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Phase 1, Febuxostat XR Relative Bioavailability Study

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ClinicalTrials.gov Identifier: NCT02504320
Recruitment Status : Completed
First Posted : July 21, 2015
Results First Posted : January 19, 2017
Last Update Posted : January 19, 2017
Sponsor:
Information provided by (Responsible Party):
Takeda

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Basic Science
Condition Healthy Volunteers
Interventions Drug: Febuxostat XR 80 mg Capsule F1
Drug: Febuxostat XR 80 mg Capsule F2
Drug: Febuxostat XR 80 mg Capsule F3
Drug: Febuxostat XR 80 mg Capsule F4
Enrollment 78
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.
Arm/Group Title Treatment Sequence ABDC Treatment Sequence DACB Treatment Sequence CDBA Treatment Sequence BCAD
Hide Arm/Group Description 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). 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). 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). 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).
Period Title: Treatment Period 1
Started 19 19 20 20
Completed 19 19 19 20
Not Completed 0 0 1 0
Reason Not Completed
Positive Drug Screen             0             0             1             0
Period Title: Treatment Period 2
Started 19 19 19 20
Completed 19 18 19 20
Not Completed 0 1 0 0
Reason Not Completed
Positive Drug Screen             0             1             0             0
Period Title: Treatment Period 3
Started 19 18 19 20
Completed 19 18 18 19
Not Completed 0 0 1 1
Reason Not Completed
Positive Drug Screen             0             0             0             1
Adverse Event             0             0             1             0
Period Title: Treatment Period 4
Started 19 18 18 19
Completed 19 18 18 19
Not Completed 0 0 0 0
Arm/Group Title Treatment Sequence ABDC Treatment Sequence DACB Treatment Sequence CDBA Treatment Sequence BCAD Total
Hide Arm/Group Description 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). 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). 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). 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). Total of all reporting groups
Overall Number of Baseline Participants 19 19 20 20 78
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 19 participants 19 participants 20 participants 20 participants 78 participants
31.7  (7.56) 30.7  (6.51) 34.0  (8.87) 31.2  (7.78) 31.9  (7.70)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 19 participants 20 participants 20 participants 78 participants
Female
10
  52.6%
10
  52.6%
9
  45.0%
14
  70.0%
43
  55.1%
Male
9
  47.4%
9
  47.4%
11
  55.0%
6
  30.0%
35
  44.9%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 19 participants 20 participants 20 participants 78 participants
Hispanic or Latino
11
  57.9%
7
  36.8%
9
  45.0%
10
  50.0%
37
  47.4%
Not Hispanic or Latino
8
  42.1%
12
  63.2%
11
  55.0%
10
  50.0%
41
  52.6%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 19 participants 20 participants 20 participants 78 participants
Asian
0
   0.0%
0
   0.0%
0
   0.0%
1
   5.0%
1
   1.3%
Black or African American
4
  21.1%
7
  36.8%
6
  30.0%
6
  30.0%
23
  29.5%
White
15
  78.9%
11
  57.9%
14
  70.0%
13
  65.0%
53
  67.9%
Multiracial
0
   0.0%
1
   5.3%
0
   0.0%
0
   0.0%
1
   1.3%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 19 participants 19 participants 20 participants 20 participants 78 participants
19
 100.0%
19
 100.0%
20
 100.0%
20
 100.0%
78
 100.0%
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 19 participants 19 participants 20 participants 20 participants 78 participants
167.6  (10.13) 171.1  (11.75) 167.5  (9.70) 165.7  (6.67) 167.9  (9.71)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 19 participants 19 participants 20 participants 20 participants 78 participants
72.98  (12.685) 79.05  (11.846) 71.22  (12.350) 69.72  (11.015) 73.17  (12.273)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 19 participants 19 participants 20 participants 20 participants 78 participants
25.84  (2.663) 26.98  (2.722) 25.29  (3.168) 25.28  (2.802) 25.83  (2.878)
Smoking Classification  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 19 participants 20 participants 20 participants 78 participants
