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Food Effect Study of Febuxostat XR in Healthy Participants

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ClinicalTrials.gov Identifier: NCT02374164
Recruitment Status : Completed
First Posted : February 27, 2015
Results First Posted : April 27, 2016
Last Update Posted : April 27, 2016
Sponsor:
Information provided by (Responsible Party):
Takeda

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Gout
Intervention Drug: Febuxostat XR
Enrollment 36
Recruitment Details Healthy participants took part in the study at 1 investigative site in the United States from 2 February 2015 to 19 April 2015.
Pre-assignment Details 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.
Arm/Group Title Treatment Sequence ABC Treatment Sequence BCA Treatment Sequence CAB
Hide Arm/Group Description 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. 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. 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.
Period Title: Treatment Period 1
Started 12 12 12
Completed 12 12 12
Not Completed 0 0 0
Period Title: Treatment Period 2
Started 12 12 12
Completed 12 12 12
Not Completed 0 0 0
Period Title: Treatment Period 3
Started 12 11 [1] 12
Completed 12 11 12
Not Completed 0 0 0
[1]
One participant was Lost-to-Follow-Up prior to treatment A.
Arm/Group Title Treatment Sequence ABC Treatment Sequence BCA Treatment Sequence CAB Total
Hide Arm/Group Description 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. 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. 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 of all reporting groups
Overall Number of Baseline Participants 12 12 12 36
Hide Baseline Analysis Population Description
Safety Set included all participants who were enrolled and received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants 12 participants 12 participants 36 participants
31.3  (8.37) 35.0  (6.32) 29.1  (5.35) 31.8  (7.05)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 12 participants 12 participants 36 participants
Female
6
  50.0%
6
  50.0%
7
  58.3%
19
  52.8%
Male
6
  50.0%
6
  50.0%
5
  41.7%
17
  47.2%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 12 participants 12 participants 12 participants 36 participants
Hispanic or Latino 5 6 5 16
Not Hispanic or Latino 7 6 7 20
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 12 participants 12 participants 12 participants 36 participants
Black or African American 2 2 3 7
White 10 10 9 29
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 12 participants 12 participants 12 participants 36 participants
12 12 12 36
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 12 participants 12 participants 12 participants 36 participants
167.6  (8.27) 168.8  (9.98) 166.6  (12.35) 167.6  (10.08)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 12 participants 12 participants 12 participants 36 participants
73.95  (10.802) 73.35  (8.867) 69.10  (8.169) 72.13  (9.335)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 12 participants 12 participants 12 participants 36 participants
26.21  (1.880) 25.76  (2.321) 25.03  (2.878) 25.67  (2.376)
Female Reproductive Status  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 12 participants 12 participants 12 participants 36 participants
N/A (Participant is Male) 6 6 5 17
Female of Childbearing Potential 5 3 7 15
Surgically Sterile 1 3 0 4
Smoking Classification  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 12 participants 12 participants 12 participants 36 participants
Has Never Smoked 8 12 10 30
Is a Current Smoker 0 0 0 0
Is an Ex-Smoker 4 0 2 6
Alcohol Classification  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 12 participants 12 participants 12 participants 36 participants
Has Never Drunk 3 5 4 12
Is a Current Drinker 7 5 6 18
Is an Ex-Drinker 2 2 2 6
Xanthine/Caffeine Consumption  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 12 participants 12 participants 12 participants 36 participants
Yes 8 7 7 22
No 4 5 5 14
Estimated Glomerular Filtration Rate (eGFR)   [1] 
Mean (Standard Deviation)
Unit of measure:  mL/min
Number Analyzed 12 participants 12 participants 12 participants 36 participants
Screening 123.38  (22.449) 125.41  (13.025) 125.87  (15.280) 124.88  (16.920)
Check-in 131.43  (25.231) 132.71  (13.999) 135.95  (19.147) 133.36  (19.509)
[1]
Measure Description: eGFR is calculated using the Cockcroft-Gault formula.
1.Primary Outcome
Title Cmax: Maximum Observed Plasma Concentration for Febuxostat XR 80 mg in Fed (Regimen A) and Fasted (Regimen C) States
Hide Description 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.
Time Frame Day 1 pre-dose and at multiple timepoints (up to 48 hours) post dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title A: Febuxostat XR 80 mg (Fed) C: Febuxostat XR 80 mg (Fasting)
Hide Arm/Group Description:
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.
Febuxostat XR 80 mg, capsules, orally, once on Day 1 in any of the 3 treatment periods after a 10-hour fast.
Overall Number of Participants Analyzed 35 35
Mean (Standard Deviation)
Unit of Measure: ng/mL
1020.0000  (398.14171) 1531.6286  (906.12813)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection A: Febuxostat XR 80 mg (Fed), C: Febuxostat XR 80 mg (Fasting)
Comments Relative bioavailability of a single dose of Febuxostat XR 80 mg in the fasted and fed (high-fat meal) states.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Point Estimate
Estimated Value 0.720
Confidence Interval (2-Sided) 90%
0.612 to 0.847
Estimation Comments Ratio Fed/Fasted. Point estimate and 90% CI were obtained from the exponentiated results of analysis of the natural logarithm–transformed data. Bioequivalence was reached if the value was 0.80 to 1.25.
2.Primary Outcome
Title Cmax: Maximum Observed Plasma Concentration for Febuxostat XR 40 mg (Regimen B) and Febuxostat XR 80 mg (Regimen C) in Fasted States
Hide Description 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.
Time Frame Day 1 pre-dose and at multiple time points (up to 48 hours) post dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title B: Febuxostat XR 40 mg (Fasting) C: Febuxostat XR 80 mg (Fasting)
Hide Arm/Group Description:
Febuxostat XR 40 mg, capsules, orally, once on Day 1 in any of the 3 treatment periods after a 10-hour fast.
Febuxostat XR 80 mg, capsules, orally, once on Day 1 in any of the 3 treatment periods after a 10-hour fast.
Overall Number of Participants Analyzed 36 36
Mean (Standard Deviation)
Unit of Measure: ng/mL
754.9167  (471.49630) 1562.1389  (911.65824)
3.Primary Outcome
Title 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
Hide Description 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.
Time Frame Day 1 pre-dose and at multiple timepoints (up to 48 hours) post dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title A: Febuxostat XR 80 mg (Fed) C: Febuxostat XR 80 mg (Fasting)
Hide Arm/Group Description:
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.
Febuxostat XR 80 mg, capsules, orally, once on Day 1 in any of the 3 treatment periods after a 10-hour fast.
Overall Number of Participants Analyzed 35 35
Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
7605.4147  (2086.85262) 7687.1220  (2853.12475)
4.Primary Outcome
Title 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
Hide Description 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.
Time Frame Day 1 pre-dose and at multiple timepoints (up to 48 hours) post dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title B: Febuxostat XR 40 mg (Fasting) C: Febuxostat XR 80 mg (Fasting)
Hide Arm/Group Description:
Febuxostat XR 40 mg, capsules, orally, once on Day 1 in any of the 3 treatment periods after a 10-hour fast.
Febuxostat XR 80 mg, capsules, orally, once on Day 1 in any of the 3 treatment periods after a 10-hour fast.
Overall Number of Participants Analyzed 36 36
Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
3646.2021  (1465.07275) 7854.2007  (2985.41297)
5.Primary Outcome
Title 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
Hide Description 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.
Time Frame Day 1 pre-dose and at multiple timepoints (up to 48 hours) post dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title A: Febuxostat XR 80 mg (Fed) C: Febuxostat XR 80 mg (Fasting)
Hide Arm/Group Description:
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.
Febuxostat XR 80 mg, capsules, orally, once on Day 1 in any of the 3 treatment periods after a 10-hour fast.
Overall Number of Participants Analyzed 34 34
Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
7816.0704  (2105.40456) 8075.5899  (2826.48142)
6.Primary Outcome
Title 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
Hide Description 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.
Time Frame Day 1 pre-dose and at multiple timepoints (up to 48 hours) post dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title B: Febuxostat XR 40 mg (Fasting) C: Febuxostat XR 80 mg (Fasting)
Hide Arm/Group Description:
Febuxostat XR 40 mg, capsules, orally, once on Day 1 in any of the 3 treatment periods after a 10-hour fast.
Febuxostat XR 80 mg, capsules, orally, once on Day 1 in any of the 3 treatment periods after a 10-hour fast.
Overall Number of Participants Analyzed 35 35
Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
3745.2837  (1452.71754) 7970.7990  (2852.78221)
Time Frame From the first dose of study drug to 30 days after the last dose of study drug (approximately 58 days)
Adverse Event Reporting Description 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.
 
