Healthy
Conditions
Keywords
Herpes, volunteers, drug-drug interaction
Brief summary
CYP2B6 is involved in the metabolism of many drugs. So, it is important to assess in vivo the effect of ASP2151 on that enzyme to determine any possible drug interactions. The aim of this trial is to investigate the potential for interaction of ASP2151 with the CYP2B6 probe substrate bupropion.
Interventions
DRUGBupropion
DRUGASP2151
Sponsors
Maruho Europe Limited
Study design
Allocation
NON_RANDOMIZED
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. * History of bleeding diathesis, head injury, intracranial mass lesions, hydrocephalus, epilepsy, seizures, depression, self-harm (or thoughts of self-harm) or eating disorders. * 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, CYP2C8, CYP2B6, CYP2D6 or CYP2C19 metabolic pathway. * 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. * Current smoker or history of regular use of tobacco or nicotine-containing products within the previous 6 months. * 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 Bupropion | prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29 |
| Area Under the Concentration-time Curve Extrapolated to Infinite Time (AUC0-∞) of Bupropion | prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29 |
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 |
|---|---|
| Area Under the Concentration-time Curve Extrapolated to Infinite Time (AUC0-∞) of Hydroxybupropion | prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29 |
| Half-life (t1/2) of Hydroxybupropion | prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29 |
| Trough Plasma Concentration (Ctrough) of ASP2151 | Days 6-14 and at pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h after dosing on Day 15 |
| Peak Plasma Concentration (Cmax) of ASP2151 | prior to initial dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h after dosing on Day 15 |
| Time of Peak Concentration (Tmax) of ASP2151 | prior to initial dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h after dosing on Day 15 |
| Area Under the Concentration-time Curve Over the Dosing Interval (AUC0-tau) of ASP2151 | prior to initial dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h after dosing on Day 15 |
| Area Under the Concentration-time Curve Extrapolated to Infinite Time (AUC0-∞) of ASP2151 | prior to initial dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h after dosing on Day 15 |
| Peak Plasma Concentration (Cmax) of Hydroxybupropion | prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29 |
| Apparent Volume of Distribution (Vd/F) of ASP2151 | prior to initial dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h after dosing on Day 15 |
| Apparent Total Body Clearance (CL/F) of ASP2151 | prior to initial dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h after dosing on Day 15 |
| Time of Peak Concentration (Tmax) of Bupropion | prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29 |
| Area Under the Curve Over up to Last No-zero Value (AUC0-tn) of Bupropion | prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29 |
| Half-life (t1/2) of Bupropion | prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29 |
| Apparent Volume of Distribution (Vd/F) of Bupropion | prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29 |
| Apparent Total Body Clearance (CL/F) of Bupropion | prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29 |
| Half-life (t1/2) of ASP2151 | prior to initial dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h after dosing on Day 15 |
| Time of Peak Concentration (Tmax) of Hydroxybupropion | prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29 |
| Area Under Concentration-Time Curve up to Last Non-zero Value (AUC0-tn) of Hydroxybupropion | prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29 |
Countries
United Kingdom
Participant flow
Recruitment details
Participants took part in the study at one investigative site in United Kingdom from 03-February 2015 to 17-April 2015
Participants by arm
| Arm | Count |
|---|---|
| Bupropion + ASP2151 400 mg ASP2151 followed by 150 mg Bupropion
Bupropion
ASP2151 | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Bupropion + ASP2151 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants |
| Age, Continuous | 32.6 year STANDARD_DEVIATION 7.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 2 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 | 18 Participants |
| Region of Enrollment United Kingdom | 24 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 24 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 / 24 | 0 / 24 | 0 / 24 | 0 / 24 |
| other Total, other adverse events | 4 / 24 | 5 / 24 | 10 / 24 | 12 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 |
Outcome results
Primary
Area Under the Concentration-time Curve Extrapolated to Infinite Time (AUC0-∞) of Bupropion
Time frame: prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Area Under the Concentration-time Curve Extrapolated to Infinite Time (AUC0-∞) of Bupropion | 777.6 h*ng/mL | Geometric Coefficient of Variation 30 |
| Day 15 | Area Under the Concentration-time Curve Extrapolated to Infinite Time (AUC0-∞) of Bupropion | 653.7 h*ng/mL | Geometric Coefficient of Variation 26.1 |
| Day 22 | Area Under the Concentration-time Curve Extrapolated to Infinite Time (AUC0-∞) of Bupropion | 785.5 h*ng/mL | Geometric Coefficient of Variation 31.1 |
| Day 29 | Area Under the Concentration-time Curve Extrapolated to Infinite Time (AUC0-∞) of Bupropion | 841.4 h*ng/mL | Geometric Coefficient of Variation 29 |
Primary
Peak Plasma Concentration (Cmax) of Bupropion
Time frame: prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Peak Plasma Concentration (Cmax) of Bupropion | 91.28 ng/mL | Geometric Coefficient of Variation 27.2 |
| Day 15 | Peak Plasma Concentration (Cmax) of Bupropion | 76.94 ng/mL | Geometric Coefficient of Variation 30.3 |
