Trial Outcomes & Findings for Food Effect Study of Febuxostat XR in Healthy Participants (NCT NCT02374164)
NCT ID: NCT02374164
Last Updated: 2016-04-27
Results Overview
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. Participant blood samples were collected pre-dose and following a single oral dose.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
36 participants
Primary outcome timeframe
Day 1 pre-dose and at multiple timepoints (up to 48 hours) post dose
Results posted on
2016-04-27
Participant Flow
Healthy participants took part in the study at 1 investigative site in the United States from 2 February 2015 to 19 April 2015.
Healthy participants were enrolled equally in 1 of 3 sequences which determined the order of treatment: Regimen A (febuxostat XR 80 mg after high fat meal), B (febuxostat XR 40 mg after fasting) and C (febuxostat XR 80 mg after fasting). Regimens included a single dose on Day 1 followed by a 7-day washout period prior to receiving the next regimen.
Participant milestones
| Measure |
Treatment Sequence ABC
Febuxostat extended release (XR) 80 mg, capsules, orally, once on Day 1 of Period 1 after a high-fat meal, followed by a 7-day washout period, followed by febuxostat XR 40 mg, capsules, orally, once on Day 1 of Period 2 after a 10-hour fast, followed by a 7-day washout period, followed by febuxostat XR 80, capsules, orally, once on Day 1 of Period 3 after a 10-hour fast.
|
Treatment Sequence BCA
Febuxostat XR 40 mg, capsules, orally, once on Day 1 of Period 1 after a 10-hour fast, followed by a 7-day washout period, followed by febuxostat XR 80 mg, capsules, orally, once on Day 1 of Period 2 after a 10-hour fast, followed by a 7-day washout period, followed by Febuxostat XR 80 mg, capsules, orally, once on Day 1 of Period 3 after a high-fat meal.
|
Treatment Sequence CAB
Febuxostat XR 80 mg, capsules, orally, once on Day 1 of Period 1 after a 10-hour fast, followed by a 7-day washout period, followed by febuxostat XR 80 mg, capsules, orally, once on Day 1 of Period 2 after a high-fat meal, followed by a 7-day washout period, followed by febuxostat XR 40 mg, capsules, orally, once on Day 1 of Period 3 after a 10-hour fast.
|
|---|---|---|---|
|
Treatment Period 1
STARTED
|
12
|
12
|
12
|
|
Treatment Period 1
COMPLETED
|
12
|
12
|
12
|
|
Treatment Period 1
NOT COMPLETED
|
0
|
0
|
0
|
|
Treatment Period 2
STARTED
|
12
|
12
|
12
|
|
Treatment Period 2
COMPLETED
|
12
|
12
|
12
|
|
Treatment Period 2
NOT COMPLETED
|
0
|
0
|
0
|
|
Treatment Period 3
STARTED
|
12
|
11
|
12
|
|
Treatment Period 3
COMPLETED
|
12
|
11
|
12
|
|
Treatment Period 3
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Food Effect Study of Febuxostat XR in Healthy Participants
Baseline characteristics by cohort
| Measure |
Treatment Sequence ABC
n=12 Participants
Febuxostat extended release (XR) 80 mg, capsules, orally, once on Day 1 of Period 1 after a high-fat meal, followed by a 7-day washout period, followed by febuxostat XR 40 mg, capsules, orally, once on Day 1 of Period 2 after a 10-hour fast, followed by a 7-day washout period, followed by febuxostat XR 80, capsules, orally, once on Day 1 of Period 3 after a 10-hour fast.
|
Treatment Sequence BCA
n=12 Participants
Febuxostat XR 40 mg, capsules, orally, once on Day 1 of Period 1 after a 10-hour fast, followed by a 7-day washout period, followed by febuxostat XR 80 mg, capsules, orally, once on Day 1 of Period 2 after a 10-hour fast, followed by a 7-day washout period, followed by Febuxostat XR 80 mg, capsules, orally, once on Day 1 of Period 3 after a high-fat meal.
|
Treatment Sequence CAB
n=12 Participants
Febuxostat XR 80 mg, capsules, orally, once on Day 1 of Period 1 after a 10-hour fast, followed by a 7-day washout period, followed by febuxostat XR 80 mg, capsules, orally, once on Day 1 of Period 2 after a high-fat meal, followed by a 7-day washout period, followed by febuxostat XR 40 mg, capsules, orally, once on Day 1 of Period 3 after a 10-hour fast.
