Effect of Antacid on Bioavailability of Febuxostat After Administration of a Febuxostat 80 mg Extended-Release Capsule

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02382640
• Collaborator: (none)
• Enrollment: 36
• Location: 1
• Arms: 4
• Duration (Months): 2
• Patients Per Site Per Month: 18

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the effect of antacid administration, and its timing, on the bioavailability of a single dose of febuxostat extended-release (XR) 80 mg.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: Febuxostat XR; Drug: Maalox Advance Regular Strength liquid	Phase 1

Detailed Description

The drug being tested in this study is called febuxostat extended-release (XR). Febuxostat XR is being tested to assess if antacids affect how the drug moves throughout the body. This study will look at lab safety and side effects in people who take febuxostat XR.

This cross-over study will enroll approximately 36 patients. Participants will be randomly assigned to one of four treatment sequences. All participants will receive the following study medications by the end of the study:

• Febuxostat XR 80 mg capsules

• Maalox Advance Regular Strength liquid containing Aluminum Hydroxide 200 mg, Magnesium Hydroxide 200 mg, and Simethicone 20 mg/5 mL or equivalent

All participants will be administered one dose of one or both of the study medications on Day 1 of four separate study periods.

This single-centre trial will be conducted in the United States. The overall time to participate in this study is up to 84 days. Participants will make 5 visits to the clinic including four 4-day periods of confinement to the clinic, and will be contacted by telephone 30 days after last dose of study drug for a follow-up assessment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Open-Label, Single Center, Single-Dose, Randomized, 4-Way Crossover Study to Assess the Effect of an Antacid on the Bioavailability of Febuxostat After Oral Administration of a 80 mg Febuxostat Extended-Release (XR) Capsule Formulation
• Study Start Date: Mar 1, 2015
• Actual Primary Completion Date: May 1, 2015
• Actual Study Completion Date: May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sequence 1: ABDC 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).	Drug: Febuxostat XR; Febuxostat extended-release (XR) capsules; Drug: Maalox Advance Regular Strength liquid; Maalox Advance Regular Strength liquid containing Aluminum Hydroxide 200 mg, Magnesium Hydroxide 200 mg, and Simethicone 20 mg/5 mL or equivalent
Experimental: Sequence 2: DACB 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.	Drug: Febuxostat XR; Febuxostat extended-release (XR) capsules; Drug: Maalox Advance Regular Strength liquid; Maalox Advance Regular Strength liquid containing Aluminum Hydroxide 200 mg, Magnesium Hydroxide 200 mg, and Simethicone 20 mg/5 mL or equivalent
Experimental: Sequence 3: CDBA 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.	Drug: Febuxostat XR; Febuxostat extended-release (XR) capsules; Drug: Maalox Advance Regular Strength liquid; Maalox Advance Regular Strength liquid containing Aluminum Hydroxide 200 mg, Magnesium Hydroxide 200 mg, and Simethicone 20 mg/5 mL or equivalent
Experimental: Sequence 4: BCAD 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.	Drug: Febuxostat XR; Febuxostat extended-release (XR) capsules; Drug: Maalox Advance Regular Strength liquid; Maalox Advance Regular Strength liquid containing Aluminum Hydroxide 200 mg, Magnesium Hydroxide 200 mg, and Simethicone 20 mg/5 mL or equivalent

Outcome Measures

Primary Outcome Measures

1. Cmax: Maximum Observed Plasma Concentration for Febuxostat [Days 1 at multiple timepoints (up to 48 hours) post-dose]

2. AUC(0-tau): Area Under the Plasma Concentration-time Curve During the Dosing Interval for Febuxostat [Days 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose]

3. AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Febuxostat [Days 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose]

4. Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) [Day 1 up to 30 days after last dose of drug (Day 31 for each of the 4 periods)]

5. Number of Participants With Clinically Significant Change From Baseline in Vital Signs [Day 1 up to 30 days after last dose of drug (Day 31 for each of the 4 periods)]

