Healthy
Conditions
Keywords
HSV, Herpes, volunteers, drug-drug interaction
Brief summary
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.
Interventions
DRUGMidazolam
DRUGASP2151
Sponsors
Maruho Europe Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* A body mass index (Quetelet index) in the range 18.0-30.9. * Sufficient intelligence to understand the nature of the trial and any hazards of participating in it. Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of, the entire trial. * Willingness to give written consent to participate after reading the information and consent form, and after having the opportunity to discuss the trial with the investigator or his delegate. * Willingness to give written consent to have data entered into The Overvolunteering Prevention System.
Exclusion criteria
* Clinically relevant abnormal history, physical findings, ECG, or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the volunteer. * Any of the following liver function tests higher than 1.5 times the ULN at the screening visit: aspartate aminotransferase (AST), alanine aminotransferase (ALT), ALP, bilirubin, gamma glutamyl transpeptidase (gamma-GT). * Platelet counts outside normal limits (129,000-346,000/µL). * Presence of acute or chronic illness or history of chronic illness sufficient to invalidate the volunteer's participation in the trial or make it unnecessarily hazardous. * Clinically significant impaired endocrine, thyroid, hepatic, respiratory or renal function, diabetes mellitus, coronary heart disease, or history of any psychotic mental illness. * Presence or history of sleep apnoea or myasthenia gravis. * History of bleeding diathesis. * Surgery (eg stomach bypass) or medical condition that might affect absorption of medicines. * Presence or history of severe adverse reaction to any drug, history of multiple drug allergies (multiple defined as \>3), or sensitivity to trial medication. * Use, during the 28 days before the first dose of trial medication, of any prescription medicine, or any other medicine or herbal remedy (such as St John's wort) known to interfere with the CYP3A4, CYP2C19, CYP2C8 or CYP2C9 metabolic pathways. * Use, during the 7 days before the first dose of trial medication, of any over the counter medicine, with the exception of paracetamol (acetaminophen). * Participation in another clinical trial of a new chemical entity or a prescription medicine within the previous 3 months. * Presence or history of drug or alcohol abuse, or intake of more than 21 units of alcohol weekly or more than 5 cigarettes daily. * Blood pressure and heart rate in seated position at the screening examination outside the ranges 90-140 mm Hg systolic, 40-90 mm Hg diastolic; heart rate 40\_100 beats/min. However, if the investigator deems the result to be not clinically significant the subject may be included. * Possibility that the volunteer will not cooperate with the requirements of the protocol. * Evidence of drug abuse on urine testing. * Positive test for hepatitis B, hepatitis C, HIV1 or HIV2. * Loss of more than 400 mL blood during the 3 months before the trial, eg as a blood donor. * Objection by General Practitioner (GP) to volunteer entering trial.
Design outcomes
Primary
| Measure | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious and Non-Serious Adverse Events | Up to 32 days after the last dose | Refer to the result of adverse event. |
Other
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
Countries
United Kingdom
Participant flow
Recruitment details
Participants took part in the study at one investigative site in United Kingdom from 18-March 2015 to 28-May 2015
Participants by arm
| Arm | Count |
|---|---|
| Midazolam + ASP2151 400 mg ASP2151 followed by 7.5 mg midazolam
Midazolam
ASP2151 | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Not eligible | 9 |
Baseline characteristics
| Characteristic | Midazolam + ASP2151 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants |
| Age, Continuous | 30.7 year STANDARD_DEVIATION 7.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Region of Enrollment United Kingdom | 18 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 18 |
| other Total, other adverse events | 17 / 18 | 4 / 18 | 17 / 18 | 18 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 18 |
Outcome results
Primary
Area Under Concentration-Time Curve Extrapolated to Infinite Time (AUC0-∞) of Midazolam
Time frame: 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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Area Under Concentration-Time Curve Extrapolated to Infinite Time (AUC0-∞) of Midazolam | 113.1 h*ng/mL | Geometric Coefficient of Variation 28.1 |
| Day 12 | Area Under Concentration-Time Curve Extrapolated to Infinite Time (AUC0-∞) of Midazolam | 58 h*ng/mL | Geometric Coefficient of Variation 29.2 |