Has Never Smoked
13
  68.4%
14
  73.7%
13
  65.0%
18
  90.0%
58
  74.4%
Is a Current Smoker
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Is an Ex-smoker
6
  31.6%
5
  26.3%
7
  35.0%
2
  10.0%
20
  25.6%
Alcohol Classification  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 19 participants 20 participants 20 participants 78 participants
Has Never Drunk
4
  21.1%
6
  31.6%
6
  30.0%
7
  35.0%
23
  29.5%
Is a Current Drinker
8
  42.1%
9
  47.4%
6
  30.0%
4
  20.0%
27
  34.6%
Is an Ex-drinker
7
  36.8%
4
  21.1%
8
  40.0%
9
  45.0%
28
  35.9%
Xanthine/Caffeine Consumption  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 19 participants 20 participants 20 participants 78 participants
Yes
12
  63.2%
13
  68.4%
12
  60.0%
14
  70.0%
51
  65.4%
No
7
  36.8%
6
  31.6%
8
  40.0%
6
  30.0%
27
  34.6%
Female Reproductive Status  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 19 participants 20 participants 20 participants 78 participants
Not Applicable (Participant is Male)
9
  47.4%
9
  47.4%
11
  55.0%
6
  30.0%
35
  44.9%
Female of Childbearing Potential
7
  36.8%
9
  47.4%
8
  40.0%
12
  60.0%
36
  46.2%
Surgically Sterile
2
  10.5%
1
   5.3%
0
   0.0%
2
  10.0%
5
   6.4%
Postmenopausal
1
   5.3%
0
   0.0%
1
   5.0%
0
   0.0%
2
   2.6%
Estimated Glomerular Filtration Rate (eGFR)   [1] 
Mean (Standard Deviation)
Unit of measure:  mL/min
Number Analyzed 19 participants 19 participants 20 participants 20 participants 78 participants
Screening (n=19, 19, 19, 20) 111.42  (11.815) 112.84  (11.987) 108.05  (11.664) 114.00  (13.377) 111.61  (12.211)
Check-in (n=19, 19, 20, 20) 115.53  (12.294) 115.26  (12.229) 112.00  (10.964) 116.55  (12.845) 114.82  (11.987)
[1]
Measure Description: eGFR is calculated using the Cockcroft-Gault formula.
1.Primary Outcome
Title Mean Cmax: Maximum Observed Plasma Concentration for Febuxostat
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.
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 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/Group Title Regimen A: Febuxostat XR 80 mg Formulation 1 Regimen B: Febuxostat XR 80 mg Formulation 2 Regimen C: Febuxostat XR 80 mg Formulation 3 Regimen D: Febuxostat XR 80 mg Formulation 4
Hide Arm/Group Description:
Febuxostat XR 80 mg capsule formulation 1 (F1), orally, once on Day 1 of periods 1, 2, 3 or 4.
Febuxostat XR 80 mg capsule formulation 2 (F2), orally, once on Day 1 of periods 1, 2, 3 or 4.
Febuxostat XR 80 mg capsule formulation 3 (F3), orally, once on Day 1 of periods 1, 2, 3 or 4.
Febuxostat XR 80 mg capsule formulation 4 (F4), orally, once on Day 1 of periods 1, 2, 3 or 4.
Overall Number of Participants Analyzed 76 74 77 76
Mean (Standard Deviation)
Unit of Measure: ng/mL
2027.1184  (1278.28368) 1442.2267  (991.94583) 1730.2468  (1013.56204) 1809.3158  (1170.53245)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Regimen A: Febuxostat XR 80 mg Formulation 1, Regimen D: Febuxostat XR 80 mg Formulation 4
Comments Relative bioavailability of a single dose of Febuxostat XR 80 mg in test (Regimen A) and reference (Regimen D).
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of Febuxostat formulation 1, 2, and 3 to Febuxostat formulation 4 was declared if the 90% confidence intervals for the ratios of central values were within the pre-specified interval of 0.80 to 1.25.
Method of Estimation Estimation Parameter Point Estimate
Estimated Value 1.0848
Confidence Interval (2-Sided) 90%
0.9528 to 1.2350
Estimation Comments Point estimate and 90% CI were obtained from the exponentiated results of analysis of the natural log (ln)-transformed parameters was performed with regimen, sequence, period, and participants nested within sequence as fixed effects.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Regimen B: Febuxostat XR 80 mg Formulation 2, Regimen D: Febuxostat XR 80 mg Formulation 4
Comments Relative bioavailability of a single dose of Febuxostat XR 80 mg in test (Regimen B) and reference (Regimen D).
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of Febuxostat formulation 1, 2, and 3 to Febuxostat formulation 4 was declared if the 90% confidence intervals for the ratios of central values were within the pre-specified interval of 0.80 to 1.25.
