Healthy Volunteers
Conditions
Keywords
Drug therapy
Brief summary
This study will assess the relative bioavailability, safety and tolerability following administration of 80 mg single oral doses of 4 febuxostat extended release (XR) formulations.
Detailed description
The drug being tested is this study is febuxostat XR. Four different formulations of febuxostat XR are being tested to see how the drug moves through the body. This study will look at safety and side effects in people who take febuxostat XR. This cross-over study will enroll approximately 78 patients. Participants will be randomly assigned to 1of 4 sequences which will determine the order of the 4 treatments received: * Febuxostat XR 80 mg capsule Formulation 1 * Febuxostat XR 80 mg capsule Formulation 2 * Febuxostat XR 80 mg capsule Formulation 3 * Febuxostat XR 80 mg capsule Formulation 4 Participants will take 1 dose on Day 1 with a washout period between each period. This single-center trial will be conducted in the United States. The overall time to participate in this study is up to 80 days. Participants will make multiple visits to the clinic including a period of confinement, and will be contacted by telephone 30 days after last dose of study drug for a follow-up assessment.
Interventions
DRUGFebuxostat XR 80 mg Capsule F1
Febuxostat extended-release (XR) capsules formulation 1
DRUGFebuxostat XR 80 mg Capsule F2
Febuxostat XR capsules formulation 2
DRUGFebuxostat XR 80 mg Capsule F3
Febuxostat XR capsules formulation 3
DRUGFebuxostat XR 80 mg Capsule F4
Febuxostat XR capsules formulation 4
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements. 2. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures including requesting that a participant fast for any laboratory evaluations. 3. Is a healthy male or female and aged 18 to 55 years, inclusive, at the time of informed consent and first study medication dose. 4. Weighs at least 50.0 kg and has a body mass index (BMI) from 18.0 to 30.0 kg/m2, inclusive at Screening. 5. A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 30 days after the last dose. 6. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent, 7. Is willing to refrain from strenuous exercise from Day -1 of Period 1 until Study Exit (Day 3 of Period 4). 8. Has estimated glomerular filtration rate (eGFR) ≥90 mL/min at Screening and Check-in (Day -1 of Period 1).
Exclusion criteria
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. Is an immediate family member, study site employee, or is in a dependant relationship with a study site employee who is involved in the conduct of this study. 4. Has uncontrolled, clinically significant (CS) disease or other abnormality, which may impact the ability of the participant to participate or potentially confound the study results. 5. Has a known hypersensitivity to any component of the formulation of XO inhibitors, xanthine compounds, caffeine, or any component of the formulation of febuxostat capsules.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Cmax: Maximum Observed Plasma Concentration for Febuxostat | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose | Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. |
| Mean AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Febuxostat | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose | AUCt is a measure of total plasma exposure to the drug from time 0 to time of the last quantifiable concentration. |
| Mean AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Febuxostat | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose | AUC∞ is a measure of total plasma exposure to the drug from time zero extrapolated to infinity. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in the United States from 29 June 2015 to 01 October 2015.