6. Number of Participants With Clinically Significant Change From Baseline in Physical Examination Findings [Day 1 up to 30 days after last dose of drug (Day 31 for each of the 4 periods)]

7. Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Evaluation [Day 1 up to 30 days after last dose of drug (Day 31 for each of the 4 periods)]

8. Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) [Day 1 up to 30 days after last dose of drug (Day 31 for each of the 4 periods)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Is a healthy adult male or female aged 18 to 55 years, inclusive, by check-in (Day-1 of Period 1)

2. Weighs at least 50 kg (110 pounds), and has a body mass index (BMI) between 18.0 kg/m^{2 to 30 kg/m}2, inclusive at Screening.

3. Has estimated glomerular filtration rate ≥90 mL/min

Exclusion Criteria:

Any participant who meets any of the following criteria will not qualify for entry into the study:

1. Has received any investigational compound within 30 days prior to the first dose of study medication.

2. Has received febuxostat in a previous clinical study or as a therapeutic agent.

3. Has a known hypersensitivity to any xanthine oxidase inhibitor, xanthine compounds or any component of the formulation of febuxostat tablets (see Package Insert) or to caffeine.

4. Has a known hypersensitivity to aluminum, magnesium hydroxide, or any component of the formulation of antacid (Maalox Advanced Regular Strength or equivalent) (see Package Insert).

5. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to the Screening visit or is unwilling to agree to abstain from alcohol and drugs throughout the study. If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 30 days after participating in this study; or intending to donate ova during such time period.

6. Has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (ie, a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis frequent [more than once per week] occurrence of heartburn, or any surgical intervention [eg, cholecystectomy]).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Austin	Texas	United States	78744

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director Clinical Science, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT02382640
• Other Study ID Numbers: Febuxostat XR-1010; U1111-1163-1813
• First Posted: Mar 9, 2015
• Last Update Posted: Apr 29, 2016
• Last Verified: Mar 1, 2016

• Keywords provided by Takeda: Drug therapy
• Additional relevant MeSH terms: Febuxostat

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 1 investigative site in United States from 23-Feb-15 to 04-May-15.
Pre-assignment Detail	Healthy participants were enrolled in this 4 period cross over study to receive 4 regimens which included febuxostat extended release (XR) 80 milligram (mg) and Maalox suspension 20 milliliter (mL) based on different fasting conditions.