Method of Estimation Estimation Parameter Point Estimate
Estimated Value 0.7709
Confidence Interval (2-Sided) 90%
0.6767 to 0.8782
Estimation Comments Point estimate and 90% CI were obtained from the exponentiated results of analysis of the natural log (ln)-transformed parameters was performed with regimen, sequence, period, and participants nested within sequence as fixed effects.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Regimen C: Febuxostat XR 80 mg Formulation 3, Regimen D: Febuxostat XR 80 mg Formulation 4
Comments Relative bioavailability of a single dose of Febuxostat XR 80 mg in test (Regimen C) and reference (Regimen D).
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of Febuxostat formulation 1, 2, and 3 to Febuxostat formulation 4 was declared if the 90% confidence intervals for the ratios of central values were within the pre-specified interval of 0.80 to 1.25.
Method of Estimation Estimation Parameter Point Estimate
Estimated Value 0.9389
Confidence Interval (2-Sided) 90%
0.8246 to 1.0689
Estimation Comments Point estimate and 90% CI were obtained from the exponentiated results of analysis of the natural log (ln)-transformed parameters was performed with regimen, sequence, period, and participants nested within sequence as fixed effects.
2.Primary Outcome
Title Mean AUCt: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Febuxostat
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Regimen A: Febuxostat XR 80 mg Formulation 1 Regimen B: Febuxostat XR 80 mg Formulation 2 Regimen C: Febuxostat XR 80 mg Formulation 3 Regimen D: Febuxostat XR 80 mg Formulation 4
Hide Arm/Group Description:
Febuxostat XR 80 mg capsule formulation 1 (F1), orally, once on Day 1 of periods 1, 2, 3 or 4.
Febuxostat XR 80 mg capsule formulation 2 (F2), orally, once on Day 1 of periods 1, 2, 3 or 4.
Febuxostat XR 80 mg capsule formulation 3 (F3), orally, once on Day 1 of periods 1, 2, 3 or 4.
Febuxostat XR 80 mg capsule formulation 4 (F4), orally, once on Day 1 of periods 1, 2, 3 or 4.
Overall Number of Participants Analyzed 76 75 77 76
Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
9395.6014  (3961.55203) 7971.0624  (3291.36390) 8652.7080  (3673.91666) 8817.3600  (3429.94880)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Regimen A: Febuxostat XR 80 mg Formulation 1, Regimen D: Febuxostat XR 80 mg Formulation 4
Comments Relative bioavailability of a single dose of Febuxostat XR 80 mg in test (Regimen A) and reference (Regimen D).
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of Febuxostat formulation 1, 2, and 3 to Febuxostat formulation 4 was declared if the 90% confidence intervals for the ratios of central values were within the pre-specified interval of 0.80 to 1.25.
Method of Estimation Estimation Parameter Point Estimate
Estimated Value 1.0435
Confidence Interval (2-Sided) 90%
0.9840 to 1.1066
Estimation Comments Point estimate and 90% CI were obtained from the exponentiated results of analysis of the natural log (ln)-transformed parameters was performed with regimen, sequence, period, and participants nested within sequence as fixed effects.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Regimen B: Febuxostat XR 80 mg Formulation 2, Regimen D: Febuxostat XR 80 mg Formulation 4
Comments Relative bioavailability of a single dose of Febuxostat XR 80 mg in test (Regimen B) and reference (Regimen D).
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of Febuxostat formulation 1, 2, and 3 to Febuxostat formulation 4 was declared if the 90% confidence intervals for the ratios of central values were within the pre-specified interval of 0.80 to 1.25.
Method of Estimation Estimation Parameter Point Estimate
Estimated Value 0.8777
Confidence Interval (2-Sided) 90%
0.8274 to 0.9311
Estimation Comments Point estimate and 90% CI were obtained from the exponentiated results of analysis of the natural log (ln)-transformed parameters was performed with regimen, sequence, period, and participants nested within sequence as fixed effects.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Regimen C: Febuxostat XR 80 mg Formulation 3, Regimen D: Febuxostat XR 80 mg Formulation 4
Comments Relative bioavailability of a single dose of Febuxostat XR 80 mg in test (Regimen A) and reference (Regimen D).
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of Febuxostat formulation 1, 2, and 3 to Febuxostat formulation 4 was declared if the 90% confidence intervals for the ratios of central values were within the pre-specified interval of 0.80 to 1.25.
Method of Estimation Estimation Parameter Point Estimate
Estimated Value 0.9540
Confidence Interval (2-Sided) 90%
0.8996 to 1.0117
Estimation Comments Point estimate and 90% CI were obtained from the exponentiated results of analysis of the natural log (ln)-transformed parameters was performed with regimen, sequence, period, and participants nested within sequence as fixed effects.
