Gout
Conditions
Keywords
Dotinurad, Febuxostat
Brief summary
The primary purpose of the study is to confirm the efficacy of dotinurad 4 milligram (mg) to febuxostat 40 mg on the percentage of participants achieving a serum uric acid (SUA) level less than or equal to (\<=) 6.0 milligrams per deciliter (mg/dL) at Week 24 in Chinese participants with gout.
Interventions
DRUGDotinurad
Dotinurad oral tablets.
DRUGFebuxostat
Febuxostat oral tablets.
OTHERDotinurad Matched Placebo
Dotinurad matched placebo oral tablets.
OTHERFebuxostat Matched Placebo
Febuxostat matched placebo oral tablets.
Sponsors
Eisai Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Gout participant (with a history of gout attack or concurrent gouty tophi) with SUA level greater than (\>) 7.0 mg/dL in the screening phase (within 14 days prior to randomization) 2. Male or female participant with age greater than or equal to (\>=) 18 years at the time of informed consent 3. Provide written informed consent signed by the participant prior to entering the study or undergoing any study procedures, indicating that they understand the purpose and procedures required for the study and are willing to participate in the study
Exclusion criteria
1. Has gouty arthritis that has not resolved within 14 days prior to randomization 2. Has secondary hyperuricemia 3. Comorbidities with nephrolithiasis or clinical urinary calculi (example, haematuria, back pain) 4. Evidence of clinically significant disease (example, cardiac disease: heart failure and angina unstable, respiratory, gastrointestinal, renal, or neurological disease: cerebral infarction) that in the opinion of the investigator could affect the participant's safety or interfere with the study assessments 5. Evidence of clinical significant hepatic disease: refer to Grade 2 in the Seriousness Grading Criteria for Adverse Drug Reactions or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3 multiple (\*) upper limit of normal (ULN) in the screening phase 6. Estimated glomerular filtration rate (eGFR) of less than (\<) 30 milliliter per minute/1.73 square meters in the screening phase 7. Systolic blood pressure of \>=180 millimetre of mercury (mmHg) or diastolic blood pressure of \>=110 mmHg in the screening phase 8. Hemoglobin A1c National Glycohemoglobin Standardization Program (NGSP) value of \>=8.4 percent (%) in the screening phase 9. Hypersensitivity to the study drugs (dotinurad or febuxostat) or their excipients, or all of urine alkalinizer (potassium citrate/sodium citrate hydrate compound preparations)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Serum Uric Acid (SUA) Level <=6.0 mg/dL at Week 24 (LOCF) | At Week 24 | Percentage of participants with SUA level less than or equal to (\<=) 6.0 milligrams per deciliter (mg/dL) at Week 24 was reported. In case the SUA level was missing, this data was compensated by the last observation carried forward (LOCF) method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With SUA Level <=6.0 mg/dL at Week 12 (LOCF) | At Week 12 | Percentage of participants with SUA level \<=6.0 mg/dL at Week 12 was reported. In case the SUA level was missing, this data was compensated by the LOCF method. |
| Percentage of Participants With SUA Level <=6.0 mg/dL at Weeks 4, 8, 12, 16, 20 and 24 | At Weeks 4, 8, 12, 16, 20 and 24 | Percentage of participants with SUA level \<=6.0 mg/dL at Weeks 4, 8, 12, 16, 20 and 24 was reported. Data was reported for observed participants at specified visits. |
| Mean Percent Reduction From Baseline in SUA Level at Weeks 4, 8, 12, 16, 20 and 24 | Baseline, Weeks 4, 8, 12, 16, 20 and 24 | Mean percent reduction from baseline in SUA level at Weeks 4, 8, 12, 16, 20 and 24 was reported. |
| Mean Change From Baseline in SUA Level at Weeks 4, 8, 12, 16, 20 and 24 | Baseline, Weeks 4, 8, 12, 16, 20 and 24 | Mean change from baseline in SUA level at Weeks 4, 8, 12, 16, 20 and 24 was reported. |
| Mean SUA Level at Baseline, Weeks 4, 8, 12, 16, 20 and 24 | Baseline, Weeks 4, 8, 12, 16, 20 and 24 | Mean SUA level at Baseline, Weeks 4, 8, 12, 16, 20 and 24 was reported. |
Countries
China
Participant flow
Recruitment details
Participants took part in the study at 30 investigative sites in China from 21 December 2021 to 14 June 2023.
