Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Febuxostat · 13 trials · 8 indications
Major adverse cardiovascular events (MACE) were defined as a composite of cardiovascular (CV) death, non-fatal myocardial infarction (MI), nonfatal stroke and unstable angina with urgent coronary revascularization; these events were adjudicated by an independent cardiovascular endpoints committee.
Major adverse cardiovascular events (MACE) were defined as a composite of cardiovascular (CV) death, non-fatal myocardial infarction (MI), nonfatal stroke and unstable angina with urgent coronary revascularization; these events were adjudicated by an independent cardiovascular endpoints committee.
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.
Serum urate values were obtained at the Month 1 visit. The percentage of subjects whose serum urate was \<6.0 mg/dL at the Month 1 visit was summarized.
Serum urate values were obtained at the Month 12 visit. The percentage of subjects whose serum urate was \<6.0 mg/dL at the Month 12 visit was summarized.
Serum urate values were obtained at the Month 24 visit. The percentage of subjects whose serum urate was \<6.0 mg/dL at the Month 24 visit was summarized.
Serum urate values were obtained at the Month 36 visit. The percentage of subjects whose serum urate was \<6.0 mg/dL at the Month 36 visit was summarized.
The percentage of subjects whose serum urate was \<6.0 mg/dL at the last visit on treatment was summarized. The last visit on treatment was the last visit at which a serum urate value was collected prior to any changes in drug and/or dose from the initial treatment assignment.
Each subject's serum urate at the last 3 visits determined the subject's response for the primary efficacy variable. A subject who prematurely discontinued without least 3 postbaseline serum urate levels was considered a nonresponder; if at least 3 serum urate were obtained postbaseline, those 3 visits were used. The last 3 visits used may have differed for each subject.
Each subject's serum urate at the last 3 visits determined the subject's response for the primary efficacy variable. A subject who prematurely discontinued without least 3 postbaseline serum urate levels was considered a nonresponder; if at least 3 serum urate were obtained postbaseline, those 3 visits were used. The last 3 visits used may have differed for each subject.
The change in 24-hour mean SBP measured at final visit or Week 6 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.
Renal function was assessed by measuring the change from Baseline in serum creatinine. Analyses were conducted by the Central Laboratory.
The single affected joint was defined as the joint with the history of the first acute gout flare. Radiographs (X-rays) of this single joint in the hands or feet were evaluated using the modified Sharp/van der Heijde method. Each erosion was assessed using a 4-point scale where 0=no erosions (best) to 3=large erosion passing the mid-line (worst). Individual erosion scores were summed to a maximum erosion score of 5 for joints in the hands and 10 for joints in the feet. Higher scores indicated more joint damage. A negative change from Baseline indicated improvement.
The change from Baseline to Month 6 in 24-hour urine uric acid is expressed as a percentage of the Baseline uUA value.
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.
Serum urate values were obtained at the Month 12 visit. The percentage of subjects whose serum urate was \<6.0 mg/dL at the Month 12 visit was summarized.
Serum urate values were obtained at the Month 18 visit. The percentage of subjects whose serum urate was \<6.0 mg/dL at the Month 18 visit was summarized.
Serum urate values were obtained at the Month 24 visit. The percentage of subjects whose serum urate was \<6.0 mg/dL at the Month 24 visit was summarized.
Serum urate values were obtained at the Month 36 visit. The percentage of subjects whose serum urate was \<6.0 mg/dL at the Month 36 visit was summarized.
Serum urate values were obtained at the Month 48 visit. The percentage of subjects whose serum urate was \<6.0 mg/dL at the Month 48 visit was summarized.
Serum urate values were obtained at the Month 60 visit. The percentage of subjects whose serum urate was \<6.0 mg/dL at the Month 60 visit was summarized.
The percentage of subjects 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.
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.
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. Participant blood samples were collected pre-dose and following a single oral dose.
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. Participant blood samples were collected pre-dose and following a single oral dose.
AUCt is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration. Participant blood samples were collected pre-dose and following a single oral dose.
AUCt is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUCt) Participant blood samples were collected pre-dose and following a single oral dose.
AUCinf is a measure of total plasma exposure to the drug from time zero extrapolated to infinity. Participant blood samples were collected pre-dose and following a single oral dose.
