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CYP3A4 is involved in the metabolism of many drugs. So, it is important to assess in vivo the induction effect of ASP2151 on that enzyme to determine the extent of any possible drug interactions. The aim of this trial is to investigate the potential for interaction of ASP2151 with the CYP3A4 probe substrate midazolam.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Midazolam + ASP2151 | Other | 400 mg ASP2151 followed by 7.5 mg midazolam |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Midazolam | Drug |
|
| |
| ASP2151 |
| Measure | Description | Time Frame |
|---|---|---|
| Peak Plasma Concentration (Cmax) of Midazolam | prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26 | |
| Time of Peak Concentration (Tmax) of Midazolam | prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26 | |
| Area Under Concentration-Time Curve Extrapolated to Infinite Time (AUC0-∞) of Midazolam | prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26 | |
| Half-life (t1/2) of Midazolam | prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Serious and Non-Serious Adverse Events | Refer to the result of adverse event. | Up to 32 days after the last dose |
| Measure | Description | Time Frame |
|---|---|---|
| Peak Plasma Concentration (Cmax) of 1-hydroxymidazolam | prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26 | |
| Time of Peak Concentration (Tmax) of 1-hydroxymidazolam | prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Joachim Dr Kempeni | Maruho Europe Ltd | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hammersmith Medicines Research Ltd | London | NW10 7EW | United Kingdom |
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Participants took part in the study at one investigative site in United Kingdom from 18-March 2015 to 28-May 2015
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| ID | Title | Description |
|---|---|---|
| FG000 | Midazolam + ASP2151 | 400 mg ASP2151 followed by 7.5 mg midazolam Midazolam ASP2151 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Midazolam + ASP2151 | 400 mg ASP2151 followed by 7.5 mg midazolam Midazolam ASP2151 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Peak Plasma Concentration (Cmax) of Midazolam | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26 |
|
Up to 32 days after the last dose
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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 | Midazolam | 7.5 mg midazolam | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Somnolence | Nervous system disorders | MedDRA/18.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Maruho Co.,Ltd. Kyoto R&D Center | Clinical Development Dept. | +81-75-325-3255 | ctinfo@mii.maruho.co.jp |
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| ID | Term |
|---|---|
| D006561 | Herpes Simplex |
| ID | Term |
|---|---|
| D006566 | Herpesviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D008874 | Midazolam |
| C568714 | ASP2151 |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| Drug |
|
| Area Under Concentration-Time Curve up to Last Non-zero Value (AUC0-tn) of 1-hydroxymidazolam | prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26 |
| Half-life (t1/2) of 1-hydroxymidazolam | prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26 |
| Trough Plasma Concentration (Ctrough) of ASP2151 | Days 5 to 12 |
| Peak Plasma Concentration (Cmax) of ASP2151 | pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 12 |
| Time of Peak Concentration (Tmax) of ASP2151 | pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 12 |
| Area Under Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of ASP2151 | pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 12 |
| Area Under Concentration-Time Curve Extrapolated to Infinite Time (AUC0-∞) of ASP2151 | pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 12 |
| Half-life (t1/2) of ASP2151 | pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 12 |
| Apparent Volume of Distribution (Vd/F) of ASP2151 | pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 12 |
| Apparent Total Body Clearance (CL/F) of ASP2151 | pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 12 |
| Area Under Concentration-Time Curve up to Last Non-zero Value (AUC0-tn) of Midazolam | prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26 |
| Apparent Volume of Distribution (Vd/F) of Midazolam | prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26 |
| Apparent Total Body Clearance (CL/F) of Midazolam | prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26 |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | year |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Day 26 |
7.5 mg midazolam alone |
|
|
| Primary | Time of Peak Concentration (Tmax) of Midazolam | Posted | Median | Full Range | h | prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26 |
|
|
|