Arm/Group Title	Regimen A, Then B, Then D, Then C	Regimen D, Then A, Then C, Then B	Regimen C, Then D, Then B, Then A	Regimen B, Then C, Then A, Then D
Arm/Group Description	Regimen(Reg)A(Febuxostat XR 80mg,capsule, orally, single dose after a 10hour(hr) fast and concurrently with Maalox 20mL(200mg magnesium hydroxide, 200mg aluminum hydroxide, and 20mg simethicone/5mL)or equivalent brand antacid, suspension, orally, single dose) on Day1 of first intervention period(3 Days),followed by 1week washout period, followed by RegB(Maalox 20mL,suspension,orally, single dose after a 9hr fast,followed by Febuxostat XR 80mg,capsule, orally, single dose after a 10hr fast[or 1hr after antacid dose]) on Day1 of second intervention period(3Days),followed by 1 week washout period, followed by RegD(Febuxostat XR 80mg,capsule, orally, single dose after a 10hr fast) on Day 1 of third intervention period(3Days),followed by 1week washout period, followed by RegC(Febuxostat XR 80mg,capsule, orally, single dose after a 10hr fast followed by Maalox 20mL, suspension, orally, single dose after 11hr fast[or 1hr after Febuxostat dose]) on Day1 of fourth intervention period(3 Days).	Regimen D (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast) on Day 1 of first intervention period (3 Days), followed by Regimen A (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast and concurrently with Maalox 20 mL, suspension, orally, single dose) on Day 1 of second intervention period (3 Days), followed by 1 week washout period, followed by Regimen C (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast followed by Maalox 20 mL, suspension, orally, single dose after 11-hour fast [or 1 hour after Febuxostat dose]) on Day 1 of third intervention period (3 Days), followed by 1 week washout period, followed by Regimen B (Maalox 20 mL, suspension, orally, single dose after a 9-hour fast, followed by Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast [or 1 hour after antacid dose]).	Regimen C (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast followed by Maalox 20 mL, suspension, orally, single dose after 11-hour fast [or 1 hour after Febuxostat dose]) on Day 1 of first intervention period (3 Days), followed by 1 week washout period, Regimen D (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast) on Day 1 of second intervention period (3 Days), followed by 1 week washout period, Regimen B (Maalox 20 mL, suspension, orally, single dose after a 9-hour fast, followed by Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast [or 1 hour after antacid dose]) on Day 1 of third intervention period (3 Days), followed by Regimen A (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast and concurrently with Maalox 20 mL, suspension, orally, single dose) on Day 1 of fourth intervention period (3 Days).	Regimen B (Maalox 20 mL, suspension, orally, single dose after a 9-hour fast, followed by Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast [or 1 hour after antacid dose]) on Day 1 of first intervention period (3 Days), followed by 1 week washout period, followed by Regimen C (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast followed by Maalox 20 mL, suspension, orally, single dose after 11-hour fast [or 1 hour after Febuxostat dose]) on Day 1 of second intervention period (3 Days), followed by Regimen A (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast and concurrently with Maalox 20 mL, suspension, orally, single dose) on Day 1 of third intervention period (3 Days), Regimen D (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast) on Day 1 of fourth intervention period (3 Days).
Period Title: Intervention Period 1 (3 Days)
STARTED	9	9	9	9
COMPLETED	9	9	9	9
NOT COMPLETED	0	0	0	0
Period Title: Intervention Period 1 (3 Days)
STARTED	9	9	9	9
COMPLETED	9	9	9	9
NOT COMPLETED	0	0	0	0
Period Title: Intervention Period 1 (3 Days)
STARTED	9	9	9	9
COMPLETED	9	9	9	9
NOT COMPLETED	0	0	0	0
Period Title: Intervention Period 1 (3 Days)
STARTED	9	9	9	9
COMPLETED	9	9	9	9
NOT COMPLETED	0	0	0	0
Period Title: Intervention Period 1 (3 Days)
STARTED	9	9	9	9
COMPLETED	9	9	9	9
NOT COMPLETED	0	0	0	0
Period Title: Intervention Period 1 (3 Days)
STARTED	9	9	9	9
COMPLETED	9	9	9	9
NOT COMPLETED	0	0	0	0
Period Title: Intervention Period 1 (3 Days)
STARTED	9	9	9	9
COMPLETED	8	9	9	9
NOT COMPLETED	1	0	0	0