Pre-assignment details
A total of 604 participants were screened, of which 153 were screen failure. 451 participants were enrolled and randomized and 448 received study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Febuxostat Participants received febuxostat 20 mg tablet, orally, once daily for first 4 weeks; followed febuxostat 40 mg tablet, orally, once daily for 20 weeks. To maintain blinding, participants also received the dotinurad matching placebo up to Week 24. | 220 |
| Dotinurad Participants received dotinurad 1 mg tablet, orally, once daily for first 4 weeks; followed by dotinurad 2 mg tablet, orally, once daily for 8 weeks; further followed by dotinurad 4 mg tablet, orally, once daily for 12 weeks. To maintain blinding, participants also received the febuxostat matching placebo up to Week 24. | 221 |
| Total | 441 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 6 |
| Overall Study | Inadequate therapeutic effect or progression of disease | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Other | 5 | 4 |
| Overall Study | Participant choice | 5 | 10 |
| Overall Study | Randomized but not treated | 1 | 2 |
| Overall Study | Serum uric acid (SUA) level of <=2.0 milligram per deciliter (mg/dL) for 2 consecutive visits | 0 | 1 |
| Overall Study | Use of prohibited concomitant drug | 1 | 1 |
| Overall Study | Withdrawal of consent | 5 | 4 |
Baseline characteristics
| Characteristic | Dotinurad | Total | Febuxostat |
|---|---|---|---|
| Age, Continuous | 38.9 years STANDARD_DEVIATION 11.56 | 39.1 years STANDARD_DEVIATION 11.26 | 39.2 years STANDARD_DEVIATION 10.98 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 221 Participants | 441 Participants | 220 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 221 Participants | 441 Participants | 220 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 3 Participants | 8 Participants | 5 Participants |
| Sex: Female, Male Male | 218 Participants | 433 Participants | 215 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 225 | 0 / 223 |
| other Total, other adverse events | 203 / 225 | 201 / 223 |
| serious Total, serious adverse events | 4 / 225 | 3 / 223 |
Outcome results
Primary
Percentage of Participants With Serum Uric Acid (SUA) Level <=6.0 mg/dL at Week 24 (LOCF)
Percentage of participants with SUA level less than or equal to (\<=) 6.0 milligrams per deciliter (mg/dL) at Week 24 was reported. In case the SUA level was missing, this data was compensated by the last observation carried forward (LOCF) method.
Time frame: At Week 24
Population: Full Analysis Set was the group of randomized participants who received at least 1 dose of study drug and had at least 1 post-dose primary efficacy measurement. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Febuxostat | Percentage of Participants With Serum Uric Acid (SUA) Level <=6.0 mg/dL at Week 24 (LOCF) | 38.1 percentage of participants |
| Dotinurad | Percentage of Participants With Serum Uric Acid (SUA) Level <=6.0 mg/dL at Week 24 (LOCF) | 73.6 percentage of participants |
p-value: <0.00195% CI: [27.36, 44.37]Cochran-Mantel-Haenszel
Secondary
Mean Change From Baseline in SUA Level at Weeks 4, 8, 12, 16, 20 and 24
Mean change from baseline in SUA level at Weeks 4, 8, 12, 16, 20 and 24 was reported.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20 and 24
Population: Full Analysis Set was the group of randomized participants who received at least 1 dose of study drug and had at least 1 post-dose primary efficacy measurement. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure and number analyzed signifies those participants who were evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Febuxostat | Mean Change From Baseline in SUA Level at Weeks 4, 8, 12, 16, 20 and 24 | Change from Baseline at Week 4 | -2.60 mg/dL | Standard Deviation 1.457 |
