 Participants
|
|
Body Mass Index
≤25 kilogram per meter² (kg/m²)
|
2 participants
n=5 Participants
|
3 participants
n=7 Participants
|
3 participants
n=5 Participants
|
0 participants
n=4 Participants
|
8 participants
n=21 Participants
|
|
Body Mass Index
>25 kg/m² to 30 kg/m²
|
12 participants
n=5 Participants
|
12 participants
n=7 Participants
|
14 participants
n=5 Participants
|
13 participants
n=4 Participants
|
51 participants
n=21 Participants
|
|
Body Mass Index
>30 kg/m² to 35 kg/m²
|
16 participants
n=5 Participants
|
12 participants
n=7 Participants
|
12 participants
n=5 Participants
|
16 participants
n=4 Participants
|
56 participants
n=21 Participants
|
|
Body Mass Index
>35 kg/m² to 40 kg/m²
|
4 participants
n=5 Participants
|
7 participants
n=7 Participants
|
5 participants
n=5 Participants
|
6 participants
n=4 Participants
|
22 participants
n=21 Participants
|
|
Body Mass Index
>40 kg/m²
|
3 participants
n=5 Participants
|
6 participants
n=7 Participants
|
3 participants
n=5 Participants
|
3 participants
n=4 Participants
|
15 participants
n=21 Participants
|
|
Body Mass Index
missing
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
0 participants
n=4 Participants
|
1 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Day 28.Population: Analysis performed on intent-to-treat (ITT) subjects, defined as all randomized subjects who took at least 1 dose of study drug and who had baseline serum urate ≥8.0 mg/dL. The last observation carried forward (LOCF) method was used to impute missing data. The baseline value was carried forward if no postbaseline visits were available.
Serum urate values were obtained at the Day 28 visit. The percentage of subjects whose serum urate decreased to \<6.0 mg/dL at the Day 28 visit was summarized.
Outcome measures
| Measure |
Febuxostat 40 mg QD
n=34 Participants
Febuxostat 40 mg, orally, once daily.
|
Febuxostat 80 mg QD
n=37 Participants
Febuxostat 80 mg, orally, once daily.
|
Febuxostat 120 mg QD
n=34 Participants
Febuxostat 120 mg, orally, once daily.
|
Placebo QD
n=35 Participants
Placebo, orally, once daily
|
|---|---|---|---|---|
|
Percentage of Subjects Whose Serum Urate Level Decreased to <6.0 Milligram Per Deciliter (mg/dL) at the Day 28 Visit.
|
56 percentage of subjects
|
76 percentage of subjects
|
94 percentage of subjects
|
0 percentage of subjects
|
SECONDARY outcome
Timeframe: Day 7.Population: The analysis was performed on 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. The LOCF method was used to impute missing data. The baseline value was carried forward if no post-baseline visits were available.
Serum urate values were obtained at the Day 7 visit. The percentage of subjects whose serum urate decreased to \<6.0 mg/dL at the Day 7 visit was summarized.
Outcome measures
| Measure |
Febuxostat 40 mg QD
n=34 Participants
Febuxostat 40 mg, orally, once daily.
|
Febuxostat 80 mg QD
n=37 Participants
Febuxostat 80 mg, orally, once daily.
|
Febuxostat 120 mg QD
n=34 Participants
Febuxostat 120 mg, orally, once daily.
|
Placebo QD
n=35 Participants
Placebo, orally, once daily
|
|---|---|---|---|---|
|
Percentage of Subjects Whose Serum Urate Level Decreased to <6.0 mg/dL at the Day 7 Visit.
|
50 percentage of subjects
|
59 percentage of subjects
|
91 percentage of subjects
|
3 percentage of subjects
|
SECONDARY outcome
Timeframe: Day 14.Population: The analysis was performed on 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. The LOCF method was used to impute missing data. The baseline value was carried forward if no post-baseline visits were available.
Serum urate values were obtained at the Day 14 visit. The percentage of subjects whose serum urate decreased to \<6.0 mg/dL at the Day 14 visit was summarized.