Baseline Characteristics

Arm/Group Title	Regimen A, Then B, Then D, Then C	Regimen D, Then A, Then C, Then B	Regimen C, Then D, Then B, Then A	Regimen B, Then C, Then A, Then D	Total
Arm/Group Description	Regimen(Reg)A(Febuxostat XR 80mg,capsule, orally, single dose after a 10hour(hr) fast and concurrently with Maalox 20mL(200mg magnesium hydroxide, 200mg aluminum hydroxide, and 20mg simethicone/5mL)or equivalent brand antacid, suspension, orally, single dose) on Day1 of first intervention period(3 Days),followed by 1week washout period, followed by RegB(Maalox 20mL,suspension,orally, single dose after a 9hr fast,followed by Febuxostat XR 80mg,capsule, orally, single dose after a 10hr fast[or 1hr after antacid dose]) on Day1 of second intervention period(3Days),followed by 1 week washout period, followed by RegD(Febuxostat XR 80mg,capsule, orally, single dose after a 10hr fast) on Day 1 of third intervention period(3Days),followed by 1week washout period, followed by RegC(Febuxostat XR 80mg,capsule, orally, single dose after a 10hr fast followed by Maalox 20mL, suspension, orally, single dose after 11hr fast[or 1hr after Febuxostat dose]) on Day1 of fourth intervention period(3 Days).	Regimen D (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast) on Day 1 of first intervention period (3 Days), followed by Regimen A (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast and concurrently with Maalox 20 mL, suspension, orally, single dose) on Day 1 of second intervention period (3 Days), followed by 1 week washout period, followed by Regimen C (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast followed by Maalox 20 mL, suspension, orally, single dose after 11-hour fast [or 1 hour after Febuxostat dose]) on Day 1 of third intervention period (3 Days), followed by 1 week washout period, followed by Regimen B (Maalox 20 mL, suspension, orally, single dose after a 9-hour fast, followed by Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast [or 1 hour after antacid dose]).	Regimen C (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast followed by Maalox 20 mL, suspension, orally, single dose after 11-hour fast [or 1 hour after Febuxostat dose]) on Day 1 of first intervention period (3 Days), followed by 1 week washout period, Regimen D (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast) on Day 1 of second intervention period (3 Days), followed by 1 week washout period, Regimen B (Maalox 20 mL, suspension, orally, single dose after a 9-hour fast, followed by Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast [or 1 hour after antacid dose]) on Day 1 of third intervention period (3 Days), followed by Regimen A (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast and concurrently with Maalox 20 mL, suspension, orally, single dose) on Day 1 of fourth intervention period (3 Days).	Regimen B (Maalox 20 mL, suspension, orally, single dose after a 9-hour fast, followed by Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast [or 1 hour after antacid dose]) on Day 1 of first intervention period (3 Days), followed by 1 week washout period, followed by Regimen C (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast followed by Maalox 20 mL, suspension, orally, single dose after 11-hour fast [or 1 hour after Febuxostat dose]) on Day 1 of second intervention period (3 Days), followed by Regimen A (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast and concurrently with Maalox 20 mL, suspension, orally, single dose) on Day 1 of third intervention period (3 Days), Regimen D (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast) on Day 1 of fourth intervention period (3 Days).	Total of all reporting groups
Overall Participants	9	9	9	9	36
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.8 (7.36)	34.7 (13.42)	31.7 (9.18)	35.8 (11.38)	35.0 (10.36)
Sex: Female, Male (Count of Participants)
Female	5 55.6%	5 55.6%	5 55.6%	6 66.7%	21 58.3%
Male	4 44.4%	4 44.4%	4 44.4%	3 33.3%	15 41.7%
Race/Ethnicity, Customized (participants) [Number]
Hispanic or Latino	5 55.6%	3 33.3%	4 44.4%	5 55.6%	17 47.2%
Not Hispanic or Latino	4 44.4%	6 66.7%	5 55.6%	4 44.4%	19 52.8%
Race/Ethnicity, Customized (participants) [Number]
Black or African American	1 11.1%	2 22.2%	4 44.4%	3 33.3%	10 27.8%
White	8 88.9%	6 66.7%	5 55.6%	5 55.6%	24 66.7%
Multiracial	0 0%	1 11.1%	0 0%	1 11.1%	2 5.6%
Smoking classification (participants) [Number]
Has never smoked	8 88.9%	9 100%	8 88.9%	8 88.9%	33 91.7%
Is an ex-smoker	1 11.1%	0 0%	1 11.1%	1 11.1%	3 8.3%
Alcohol classification (participants) [Number]
Has never drunk	2 22.2%	4 44.4%	5 55.6%	4 44.4%	15 41.7%
Is a current drinker	4 44.4%	1 11.1%	1 11.1%	2 22.2%	8 22.2%
Is an ex-drinker	3 33.3%	4 44.4%	3 33.3%	3 33.3%	13 36.1%
Xanthine/caffeine consumption (participants) [Number]
Had xanthine/caffeine consumption	5 55.6%	5 55.6%	3 33.3%	5 55.6%	18 50%
Had no xanthine/caffeine consumption	4 44.4%	4 44.4%	6 66.7%	4 44.4%	18 50%
Female reproductive status (participants) [Number]
Female of childbearing potential	4 44.4%	5 55.6%	4 44.4%	4 44.4%	17 47.2%
Surgically sterile	1 11.1%	0 0%	1 11.1%	2 22.2%	4 11.1%
N/A (participant is male)	4 44.4%	4 44.4%	4 44.4%	3 33.3%	15 41.7%