| Febuxostat | Mean Change From Baseline in SUA Level at Weeks 4, 8, 12, 16, 20 and 24 | Change from Baseline at Week 8 | -3.62 mg/dL | Standard Deviation 1.597 |
| Febuxostat | Mean Change From Baseline in SUA Level at Weeks 4, 8, 12, 16, 20 and 24 | Change from Baseline at Week 12 | -3.52 mg/dL | Standard Deviation 1.691 |
| Febuxostat | Mean Change From Baseline in SUA Level at Weeks 4, 8, 12, 16, 20 and 24 | Change from Baseline at Week 16 | -3.44 mg/dL | Standard Deviation 1.731 |
| Febuxostat | Mean Change From Baseline in SUA Level at Weeks 4, 8, 12, 16, 20 and 24 | Change from Baseline at Week 20 | -3.52 mg/dL | Standard Deviation 1.757 |
| Febuxostat | Mean Change From Baseline in SUA Level at Weeks 4, 8, 12, 16, 20 and 24 | Change from Baseline at Week 24 | -3.20 mg/dL | Standard Deviation 1.8 |
| Dotinurad | Mean Change From Baseline in SUA Level at Weeks 4, 8, 12, 16, 20 and 24 | Change from Baseline at Week 20 | -4.92 mg/dL | Standard Deviation 2.201 |
| Dotinurad | Mean Change From Baseline in SUA Level at Weeks 4, 8, 12, 16, 20 and 24 | Change from Baseline at Week 4 | -2.70 mg/dL | Standard Deviation 1.508 |
| Dotinurad | Mean Change From Baseline in SUA Level at Weeks 4, 8, 12, 16, 20 and 24 | Change from Baseline at Week 16 | -5.05 mg/dL | Standard Deviation 2.078 |
| Dotinurad | Mean Change From Baseline in SUA Level at Weeks 4, 8, 12, 16, 20 and 24 | Change from Baseline at Week 8 | -3.80 mg/dL | Standard Deviation 1.973 |
| Dotinurad | Mean Change From Baseline in SUA Level at Weeks 4, 8, 12, 16, 20 and 24 | Change from Baseline at Week 24 | -4.71 mg/dL | Standard Deviation 2.415 |
| Dotinurad | Mean Change From Baseline in SUA Level at Weeks 4, 8, 12, 16, 20 and 24 | Change from Baseline at Week 12 | -3.78 mg/dL | Standard Deviation 1.817 |
Secondary
Mean Percent Reduction From Baseline in SUA Level at Weeks 4, 8, 12, 16, 20 and 24
Mean percent reduction from baseline in SUA level at Weeks 4, 8, 12, 16, 20 and 24 was reported.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20 and 24
Population: Full Analysis Set was the group of randomized participants who received at least 1 dose of study drug and had at least 1 post-dose primary efficacy measurement. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure and number analyzed signifies those participants who were evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Febuxostat | Mean Percent Reduction From Baseline in SUA Level at Weeks 4, 8, 12, 16, 20 and 24 | Percent Reduction from Baseline at Week 12 | 36.06 Percent change in SUA level | Standard Deviation 15.383 |
| Febuxostat | Mean Percent Reduction From Baseline in SUA Level at Weeks 4, 8, 12, 16, 20 and 24 | Percent Reduction from Baseline at Week 16 | 35.13 Percent change in SUA level | Standard Deviation 16.016 |
| Febuxostat | Mean Percent Reduction From Baseline in SUA Level at Weeks 4, 8, 12, 16, 20 and 24 | Percent Reduction from Baseline at Week 20 | 35.71 Percent change in SUA level | Standard Deviation 15.728 |
| Febuxostat | Mean Percent Reduction From Baseline in SUA Level at Weeks 4, 8, 12, 16, 20 and 24 | Percent Reduction from Baseline at Week 24 | 32.28 Percent change in SUA level | Standard Deviation 16.907 |
| Febuxostat | Mean Percent Reduction From Baseline in SUA Level at Weeks 4, 8, 12, 16, 20 and 24 | Percent Reduction from Baseline at Week 8 | 37.06 Percent change in SUA level | Standard Deviation 14.018 |
| Febuxostat | Mean Percent Reduction From Baseline in SUA Level at Weeks 4, 8, 12, 16, 20 and 24 | Percent Reduction from Baseline at Week 4 | 26.43 Percent change in SUA level | Standard Deviation 13.2 |