Outcome measures
| Measure |
Febuxostat 40 mg QD
n=34 Participants
Febuxostat 40 mg, orally, once daily.
|
Febuxostat 80 mg QD
n=37 Participants
Febuxostat 80 mg, orally, once daily.
|
Febuxostat 120 mg QD
n=34 Participants
Febuxostat 120 mg, orally, once daily.
|
Placebo QD
n=35 Participants
Placebo, orally, once daily
|
|---|---|---|---|---|
|
Percentage of Subjects Whose Serum Urate Level Decreased to <6.0 mg/dL at the Day 14 Visit.
|
56 percentage of subjects
|
68 percentage of subjects
|
94 percentage of subjects
|
0 percentage of subjects
|
SECONDARY outcome
Timeframe: Day 21.Population: The analysis was performed on 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. The LOCF method was used to impute missing data. The baseline value was carried forward if no post-baseline visits were available.
Serum urate values were obtained at the Day 21 visit. The percentage of subjects whose serum urate decreased to \<6.0 mg/dL at the Day 21 visit was summarized.
Outcome measures
| Measure |
Febuxostat 40 mg QD
n=34 Participants
Febuxostat 40 mg, orally, once daily.
|
Febuxostat 80 mg QD
n=37 Participants
Febuxostat 80 mg, orally, once daily.
|
Febuxostat 120 mg QD
n=34 Participants
Febuxostat 120 mg, orally, once daily.
|
Placebo QD
n=35 Participants
Placebo, orally, once daily
|
|---|---|---|---|---|
|
Percentage of Subjects Whose Serum Urate Level Decreased to <6.0 mg/dL at the Day 21 Visit.
|
59 percentage of subjects
|
76 percentage of subjects
|
97 percentage of subjects
|
0 percentage of subjects
|
SECONDARY outcome
Timeframe: Baseline and Day 7.Population: The analysis was performed on 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. The LOCF method was used to impute missing data. The baseline value was carried forward if no post-baseline visits were available.
Serum urate values were obtained at the Day 7 visit. The percent change in serum urate from baseline to the Day 7 visit was summarized.
Outcome measures
| Measure |
Febuxostat 40 mg QD
n=34 Participants
Febuxostat 40 mg, orally, once daily.
|
Febuxostat 80 mg QD
n=37 Participants
Febuxostat 80 mg, orally, once daily.
|
Febuxostat 120 mg QD
n=34 Participants
Febuxostat 120 mg, orally, once daily.
|
Placebo QD
n=35 Participants
Placebo, orally, once daily
|
|---|---|---|---|---|
|
Percent Change in Serum Urate Levels From Baseline to the Day 7 Visit.
|
-35.0 percent change from baseline
Standard Deviation 9.67
|
-39.2 percent change from baseline
Standard Deviation 15.9
|
-53.44 percent change from baseline
Standard Deviation 12.3
|
0.71 percent change from baseline
Standard Deviation 12.6
|
SECONDARY outcome
Timeframe: Baseline and Day 14.Population: The analysis was performed on 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. The LOCF method was used to impute missing data. The baseline value was carried forward if no post-baseline visits were available.
Serum urate values were obtained at the Day 14 visit. The percent change in serum urate from baseline to the Day 14 visit was summarized.
Outcome measures
| Measure |
Febuxostat 40 mg QD
n=34 Participants
Febuxostat 40 mg, orally, once daily.
|
Febuxostat 80 mg QD
n=37 Participants
Febuxostat 80 mg, orally, once daily.
|
Febuxostat 120 mg QD
n=34 Participants
Febuxostat 120 mg, orally, once daily.
|
Placebo QD
n=35 Participants
Placebo, orally, once daily
|
|---|---|---|---|---|
|
Percent Change in Serum Urate Levels From Baseline to the Day 14 Visit.
|
-37.1 percent change from baseline
Standard Deviation 11.70
|
-41.8 percent change from baseline
Standard Deviation 14.63
|
-56.9 percent change from baseline
Standard Deviation 8.36
|
1.62 percent change from baseline
Standard Deviation 10.21
|
SECONDARY outcome
Timeframe: Baseline and Day 21.Population: The analysis was performed on 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. The last observation carried forward (LOCF) method was used to impute missing data. The baseline value was carried forward if no post-baseline visits were available.
Serum urate values were obtained at the Day 21 visit. The percent change in serum urate from baseline to the Day 21 visit was summarized.