Pre-assignment details
Healthy participants were enrolled equally in 1 of 4 sequences which determined order of treatment: Regimen A (Febuxostat extended release \[XR\] 80 mg capsule \[cap\] Formulation \[F\] 1), B (Febuxostat XR 80 mg cap F2), C (Febuxostat XR 80 mg cap F3) and D (Febuxostat XR 80 mg cap F4). Each regimen is separated by a 7-day washout period.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Sequence ABDC Febuxostat XR 80 mg capsule Formulation 1 (F1), orally, once on Day 1 of Period 1 (A), followed by at least a 7-day washout period, followed by Febuxostat XR 80 mg capsule Formulation 2 (F2), orally, once on Day 1 of Period 2 (B), followed by at least a 7-day washout period, followed by Febuxostat XR 80 mg capsule Formulation 4 (F4), orally, once on Day 1 of Period 3 (D), followed by at least a 7-day washout period, followed by Febuxostat XR 80 mg capsule Formulation 3 (F3), orally, once on Day 1 of Period 4 (C). | 19 |
| Treatment Sequence DACB Febuxostat XR 80 mg capsule F4, orally, once on Day 1 of Period 1 (D), followed by at least a 7-day washout period, followed by Febuxostat XR 80 mg capsule F1 orally, once on Day 1 of Period 2 (A), followed by at least a 7-day washout period, followed by Febuxostat XR 80 mg capsule F3, orally, once on Day 1 of Period 3 (C), followed by at least a 7-day washout period, followed by Febuxostat XR 80 mg capsule F2, orally, once on Day 1 of Period 4 (B). | 19 |
| Treatment Sequence CDBA Febuxostat XR 80 mg capsule F3, orally, once on Day 1 of Period 1 (C), followed by at least a 7-day washout period, followed by Febuxostat XR 80 mg capsule F4 orally, once on Day 1 of Period 2 (D), followed by at least a 7-day washout period, followed by Febuxostat XR 80 mg capsule F2, orally, once on Day 1 of Period 3 (B), followed by at least a 7-day washout period, followed by Febuxostat XR 80 mg capsule F1, orally, once on Day 1 of Period 4 (A). | 20 |
| Treatment Sequence BCAD Febuxostat XR 80 mg capsule F2, orally, once on Day 1 of Period 1 (B), followed by at least a 7-day washout period, followed by Febuxostat XR 80 mg capsule F3 orally, once on Day 1 of Period 2 (C), followed by at least a 7-day washout period, followed by Febuxostat XR 80 mg capsule F1, orally, once on Day 1 of Period 3 (A), followed by at least a 7-day washout period, followed by Febuxostat XR 80 mg capsule F4, orally, once on Day 1 of Period 4 (D). | 20 |
| Total | 78 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Treatment Period 1 | Positive Drug Screen | 0 | 0 | 1 | 0 |
| Treatment Period 2 | Positive Drug Screen | 0 | 1 | 0 | 0 |
| Treatment Period 3 | Adverse Event | 0 | 0 | 1 | 0 |
| Treatment Period 3 | Positive Drug Screen | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Treatment Sequence ABDC | Treatment Sequence DACB | Treatment Sequence CDBA | Treatment Sequence BCAD |
|---|---|---|---|---|---|
| Age, Continuous | 31.9 years STANDARD_DEVIATION 7.7 | 31.7 years STANDARD_DEVIATION 7.56 | 30.7 years STANDARD_DEVIATION 6.51 | 34.0 years STANDARD_DEVIATION 8.87 | 31.2 years STANDARD_DEVIATION 7.78 |
| Alcohol Classification Has Never Drunk | 23 Participants | 4 Participants | 6 Participants | 6 Participants | 7 Participants |
| Alcohol Classification Is a Current Drinker | 27 Participants | 8 Participants | 9 Participants | 6 Participants | 4 Participants |
| Alcohol Classification Is an Ex-drinker | 28 Participants | 7 Participants | 4 Participants | 8 Participants | 9 Participants |
