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

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02382640
• Other study ID #: Febuxostat XR-1010
• Secondary ID: U1111-1163-1813
• Status: Completed
• Phase: Phase 1
• First received: March 3, 2015
• Last updated: May 20, 2015
• Start date: March 2015
• Est. completion date: May 2015

Study information

• Verified date: May 2015
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Febuxostat XR
Febuxostat extended-release (XR) capsules
• 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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmax: Maximum Observed Plasma Concentration for Febuxostat	Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.	Day 1 of Periods 1, 2, 3 and 4 pre-dose and at multiple timepoints (up to 48 hours) post-dose.	No
Primary	AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Febuxostat	(AUCt is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration.	Day 1 of Periods 1, 2, 3 and 4 pre-dose and at multiple timepoints (up to 48 hours) post-dose.	No
Primary	AUC8: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Febuxostat	AUC8: is a measure of total plasma exposure to the drug from time zero extrapolated to infinity.	Day 1 of Periods 1, 2, 3 and 4 pre-dose and at multiple timepoints (up to 48 hours) post-dose.	No
Secondary	Percentage of Participants With Abnormal Physical Exam Findings	The percentage of participants with any markedly abnormal physical exam findings including the following body systems: (1) eyes; (2) ears, nose, throat; (3) cardiovascular system; (4) respiratory system; (5) gastrointestinal system; (6) dermatologic system; (7) extremities; (8) musculoskeletal system; (9) nervous system; and (10) lymph nodes.	From Day 1 of Period 1 to 30 days after the last dose of study medication (approximately 56 days).	Yes
Secondary	Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event is defined as an adverse event with an onset that occurs after receiving study drug.	From Day 1 of Period 1 to 30 days after the last dose of study medication (approximately 56 days).	Yes
Secondary	Percentage of Participants with Serious Adverse Events (SAEs)	A serious adverse event (SAE) is any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect or is medically important due to other reasons than the above mentioned criteria.	From Day 1 of Period 1 to 30 days after the last dose of study medication (approximately 56 days).	Yes
Secondary	Percentage of Participants With Abnormal Clinical Laboratory Findings	The percentage of participants with any markedly abnormal clinical laboratory values including hematology, serum chemistry and urinalysis.	From Day 1 of Period 1 to 30 days after the last dose of study medication (approximately 56 days).	Yes
Secondary	Percentage of Participants With Abnormal Vital Sign Measurements	The percentage of participants with any markedly abnormal vital sign measurements including oral body temperature, respiratory rate, sitting blood pressure (after resting 5 minutes), and pulse (bpm).	From Day 1 of Period 1 to 30 days after the last dose of study medication (approximately 56 days).	Yes
Secondary	Percentage of Participants With Abnormal Electrocardiogram (ECG) Findings	The percentage of participants with any markedly abnormal 12-lead ECG findings.	From Day 1 of Period 1 to 30 days after the last dose of study medication (approximately 56 days).	Yes