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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1167-0017 | Registry Identifier | WHO | |
| JapicCTI-152810 | Registry Identifier | JapicCTI |
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The purpose of this study is to evaluate the effect of repeated-dose administration of itraconazole on the pharmacokinetics of TAK-272, as well as the effect of repeated-dose administration of TAK-272 on the pharmacokinetics of digoxin or midazolam in healthy Japanese adult males.
In Cohort 1, the effect of repeated-dose administration of itraconazole on the pharmacokinetics of TAK-272 was evaluated by comparing between participants receiving TAK-272 alone and those receiving TAK-272 in combination with itraconazole. In Cohort 2, the effect of repeated-dose administration of TAK-272 on the pharmacokinetics of digoxin or midazolam was evaluated by comparing between participants receiving digoxin or midazolam alone and those receiving either of the drugs in combination with TAK-272.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: TAK-272 + Itraconazole | Experimental | TAK-272 40 mg, tablet, orally, once on Day 1 and 10, followed by Itraconazole 200 mg, solution, orally, twice on Day 4, further followed by Itraconazole 200 mg, solution, orally, once from Day 5 to 12. |
|
| Cohort 2: Midazolam + Digoxin + TAK-272 | Experimental | Midazolam 2 mg, syrup, and Digoxin 0.25 mg, tablet, orally, once on Day 1 and 7, followed by TAK-272 80 mg, tablet, orally, once from Day 3 to 8. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TAK-272 | Drug | TAK-272 tablet. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cmax: Maximum Observed Plasma Concentration for TAK 272F and TAK 272-Metabolite (M-I) in Cohort 1 | Day 1 and Day 10: pre-dose and at multiple time-points (upto 72 hours) postdose; Day 1 for Cohort 1: TAK-272 and Day 10 for Cohort 1: TAK-272 + Itraconazole | |
| AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK 272F and TAK 272-M-I in Cohort 1 | Day 1 and Day 10: pre-dose and at multiple time-points (upto 72 hours) postdose; Day 1 for Cohort 1: TAK-272 and Day 10 for Cohort 1: TAK-272 + Itraconazole | |
| AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK 272F and TAK 272-M-I in Cohort 1 | Day 1 and Day 10: pre-dose and at multiple time-points (upto 72 hours) postdose; Day 1 for Cohort 1: TAK-272 and Day 10 for Cohort 1: TAK-272 + Itraconazole | |
| Cumulative Urinary Excretion Ratio of TAK 272F and TAK 272-M-I From 0 to 72 Hours Postdose in Cohort 1 | Day 1 and Day 10: pre-dose and at multiple time-points (upto 72 hours) postdose; Day 1 for Cohort 1: TAK-272 and Day 10 for Cohort 1: TAK-272 + Itraconazole | |
| Cmax: Maximum Observed Plasma Concentration for Digoxin in Cohort 2 | Day 1 and Day 7: pre-dose and at multiple time-points (upto 48 hours) postdose; Day 1 for Cohort 2: Digoxin and Day 7 for Cohort 2: Digoxin + TAK-272 | |
| AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Digoxin in Cohort 2 | Day 1 and Day 7: pre-dose and at multiple time-points (upto 48 hours) postdose; Day 1 for Cohort 2: Digoxin and Day 7 for Cohort 2: Digoxin + TAK-272 | |
| AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Digoxin in Cohort 2 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Takeda | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Osaka | Osaka | Japan |
Healthy Japanese adult male participants were enrolled to receive TAK-272 and itraconazole in cohort 1 or TAK-272 and digoxin/midazolam in cohort 2.
