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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1225-5005 | Other Identifier | WHO | |
| JapicCTI-194587 | Registry Identifier | JapicCTI |
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The purpose of this study is to evaluate the BE of single oral dose of TAK-438 OD 20 milligram (mg) tablet without water and TAK-438 20 mg tablet with water (Study 1), and TAK-438 OD 20 mg tablet with water and TAK-438 20 mg tablet with water (Study 2) in Japanese healthy adult male participants.
The drug being tested in this study is called TAK-438 OD tablet. TAK-438 OD tablet is being tested in Japanese healthy adult men. This study will evaluate bioequivalence of single oral dose of TAK-438 OD 20 mg tablet without water and TAK-438 20 mg tablet with water (Study 1), and TAK-438 OD 20 mg tablet with water and TAK-438 20 mg tablet with water (Study 2).
The study will enroll up to 144 participants in total (Study 1 + 2). In Study 1 and 2, participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups;
Study 1:
Study 2:
This single-center trial will be conducted in Japan. The overall time to participate in this study is approximately 11 days. Participants will make two visits to the clinic and be hospitalized for four days each in Periods 1 and 2.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Study 1, TAK-438 OD + TAK-438 | Experimental | One TAK-438 OD 20 mg tablet, orally without water under fasted condition, on Period 1 Day 1 in Study 1 (Day 1), followed by a wash-out period (Days 2 to 8), followed by one TAK-438 20 mg tablet, orally with water under fasted condition, on Period 2 Day 1 in Study 1 (Day 9). |
|
| Study 1, TAK-438 + TAK-438 OD | Experimental | One TAK-438 20 mg tablet, orally with water under fasted condition, on Period 1 Day 1 in Study 1 (Day 1), followed by a wash-out period (Days 2 to 8), followed by one TAK-438 OD 20 mg tablet, orally without water under fasted condition, on Period 2 Day 1 in Study 1 (Day 9). |
|
| Study 2, TAK-438 OD + TAK-438 | Experimental | One TAK-438 OD 20 mg tablet, orally with water under fasted condition, on Period 1 Day 1 in Study 2 (Day 1), followed by a wash-out period (Days 2 to 8), followed by one TAK-438 20 mg tablet, orally with water under fasted condition, on Period 2 Day 1 in Study 2 (Day 9). |
|
| Study 2, TAK-438 + TAK-438 OD | Experimental | One TAK-438 20 mg tablet, orally with water under fasted condition, on Period 1 Day 1 in Study 2 (Day 1), followed by a wash-out period (Days 2 to 8), followed by one TAK-438 OD 20 mg tablet, orally with water under fasted condition, on Period 2 Day 1 in Study 2 (Day 9). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TAK-438 OD | Drug | TAK-438 OD tablet |
|
| Measure | Description | Time Frame |
|---|---|---|
| AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Plasma Concentration for TAK-438 Free Base (TAK-438F) | Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose | |
| Cmax: Maximum Observed Plasma Concentration for TAK-438F | Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F | Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose | |
| Tmax: Time of First Occurrence of Maximum Plasma Concentration (Cmax) for TAK-438F |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sekino Clinical Pharmacology Clininc | Toshima-ku | Tokyo | Japan |
Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
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Healthy Japanese male participants were enrolled in 1 of the 2 treatment sequences to receive TAK-438 OD 20 milligram (mg) or TAK-438 20 mg with or without water in Study 1, and TAK-438 OD 20 mg or TAK-438 20 mg with water in Study 2. Study was completed with Pilot study since results from interim analysis satisfied the criteria of bioequivalence.
Participants took part in the study at 1 investigative site in Japan from 30 January 2019 to 12 March 2019.
