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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1168-1117 | Other Identifier | WHO |
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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.
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment Sequence ABDC | Experimental | 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). |
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| Treatment Sequence DACB | Experimental | 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). |
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| Treatment Sequence CDBA | Experimental | 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). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Febuxostat XR 80 mg Capsule F1 | Drug | Febuxostat extended-release (XR) capsules formulation 1 |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
| 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. | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
| 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. | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director Clinical Science | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Austin | Texas | 78744 | United States |
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 took part in the study at 1 investigative site in the United States from 29 June 2015 to 01 October 2015.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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). |
| FG001 | 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). |
| FG002 | 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). |
| FG003 | 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). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 |
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| Treatment Period 2 |
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| Treatment Period 3 |
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| Treatment Period 4 |
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Safety Set included all participants who were enrolled and received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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). |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Mean | Standard Deviation | ng/mL | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
|
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)
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Regimen A: Febuxostat XR 80 mg Formulation 1 | Febuxostat XR 80 mg capsule formulation 1 (F1), orally, once on Day 1 of periods 1, 2, 3 or 4. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Blood creatine phosphokinase increased | Investigations | MedDRA version 18.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA version 18.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director, Clinical Science | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
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| ID | Term |
|---|---|
| C006011 | F 4 |
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| Treatment Sequence BCAD | Experimental | 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). |
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| Febuxostat XR 80 mg Capsule F2 | Drug | Febuxostat XR capsules formulation 2 |
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| Febuxostat XR 80 mg Capsule F3 | Drug | Febuxostat XR capsules formulation 3 |
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| Febuxostat XR 80 mg Capsule F4 | Drug | Febuxostat XR capsules formulation 4 |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| BG001 | 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). |
| BG002 | 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). |
| BG003 | 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). |
| BG004 | Total | Total of all reporting groups |
| years |
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| Gender | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Height | Mean | Standard Deviation | cm |
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| Weight | Mean | Standard Deviation | kg |
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| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
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| Smoking Classification | Count of Participants | Participants |
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| Alcohol Classification | Count of Participants | Participants |
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| Xanthine/Caffeine Consumption | Count of Participants | Participants |
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| Female Reproductive Status | Count of Participants | Participants |
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| Estimated Glomerular Filtration Rate (eGFR) | eGFR is calculated using the Cockcroft-Gault formula. | Mean | Standard Deviation | mL/min |
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| Regimen B: Febuxostat XR 80 mg Formulation 2 |
Febuxostat XR 80 mg capsule formulation 2 (F2), orally, once on Day 1 of periods 1, 2, 3 or 4. |
| OG002 | Regimen C: Febuxostat XR 80 mg Formulation 3 | Febuxostat XR 80 mg capsule formulation 3 (F3), orally, once on Day 1 of periods 1, 2, 3 or 4. |
| OG003 | Regimen D: Febuxostat XR 80 mg Formulation 4 | Febuxostat XR 80 mg capsule formulation 4 (F4), orally, once on Day 1 of periods 1, 2, 3 or 4. |
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| 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. | 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. | Posted | Mean | Standard Deviation | ng*hr/mL | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
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| 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. | 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. | Posted | Mean | Standard Deviation | ng*hr/mL | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
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| 0 |
| 76 |
| 6 |
| 76 |
| EG001 | Regimen B: Febuxostat XR 80 mg Formulation 2 | Febuxostat XR 80 mg capsule formulation 2 (F2), orally, once on Day 1 of periods 1, 2, 3 or 4. | 1 | 76 | 9 | 76 |
| EG002 | Regimen C: Febuxostat XR 80 mg Formulation 3 | Febuxostat XR 80 mg capsule formulation 3 (F3), orally, once on Day 1 of periods 1, 2, 3 or 4. | 0 | 77 | 7 | 77 |
| EG003 | Regimen D: Febuxostat XR 80 mg Formulation 4 | Febuxostat XR 80 mg capsule formulation 4 (F4), orally, once on Day 1 of periods 1, 2, 3 or 4. | 0 | 76 | 7 | 76 |
| Nausea | Gastrointestinal disorders | MedDRA version 18.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA version 18.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA version 18.0 | Systematic Assessment |
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| Bacterial vaginosis | Infections and infestations | MedDRA version 18.0 | Systematic Assessment |
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| Oral herpes | Infections and infestations | MedDRA version 18.0 | Systematic Assessment |
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| Trichomoniasis | Infections and infestations | MedDRA version 18.0 | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA version 18.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 18.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA version 18.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA version 18.0 | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA version 18.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA version 18.0 | Systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA version 18.0 | Systematic Assessment |
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| Libido decreased | Psychiatric disorders | MedDRA version 18.0 | Systematic Assessment |
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| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA version 18.0 | Systematic Assessment |
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| Vaginal discharge | Reproductive system and breast disorders | MedDRA version 18.0 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 18.0 | Systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | MedDRA version 18.0 | Systematic Assessment |
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| Papule | Skin and subcutaneous tissue disorders | MedDRA version 18.0 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA version 18.0 | Systematic Assessment |
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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.
| Relative bioavailability of a single dose of Febuxostat XR 80 mg in test (Regimen B) and reference (Regimen D). | Point Estimate | 0.8777 | 2-Sided | 90 | 0.8274 | 0.9311 | 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. | Yes | Non-Inferiority or Equivalence | 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. |
| Relative bioavailability of a single dose of Febuxostat XR 80 mg in test (Regimen A) and reference (Regimen D). | Point Estimate | 0.9540 | 2-Sided | 90 | 0.8996 | 1.0117 | 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. | Yes | Non-Inferiority or Equivalence | 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. |
| Relative bioavailability of a single dose of Febuxostat XR 80 mg in test (Regimen B) and reference (Regimen D). | Point Estimate | 0.9056 | 2-Sided | 90 | 0.8516 | 0.9630 | 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. | Yes | Non-Inferiority or Equivalence | 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. |
| Relative bioavailability of a single dose of Febuxostat XR 80 mg in test (Regimen C) and reference (Regimen D). | Point Estimates | 0.9463 | 2-Sided | 90 | 0.8909 | 1.0051 | 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. | Yes | Non-Inferiority or Equivalence | 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. |