Participants took part in the study at 1 investigative site in Japan from 25-February-2015 to 16-April-2015.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1: TAK-272 + Itraconazole | TAK-272 40 milligram (mg), tablet, orally, once on Day 1 and 10, followed by Itraconazole 200 mg, solution, orally, twice on Day 4, further followed by Itraconazole 200 mg, solution, orally, once from Day 5 to 12. |
| FG001 | Cohort 2: Midazolam + Digoxin + TAK-272 | Midazolam 2 mg, syrup, and Digoxin 0.25 mg, tablet, orally, once on Day 1 and 7, followed by TAK-272 80 mg, tablet, orally, once from Day 3 to 8. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The pharmacokinetic analysis set was defined as the set of participants treated with the study drug that had no significant protocol deviation, satisfied the minimum protocol provisions, and could be evaluated for pharmacokinetics.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1: TAK-272 + Itraconazole | TAK-272 40 milligram (mg), tablet, orally, once on Day 1 and 10, followed by Itraconazole 200 mg, solution, orally, twice on Day 4, further followed by Itraconazole 200 mg, solution, orally, once from Day 5 to 12. |
| BG001 | Cohort 2: Midazolam + Digoxin + TAK-272 |
| 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 | Cmax: Maximum Observed Plasma Concentration for TAK 272F and TAK 272-Metabolite (M-I) in Cohort 1 | The pharmacokinetic analysis set was defined as the set of participants treated with the study drug that had no significant protocol deviation, satisfied the minimum protocol provisions, and could be evaluated for pharmacokinetics. | Posted | Geometric Mean | Standard Deviation | nanogram per milliliter (ng/mL) | Day 1 and Day 10: pre-dose and at multiple time-points (upto 72 hours) postdose; Day 1 for Cohort 1: TAK-272 and Day 10 for Cohort 1: TAK-272 + Itraconazole |
|
Collection of AEs commenced from the time that the participant was first administered study drug (Day 1) until the follow-up examination (Day 19 for Cohort 1, Day 15 for Cohort 2)
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 | Cohort 1: TAK-272 + Itraconazole | TAK-272 40 milligram (mg), tablet, orally, once on Day 1 and 10, followed by Itraconazole 200 mg, solution, orally, twice on Day 4, further followed by Itraconazole 200 mg, solution, orally, once from Day 5 to 12. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
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| ID | Term |
|---|---|
| C000628410 | imarikiren hydrochloride |
| D004077 | Digoxin |
| D017964 | Itraconazole |
| D008874 | Midazolam |
| ID | Term |
|---|---|
| D004071 | Digitalis Glycosides |
| D002298 | Cardenolides |
| D002301 | Cardiac Glycosides |
| D002297 | Cardanolides |
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| Digoxin | Drug | Digoxin tablet. |
|
| Itraconazole | Drug | Itraconazole oral solution |
|
| Midazolam | Drug | Midazolam syrup. |
|
| Day 1 and Day 7: pre-dose and at multiple time-points (upto 48 hours) postdose; Day 1 for Cohort 2: Digoxin and Day 7 for Cohort 2: Digoxin + TAK-272 |
| Urinary Excretion Ratio of Digoxin From 0 to 48 Hours Postdose in Cohort 2 | Day 1 and Day 7: pre-dose and at multiple time-points (upto 48 hours) postdose; Day 1 for Cohort 2: Digoxin and Day 7 for Cohort 2: Digoxin + TAK-272 |
| Cmax: Maximum Observed Plasma Concentration for Midazolam and 1'Hydroxymidazolam in Cohort 2 | Day 1 and Day 7: pre-dose and at multiple time-points (upto 24 hours) postdose; Day 1 for Cohort 2: Midazolam and Day 7 for Cohort 2: Midazolam + TAK-272 |
| AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Midazolam and 1'Hydroxymidazolam in Cohort 2 | Day 1 and Day 7: pre-dose and at multiple time-points (upto 24 hours) postdose; Day 1 for Cohort 2: Midazolam and Day 7 for Cohort 2: Midazolam + TAK-272 |
| AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Midazolam and 1'Hydroxymidazolam in Cohort 2 | Day 1 and Day 7: pre-dose and at multiple time-points (upto 24 hours) postdose; Day 1 for Cohort 2: Midazolam and Day 7 for Cohort 2: Midazolam + TAK-272 |
| Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15 |
| Number of Participants With TEAEs Related to Vital Signs | Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15 |
| Number of Participants With TEAEs Related to Body Weight | Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15 |
| Number of Participants Who Had Clinically Significant Changes From Baseline in 12-lead Electrocardiograms | Number of participants who had ECG findings changed from "within normal limit" or "abnormal, clinically significant" to "abnormal and clinically significant" after study drug administration. | Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15 |
| Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis | Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15 |
| Number of Participants With Clinically Significant Change From Baseline in Continuous Pulse Oximetry (SpO2) in Cohort 2 | Cohort 2: Baseline up to Day 15 |