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| ID | Title | Description |
|---|---|---|
| FG000 | Pilot BE Study 1, Sequence A: TAK-438 OD 20 mg + TAK-438 20 mg | TAK-438 orally disintegrating (OD) 20 mg, tablet, orally without water under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 7 days, further followed by TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of Period 2. |
| FG001 | Pilot BE Study 1, Sequence B: TAK-438 20 mg + TAK-438 OD 20 mg | TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of Period 1 followed by a washout period of at least 7 days, further followed TAK-438 OD 20 mg, tablet, orally without water under fasted condition, once on Day 1 of Period 2. |
| FG002 | Pilot BE Study 2, Sequence C: TAK-438 OD 20 mg + TAK-438 20 mg | TAK-438 OD 20 mg, tablet, orally with water under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 7 days, further followed by TAK-438 20 mg tablet, orally with water under fasted condition, once on Day 1 of Period 2. |
| FG003 | Pilot BE Study 2, Sequence D: TAK-438 20 mg + TAK-438 OD 20 mg | TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 7 days, further followed by TAK-438 OD 20 mg tablet, orally with water under fasted condition, once on Day 1 of Period 2. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
The safety analysis set was defined as all participants who received at least one dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Pilot BE Study 1, Sequence A: TAK-438 OD 20 mg + TAK-438 20 mg | TAK-438 OD 20 mg, tablet, orally without water under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 7 days, further followed by TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of Period 2. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| 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 | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Plasma Concentration for TAK-438 Free Base (TAK-438F) | The pharmacokinetic (PK) analysis set was defined as all participants who received at least one dose of study drug, and whose PK data were evaluable. | Posted | Geometric Mean | Standard Deviation | hour*nanogram per milliliter (h*ng/mL) | Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose |
|
Treatment-emergent adverse events (TEAEs) are adverse events (AE) that started after the first dose of study drug until Day 3 in Period 2 (up to Day 13)
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.
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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 | Pilot BE Study 1: TAK-438 OD 20 mg | TAK-438 OD 20 mg, tablet, orally without water under fasted condition, once on Day 1 of either Period 1 or 2. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 12, 2018 | Mar 9, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 27, 2018 | Mar 9, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| C552956 | 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine |
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| TAK-438 | Drug | TAK-438 tablet |
|
| Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose |
| MRT∞,ev: Mean Residence Time After Extravascular Administration From Time 0 to Infinity for TAK-438F | Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose |
| λz: Terminal Disposition Phase Rate Constant for TAK-438F | Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose |
| Pilot BE Study 1, Sequence B: TAK-438 20 mg + TAK-438 OD 20 mg |
TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of Period 1 followed by a washout period of at least 7 days, further followed TAK-438 OD 20 mg, tablet, orally without water under fasted condition, once on Day 1 of Period 2. |
| BG002 | Pilot BE Study 2, Sequence C: TAK-438 OD 20 mg + TAK-438 20 mg | TAK-438 OD 20 mg, tablet, orally with water under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 7 days, further followed by TAK-438 20 mg tablet, orally with water under fasted condition, once on Day 1 of Period 2. |
| BG003 | Pilot BE Study 2, Sequence D: TAK-438 20 mg + TAK-438 OD 20 mg | TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 7 days, further followed by TAK-438 OD 20 mg tablet, orally with water under fasted condition, once on Day 1 of Period 2. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Height | Mean | Standard Deviation | centimeter (cm) |
|
| Weight | Mean | Standard Deviation | kilogram (kg) |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kilogram per square meter (kg/m^2) |
|
| Caffeine Consumption | Count of Participants | Participants |
|
| Alcohol Consumption | Count of Participants | Participants |
|
| Smoking Classification | Count of Participants | Participants |
|
TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of either Period 1 or 2.