|
Total
n=36 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
31.3 years
STANDARD_DEVIATION 8.37 • n=5 Participants
|
35.0 years
STANDARD_DEVIATION 6.32 • n=7 Participants
|
29.1 years
STANDARD_DEVIATION 5.35 • n=5 Participants
|
31.8 years
STANDARD_DEVIATION 7.05 • n=4 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
19 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
17 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
5 participants
n=5 Participants
|
6 participants
n=7 Participants
|
5 participants
n=5 Participants
|
16 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
7 participants
n=5 Participants
|
6 participants
n=7 Participants
|
7 participants
n=5 Participants
|
20 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
2 participants
n=5 Participants
|
2 participants
n=7 Participants
|
3 participants
n=5 Participants
|
7 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
10 participants
n=5 Participants
|
10 participants
n=7 Participants
|
9 participants
n=5 Participants
|
29 participants
n=4 Participants
|
|
Region of Enrollment
United States
|
12 participants
n=5 Participants
|
12 participants
n=7 Participants
|
12 participants
n=5 Participants
|
36 participants
n=4 Participants
|
|
Height
|
167.6 cm
STANDARD_DEVIATION 8.27 • n=5 Participants
|
168.8 cm
STANDARD_DEVIATION 9.98 • n=7 Participants
|
166.6 cm
STANDARD_DEVIATION 12.35 • n=5 Participants
|
167.6 cm
STANDARD_DEVIATION 10.08 • n=4 Participants
|
|
Weight
|
73.95 kg
STANDARD_DEVIATION 10.802 • n=5 Participants
|
73.35 kg
STANDARD_DEVIATION 8.867 • n=7 Participants
|
69.10 kg
STANDARD_DEVIATION 8.169 • n=5 Participants
|
72.13 kg
STANDARD_DEVIATION 9.335 • n=4 Participants
|
|
Body Mass Index (BMI)
|
26.21 kg/m^2
STANDARD_DEVIATION 1.880 • n=5 Participants
|
25.76 kg/m^2
STANDARD_DEVIATION 2.321 • n=7 Participants
|
25.03 kg/m^2
STANDARD_DEVIATION 2.878 • n=5 Participants
|
25.67 kg/m^2
STANDARD_DEVIATION 2.376 • n=4 Participants
|
|
Female Reproductive Status
N/A (Participant is Male)
|
6 participants
n=5 Participants
|
6 participants
n=7 Participants
|
5 participants
n=5 Participants
|
17 participants
n=4 Participants
|
|
Female Reproductive Status
Female of Childbearing Potential
|
5 participants
n=5 Participants
|
3 participants
n=7 Participants
|
7 participants
n=5 Participants
|
15 participants
n=4 Participants
|
|
Female Reproductive Status
Surgically Sterile
|
1 participants
n=5 Participants
|
3 participants
n=7 Participants
|
0 participants
n=5 Participants
|
4 participants
n=4 Participants
|
|
Smoking Classification
Has Never Smoked
|
8 participants
n=5 Participants
|
12 participants
n=7 Participants
|
10 participants
n=5 Participants
|
30 participants
n=4 Participants
|
|
Smoking Classification
Is a Current Smoker
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
|
Smoking Classification
Is an Ex-Smoker
|
4 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
6 participants
n=4 Participants
|
|
Alcohol Classification
Has Never Drunk
|
3 participants
n=5 Participants
|
5 participants
n=7 Participants
|
4 participants
n=5 Participants
|
12 participants
n=4 Participants
|
|
Alcohol Classification
Is a Current Drinker
|
7 participants
n=5 Participants
|
5 participants
n=7 Participants
|
6 participants
n=5 Participants
|
18 participants
n=4 Participants
|
|
Alcohol Classification
Is an Ex-Drinker
|
2 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2 participants
n=5 Participants
|
6 participants
n=4 Participants
|
|
Xanthine/Caffeine Consumption
Yes
|
8 participants
n=5 Participants
|
7 participants
n=7 Participants
|
7 participants
n=5 Participants
|
22 participants
n=4 Participants
|
|
Xanthine/Caffeine Consumption
No
|
4 participants
n=5 Participants
|
5 participants
n=7 Participants
|
5 participants
n=5 Participants
|
14 participants
n=4 Participants
|
|
Estimated Glomerular Filtration Rate (eGFR)
Screening
|
123.38 mL/min
STANDARD_DEVIATION 22.449 • n=5 Participants
|
125.41 mL/min
STANDARD_DEVIATION 13.025 • n=7 Participants
|
125.87 mL/min
STANDARD_DEVIATION 15.280 • n=5 Participants
|
124.88 mL/min
STANDARD_DEVIATION 16.920 • n=4 Participants
|
|
Estimated Glomerular Filtration Rate (eGFR)
Check-in
|
131.43 mL/min
STANDARD_DEVIATION 25.231 • n=5 Participants
|
132.71 mL/min
STANDARD_DEVIATION 13.999 • n=7 Participants
|
135.95 mL/min
STANDARD_DEVIATION 19.147 • n=5 Participants
|
133.36 mL/min
STANDARD_DEVIATION 19.509 • n=4 Participants
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple timepoints (up to 48 hours) post dosePopulation: Participants from the Pharmacokinetic population (PK), all participants who received study drug and had at least 1 measurable plasma concentration, who received a single dose of study drug in Regimen A and C.