| Body Mass Index (BMI) | 25.83 kg/m^2 STANDARD_DEVIATION 2.878 | 25.84 kg/m^2 STANDARD_DEVIATION 2.663 | 26.98 kg/m^2 STANDARD_DEVIATION 2.722 | 25.29 kg/m^2 STANDARD_DEVIATION 3.168 | 25.28 kg/m^2 STANDARD_DEVIATION 2.802 |
| Estimated Glomerular Filtration Rate (eGFR) Check-in (n=19, 19, 20, 20) | 114.82 mL/min STANDARD_DEVIATION 11.987 | 115.53 mL/min STANDARD_DEVIATION 12.294 | 115.26 mL/min STANDARD_DEVIATION 12.229 | 112.00 mL/min STANDARD_DEVIATION 10.964 | 116.55 mL/min STANDARD_DEVIATION 12.845 |
| Estimated Glomerular Filtration Rate (eGFR) Screening (n=19, 19, 19, 20) | 111.61 mL/min STANDARD_DEVIATION 12.211 | 111.42 mL/min STANDARD_DEVIATION 11.815 | 112.84 mL/min STANDARD_DEVIATION 11.987 | 108.05 mL/min STANDARD_DEVIATION 11.664 | 114.00 mL/min STANDARD_DEVIATION 13.377 |
| Female Reproductive Status Female of Childbearing Potential | 36 Participants | 7 Participants | 9 Participants | 8 Participants | 12 Participants |
| Female Reproductive Status Not Applicable (Participant is Male) | 35 Participants | 9 Participants | 9 Participants | 11 Participants | 6 Participants |
| Female Reproductive Status Postmenopausal | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Female Reproductive Status Surgically Sterile | 5 Participants | 2 Participants | 1 Participants | 0 Participants | 2 Participants |
| Gender Female | 43 Participants | 10 Participants | 10 Participants | 9 Participants | 14 Participants |
| Gender Male | 35 Participants | 9 Participants | 9 Participants | 11 Participants | 6 Participants |
| Height | 167.9 cm STANDARD_DEVIATION 9.71 | 167.6 cm STANDARD_DEVIATION 10.13 | 171.1 cm STANDARD_DEVIATION 11.75 | 167.5 cm STANDARD_DEVIATION 9.7 | 165.7 cm STANDARD_DEVIATION 6.67 |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 23 Participants | 4 Participants | 7 Participants | 6 Participants | 6 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 37 Participants | 11 Participants | 7 Participants | 9 Participants | 10 Participants |
| Race/Ethnicity, Customized Multiracial | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 41 Participants | 8 Participants | 12 Participants | 11 Participants | 10 Participants |
| Race/Ethnicity, Customized White | 53 Participants | 15 Participants | 11 Participants | 14 Participants | 13 Participants |
| Region of Enrollment United States | 78 Participants | 19 Participants | 19 Participants | 20 Participants | 20 Participants |
| Smoking Classification Has Never Smoked | 58 Participants | 13 Participants | 14 Participants | 13 Participants | 18 Participants |
| Smoking Classification Is a Current Smoker | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Smoking Classification Is an Ex-smoker | 20 Participants | 6 Participants | 5 Participants | 7 Participants | 2 Participants |
| Weight | 73.17 kg STANDARD_DEVIATION 12.273 | 72.98 kg STANDARD_DEVIATION 12.685 | 79.05 kg STANDARD_DEVIATION 11.846 | 71.22 kg STANDARD_DEVIATION 12.35 | 69.72 kg STANDARD_DEVIATION 11.015 |
| Xanthine/Caffeine Consumption No | 27 Participants | 7 Participants | 6 Participants | 8 Participants | 6 Participants |
| Xanthine/Caffeine Consumption Yes | 51 Participants | 12 Participants | 13 Participants | 12 Participants | 14 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 | 6 / 76 | 9 / 76 | 7 / 77 | 7 / 76 |
| serious Total, serious adverse events | 0 / 76 | 1 / 76 | 0 / 77 | 0 / 76 |
Outcome results
Primary
Mean AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Febuxostat
AUC∞ is a measure of total plasma exposure to the drug from time zero extrapolated to infinity.