| Dotinurad | Mean Percent Reduction From Baseline in SUA Level at Weeks 4, 8, 12, 16, 20 and 24 | Percent Reduction from Baseline at Week 8 | 39.10 Percent change in SUA level | Standard Deviation 18.931 |
| Dotinurad | Mean Percent Reduction From Baseline in SUA Level at Weeks 4, 8, 12, 16, 20 and 24 | Percent Reduction from Baseline at Week 12 | 38.62 Percent change in SUA level | Standard Deviation 17.305 |
| Dotinurad | Mean Percent Reduction From Baseline in SUA Level at Weeks 4, 8, 12, 16, 20 and 24 | Percent Reduction from Baseline at Week 24 | 48.07 Percent change in SUA level | Standard Deviation 23.243 |
| Dotinurad | Mean Percent Reduction From Baseline in SUA Level at Weeks 4, 8, 12, 16, 20 and 24 | Percent Reduction from Baseline at Week 16 | 51.47 Percent change in SUA level | Standard Deviation 18.542 |
| Dotinurad | Mean Percent Reduction From Baseline in SUA Level at Weeks 4, 8, 12, 16, 20 and 24 | Percent Reduction from Baseline at Week 4 | 27.43 Percent change in SUA level | Standard Deviation 14.754 |
| Dotinurad | Mean Percent Reduction From Baseline in SUA Level at Weeks 4, 8, 12, 16, 20 and 24 | Percent Reduction from Baseline at Week 20 | 50.22 Percent change in SUA level | Standard Deviation 20.714 |
Secondary
Mean SUA Level at Baseline, Weeks 4, 8, 12, 16, 20 and 24
Mean SUA level at Baseline, Weeks 4, 8, 12, 16, 20 and 24 was reported.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20 and 24
Population: Full Analysis Set was the group of randomized participants who received at least 1 dose of study drug and had at least 1 post-dose primary efficacy measurement. Here, number analyzed signifies those participants who were evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Febuxostat | Mean SUA Level at Baseline, Weeks 4, 8, 12, 16, 20 and 24 | Week 4 | 7.07 mg/dL | Standard Deviation 1.432 |
| Febuxostat | Mean SUA Level at Baseline, Weeks 4, 8, 12, 16, 20 and 24 | Week 8 | 6.01 mg/dL | Standard Deviation 1.372 |
| Febuxostat | Mean SUA Level at Baseline, Weeks 4, 8, 12, 16, 20 and 24 | Week 12 | 6.12 mg/dL | Standard Deviation 1.546 |
| Febuxostat | Mean SUA Level at Baseline, Weeks 4, 8, 12, 16, 20 and 24 | Week 16 | 6.24 mg/dL | Standard Deviation 1.605 |
| Febuxostat | Mean SUA Level at Baseline, Weeks 4, 8, 12, 16, 20 and 24 | Week 20 | 6.14 mg/dL | Standard Deviation 1.467 |
| Febuxostat | Mean SUA Level at Baseline, Weeks 4, 8, 12, 16, 20 and 24 | Week 24 | 6.49 mg/dL | Standard Deviation 1.575 |
| Febuxostat | Mean SUA Level at Baseline, Weeks 4, 8, 12, 16, 20 and 24 | Baseline | 9.65 mg/dL | Standard Deviation 1.426 |
| Dotinurad | Mean SUA Level at Baseline, Weeks 4, 8, 12, 16, 20 and 24 | Week 4 | 6.93 mg/dL | Standard Deviation 1.447 |
| Dotinurad | Mean SUA Level at Baseline, Weeks 4, 8, 12, 16, 20 and 24 | Week 20 | 4.76 mg/dL | Standard Deviation 1.9 |
| Dotinurad | Mean SUA Level at Baseline, Weeks 4, 8, 12, 16, 20 and 24 | Week 8 | 5.80 mg/dL | Standard Deviation 1.857 |
| Dotinurad | Mean SUA Level at Baseline, Weeks 4, 8, 12, 16, 20 and 24 | Baseline | 9.67 mg/dL | Standard Deviation 1.451 |
| Dotinurad | Mean SUA Level at Baseline, Weeks 4, 8, 12, 16, 20 and 24 | Week 12 | 5.88 mg/dL | Standard Deviation 1.708 |
| Dotinurad | Mean SUA Level at Baseline, Weeks 4, 8, 12, 16, 20 and 24 | Week 24 | 5.00 mg/dL | Standard Deviation 2.296 |
| Dotinurad | Mean SUA Level at Baseline, Weeks 4, 8, 12, 16, 20 and 24 | Week 16 | 4.65 mg/dL | Standard Deviation 1.776 |
Secondary
Percentage of Participants With SUA Level <=6.0 mg/dL at Week 12 (LOCF)
Percentage of participants with SUA level \<=6.0 mg/dL at Week 12 was reported. In case the SUA level was missing, this data was compensated by the LOCF method.
