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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Febuxostat XR; Drug: Maalox Advance Regular Strength liquid

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 Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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]).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax: Maximum Observed Plasma Concentration for Febuxostat	Days 1 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
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
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)
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)
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 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 12-lead Electrocardiogram (ECG)	Day 1 up to 30 days after last dose of drug (Day 31 for each of the 4 periods)

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: March 3, 2015
• First Submitted That Met QC Criteria: March 3, 2015
• First Posted (Estimate): March 9, 2015

Study Record Updates

• Last Update Posted (Estimate): April 29, 2016
• Last Update Submitted That Met QC Criteria: March 28, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Drug therapy
• Additional Relevant MeSH Terms: Antirheumatic Agents; Gout Suppressants; Febuxostat
• Other Study ID Numbers: Febuxostat XR-1010; U1111-1163-1813 (Registry Identifier: WHO)