Midazolam 2 mg, syrup, and Digoxin 0.25 mg, tablet, orally, once on Day 1 and 7, followed by TAK-272 80 mg, tablet, orally, once on Day 3 to 8. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex/Gender, Customized | Number | participants |
|
| Smoking Classification | Number | participants |
|
| Alcohol Classification | Number | participants |
|
| Caffeine Classification | Number | participants |
|
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|
|
| Primary | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK 272F and TAK 272-M-I in Cohort 1 | The pharmacokinetic analysis set was defined as the set of participants treated with the study drug that had no significant protocol deviation, satisfied the minimum protocol provisions, and could be evaluated for pharmacokinetics. | Posted | Geometric Mean | Standard Deviation | nanogram hours per milliliter (ng*hr/mL) | Day 1 and Day 10: pre-dose and at multiple time-points (upto 72 hours) postdose; Day 1 for Cohort 1: TAK-272 and Day 10 for Cohort 1: TAK-272 + Itraconazole |
|
|
|
|
| Primary | AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK 272F and TAK 272-M-I in Cohort 1 | The pharmacokinetic analysis set was defined as the set of participants treated with the study drug that had no significant protocol deviation, satisfied the minimum protocol provisions, and could be evaluated for pharmacokinetics. | Posted | Geometric Mean | Standard Deviation | ng*hr/mL | Day 1 and Day 10: pre-dose and at multiple time-points (upto 72 hours) postdose; Day 1 for Cohort 1: TAK-272 and Day 10 for Cohort 1: TAK-272 + Itraconazole |
|
|
|
|
| Primary | Cumulative Urinary Excretion Ratio of TAK 272F and TAK 272-M-I From 0 to 72 Hours Postdose in Cohort 1 | The pharmacokinetic analysis set was defined as the set of participants treated with the study drug that had no significant protocol deviation, satisfied the minimum protocol provisions, and could be evaluated for pharmacokinetics. | Posted | Mean | Standard Deviation | percentage of dose | Day 1 and Day 10: pre-dose and at multiple time-points (upto 72 hours) postdose; Day 1 for Cohort 1: TAK-272 and Day 10 for Cohort 1: TAK-272 + Itraconazole |
|
|
|
| Primary | Cmax: Maximum Observed Plasma Concentration for Digoxin in Cohort 2 | The pharmacokinetic analysis set was defined as the set of participants treated with the study drug that had no significant protocol deviation, satisfied the minimum protocol provisions, and could be evaluated for pharmacokinetics. | Posted | Geometric Mean | Standard Deviation | ng/mL | Day 1 and Day 7: pre-dose and at multiple time-points (upto 48 hours) postdose; Day 1 for Cohort 2: Digoxin and Day 7 for Cohort 2: Digoxin + TAK-272 |
|
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|
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| Primary | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Digoxin in Cohort 2 | The pharmacokinetic analysis set was defined as the set of participants treated with the study drug that had no significant protocol deviation, satisfied the minimum protocol provisions, and could be evaluated for pharmacokinetics. | Posted | Geometric Mean | Standard Deviation | ng*hr/mL | Day 1 and Day 7: pre-dose and at multiple time-points (upto 48 hours) postdose; Day 1 for Cohort 2: Digoxin and Day 7 for Cohort 2: Digoxin + TAK-272 |
|
|
|
|
| Primary | AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Digoxin in Cohort 2 | The pharmacokinetic analysis set was defined as the set of participants treated with the study drug that had no significant protocol deviation, satisfied the minimum protocol provisions, and could be evaluated for pharmacokinetics. | Posted | Geometric Mean | Standard Deviation | ng*hr/mL | Day 1 and Day 7: pre-dose and at multiple time-points (upto 48 hours) postdose; Day 1 for Cohort 2: Digoxin and Day 7 for Cohort 2: Digoxin + TAK-272 |
|
|
|
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| Primary | Urinary Excretion Ratio of Digoxin From 0 to 48 Hours Postdose in Cohort 2 | The pharmacokinetic analysis set was defined as the set of participants treated with the study drug that had no significant protocol deviation, satisfied the minimum protocol provisions, and could be evaluated for pharmacokinetics. | Posted | Mean | Standard Deviation | percentage of dose | Day 1 and Day 7: pre-dose and at multiple time-points (upto 48 hours) postdose; Day 1 for Cohort 2: Digoxin and Day 7 for Cohort 2: Digoxin + TAK-272 |
|
|
|
| Primary | Cmax: Maximum Observed Plasma Concentration for Midazolam and 1'Hydroxymidazolam in Cohort 2 | The pharmacokinetic analysis set was defined as the set of participants treated with the study drug that had no significant protocol deviation, satisfied the minimum protocol provisions, and could be evaluated for pharmacokinetics. | Posted | Geometric Mean | Standard Deviation | ng/mL | Day 1 and Day 7: pre-dose and at multiple time-points (upto 24 hours) postdose; Day 1 for Cohort 2: Midazolam and Day 7 for Cohort 2: Midazolam + TAK-272 |
|
|
|