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. Participant blood samples were collected pre-dose and following a single oral dose.
Outcome measures
| Measure |
A: Febuxostat XR 80 mg (Fed)
n=35 Participants
Febuxostat XR 80 mg, capsules, orally, once on Day 1 in any of the 3 treatment periods 30 minutes after starting to ingest a high-fat meal.
|
C: Febuxostat XR 80 mg (Fasting)
n=35 Participants
Febuxostat XR 80 mg, capsules, orally, once on Day 1 in any of the 3 treatment periods after a 10-hour fast.
|
|---|---|---|
|
Cmax: Maximum Observed Plasma Concentration for Febuxostat XR 80 mg in Fed (Regimen A) and Fasted (Regimen C) States
|
1020.0000 ng/mL
Standard Deviation 398.14171
|
1531.6286 ng/mL
Standard Deviation 906.12813
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post dosePopulation: Participants from the PK population, all participants who received study drug and had at least 1 measurable plasma concentration who received a single dose of study drug in Regimen B and C.
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. Participant blood samples were collected pre-dose and following a single oral dose.
Outcome measures
| Measure |
A: Febuxostat XR 80 mg (Fed)
n=36 Participants
Febuxostat XR 80 mg, capsules, orally, once on Day 1 in any of the 3 treatment periods 30 minutes after starting to ingest a high-fat meal.
|
C: Febuxostat XR 80 mg (Fasting)
n=36 Participants
Febuxostat XR 80 mg, capsules, orally, once on Day 1 in any of the 3 treatment periods after a 10-hour fast.
|
|---|---|---|
|
Cmax: Maximum Observed Plasma Concentration for Febuxostat XR 40 mg (Regimen B) and Febuxostat XR 80 mg (Regimen C) in Fasted States
|
754.9167 ng/mL
Standard Deviation 471.49630
|
1562.1389 ng/mL
Standard Deviation 911.65824
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple timepoints (up to 48 hours) post dosePopulation: Participants from the PK population, all participants who received study drug and had at least 1 measurable plasma concentration, who received a single dose of study drug in Regimen A and C.
AUCt is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration. Participant blood samples were collected pre-dose and following a single oral dose.
Outcome measures
| Measure |
A: Febuxostat XR 80 mg (Fed)
n=35 Participants
Febuxostat XR 80 mg, capsules, orally, once on Day 1 in any of the 3 treatment periods 30 minutes after starting to ingest a high-fat meal.
|
C: Febuxostat XR 80 mg (Fasting)
n=35 Participants
Febuxostat XR 80 mg, capsules, orally, once on Day 1 in any of the 3 treatment periods after a 10-hour fast.
|
|---|---|---|
|
AUCt: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration for Febuxostat XR 80 mg in Fed (Regimen A) and Fasted (Regimen C) States
|
7605.4147 ng*hr/mL
Standard Deviation 2086.85262
|
7687.1220 ng*hr/mL
Standard Deviation 2853.12475
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple timepoints (up to 48 hours) post dosePopulation: Participants from the PK population, all participants who received study drug and had at least 1 measurable plasma concentration, who received a single dose of study drug in Regimen B and C.
AUCt is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUCt) Participant blood samples were collected pre-dose and following a single oral dose.