| Day 19 | Area Under Concentration-Time Curve Extrapolated to Infinite Time (AUC0-∞) of Midazolam | 124.4 h*ng/mL | Geometric Coefficient of Variation 31.7 |
| Day 26 | Area Under Concentration-Time Curve Extrapolated to Infinite Time (AUC0-∞) of Midazolam | 122.1 h*ng/mL | Geometric Coefficient of Variation 37.3 |
Primary
Half-life (t1/2) of Midazolam
Time frame: 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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Half-life (t1/2) of Midazolam | 4.2 h | Geometric Coefficient of Variation 37 |
| Day 12 | Half-life (t1/2) of Midazolam | 3.3 h | Geometric Coefficient of Variation 52.7 |
| Day 19 | Half-life (t1/2) of Midazolam | 4.3 h | Geometric Coefficient of Variation 43.7 |
| Day 26 | Half-life (t1/2) of Midazolam | 4.1 h | Geometric Coefficient of Variation 52.3 |
Primary
Peak Plasma Concentration (Cmax) of Midazolam
Time frame: 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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Peak Plasma Concentration (Cmax) of Midazolam | 34.5 ng/mL | Geometric Coefficient of Variation 21.2 |
| Day 12 | Peak Plasma Concentration (Cmax) of Midazolam | 23.4 ng/mL | Geometric Coefficient of Variation 32.5 |
| Day 19 | Peak Plasma Concentration (Cmax) of Midazolam | 38.8 ng/mL | Geometric Coefficient of Variation 23.1 |
| Day 26 | Peak Plasma Concentration (Cmax) of Midazolam | 36.8 ng/mL | Geometric Coefficient of Variation 41.4 |
Primary
Time of Peak Concentration (Tmax) of Midazolam
Time frame: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Day 1 | Time of Peak Concentration (Tmax) of Midazolam | 0.5 h |
| Day 12 | Time of Peak Concentration (Tmax) of Midazolam | 0.5 h |
| Day 19 | Time of Peak Concentration (Tmax) of Midazolam | 0.5 h |
| Day 26 | Time of Peak Concentration (Tmax) of Midazolam | 0.5 h |
Secondary
Number of Participants With Serious and Non-Serious Adverse Events
Refer to the result of adverse event.
Time frame: Up to 32 days after the last dose
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Day 1 | Number of Participants With Serious and Non-Serious Adverse Events | Non-serious adverse event | 18 participants |
| Day 1 | Number of Participants With Serious and Non-Serious Adverse Events | serious adverse event | 0 participants |
Other Pre-specified
Apparent Total Body Clearance (CL/F) of ASP2151
Time frame: 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Apparent Total Body Clearance (CL/F) of ASP2151 | 21.61 L/h | Standard Deviation 6.35 |
Other Pre-specified
Apparent Total Body Clearance (CL/F) of Midazolam
Time frame: 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Apparent Total Body Clearance (CL/F) of Midazolam | 444 L/h | Standard Deviation 187.33 |
| Day 12 | Apparent Total Body Clearance (CL/F) of Midazolam | 679.1 L/h | Standard Deviation 276.5 |
| Day 19 | Apparent Total Body Clearance (CL/F) of Midazolam | 401.3 L/h | Standard Deviation 163.74 |
| Day 26 | Apparent Total Body Clearance (CL/F) of Midazolam | 394 L/h | Standard Deviation 153.76 |
Other Pre-specified
Apparent Volume of Distribution (Vd/F) of ASP2151
Time frame: 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Apparent Volume of Distribution (Vd/F) of ASP2151 | 225.9 L | Standard Deviation 65.66 |
Other Pre-specified
Apparent Volume of Distribution (Vd/F) of Midazolam
Time frame: 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Apparent Volume of Distribution (Vd/F) of Midazolam | 406.5 L | Standard Deviation 46.3 |
| Day 12 | Apparent Volume of Distribution (Vd/F) of Midazolam | 622 L | Standard Deviation 47 |
| Day 19 | Apparent Volume of Distribution (Vd/F) of Midazolam | 370.8 L | Standard Deviation 43.1 |
| Day 26 | Apparent Volume of Distribution (Vd/F) of Midazolam | 366.6 L | Standard Deviation 41 |
Other Pre-specified
Area Under Concentration-Time Curve Extrapolated to Infinite Time (AUC0-∞) of ASP2151
Time frame: 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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Area Under Concentration-Time Curve Extrapolated to Infinite Time (AUC0-∞) of ASP2151 | 19334.2 h*ng/mL | Geometric Coefficient of Variation 31.7 |
Other Pre-specified
Area Under Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of ASP2151
Time frame: 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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Area Under Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of ASP2151 | 17167 h*ng/mL | Geometric Coefficient of Variation 31.7 |
Other Pre-specified
Area Under Concentration-Time Curve up to Last Non-zero Value (AUC0-tn) of 1-hydroxymidazolam
Time frame: 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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Area Under Concentration-Time Curve up to Last Non-zero Value (AUC0-tn) of 1-hydroxymidazolam | 44 h*ng/mL | Geometric Coefficient of Variation 30.3 |