Time frame: At Week 12
Population: Full Analysis Set was the group of randomized participants who received at least 1 dose of study drug and had at least 1 post-dose primary efficacy measurement. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Febuxostat | Percentage of Participants With SUA Level <=6.0 mg/dL at Week 12 (LOCF) | 50.5 percentage of participants |
| Dotinurad | Percentage of Participants With SUA Level <=6.0 mg/dL at Week 12 (LOCF) | 55.5 percentage of participants |
95% CI: [-3.69, 14.17]
Secondary
Percentage of Participants With SUA Level <=6.0 mg/dL at Weeks 4, 8, 12, 16, 20 and 24
Percentage of participants with SUA level \<=6.0 mg/dL at Weeks 4, 8, 12, 16, 20 and 24 was reported. Data was reported for observed participants at specified visits.
Time frame: At Weeks 4, 8, 12, 16, 20 and 24
Population: Full Analysis Set was the group of randomized participants who received at least 1 dose of study drug and had at least 1 post-dose primary efficacy measurement. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure and number analyzed signifies those participants who were evaluable at specified timepoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Febuxostat | Percentage of Participants With SUA Level <=6.0 mg/dL at Weeks 4, 8, 12, 16, 20 and 24 | Week 4 | 26.3 percentage of participants |
| Febuxostat | Percentage of Participants With SUA Level <=6.0 mg/dL at Weeks 4, 8, 12, 16, 20 and 24 | Week 8 | 55.6 percentage of participants |
| Febuxostat | Percentage of Participants With SUA Level <=6.0 mg/dL at Weeks 4, 8, 12, 16, 20 and 24 | Wee 12 | 52.8 percentage of participants |
| Febuxostat | Percentage of Participants With SUA Level <=6.0 mg/dL at Weeks 4, 8, 12, 16, 20 and 24 | Week 16 | 48.7 percentage of participants |
| Febuxostat | Percentage of Participants With SUA Level <=6.0 mg/dL at Weeks 4, 8, 12, 16, 20 and 24 | Week 20 | 53.7 percentage of participants |
| Febuxostat | Percentage of Participants With SUA Level <=6.0 mg/dL at Weeks 4, 8, 12, 16, 20 and 24 | Week 24 | 40.2 percentage of participants |
| Dotinurad | Percentage of Participants With SUA Level <=6.0 mg/dL at Weeks 4, 8, 12, 16, 20 and 24 | Week 20 | 83.0 percentage of participants |
| Dotinurad | Percentage of Participants With SUA Level <=6.0 mg/dL at Weeks 4, 8, 12, 16, 20 and 24 | Week 4 | 27.6 percentage of participants |
| Dotinurad | Percentage of Participants With SUA Level <=6.0 mg/dL at Weeks 4, 8, 12, 16, 20 and 24 | Week 16 | 84.7 percentage of participants |
| Dotinurad | Percentage of Participants With SUA Level <=6.0 mg/dL at Weeks 4, 8, 12, 16, 20 and 24 | Week 8 | 62.7 percentage of participants |
| Dotinurad | Percentage of Participants With SUA Level <=6.0 mg/dL at Weeks 4, 8, 12, 16, 20 and 24 | Week 24 | 78.1 percentage of participants |
| Dotinurad | Percentage of Participants With SUA Level <=6.0 mg/dL at Weeks 4, 8, 12, 16, 20 and 24 | Wee 12 | 56.9 percentage of participants |