Outcome measures
| Measure |
A: Febuxostat XR 80 mg (Fed)
n=36 Participants
Febuxostat XR 80 mg, capsules, orally, once on Day 1 in any of the 3 treatment periods 30 minutes after starting to ingest a high-fat meal.
|
C: Febuxostat XR 80 mg (Fasting)
n=36 Participants
Febuxostat XR 80 mg, capsules, orally, once on Day 1 in any of the 3 treatment periods after a 10-hour fast.
|
|---|---|---|
|
AUCt: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration for Febuxostat XR 40 mg (Regimen B) and Febuxostat XR 80 mg (Regimen C) in Fasted States
|
3646.2021 ng*hr/mL
Standard Deviation 1465.07275
|
7854.2007 ng*hr/mL
Standard Deviation 2985.41297
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple timepoints (up to 48 hours) post dosePopulation: Participants from the PK population, all participants who received study drug and had at least 1 measurable plasma concentration, who received a single dose of study drug in Regimen A and C.
AUCinf is a measure of total plasma exposure to the drug from time zero extrapolated to infinity. Participant blood samples were collected pre-dose and following a single oral dose.
Outcome measures
| Measure |
A: Febuxostat XR 80 mg (Fed)
n=34 Participants
Febuxostat XR 80 mg, capsules, orally, once on Day 1 in any of the 3 treatment periods 30 minutes after starting to ingest a high-fat meal.
|
C: Febuxostat XR 80 mg (Fasting)
n=34 Participants
Febuxostat XR 80 mg, capsules, orally, once on Day 1 in any of the 3 treatment periods after a 10-hour fast.
|
|---|---|---|
|
AUCinf: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for Febuxostat XR 80 mg in Fed (Regimen A) and Fasted (Regimen C) States
|
7816.0704 ng*hr/mL
Standard Deviation 2105.40456
|
8075.5899 ng*hr/mL
Standard Deviation 2826.48142
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple timepoints (up to 48 hours) post dosePopulation: Participants from the PK population, all participants who received study drug and had at least 1 measurable plasma concentration, who received a single dose of study drug in Regimen B and C.
AUCinf is a measure of total plasma exposure to the drug from time zero extrapolated to infinity. Participant blood samples were collected pre-dose and following a single oral dose.
Outcome measures
| Measure |
A: Febuxostat XR 80 mg (Fed)
n=35 Participants
Febuxostat XR 80 mg, capsules, orally, once on Day 1 in any of the 3 treatment periods 30 minutes after starting to ingest a high-fat meal.
|
C: Febuxostat XR 80 mg (Fasting)
n=35 Participants
Febuxostat XR 80 mg, capsules, orally, once on Day 1 in any of the 3 treatment periods after a 10-hour fast.
|
|---|---|---|
|
AUCinf: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for Febuxostat XR 40 mg (Regimen B) and Febuxostate XR 80 mg (Regimen C) in Fasted States
|
3745.2837 ng*hr/mL
Standard Deviation 1452.71754
|
7970.7990 ng*hr/mL
Standard Deviation 2852.78221
|
Adverse Events
A: Febuxostat XR 80 mg (Fed)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
B: Febuxostat XR 40 mg (Fasting)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
C: Febuxostat XR 80 mg (Fasting)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
A: Febuxostat XR 80 mg (Fed)
n=35 participants at risk
Febuxostat XR 80 mg, capsules, orally, once on Day 1 in any of the 3 treatment periods 30 minutes after starting to ingest a high-fat meal.
|
B: Febuxostat XR 40 mg (Fasting)
n=36 participants at risk
Febuxostat XR 40 mg, capsules, orally, once on Day 1 in any of the 3 treatment periods after a 10-hour fast.
|
C: Febuxostat XR 80 mg (Fasting)
n=36 participants at risk
Febuxostat XR 80 mg, capsules, orally, once on Day 1 in any of the 3 treatment periods after a 10-hour fast.
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/35 • From the first dose of study drug to 30 days after the last dose of study drug (approximately 58 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Set included all participants who received at least 1 dose of study drug.
|
5.6%
2/36 • From the first dose of study drug to 30 days after the last dose of study drug (approximately 58 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Set included all participants who received at least 1 dose of study drug.
|
2.8%
1/36 • From the first dose of study drug to 30 days after the last dose of study drug (approximately 58 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Set included all participants who received at least 1 dose of study drug.
|
|
Nervous system disorders
Headache
|
2.9%
1/35 • From the first dose of study drug to 30 days after the last dose of study drug (approximately 58 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Set included all participants who received at least 1 dose of study drug.
|
5.6%
2/36 • From the first dose of study drug to 30 days after the last dose of study drug (approximately 58 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Set included all participants who received at least 1 dose of study drug.
|
5.6%
2/36 • From the first dose of study drug to 30 days after the last dose of study drug (approximately 58 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Set included all participants who received at least 1 dose of study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
- Publication restrictions are in place
Restriction type: OTHER