| Day 12 | Area Under Concentration-Time Curve up to Last Non-zero Value (AUC0-tn) of 1-hydroxymidazolam | 39 h*ng/mL | Geometric Coefficient of Variation 32.3 |
| Day 19 | Area Under Concentration-Time Curve up to Last Non-zero Value (AUC0-tn) of 1-hydroxymidazolam | 42.2 h*ng/mL | Geometric Coefficient of Variation 31.3 |
| Day 26 | Area Under Concentration-Time Curve up to Last Non-zero Value (AUC0-tn) of 1-hydroxymidazolam | 40.4 h*ng/mL | Geometric Coefficient of Variation 36.5 |
Other Pre-specified
Area Under Concentration-Time Curve up to Last Non-zero Value (AUC0-tn) of Midazolam
Time frame: 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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Area Under Concentration-Time Curve up to Last Non-zero Value (AUC0-tn) of Midazolam | 111 h*ng/mL | Geometric Coefficient of Variation 28 |
| Day 12 | Area Under Concentration-Time Curve up to Last Non-zero Value (AUC0-tn) of Midazolam | 56.7 h*ng/mL | Geometric Coefficient of Variation 28.8 |
| Day 19 | Area Under Concentration-Time Curve up to Last Non-zero Value (AUC0-tn) of Midazolam | 121.9 h*ng/mL | Geometric Coefficient of Variation 30.7 |
| Day 26 | Area Under Concentration-Time Curve up to Last Non-zero Value (AUC0-tn) of Midazolam | 118.9 h*ng/mL | Geometric Coefficient of Variation 36.2 |
Other Pre-specified
Half-life (t1/2) of 1-hydroxymidazolam
Time frame: 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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Half-life (t1/2) of 1-hydroxymidazolam | 3.8 h | Geometric Coefficient of Variation 39.7 |
| Day 12 | Half-life (t1/2) of 1-hydroxymidazolam | 3.1 h | Geometric Coefficient of Variation 47.4 |
| Day 19 | Half-life (t1/2) of 1-hydroxymidazolam | 3.5 h | Geometric Coefficient of Variation 35.4 |
| Day 26 | Half-life (t1/2) of 1-hydroxymidazolam | 3.3 h | Geometric Coefficient of Variation 42 |
Other Pre-specified
Half-life (t1/2) of ASP2151
Time frame: 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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Half-life (t1/2) of ASP2151 | 7.3 h | Geometric Coefficient of Variation 12 |
Other Pre-specified
Peak Plasma Concentration (Cmax) of 1-hydroxymidazolam
Time frame: 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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Peak Plasma Concentration (Cmax) of 1-hydroxymidazolam | 15.7 ng/mL | Geometric Coefficient of Variation 33.2 |
| Day 12 | Peak Plasma Concentration (Cmax) of 1-hydroxymidazolam | 15.9 ng/mL | Geometric Coefficient of Variation 40.9 |
| Day 19 | Peak Plasma Concentration (Cmax) of 1-hydroxymidazolam | 14.9 ng/mL | Geometric Coefficient of Variation 35 |
| Day 26 | Peak Plasma Concentration (Cmax) of 1-hydroxymidazolam | 14.2 ng/mL | Geometric Coefficient of Variation 59.3 |
Other Pre-specified
Peak Plasma Concentration (Cmax) of ASP2151
Time frame: 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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Peak Plasma Concentration (Cmax) of ASP2151 | 1761.4 ng/mL | Geometric Coefficient of Variation 37.9 |
Other Pre-specified
Time of Peak Concentration (Tmax) of 1-hydroxymidazolam
Time frame: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Day 1 | Time of Peak Concentration (Tmax) of 1-hydroxymidazolam | 0.5 h |
| Day 12 | Time of Peak Concentration (Tmax) of 1-hydroxymidazolam | 0.5 h |
| Day 19 | Time of Peak Concentration (Tmax) of 1-hydroxymidazolam | 0.5 h |
| Day 26 | Time of Peak Concentration (Tmax) of 1-hydroxymidazolam | 0.5 h |
Other Pre-specified
Time of Peak Concentration (Tmax) of ASP2151
Time frame: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Day 1 | Time of Peak Concentration (Tmax) of ASP2151 | 3 h |
Other Pre-specified
Trough Plasma Concentration (Ctrough) of ASP2151
Time frame: Days 5 to 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Trough Plasma Concentration (Ctrough) of ASP2151 | 277.6 ng/mL | Standard Deviation 73.47 |
| Day 12 | Trough Plasma Concentration (Ctrough) of ASP2151 | 265.7 ng/mL | Standard Deviation 64.57 |
| Day 19 | Trough Plasma Concentration (Ctrough) of ASP2151 | 238.9 ng/mL | Standard Deviation 65.6 |
| Day 26 | Trough Plasma Concentration (Ctrough) of ASP2151 | 240.7 ng/mL | Standard Deviation 67.73 |
| Day 9 | Trough Plasma Concentration (Ctrough) of ASP2151 | 223.9 ng/mL | Standard Deviation 63.68 |
| Day 10 | Trough Plasma Concentration (Ctrough) of ASP2151 | 228.5 ng/mL | Standard Deviation 67.44 |
| Day 11 | Trough Plasma Concentration (Ctrough) of ASP2151 | 209.7 ng/mL | Standard Deviation 66.47 |
| Day 12 | Trough Plasma Concentration (Ctrough) of ASP2151 | 214.2 ng/mL | Standard Deviation 50.89 |