Arm/Group Title A: Febuxostat XR 80 mg (Fed) B: Febuxostat XR 40 mg (Fasting) C: Febuxostat XR 80 mg (Fasting)
Hide Arm/Group Description 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. Febuxostat XR 40 mg, capsules, orally, once on Day 1 in any of the 3 treatment periods after a 10-hour fast. Febuxostat XR 80 mg, capsules, orally, once on Day 1 in any of the 3 treatment periods after a 10-hour fast.
All-Cause Mortality
A: Febuxostat XR 80 mg (Fed) B: Febuxostat XR 40 mg (Fasting) C: Febuxostat XR 80 mg (Fasting)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
A: Febuxostat XR 80 mg (Fed) B: Febuxostat XR 40 mg (Fasting) C: Febuxostat XR 80 mg (Fasting)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/35 (0.00%)   0/36 (0.00%)   0/36 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
A: Febuxostat XR 80 mg (Fed) B: Febuxostat XR 40 mg (Fasting) C: Febuxostat XR 80 mg (Fasting)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/35 (2.86%)   3/36 (8.33%)   2/36 (5.56%) 
Gastrointestinal disorders       
Nausea  1  0/35 (0.00%)  2/36 (5.56%)  1/36 (2.78%) 
Nervous system disorders       
Headache  1  1/35 (2.86%)  2/36 (5.56%)  2/36 (5.56%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Medical Director, Clinical Science
Organization: Takeda
Phone: +1-877-825-3327
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT02374164     History of Changes
Other Study ID Numbers: Febuxostat-XR-1009
U1111-1165-0441 ( Registry Identifier: UTN (WHO) )
First Submitted: February 22, 2015
First Posted: February 27, 2015
Results First Submitted: March 25, 2016
Results First Posted: April 27, 2016
Last Update Posted: April 27, 2016