| OG002 | Pilot BE Study 2: TAK-438 OD 20 mg | TAK-438 OD 20 mg, tablet, orally with water under fasted condition, once on Day 1 of either Period 1 or 2. |
| OG003 | Pilot BE Study 2: TAK-438 20 mg | TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of either Period 1 or 2. |
|
|
|
| Primary | Cmax: Maximum Observed Plasma Concentration for TAK-438F | The PK analysis set was defined as all participants who received at least one dose of study drug, and whose PK data were evaluable. | Posted | Geometric Mean | Standard Deviation | nanogram per milliliter (ng/mL) | Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose |
|
|
|
|
| Secondary | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F | The PK analysis set was defined as all participants who received at least one dose of study drug, and whose PK data were evaluable. | Posted | Geometric Mean | Standard Deviation | h*ng/mL | Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose |
|
|
|
|
| Secondary | Tmax: Time of First Occurrence of Maximum Plasma Concentration (Cmax) for TAK-438F | The PK analysis set was defined as all participants who received at least one dose of study drug, and whose PK data were evaluable. | Posted | Median | Full Range | hour | Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose |
|
|
|
|
| Secondary | MRT∞,ev: Mean Residence Time After Extravascular Administration From Time 0 to Infinity for TAK-438F | The PK analysis set was defined as all participants who received at least one dose of study drug, and whose PK data were evaluable. | Posted | Mean | Standard Deviation | hour | Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose |
|
|
|
|
| Secondary | λz: Terminal Disposition Phase Rate Constant for TAK-438F | The PK analysis set was defined as all participants who received at least one dose of study drug, and whose PK data were evaluable. | Posted | Mean | Standard Deviation | per hour (1/hour) | Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose |
|
|
|
|
| 0 |
| 24 |
| 0 |
| 24 |
| 0 |
| 24 |
| EG001 | Pilot BE Study 1: TAK-438 20 mg | TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of either Period 1 or 2. | 0 | 24 | 0 | 24 | 0 | 24 |
| EG002 | Pilot BE Study 2: TAK-438 OD 20 mg | TAK-438 OD 20 mg, tablet, orally with water under fasted condition, once on Day 1 of either Period 1 or 2. | 0 | 24 | 0 | 24 | 0 | 24 |
| EG003 | Pilot BE Study 2: TAK-438 20 mg | TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of either Period 1 or 2. | 0 | 24 | 0 | 24 | 0 | 24 |
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.
| Male |
|
|
|
|
|
| LS-Means Difference |
| -0.0811 |
| 2-Sided |
| 90 |
| -0.1658 |
| 0.0036 |
| Equivalence |
For log-transformed (natural log) Cmax, the two-sided 90% CI of the difference in the LS-Means between the formulations (TAK-438 OD tablet-TAK-438 tablet) was provided using the ANOVA model. |
| LS-Means Difference |
| 0.0035 |
| 2-Sided |
| 90 |
| -0.0760 |
| 0.0830 |
| Equivalence |
For log-transformed (natural log) AUC∞, the two-sided 90% CI of the difference in the LS-Means between the formulations (TAK-438 OD tablet-TAK-438 tablet) was provided using the ANOVA model. |
| LS-Means Difference |
| 0.2142 |
| 2-Sided |
| 90 |
| 0.0558 |
| 0.3725 |
| Equivalence |
For log-transformed (natural log) Tmax, the two-sided 90% CI of the difference in the LS-Means between the formulations (TAK-438 OD tablet-TAK-438 tablet) was provided using the ANOVA model. |
| LS-Means Difference |
| 0.0306 |
| 2-Sided |
| 90 |
| -0.0003 |
| 0.0616 |
| Equivalence |
For log-transformed (natural log) MRT∞,ev, the two-sided 90% CI of the difference in the LS-Means between the formulations (TAK-438 OD tablet-TAK-438 tablet) was provided using the ANOVA model. |
| LS-Means Difference |
| -0.0135 |
| 2-Sided |
| 90 |
| -0.0508 |
| 0.0238 |
| Equivalence |
For log-transformed (natural log) λz, the two-sided 90% CI of the difference in the LS-Means between the formulations (TAK-438 OD tablet-TAK-438 tablet) was provided using the ANOVA model. |