AUCinf is a measure of total plasma exposure to the drug from time zero extrapolated to infinity. Participant blood samples were collected pre-dose and following a single oral dose.
| Arm | Type | Description |
|---|---|---|
| Febuxostat | EXPERIMENTAL | Febuxostat 40 mg (or 80 mg beginning on week 4 if serum uric acid level was ≥6.0 mg/dL), tablets, orally, once daily for up to approximately 82 months. |
| Allopurinol | ACTIVE_COMPARATOR | Allopurinol 300 mg to 600 mg (increased in 100 mg increments each month until serum uric acid was \<6.0 mg/dL), tablets, orally, once daily for up to approximately 83 months to participants with mildly impaired renal function or normal renal function (estimated creatinine clearance \[eCLcr\] ≥60 mL/min) or allopurinol 200 mg to 400 mg (increased in 100 mg increments each month until serum uric acid was \<6.0 mg/dL), tablets, orally, once daily for up to approximately 83 months to participants with moderately impaired renal function (eCLcr ≥30 but \<60 mL/min). |
| Febuxostat 40 mg QD | EXPERIMENTAL | - |
| Febuxostat 80 mg QD | EXPERIMENTAL | - |
| Allopurinol 200 mg or 300 mg QD | ACTIVE_COMPARATOR | (dependent on renal function) |
| Febuxostat 120 mg QD | EXPERIMENTAL | - |
| Allopurinol QD | ACTIVE_COMPARATOR | - |
| Febuxostat 240 mg QD | EXPERIMENTAL | - |
| Placebo QD | PLACEBO_COMPARATOR | - |
| Allopurinol 300 mg QD | ACTIVE_COMPARATOR | - |
| Placebo | PLACEBO_COMPARATOR | Placebo-matching capsules, orally, twice daily for up to 12 months. |
| Febuxostat 30 mg BID | EXPERIMENTAL | Febuxostat 30 mg, capsules, orally, twice daily (BID) for up to 12 months. |
| Febuxostat 40/80 mg QD | EXPERIMENTAL | Participants initially received febuxostat 40 mg, capsules, once daily (QD) and one placebo-matching capsule QD and remained on this dose for up to 12 months if their serum urate (sUA) was \<6.0 mg/dL at the Day 14 visit. Participants whose sUA was ≥6.0 mg/dL at the Day 14 visit received febuxostat 80 mg, capsule, QD, and one placebo-matching capsule QD at the Month 1 visit, and for the remainder of the study. |
| Febuxostat 40 mg or 80 mg | EXPERIMENTAL | Febuxostat 40 mg or 80 mg (based on serum urate levels at Day 14), capsules, orally, once daily for up to 24 Months. |
| 1 | EXPERIMENTAL | - |
| 2 | EXPERIMENTAL | - |
| 3 | EXPERIMENTAL | - |
| Sequence 1: ABDC | EXPERIMENTAL | Experimental: Sequence 1: ABDC Febuxostat 80 mg extended-release (XR) capsule, orally, once, after a 10-hour fast, and 20 mL Maalox Advance Regular Strength liquid containing Aluminum Hydroxide 200 mg, Magnesium Hydroxide 200 mg, and Simethicone 20 mg/5 mL (hereafter referred as Maalox) or equivalent, orally, once, after a 10-hour fast, on Day 1 of Period 1 (A), followed by a 7-day washout period, followed by Maalox or equivalent, orally, once, after a 9-hour fast, and febuxostat 80 mg XR capsule, orally, once, after a 10-hour fast (1 hour after Maalox or equivalent), on Day 1 of Period 2 (B), followed by a 7-day washout period, followed by febuxostat 80 mg XR capsule, orally, once, after a 10-hour fast, on Day 1 of Period 3 (D), followed by a 7-day washout period, followed by febuxostat 80 mg XR capsule, orally, once, after a 10-hour fast, and Maalox or equivalent, orally, once, after an 11-hour fast (1 hour after febuxostat), on Day 1 of Period 4 (C). |
| Sequence 2: DACB | EXPERIMENTAL | Experimental: Sequence 2: DACB Febuxostat 80 mg XR capsule, orally, once, after a 10-hour fast, on Day 1 of Period 1, followed by a 7-day washout period, followed by febuxostat 80 mg extended-release (XR) capsule, orally, once, after a 10-hour fast, and Maalox or equivalent, orally, once, after a 10-hour fast, on Day 1 of Period 2, followed by a 7-day washout period, followed by febuxostat 80 mg XR capsule, orally, once, after a 10-hour fast, and Maalox or equivalent, orally, once, after an 11-hour fast (1 hour after febuxostat), on Day 1 of Period 3, followed by a 7-day washout period, followed by Maalox or equivalent, orally, once, after a 9-hour fast, and febuxostat 80 mg XR capsule, orally, once, after a 10-hour fast (1 hour after Maalox or equivalent), on Day 1 of Period 4. |
| Sequence 3: CDBA | EXPERIMENTAL | Febuxostat 80 mg XR capsule, orally, once, after a 10-hour fast, and Maalox or equivalent, orally, once, after an 11-hour fast (1 hour after febuxostat), on Day 1 of Period 1, followed by a 7-day washout period, followed by febuxostat 80 mg XR capsule, orally, once, after a 10-hour fast, on Day 1 of Period 2, followed by a 7-day washout period, followed by Maalox or equivalent, orally, once, after a 9-hour fast, and febuxostat 80 mg XR capsule, orally, once, after a 10-hour fast (1 hour after Maalox or equivalent), on Day 1 of Period 3, followed by a 7-day washout period, followed by Febuxostat 80 mg extended-release (XR) capsule, orally, once, after a 10-hour fast, and Maalox or equivalent, orally, once, after a 10-hour fast, on Day 1 of Period 4. |