| Primary | Area Under Concentration-Time Curve Extrapolated to Infinite Time (AUC0-∞) of Midazolam | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26 |
|
|
|
| Primary | Half-life (t1/2) of Midazolam | Posted | Geometric Mean | Geometric Coefficient of Variation | h | prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26 |
|
|
|
| Secondary | Number of Participants With Serious and Non-Serious Adverse Events | Refer to the result of adverse event. | Posted | Number | participants | Up to 32 days after the last dose |
|
|
|
| Other Pre-specified | Peak Plasma Concentration (Cmax) of 1-hydroxymidazolam | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26 |
|
|
|
| Other Pre-specified | Time of Peak Concentration (Tmax) of 1-hydroxymidazolam | Posted | Median | Full Range | h | prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26 |
|
|
|
| Other Pre-specified | Area Under Concentration-Time Curve up to Last Non-zero Value (AUC0-tn) of 1-hydroxymidazolam | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26 |
|
|
|
| Other Pre-specified | Half-life (t1/2) of 1-hydroxymidazolam | Posted | Geometric Mean | Geometric Coefficient of Variation | h | prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26 |
|
|
|
| Other Pre-specified | Trough Plasma Concentration (Ctrough) of ASP2151 | Posted | Mean | Standard Deviation | ng/mL | Days 5 to 12 |
|
|
|
| Other Pre-specified | Peak Plasma Concentration (Cmax) of ASP2151 | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 12 |
|
|
|
| Other Pre-specified | Time of Peak Concentration (Tmax) of ASP2151 | Posted | Median | Full Range | h | pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 12 |
|
|
|
| Other Pre-specified | Area Under Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of ASP2151 | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 12 |
|
|
|
| Other Pre-specified | Area Under Concentration-Time Curve Extrapolated to Infinite Time (AUC0-∞) of ASP2151 | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 12 |
|
|
|
| Other Pre-specified | Half-life (t1/2) of ASP2151 | Posted | Geometric Mean | Geometric Coefficient of Variation | h | pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 12 |
|
|
|
| Other Pre-specified | Apparent Volume of Distribution (Vd/F) of ASP2151 | Posted | Mean | Standard Deviation | L | pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 12 |
|
|
|
| Other Pre-specified | Apparent Total Body Clearance (CL/F) of ASP2151 | Posted | Mean | Standard Deviation | L/h | pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 12 |
|
|
|
| Other Pre-specified | Area Under Concentration-Time Curve up to Last Non-zero Value (AUC0-tn) of Midazolam | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26 |
|
|
|
| Other Pre-specified | Apparent Volume of Distribution (Vd/F) of Midazolam | Posted | Mean | Standard Deviation | L | prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26 |
|
|
|
| Other Pre-specified | Apparent Total Body Clearance (CL/F) of Midazolam | Posted | Mean | Standard Deviation | L/h | prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26 |
|
|
|
| 18 |
| 0 |
| 18 |
| 17 |
| 18 |
| EG001 | ASP2151 After Midazolam | 400 mg ASP2151 after 7.5 mg midazolam | 0 | 18 | 0 | 18 | 4 | 18 |
| EG002 | Midazolam With ASP2151 | 7.5 mg midazolam with 400 mg ASP2151 | 0 | 18 | 0 | 18 | 17 | 18 |
| EG003 | Total | 0 | 18 | 0 | 18 | 18 | 18 |
| Headache | Nervous system disorders | MedDRA/18.0 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA/18.0 | Non-systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA/18.0 | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA/18.0 | Non-systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA/18.0 | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA/18.0 | Non-systematic Assessment |
|
| Catheter site inflammation | General disorders | MedDRA/18.0 | Non-systematic Assessment |
|
| Energy increased | General disorders | MedDRA/18.0 | Non-systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA/18.0 | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA/18.0 | Non-systematic Assessment |
|
| Lip haemorrhage | Gastrointestinal disorders | MedDRA/18.0 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA/18.0 | Non-systematic Assessment |
|
| Rhabdomyolysis | Musculoskeletal and connective tissue disorders | MedDRA/18.0 | Non-systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA/18.0 | Non-systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA/18.0 | Non-systematic Assessment |
|
| Ear discomfort | Ear and labyrinth disorders | MedDRA/18.0 | Non-systematic Assessment |
|
| Conjunctivitis allergic | Eye disorders | MedDRA/18.0 | Non-systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA/18.0 | Non-systematic Assessment |
|
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| D017193 |
| Skin Diseases, Viral |
| D012874 | Skin Diseases, Infectious |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D006571 | Heterocyclic Compounds |