3.Primary Outcome
Title Mean AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Febuxostat
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Regimen A: Febuxostat XR 80 mg Formulation 1 Regimen B: Febuxostat XR 80 mg Formulation 2 Regimen C: Febuxostat XR 80 mg Formulation 3 Regimen D: Febuxostat XR 80 mg Formulation 4
Hide Arm/Group Description:
Febuxostat XR 80 mg capsule formulation 1 (F1), orally, once on Day 1 of periods 1, 2, 3 or 4.
Febuxostat XR 80 mg capsule formulation 2 (F2), orally, once on Day 1 of periods 1, 2, 3 or 4.
Febuxostat XR 80 mg capsule formulation 3 (F3), orally, once on Day 1 of periods 1, 2, 3 or 4.
Febuxostat XR 80 mg capsule formulation 4 (F4), orally, once on Day 1 of periods 1, 2, 3 or 4.
Overall Number of Participants Analyzed 69 62 69 69
Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
9368.0744  (3944.01280) 8278.6143  (3205.31556) 8938.8765  (3746.60153) 9102.3700  (3430.45699)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Regimen A: Febuxostat XR 80 mg Formulation 1, Regimen D: Febuxostat XR 80 mg Formulation 4
Comments Relative bioavailability of a single dose of Febuxostat XR 80 mg in test (Regimen A) and reference (Regimen D).
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of Febuxostat formulation 1, 2, and 3 to Febuxostat formulation 4 was declared if the 90% confidence intervals for the ratios of central values were within the pre-specified interval of 0.80 to 1.25.
Method of Estimation Estimation Parameter Point Estimate
Estimated Value 1.0283
Confidence Interval (2-Sided) 90%
0.9691 to 1.0911
Estimation Comments Point estimate and 90% CI were obtained from the exponentiated results of analysis of the natural log (ln)-transformed parameters was performed with regimen, sequence, period, and participants nested within sequence as fixed effects.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Regimen B: Febuxostat XR 80 mg Formulation 2, Regimen D: Febuxostat XR 80 mg Formulation 4
Comments Relative bioavailability of a single dose of Febuxostat XR 80 mg in test (Regimen B) and reference (Regimen D).
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of Febuxostat formulation 1, 2, and 3 to Febuxostat formulation 4 was declared if the 90% confidence intervals for the ratios of central values were within the pre-specified interval of 0.80 to 1.25.
Method of Estimation Estimation Parameter Point Estimate
Estimated Value 0.9056
Confidence Interval (2-Sided) 90%
0.8516 to 0.9630
Estimation Comments Point estimate and 90% CI were obtained from the exponentiated results of analysis of the natural log (ln)-transformed parameters was performed with regimen, sequence, period, and participants nested within sequence as fixed effects.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Regimen C: Febuxostat XR 80 mg Formulation 3, Regimen D: Febuxostat XR 80 mg Formulation 4
Comments Relative bioavailability of a single dose of Febuxostat XR 80 mg in test (Regimen C) and reference (Regimen D).
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence of Febuxostat formulation 1, 2, and 3 to Febuxostat formulation 4 was declared if the 90% confidence intervals for the ratios of central values were within the pre-specified interval of 0.80 to 1.25.
Method of Estimation Estimation Parameter Point Estimates
Estimated Value 0.9463
Confidence Interval (2-Sided) 90%
0.8909 to 1.0051
Estimation Comments Point estimate and 90% CI were obtained from the exponentiated results of analysis of the natural log (ln)-transformed parameters was performed with regimen, sequence, period, and participants nested within sequence as fixed effects.
Time Frame From the first administration of study drug on Day 1 of Period 1 up to 30 days after the last dose of study drug or Early termination visit (approximately up to 95 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 Regimen A: Febuxostat XR 80 mg Formulation 1 Regimen B: Febuxostat XR 80 mg Formulation 2 Regimen C: Febuxostat XR 80 mg Formulation 3 Regimen D: Febuxostat XR 80 mg Formulation 4
Hide Arm/Group Description Febuxostat XR 80 mg capsule formulation 1 (F1), orally, once on Day 1 of periods 1, 2, 3 or 4. Febuxostat XR 80 mg capsule formulation 2 (F2), orally, once on Day 1 of periods 1, 2, 3 or 4. Febuxostat XR 80 mg capsule formulation 3 (F3), orally, once on Day 1 of periods 1, 2, 3 or 4. Febuxostat XR 80 mg capsule formulation 4 (F4), orally, once on Day 1 of periods 1, 2, 3 or 4.