Time frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
Population: Participants with valid parameters for Regimen D and at least one of the test regimen were included in the analyses for this outcome measure. Here, number of participants analyzed is the participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Regimen A: Febuxostat XR 80 mg Formulation 1 | Mean AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Febuxostat | 9368.0744 ng*hr/mL | Standard Deviation 3944.0128 |
| Regimen B: Febuxostat XR 80 mg Formulation 2 | Mean AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Febuxostat | 8278.6143 ng*hr/mL | Standard Deviation 3205.31556 |
| Regimen C: Febuxostat XR 80 mg Formulation 3 | Mean AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Febuxostat | 8938.8765 ng*hr/mL | Standard Deviation 3746.60153 |
| Regimen D: Febuxostat XR 80 mg Formulation 4 | Mean AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Febuxostat | 9102.3700 ng*hr/mL | Standard Deviation 3430.45699 |
Comparison: Relative bioavailability of a single dose of Febuxostat XR 80 mg in test (Regimen A) and reference (Regimen D).90% CI: [0.9691, 1.0911]
Comparison: Relative bioavailability of a single dose of Febuxostat XR 80 mg in test (Regimen B) and reference (Regimen D).90% CI: [0.8516, 0.963]
Comparison: Relative bioavailability of a single dose of Febuxostat XR 80 mg in test (Regimen C) and reference (Regimen D).90% CI: [0.8909, 1.0051]
Primary
Mean 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.
Time frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
Population: Participants with valid parameters for Regimen D and at least one of the test regimen were included in the analyses for this outcome measure. Here, number of participants analyzed is the participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Regimen A: Febuxostat XR 80 mg Formulation 1 | Mean AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Febuxostat | 9395.6014 ng*hr/mL | Standard Deviation 3961.55203 |
| Regimen B: Febuxostat XR 80 mg Formulation 2 | Mean AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Febuxostat | 7971.0624 ng*hr/mL | Standard Deviation 3291.3639 |
| Regimen C: Febuxostat XR 80 mg Formulation 3 | Mean AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Febuxostat | 8652.7080 ng*hr/mL | Standard Deviation 3673.91666 |
| Regimen D: Febuxostat XR 80 mg Formulation 4 | Mean AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Febuxostat | 8817.3600 ng*hr/mL | Standard Deviation 3429.9488 |
Comparison: Relative bioavailability of a single dose of Febuxostat XR 80 mg in test (Regimen A) and reference (Regimen D).90% CI: [0.984, 1.1066]
Comparison: Relative bioavailability of a single dose of Febuxostat XR 80 mg in test (Regimen B) and reference (Regimen D).90% CI: [0.8274, 0.9311]
Comparison: Relative bioavailability of a single dose of Febuxostat XR 80 mg in test (Regimen A) and reference (Regimen D).90% CI: [0.8996, 1.0117]
Primary
Mean 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.
Time frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
Population: Participants with valid parameters for Regimen D and at least one of the test regimen were included in the analyses for this outcome measure. Here, number of participants analyzed is the participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Regimen A: Febuxostat XR 80 mg Formulation 1 | Mean Cmax: Maximum Observed Plasma Concentration for Febuxostat | 2027.1184 ng/mL | Standard Deviation 1278.28368 |
| Regimen B: Febuxostat XR 80 mg Formulation 2 | Mean Cmax: Maximum Observed Plasma Concentration for Febuxostat | 1442.2267 ng/mL | Standard Deviation 991.94583 |
| Regimen C: Febuxostat XR 80 mg Formulation 3 | Mean Cmax: Maximum Observed Plasma Concentration for Febuxostat | 1730.2468 ng/mL | Standard Deviation 1013.56204 |
| Regimen D: Febuxostat XR 80 mg Formulation 4 | Mean Cmax: Maximum Observed Plasma Concentration for Febuxostat | 1809.3158 ng/mL | Standard Deviation 1170.53245 |
Comparison: Relative bioavailability of a single dose of Febuxostat XR 80 mg in test (Regimen A) and reference (Regimen D).90% CI: [0.9528, 1.235]
Comparison: Relative bioavailability of a single dose of Febuxostat XR 80 mg in test (Regimen B) and reference (Regimen D).90% CI: [0.6767, 0.8782]
Comparison: Relative bioavailability of a single dose of Febuxostat XR 80 mg in test (Regimen C) and reference (Regimen D).90% CI: [0.8246, 1.0689]