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| Primary | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Midazolam and 1'Hydroxymidazolam in Cohort 2 | The pharmacokinetic analysis set was defined as the set of participants treated with the study drug that had no significant protocol deviation, satisfied the minimum protocol provisions, and could be evaluated for pharmacokinetics. | Posted | Geometric Mean | Standard Deviation | ng*hr/mL | Day 1 and Day 7: pre-dose and at multiple time-points (upto 24 hours) postdose; Day 1 for Cohort 2: Midazolam and Day 7 for Cohort 2: Midazolam + TAK-272 |
|
|
|
|
| Primary | AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Midazolam and 1'Hydroxymidazolam in Cohort 2 | The pharmacokinetic analysis set was defined as the set of participants treated with the study drug that had no significant protocol deviation, satisfied the minimum protocol provisions, and could be evaluated for pharmacokinetics. | Posted | Geometric Mean | Standard Deviation | ng*hr/mL | Day 1 and Day 7: pre-dose and at multiple time-points (upto 24 hours) postdose; Day 1 for Cohort 2: Midazolam and Day 7 for Cohort 2: Midazolam + TAK-272 |
|
|
|
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| Primary | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | The safety analysis set was defined as all participants who received at least one dose of study drug. | Posted | Number | participants | Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15 |
|
|
|
| Primary | Number of Participants With TEAEs Related to Vital Signs | The safety analysis set was defined as all participants who received at least one dose of study drug. | Posted | Number | participants | Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15 |
|
|
|
| Primary | Number of Participants With TEAEs Related to Body Weight | The safety analysis set was defined as all participants who received at least one dose of study drug. | Posted | Number | participants | Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15 |
|
|
|
| Primary | Number of Participants Who Had Clinically Significant Changes From Baseline in 12-lead Electrocardiograms | Number of participants who had ECG findings changed from "within normal limit" or "abnormal, clinically significant" to "abnormal and clinically significant" after study drug administration. | The safety analysis set was defined as all participants who received at least one dose of study drug. | Posted | Number | participants | Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15 |
|
|
|
| Primary | Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis | The safety analysis set was defined as all participants who received at least one dose of study drug. | Posted | Number | participants | Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15 |
|
|
|
| Primary | Number of Participants With Clinically Significant Change From Baseline in Continuous Pulse Oximetry (SpO2) in Cohort 2 | The safety analysis set was defined as all participants who received at least one dose of study drug. | Posted | Number | participants | Cohort 2: Baseline up to Day 15 |
|
|
|
| 0 |
| 16 |
| 10 |
| 16 |
| EG001 | Cohort 2: Midazolam + Digoxin + TAK-272 | Midazolam 2 mg, syrup, and Digoxin 0.25 mg, tablet, orally, once on Day 1 and 7, followed by TAK-272 80 mg, tablet, orally, once from Day 3 to 8. | 0 | 18 | 7 | 18 |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA (18.0) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (18.0) | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA (18.0) | Systematic Assessment |
|
| Blood pressure decreased | Investigations | MedDRA (18.0) | Systematic Assessment |
|
| Blood triglycerides increased | Investigations | MedDRA (18.0) | Systematic Assessment |
|
| Heart rate increased | Investigations | MedDRA (18.0) | Systematic Assessment |
|
| Urine ketone body present | Investigations | MedDRA (18.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
|
| Dizziness postural | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (18.0) | Systematic Assessment |
|
No publication related to study results will be made without Sponsor's prior written approval. Any proposed publication or presentation will be submitted to Sponsor for review 60 days in advance of publication. Institution will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for an additional 60 days to preserve intellectual property.
| D013256 |
| Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D010879 | Piperazines |
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| Geometric Mean Ratio (Day 10/Day 1) |
| 0.023 |
| 2-Sided |
| 90 |
| 0.012 |
| 0.045 |
| No |
| Superiority or Other |
| Geometric Mean Ratio (Day 7/Day 1) |
| 0.887 |
| 2-Sided |
| 90 |
| 0.781 |
| 1.008 |
| No |
| Superiority or Other |
| Geometric Mean Ratio (Day 7/Day 1) |
| 1.081 |
| 2-Sided |
| 90 |
| 1.008 |
| 1.160 |
| No |
| Superiority or Other |
| Geometric Mean Ratio (Day 7/Day 1) |
| 1.061 |
| 2-Sided |
| 90 |
| 0.986 |
| 1.143 |
| No |
| Superiority or Other |
| Heart rate increased |
|
| Blood triglycerides increased |
|
| Urine ketone body present |
|