All-Cause Mortality
Regimen A: Febuxostat XR 80 mg Formulation 1 Regimen B: Febuxostat XR 80 mg Formulation 2 Regimen C: Febuxostat XR 80 mg Formulation 3 Regimen D: Febuxostat XR 80 mg Formulation 4
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Regimen A: Febuxostat XR 80 mg Formulation 1 Regimen B: Febuxostat XR 80 mg Formulation 2 Regimen C: Febuxostat XR 80 mg Formulation 3 Regimen D: Febuxostat XR 80 mg Formulation 4
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/76 (0.00%)   1/76 (1.32%)   0/77 (0.00%)   0/76 (0.00%) 
Investigations         
Blood creatine phosphokinase increased  1  0/76 (0.00%)  1/76 (1.32%)  0/77 (0.00%)  0/76 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 18.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Regimen A: Febuxostat XR 80 mg Formulation 1 Regimen B: Febuxostat XR 80 mg Formulation 2 Regimen C: Febuxostat XR 80 mg Formulation 3 Regimen D: Febuxostat XR 80 mg Formulation 4
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/76 (7.89%)   9/76 (11.84%)   7/77 (9.09%)   7/76 (9.21%) 
Gastrointestinal disorders         
Diarrhoea  1  0/76 (0.00%)  0/76 (0.00%)  2/77 (2.60%)  0/76 (0.00%) 
Nausea  1  1/76 (1.32%)  0/76 (0.00%)  0/77 (0.00%)  1/76 (1.32%) 
Vomiting  1  0/76 (0.00%)  1/76 (1.32%)  0/77 (0.00%)  0/76 (0.00%) 
Infections and infestations         
Nasopharyngitis  1  0/76 (0.00%)  2/76 (2.63%)  0/77 (0.00%)  0/76 (0.00%) 
Bacterial vaginosis  1  1/76 (1.32%)  0/76 (0.00%)  0/77 (0.00%)  0/76 (0.00%) 
Oral herpes  1  0/76 (0.00%)  0/76 (0.00%)  0/77 (0.00%)  1/76 (1.32%) 
Trichomoniasis  1  0/76 (0.00%)  1/76 (1.32%)  0/77 (0.00%)  0/76 (0.00%) 
Injury, poisoning and procedural complications         
Contusion  1  0/76 (0.00%)  0/76 (0.00%)  0/77 (0.00%)  1/76 (1.32%) 
Musculoskeletal and connective tissue disorders         
Back pain  1  1/76 (1.32%)  1/76 (1.32%)  0/77 (0.00%)  0/76 (0.00%) 
Myalgia  1  1/76 (1.32%)  0/76 (0.00%)  0/77 (0.00%)  0/76 (0.00%) 
Nervous system disorders         
Headache  1  1/76 (1.32%)  2/76 (2.63%)  1/77 (1.30%)  3/76 (3.95%) 
Syncope  1  1/76 (1.32%)  0/76 (0.00%)  1/77 (1.30%)  0/76 (0.00%) 
Dizziness  1  0/76 (0.00%)  1/76 (1.32%)  0/77 (0.00%)  0/76 (0.00%) 
Presyncope  1  0/76 (0.00%)  0/76 (0.00%)  1/77 (1.30%)  0/76 (0.00%) 
Psychiatric disorders         
Libido decreased  1  0/76 (0.00%)  0/76 (0.00%)  1/77 (1.30%)  0/76 (0.00%) 
Reproductive system and breast disorders         
Dysmenorrhoea  1  0/76 (0.00%)  1/76 (1.32%)  0/77 (0.00%)  0/76 (0.00%) 
Vaginal discharge  1  0/76 (0.00%)  1/76 (1.32%)  0/77 (0.00%)  0/76 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Dyspnoea  1  0/76 (0.00%)  1/76 (1.32%)  0/77 (0.00%)  0/76 (0.00%) 
Skin and subcutaneous tissue disorders         
Dry skin  1  0/76 (0.00%)  1/76 (1.32%)  0/77 (0.00%)  0/76 (0.00%) 
Papule  1  0/76 (0.00%)  0/76 (0.00%)  0/77 (0.00%)  1/76 (1.32%) 
Pruritus  1  0/76 (0.00%)  0/76 (0.00%)  1/77 (1.30%)  0/76 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 18.0
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: NCT02504320     History of Changes
Other Study ID Numbers: Febuxostat XR-1011
U1111-1168-1117 ( Other Identifier: WHO )
First Submitted: July 20, 2015
First Posted: July 21, 2015
Results First Submitted: September 29, 2016
Results First Posted: January 19, 2017
Last Update Posted: January 19, 2017