Outcome measures
| Measure |
Febuxostat 40 mg QD
n=34 Participants
Febuxostat 40 mg, orally, once daily.
|
Febuxostat 80 mg QD
n=37 Participants
Febuxostat 80 mg, orally, once daily.
|
Febuxostat 120 mg QD
n=34 Participants
Febuxostat 120 mg, orally, once daily.
|
Placebo QD
n=35 Participants
Placebo, orally, once daily
|
|---|---|---|---|---|
|
Percent Change in Serum Urate Levels From Baseline to the Day 21 Visit
|
-37.3 percent change from baseline
Standard Deviation 11.30
|
-43.9 percent change from baseline
Standard Deviation 16.3
|
-59.4 percent change from baseline
Standard Deviation 7.58
|
-0.57 percent change from baseline
Standard Deviation 10.63
|
SECONDARY outcome
Timeframe: Baseline and Day 28.Population: The analysis was performed on 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. The LOCF method was used to impute missing data. The baseline value was carried forward if no post-baseline visits were available.
Serum urate values were obtained at the Day 28 visit. The percent change in serum urate from baseline to the Day 28 visit was summarized.
Outcome measures
| Measure |
Febuxostat 40 mg QD
n=34 Participants
Febuxostat 40 mg, orally, once daily.
|
Febuxostat 80 mg QD
n=37 Participants
Febuxostat 80 mg, orally, once daily.
|
Febuxostat 120 mg QD
n=34 Participants
Febuxostat 120 mg, orally, once daily.
|
Placebo QD
n=35 Participants
Placebo, orally, once daily
|
|---|---|---|---|---|
|
Percent Change in Serum Urate Levels From Baseline to the Day 28 Visit.
|
-36.6 percent change from baseline
Standard Deviation 12.07
|
-44.3 percent change from baseline
Standard Deviation 17.53
|
-59.1 percent change from baseline
Standard Deviation 9.92
|
-2.2 percent change from baseline
Standard Deviation 12.5
|
SECONDARY outcome
Timeframe: Baseline and Any visit (Day 7, 14, 21,or 28)Population: The analysis was performed on 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.
Serum urate values were obtained at the Day 7, 14, 21,and 28 visits. The maximum percent change in serum urate levels obtained at any visit was summarized.
Outcome measures
| Measure |
Febuxostat 40 mg QD
n=34 Participants
Febuxostat 40 mg, orally, once daily.
|
Febuxostat 80 mg QD
n=37 Participants
Febuxostat 80 mg, orally, once daily.
|
Febuxostat 120 mg QD
n=34 Participants
Febuxostat 120 mg, orally, once daily.
|
Placebo QD
n=35 Participants
Placebo, orally, once daily
|
|---|---|---|---|---|
|
Maximum Percent Change in Serum Urate Level From Baseline During the Entire Treatment Period.
|
42.5 percent change from baseline
Standard Deviation 10.04
|
49.2 percent change from baseline
Standard Deviation 13.24
|
62.8 percent change from baseline
Standard Deviation 7.05
|
10.0 percent change from baseline
Standard Deviation 11.12
|
SECONDARY outcome
Timeframe: Baseline and Day 28.Population: The analysis was performed on 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. Missing data was not imputed
24-hour urine uric acid levels were obtained at the Day 28 visit. The percent change in 24-hour urine uric acid level from baseline to the Day 28 visit was summarized.
Outcome measures
| Measure |
Febuxostat 40 mg QD
n=33 Participants
Febuxostat 40 mg, orally, once daily.
|
Febuxostat 80 mg QD
n=35 Participants
Febuxostat 80 mg, orally, once daily.
|
Febuxostat 120 mg QD
n=34 Participants
Febuxostat 120 mg, orally, once daily.
|
Placebo QD
n=34 Participants
Placebo, orally, once daily
|
|---|---|---|---|---|
|
Percent Change in 24-hour Urine Uric Acid Level From Baseline to Day 28.
