Healthy Volunteers
Conditions
Keywords
Drug therapy
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.
Interventions
DRUGFebuxostat XR
Febuxostat extended-release (XR) capsules
DRUGMaalox 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
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
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 \[eg, cholecystectomy\]).
Design outcomes
Primary
| 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) |
Countries
United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Regimen A, Then B, Then D, Then C 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). | 9 |
| Regimen D, Then A, Then C, Then B 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 \[or 1 hour after antacid dose\]). | 9 |
| Regimen C, Then D, Then B, Then A 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). | 9 |
| Regimen B, Then C, Then A, Then D 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). | 9 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Intervention Period 4 (3 Days) | Laboratory Abnormality | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Regimen B, Then C, Then A, Then D | Regimen D, Then A, Then C, Then B | Regimen A, Then B, Then D, Then C | Regimen C, Then D, Then B, Then A |
|---|---|---|---|---|---|
| Age, Continuous | 35.0 years STANDARD_DEVIATION 10.36 | 35.8 years STANDARD_DEVIATION 11.38 | 34.7 years STANDARD_DEVIATION 13.42 | 37.8 years STANDARD_DEVIATION 7.36 | 31.7 years STANDARD_DEVIATION 9.18 |
| Alcohol classification Has never drunk | 15 participants | 4 participants | 4 participants | 2 participants | 5 participants |
| Alcohol classification Is a current drinker | 8 participants | 2 participants | 1 participants | 4 participants | 1 participants |
| Alcohol classification Is an ex-drinker | 13 participants | 3 participants | 4 participants | 3 participants | 3 participants |
| Female reproductive status Female of childbearing potential | 17 participants | 4 participants | 5 participants | 4 participants | 4 participants |
| Female reproductive status N/A (participant is male) | 15 participants | 3 participants | 4 participants | 4 participants | 4 participants |
| Female reproductive status Surgically sterile | 4 participants | 2 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Black or African American | 10 participants | 3 participants | 2 participants | 1 participants | 4 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 17 participants | 5 participants | 3 participants | 5 participants | 4 participants |
| Race/Ethnicity, Customized Multiracial | 2 participants | 1 participants | 1 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 19 participants | 4 participants | 6 participants | 4 participants | 5 participants |
| Race/Ethnicity, Customized White | 24 participants | 5 participants | 6 participants | 8 participants | 5 participants |
| Sex: Female, Male Female | 21 Participants | 6 Participants | 5 Participants | 5 Participants | 5 Participants |
| Sex: Female, Male Male | 15 Participants | 3 Participants | 4 Participants | 4 Participants | 4 Participants |
| Smoking classification Has never smoked | 33 participants | 8 participants | 9 participants | 8 participants | 8 participants |
| Smoking classification Is an ex-smoker | 3 participants | 1 participants | 0 participants | 1 participants | 1 participants |
| Xanthine/caffeine consumption Had no xanthine/caffeine consumption | 18 participants | 4 participants | 4 participants | 4 participants | 6 participants |
| Xanthine/caffeine consumption Had xanthine/caffeine consumption | 18 participants | 5 participants | 5 participants | 5 participants | 3 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 36 | 1 / 36 | 3 / 35 | 2 / 36 |
| serious Total, serious adverse events | 0 / 36 | 0 / 36 | 0 / 35 | 0 / 36 |
Outcome results
Primary
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
Population: The pharmacokinetic set consisted of all participants who received study drug and had at least 1 measurable plasma concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Regimen A | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Febuxostat | 5901 ng*hr/mL | Standard Deviation 2739.92 |
| Regimen B | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Febuxostat | 6999.9 ng*hr/mL | Standard Deviation 2912.71 |
| Regimen C | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Febuxostat | 4844.33 ng*hr/mL | Standard Deviation 1918.73 |
| Regimen D | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Febuxostat | 7697.85 ng*hr/mL | Standard Deviation 2732.63 |
Primary
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
Population: The pharmacokinetic set consisted of all participants who received study drug and had at least 1 measurable plasma concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Regimen A | AUC(0-tau): Area Under the Plasma Concentration-time Curve During the Dosing Interval for Febuxostat | 4680.69 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 2427.11 |
| Regimen B | AUC(0-tau): Area Under the Plasma Concentration-time Curve During the Dosing Interval for Febuxostat | 5877.99 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 2888.9 |
| Regimen C | AUC(0-tau): Area Under the Plasma Concentration-time Curve During the Dosing Interval for Febuxostat | 4412.22 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 1718.42 |
| Regimen D | AUC(0-tau): Area Under the Plasma Concentration-time Curve During the Dosing Interval for Febuxostat | 7316.21 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 2811.1 |
Primary
Cmax: Maximum Observed Plasma Concentration for Febuxostat
Time frame: Days 1 at multiple timepoints (up to 48 hours) post-dose
Population: The pharmacokinetic set consisted of all participants who received study drug and had at least 1 measurable plasma concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Regimen A | Cmax: Maximum Observed Plasma Concentration for Febuxostat | 883.58 nanogram per milliliter (ng/mL) | Standard Deviation 898.49 |
| Regimen B | Cmax: Maximum Observed Plasma Concentration for Febuxostat | 1075.08 nanogram per milliliter (ng/mL) | Standard Deviation 941.46 |
| Regimen C | Cmax: Maximum Observed Plasma Concentration for Febuxostat | 765.89 nanogram per milliliter (ng/mL) | Standard Deviation 480.2 |
| Regimen D | Cmax: Maximum Observed Plasma Concentration for Febuxostat | 1456.42 nanogram per milliliter (ng/mL) | Standard Deviation 875.39 |
Primary
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)
Population: The safety set was defined as all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Regimen A | Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) | 0 participants |
| Regimen B | Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) | 0 participants |
| Regimen C | Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) | 0 participants |
| Regimen D | Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) | 0 participants |
Primary
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)
Population: The safety set was defined as all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Regimen A | Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Evaluation | 0 participants |
| Regimen B | Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Evaluation | 0 participants |
| Regimen C | Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Evaluation | 0 participants |
| Regimen D | Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Evaluation | 0 participants |
Primary
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)
Population: The safety set was defined as all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Regimen A | Number of Participants With Clinically Significant Change From Baseline in Physical Examination Findings | 0 participants |
| Regimen B | Number of Participants With Clinically Significant Change From Baseline in Physical Examination Findings | 0 participants |
| Regimen C | Number of Participants With Clinically Significant Change From Baseline in Physical Examination Findings | 0 participants |
| Regimen D | Number of Participants With Clinically Significant Change From Baseline in Physical Examination Findings | 0 participants |
Primary
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)
Population: The safety set was defined as all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Regimen A | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 participants |
| Regimen B | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 participants |
| Regimen C | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 participants |
| Regimen D | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 participants |
Primary
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)
Population: The safety set was defined as all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Regimen A | Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | TEAE | 2 participants |
| Regimen A | Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAE | 0 participants |
| Regimen B | Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAE | 0 participants |
| Regimen B | Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | TEAE | 1 participants |
| Regimen C | Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | TEAE | 3 participants |
| Regimen C | Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAE | 0 participants |
| Regimen D | Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | TEAE | 2 participants |
| Regimen D | Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAE | 0 participants |