Outcome Measures

1. Primary Outcome

Title	Cmax: Maximum Observed Plasma Concentration for Febuxostat
Time Frame	Days 1 at multiple timepoints (up to 48 hours) post-dose

Outcome Measure Data

Analysis Population Description

The pharmacokinetic set consisted of all participants who received study drug and had at least 1 measurable plasma concentration.

Arm/Group Title	Regimen A	Regimen B	Regimen C	Regimen D
Arm/Group Description	Regimen A (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast and concurrently with Maalox 20 mL, suspension, orally, single dose) on Day 1 in either of the 4 intervention periods	Regimen B (Maalox 20 mL, suspension, orally, single dose after a 9-hour fast, followed by Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast [or 1 hour after antacid dose]) on Day 1 in either of the 4 intervention periods.	Regimen C (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast followed by Maalox 20 mL, suspension, orally, single dose after 11-hour fast [or 1 hour after Febuxostat dose]) on Day 1 in either of the 4 intervention periods.	Regimen D (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast) on Day 1 in either of the 4 intervention periods.
Measure Participants	36	36	35	36
Mean (Standard Deviation) [nanogram per milliliter (ng/mL)]	883.58 (898.49)	1075.08 (941.46)	765.89 (480.2)	1456.42 (875.39)

2. Primary Outcome

Title	AUC(0-tau): Area Under the Plasma Concentration-time Curve During the Dosing Interval for Febuxostat
Time Frame	Days 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose

Outcome Measure Data

Analysis Population Description

The pharmacokinetic set consisted of all participants who received study drug and had at least 1 measurable plasma concentration.

Arm/Group Title	Regimen A	Regimen B	Regimen C	Regimen D
Arm/Group Description	Regimen A (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast and concurrently with Maalox 20 mL, suspension, orally, single dose) on Day 1 in either of the 4 intervention periods	Regimen B (Maalox 20 mL, suspension, orally, single dose after a 9-hour fast, followed by Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast [or 1 hour after antacid dose]) on Day 1 in either of the 4 intervention periods.	Regimen C (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast followed by Maalox 20 mL, suspension, orally, single dose after 11-hour fast [or 1 hour after Febuxostat dose]) on Day 1 in either of the 4 intervention periods.	Regimen D (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast) on Day 1 in either of the 4 intervention periods.
Measure Participants	36	36	35	36
Mean (Standard Deviation) [nanogram*hour per milliliter (ng*hr/mL)]	4680.69 (2427.11)	5877.99 (2888.9)	4412.22 (1718.42)	7316.21 (2811.1)

3. Primary Outcome

Title	AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Febuxostat
Time Frame	Days 1 pre-dose and at multiple timepoints (up to 48 hours) post-dose

Outcome Measure Data

Analysis Population Description

The pharmacokinetic set consisted of all participants who received study drug and had at least 1 measurable plasma concentration.

Arm/Group Title	Regimen A	Regimen B	Regimen C	Regimen D
Arm/Group Description	Regimen A (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast and concurrently with Maalox 20 mL, suspension, orally, single dose) on Day 1 in either of the 4 intervention periods	Regimen B (Maalox 20 mL, suspension, orally, single dose after a 9-hour fast, followed by Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast [or 1 hour after antacid dose]) on Day 1 in either of the 4 intervention periods.	Regimen C (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast followed by Maalox 20 mL, suspension, orally, single dose after 11-hour fast [or 1 hour after Febuxostat dose]) on Day 1 in either of the 4 intervention periods.	Regimen D (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast) on Day 1 in either of the 4 intervention periods.
Measure Participants	36	36	35	36
Mean (Standard Deviation) [ng*hr/mL]	5901 (2739.92)	6999.9 (2912.71)	4844.33 (1918.73)	7697.85 (2732.63)

4. Primary Outcome

Title	Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame	Day 1 up to 30 days after last dose of drug (Day 31 for each of the 4 periods)

Outcome Measure Data

Analysis Population Description

The safety set was defined as all participants who were enrolled and received at least 1 dose of study drug.