|
-43.6 percent change from baseline
Standard Deviation 28.9
|
-46.5 percent change from baseline
Standard Deviation 27.0
|
-45.7 percent change from baseline
Standard Deviation 30.1
|
5.9 percent change from baseline
Standard Deviation 37.1
|
Adverse Events
Febuxostat 40 mg QD
Febuxostat 80 mg QD
Febuxostat 120 mg QD
Placebo QD
Serious adverse events
| Measure |
Febuxostat 40 mg QD
n=37 participants at risk
Febuxostat 40 mg, orally, once daily.
|
Febuxostat 80 mg QD
n=40 participants at risk
Febuxostat 80 mg, orally, once daily.
|
Febuxostat 120 mg QD
n=38 participants at risk
Febuxostat 120 mg, orally, once daily.
|
Placebo QD
n=38 participants at risk
Placebo, orally, once daily
|
|---|---|---|---|---|
|
Psychiatric disorders
Suicide Attempt
|
0.00%
0/37
|
0.00%
0/40
|
2.6%
1/38
|
0.00%
0/38
|
|
Nervous system disorders
Delirium
|
0.00%
0/37
|
2.5%
1/40
|
0.00%
0/38
|
0.00%
0/38
|
|
Nervous system disorders
Guillian Barre Syndrome
|
0.00%
0/37
|
2.5%
1/40
|
0.00%
0/38
|
0.00%
0/38
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
0.00%
0/37
|
2.5%
1/40
|
0.00%
0/38
|
0.00%
0/38
|
|
General disorders
Back Pain
|
0.00%
0/37
|
0.00%
0/40
|
2.6%
1/38
|
0.00%
0/38
|
Other adverse events
| Measure |
Febuxostat 40 mg QD
n=37 participants at risk
Febuxostat 40 mg, orally, once daily.
|
Febuxostat 80 mg QD
n=40 participants at risk
Febuxostat 80 mg, orally, once daily.
|
Febuxostat 120 mg QD
n=38 participants at risk
Febuxostat 120 mg, orally, once daily.
|
Placebo QD
n=38 participants at risk
Placebo, orally, once daily
|
|---|---|---|---|---|
|
General disorders
Abdominal Pain
|
2.7%
1/37
|
2.5%
1/40
|
5.3%
2/38
|
7.9%
3/38
|
|
Injury, poisoning and procedural complications
Accidental Injury
|
0.00%
0/37
|
5.0%
2/40
|
2.6%
1/38
|
0.00%
0/38
|
|
General disorders
Back Pain
|
8.1%
3/37
|
5.0%
2/40
|
5.3%
2/38
|
2.6%
1/38
|
|
General disorders
Flu Syndrome
|
2.7%
1/37
|
0.00%
0/40
|
2.6%
1/38
|
5.3%
2/38
|
|
Nervous system disorders
Headache
|
8.1%
3/37
|
5.0%
2/40
|
5.3%
2/38
|
2.6%
1/38
|
|
Infections and infestations
Infection
|
2.7%
1/37
|
0.00%
0/40
|
2.6%
1/38
|
5.3%
2/38
|
|
General disorders
Pain
|
16.2%
6/37
|
7.5%
3/40
|
5.3%
2/38
|
10.5%
4/38
|
|
Gastrointestinal disorders
Diarrhoea
|
2.7%
1/37
|
20.0%
8/40
|
10.5%
4/38
|
10.5%
4/38
|
|
Gastrointestinal disorders
Dyspepsia
|
2.7%
1/37
|
5.0%
2/40
|
0.00%
0/38
|
0.00%
0/38
|
|
Gastrointestinal disorders
Increased Appetite
|
5.4%
2/37
|
0.00%
0/40
|
0.00%
0/38
|
0.00%
0/38
|
|
Investigations
Liver Function Tests Abnormal
|
5.4%
2/37
|
2.5%
1/40
|
2.6%
1/38
|
2.6%
1/38
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.4%
2/37
|
2.5%
1/40
|
5.3%
2/38
|
0.00%
0/38
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
2.7%
1/37
|
2.5%
1/40
|
5.3%
2/38
|
5.3%
2/38
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngitis
|
0.00%
0/37
|
2.5%
1/40
|
0.00%
0/38
|
5.3%
2/38
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/37
|
2.5%
1/40
|
7.9%
3/38
|
0.00%
0/38
|
Additional Information
Sr. VP, Clinical Science
Takeda Global Research & Development Center, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER