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

Phase 1

Completed

• Conditions: Healthy Volunteers
• Interventions: Drug: Febuxostat XR; Drug: Maalox Advance Regular Strength liquid

• Registration Number: NCT02382640
• Lead Sponsor: Takeda

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.

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 Timeline

• Study Start: 2015-03
• Study First Submitted: 2015-03-03
• Study First Submitted QC: 2015-03-03
• Study First Posted: 2015-03-09
• Primary Completion: 2015-05
• Study Completion: 2015-05
• Status Verified: 2016-03
• Results First Submitted: 2016-03-28
• Results First Submitted QC: 2016-03-28
• Last Update Submitted: 2016-03-28
• Results First Posted: 2016-04-29
• Last Update Posted: 2016-04-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

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

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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]).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sequence 1: ABDC	Febuxostat XR	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	Febuxostat XR	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	Febuxostat XR	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	Febuxostat XR	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.
Sequence 2: DACB	Maalox Advance Regular Strength liquid	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 4: BCAD	Maalox Advance Regular Strength liquid	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.
Sequence 3: CDBA	Maalox Advance Regular Strength liquid	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 1: ABDC	Maalox Advance Regular Strength liquid	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).

Primary Outcome Measures

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