Arm/Group Title	Regimen A	Regimen B	Regimen C	Regimen D
Arm/Group Description	Regimen A (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast and concurrently with Maalox 20 mL, suspension, orally, single dose) on Day 1 in either of the 4 intervention periods	Regimen B (Maalox 20 mL, suspension, orally, single dose after a 9-hour fast, followed by Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast [or 1 hour after antacid dose]) on Day 1 in either of the 4 intervention periods.	Regimen C (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast followed by Maalox 20 mL, suspension, orally, single dose after 11-hour fast [or 1 hour after Febuxostat dose]) on Day 1 in either of the 4 intervention periods.	Regimen D (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast) on Day 1 in either of the 4 intervention periods.
Measure Participants	36	36	35	36
TEAE	2 22.2%	1 11.1%	3 33.3%	2 22.2%
SAE	0 0%	0 0%	0 0%	0 0%

5. Primary Outcome

Title	Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Time Frame	Day 1 up to 30 days after last dose of drug (Day 31 for each of the 4 periods)

Outcome Measure Data

Analysis Population Description

The safety set was defined as all participants who were enrolled and received at least 1 dose of study drug.

Arm/Group Title	Regimen A	Regimen B	Regimen C	Regimen D
Arm/Group Description	Regimen A (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast and concurrently with Maalox 20 mL, suspension, orally, single dose) on Day 1 in either of the 4 intervention periods	Regimen B (Maalox 20 mL, suspension, orally, single dose after a 9-hour fast, followed by Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast [or 1 hour after antacid dose]) on Day 1 in either of the 4 intervention periods.	Regimen C (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast followed by Maalox 20 mL, suspension, orally, single dose after 11-hour fast [or 1 hour after Febuxostat dose]) on Day 1 in either of the 4 intervention periods.	Regimen D (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast) on Day 1 in either of the 4 intervention periods.
Measure Participants	36	36	35	36
Number [participants]	0 0%	0 0%	0 0%	0 0%

6. Primary Outcome

Title	Number of Participants With Clinically Significant Change From Baseline in Physical Examination Findings
Time Frame	Day 1 up to 30 days after last dose of drug (Day 31 for each of the 4 periods)

Outcome Measure Data

Analysis Population Description

The safety set was defined as all participants who were enrolled and received at least 1 dose of study drug.

Arm/Group Title	Regimen A	Regimen B	Regimen C	Regimen D
Arm/Group Description	Regimen A (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast and concurrently with Maalox 20 mL, suspension, orally, single dose) on Day 1 in either of the 4 intervention periods	Regimen B (Maalox 20 mL, suspension, orally, single dose after a 9-hour fast, followed by Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast [or 1 hour after antacid dose]) on Day 1 in either of the 4 intervention periods.	Regimen C (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast followed by Maalox 20 mL, suspension, orally, single dose after 11-hour fast [or 1 hour after Febuxostat dose]) on Day 1 in either of the 4 intervention periods.	Regimen D (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast) on Day 1 in either of the 4 intervention periods.
Measure Participants	36	36	35	36
Number [participants]	0 0%	0 0%	0 0%	0 0%

7. Primary Outcome

Title	Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Evaluation
Time Frame	Day 1 up to 30 days after last dose of drug (Day 31 for each of the 4 periods)

Outcome Measure Data

Analysis Population Description

The safety set was defined as all participants who were enrolled and received at least 1 dose of study drug.