| Sequence 4: BCAD | EXPERIMENTAL | Maalox or equivalent, orally, once, after a 9-hour fast, and febuxostat 80 mg XR capsule, orally, once, after a 10-hour fast (1 hour after Maalox), on Day 1 of Period 1, followed by a 7-day washout period, followed by febuxostat 80 mg XR capsule, orally, once, after a 10-hour fast, and Maalox or equivalent, orally, once, after an 11-hour fast (1 hour after febuxostat), on Day 1 of Period 2, followed by a 7-day washout period, followed by febuxostat 80 mg extended-release (XR) capsule, orally, once, after a 10-hour fast, and Maalox or equivalent, orally, once, after a 10-hour fast, on Day 1 of Period 3, followed by a 7-day washout period, followed by febuxostat 80 mg XR capsule, orally, once, after a 10-hour fast, on Day 1 of Period 4. |
| Treatment Sequence ABC | EXPERIMENTAL | Febuxostat extended release (XR) 80 mg, capsules, orally, once on Day 1 of Period 1 after a high-fat meal, followed by a 7-day washout period, followed by febuxostat XR 40 mg, capsules, orally, once on Day 1 of Period 2 after a 10-hour fast, followed by a 7-day washout period, followed by febuxostat XR 80, capsules, orally, once on Day 1 of Period 3 after a 10-hour fast. |
| Treatment Sequence BCA | EXPERIMENTAL | Febuxostat XR 40 mg, capsules, orally, once on Day 1 of Period 1 after a 10-hour fast, followed by a 7-day washout period, followed by febuxostat XR 80 mg, capsules, orally, once on Day 1 of Period 2 after a 10-hour fast, followed by a 7-day washout period, followed by Febuxostat XR 80 mg, capsules, orally, once on Day 1 of Period 3 after a high-fat meal. |
| Treatment Sequence CAB | EXPERIMENTAL | Febuxostat XR 80 mg, capsules, orally, once on Day 1 of Period 1 after a 10-hour fast, followed by a 7-day washout period, followed by febuxostat XR 80 mg, capsules, orally, once on Day 1 of Period 2 after a high-fat meal, followed by a 7-day washout period, followed by febuxostat XR 40 mg, capsules, orally, once on Day 1 of Period 3 after a 10-hour fast. |
| Name | Type | Description |
|---|---|---|
| Febuxostat | DRUG | Febuxostat tablets |
| Allopurinol | DRUG | Allopurinol tablets |
| Placebo | DRUG | Placebo, orally, once daily for up to 28 weeks. |
| Placebo for Febuxostat | DRUG | Febuxostat placebo-matching capsules |
| Febuxostat XR | DRUG | Febuxostat extended-release (XR) capsules |
| Maalox Advance Regular Strength liquid | DRUG | Maalox Advance Regular Strength liquid containing Aluminum Hydroxide 200 mg, Magnesium Hydroxide 200 mg, and Simethicone 20 mg/5 mL or equivalent |
Inclusion Criteria: 1. The participant or the participant's legally acceptable representative signs and dates a written, informed consent form/Health Insurance Portability and Accountability Act (HIPAA) Authorization prior to the initiation of any study procedures. 2. The participant is male ≥50 ye...
Febuxostat is a small molecule being studied for use in cardiovascular disease, gout, hyperuricosuria, joint damage, and renal impairment. It is also being evaluated in healthy volunteers. The drug is developed by Takeda Pharmaceutical Company Limited and is currently in Phase 3 clinical development.
Febuxostat is a xanthine oxidase inhibitor that works by reducing the production of uric acid in the body. It is being studied for its effects on conditions related to high uric acid levels, such as gout and hyperuricosuria, as well as for potential benefits in cardiovascular disease and joint damage.
Febuxostat is developed by Takeda Pharmaceutical Company Limited, which is publicly traded under the ticker symbol TAK. The drug is a small molecule in Phase 3 clinical development for cardiovascular disease and other indications.
Febuxostat is in Phase 3 clinical development. It is an investigational drug and has not been approved by regulatory authorities. The drug has completed seven clinical trials, with no active trials currently ongoing.
Febuxostat has completed seven clinical trials, including NCT01077284 for hyperuricosuria and kidney stones, NCT01078389 for joint damage in gout, NCT01496469 for hypertension, and NCT02382640 for healthy volunteers. All trials are completed, with no active trials ongoing.
Febuxostat is also known by the brand name Uloric. It is a xanthine oxidase inhibitor used to treat gout and hyperuricemia. The drug is being studied for additional indications such as cardiovascular disease and joint damage.