Arm/Group Title	Regimen A	Regimen B	Regimen C	Regimen D
Arm/Group Description	Regimen A (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast and concurrently with Maalox 20 mL, suspension, orally, single dose) on Day 1 in either of the 4 intervention periods	Regimen B (Maalox 20 mL, suspension, orally, single dose after a 9-hour fast, followed by Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast [or 1 hour after antacid dose]) on Day 1 in either of the 4 intervention periods.	Regimen C (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast followed by Maalox 20 mL, suspension, orally, single dose after 11-hour fast [or 1 hour after Febuxostat dose]) on Day 1 in either of the 4 intervention periods.	Regimen D (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast) on Day 1 in either of the 4 intervention periods.
Measure Participants	36	36	35	36
Number [participants]	0 0%	0 0%	0 0%	0 0%

8. Primary Outcome

Title	Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG)
Time Frame	Day 1 up to 30 days after last dose of drug (Day 31 for each of the 4 periods)

Outcome Measure Data

Analysis Population Description

The safety set was defined as all participants who were enrolled and received at least 1 dose of study drug.

Arm/Group Title	Regimen A	Regimen B	Regimen C	Regimen D
Arm/Group Description	Regimen A (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast and concurrently with Maalox 20 mL, suspension, orally, single dose) on Day 1 in either of the 4 intervention periods	Regimen B (Maalox 20 mL, suspension, orally, single dose after a 9-hour fast, followed by Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast [or 1 hour after antacid dose]) on Day 1 in either of the 4 intervention periods.	Regimen C (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast followed by Maalox 20 mL, suspension, orally, single dose after 11-hour fast [or 1 hour after Febuxostat dose]) on Day 1 in either of the 4 intervention periods.	Regimen D (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast) on Day 1 in either of the 4 intervention periods.
Measure Participants	36	36	35	36
Number [participants]	0 0%	0 0%	0 0%	0 0%

Adverse Events

Time Frame	Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug.
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title	Regimen A		Regimen B		Regimen C		Regimen D
Arm/Group Description	Regimen A (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast and concurrently with Maalox 20 mL, suspension, orally, single dose) on Day 1 in either of the 4 intervention periods		Regimen B (Maalox 20 mL, suspension, orally, single dose after a 9-hour fast, followed by Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast [or 1 hour after antacid dose]) on Day 1 in either of the 4 intervention periods.		Regimen C (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast followed by Maalox 20 mL, suspension, orally, single dose after 11-hour fast [or 1 hour after Febuxostat dose]) on Day 1 in either of the 4 intervention periods.		Regimen D (Febuxostat XR 80 mg, capsule, orally, single dose after a 10-hour fast) on Day 1 in either of the 4 intervention periods.
All Cause Mortality
	Regimen A		Regimen B		Regimen C		Regimen D
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Regimen A		Regimen B		Regimen C		Regimen D
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/36 (0%)		0/36 (0%)		0/35 (0%)		0/36 (0%)
Other (Not Including Serious) Adverse Events
	Regimen A		Regimen B		Regimen C		Regimen D
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/36 (5.6%)		1/36 (2.8%)		3/35 (8.6%)		2/36 (5.6%)
Gastrointestinal disorders
Diarrhoea	1/36 (2.8%)		0/36 (0%)		1/35 (2.9%)		0/36 (0%)
Nausea	0/36 (0%)		0/36 (0%)		1/35 (2.9%)		0/36 (0%)
Injury, poisoning and procedural complications
Oral herpes	1/36 (2.8%)		0/36 (0%)		0/35 (0%)		0/36 (0%)
Musculoskeletal and connective tissue disorders
Myalgia	0/36 (0%)		0/36 (0%)		0/35 (0%)		1/36 (2.8%)
Nervous system disorders
Dizziness	0/36 (0%)		0/36 (0%)		0/35 (0%)		1/36 (2.8%)
Headache	0/36 (0%)		0/36 (0%)		1/35 (2.9%)		0/36 (0%)
Skin and subcutaneous tissue disorders
Ecchymosis	0/36 (0%)		1/36 (2.8%)		0/35 (0%)		0/36 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.