| Day 22 | Peak Plasma Concentration (Cmax) of Bupropion | 92.21 ng/mL | Geometric Coefficient of Variation 28 |
| Day 29 | Peak Plasma Concentration (Cmax) of Bupropion | 95 ng/mL | Geometric Coefficient of Variation 25.2 |
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 | 12 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: prior to initial dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h after dosing on Day 15
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Apparent Total Body Clearance (CL/F) of ASP2151 | 26.43 L/h | Standard Deviation 8.65 |
Other Pre-specified
Apparent Total Body Clearance (CL/F) of Bupropion
Time frame: prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Apparent Total Body Clearance (CL/F) of Bupropion | 200.64 L/h | Standard Deviation 56.33 |
| Day 15 | Apparent Total Body Clearance (CL/F) of Bupropion | 236.46 L/h | Standard Deviation 57.2 |
| Day 22 | Apparent Total Body Clearance (CL/F) of Bupropion | 199.59 L/h | Standard Deviation 62.04 |
| Day 29 | Apparent Total Body Clearance (CL/F) of Bupropion | 185.59 L/h | Standard Deviation 57.71 |
Other Pre-specified
Apparent Volume of Distribution (Vd/F) of ASP2151
Time frame: prior to initial dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h after dosing on Day 15
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Apparent Volume of Distribution (Vd/F) of ASP2151 | 274 L | Standard Deviation 97.85 |
Other Pre-specified
Apparent Volume of Distribution (Vd/F) of Bupropion
Time frame: prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Apparent Volume of Distribution (Vd/F) of Bupropion | 2801.5 L | Standard Deviation 723.1 |
| Day 15 | Apparent Volume of Distribution (Vd/F) of Bupropion | 2791.4 L | Standard Deviation 747.05 |
| Day 22 | Apparent Volume of Distribution (Vd/F) of Bupropion | 2581.2 L | Standard Deviation 588.69 |
| Day 29 | Apparent Volume of Distribution (Vd/F) of Bupropion | 2979.7 L | Standard Deviation 1124.63 |
Other Pre-specified
Area Under Concentration-Time Curve up to Last Non-zero Value (AUC0-tn) of Hydroxybupropion
Time frame: prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Area Under Concentration-Time Curve up to Last Non-zero Value (AUC0-tn) of Hydroxybupropion | 10524.7 h*ng/mL | Geometric Coefficient of Variation 32.9 |
| Day 15 | Area Under Concentration-Time Curve up to Last Non-zero Value (AUC0-tn) of Hydroxybupropion | 10160.7 h*ng/mL | Geometric Coefficient of Variation 37.7 |
| Day 22 | Area Under Concentration-Time Curve up to Last Non-zero Value (AUC0-tn) of Hydroxybupropion | 11135.4 h*ng/mL | Geometric Coefficient of Variation 34.1 |
| Day 29 | Area Under Concentration-Time Curve up to Last Non-zero Value (AUC0-tn) of Hydroxybupropion | 10963 h*ng/mL | Geometric Coefficient of Variation 37.4 |
Other Pre-specified
Area Under the Concentration-time Curve Extrapolated to Infinite Time (AUC0-∞) of ASP2151
Time frame: prior to initial dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h after dosing on Day 15
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Area Under the Concentration-time Curve Extrapolated to Infinite Time (AUC0-∞) of ASP2151 | 15968.1 h*ng/mL | Geometric Coefficient of Variation 35.1 |
Other Pre-specified
Area Under the Concentration-time Curve Extrapolated to Infinite Time (AUC0-∞) of Hydroxybupropion
Time frame: prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Area Under the Concentration-time Curve Extrapolated to Infinite Time (AUC0-∞) of Hydroxybupropion | 11195.7 h*ng/mL | Geometric Coefficient of Variation 33.7 |
| Day 15 | Area Under the Concentration-time Curve Extrapolated to Infinite Time (AUC0-∞) of Hydroxybupropion | 10838.3 h*ng/mL | Geometric Coefficient of Variation 38 |
| Day 22 | Area Under the Concentration-time Curve Extrapolated to Infinite Time (AUC0-∞) of Hydroxybupropion | 12037.2 h*ng/mL | Geometric Coefficient of Variation 36.1 |
| Day 29 | Area Under the Concentration-time Curve Extrapolated to Infinite Time (AUC0-∞) of Hydroxybupropion | 11825.3 h*ng/mL | Geometric Coefficient of Variation 38 |
Other Pre-specified
Area Under the Concentration-time Curve Over the Dosing Interval (AUC0-tau) of ASP2151
Time frame: prior to initial dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h after dosing on Day 15
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Area Under the Concentration-time Curve Over the Dosing Interval (AUC0-tau) of ASP2151 | 14201.4 h*ng/mL | Geometric Coefficient of Variation 33.5 |
Other Pre-specified
Area Under the Curve Over up to Last No-zero Value (AUC0-tn) of Bupropion
Time frame: prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Area Under the Curve Over up to Last No-zero Value (AUC0-tn) of Bupropion | 732.3 h*ng/mL | Geometric Coefficient of Variation 29.9 |
| Day 15 | Area Under the Curve Over up to Last No-zero Value (AUC0-tn) of Bupropion | 608.9 h*ng/mL | Geometric Coefficient of Variation 26.5 |
| Day 22 | Area Under the Curve Over up to Last No-zero Value (AUC0-tn) of Bupropion | 742.8 h*ng/mL | Geometric Coefficient of Variation 31.8 |
| Day 29 | Area Under the Curve Over up to Last No-zero Value (AUC0-tn) of Bupropion | 794.2 h*ng/mL | Geometric Coefficient of Variation 29.4 |
Other Pre-specified
Half-life (t1/2) of ASP2151
Time frame: prior to initial dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h after dosing on Day 15
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Half-life (t1/2) of ASP2151 | 7.198 h | Geometric Coefficient of Variation 16.7 |
Other Pre-specified
Half-life (t1/2) of Bupropion
Time frame: prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Half-life (t1/2) of Bupropion | 9.76 h | Geometric Coefficient of Variation 47.7 |
| Day 15 | Half-life (t1/2) of Bupropion | 8.16 h | Geometric Coefficient of Variation 42.1 |
| Day 22 | Half-life (t1/2) of Bupropion | 9.13 h | Geometric Coefficient of Variation 37 |
| Day 29 | Half-life (t1/2) of Bupropion | 10.92 h | Geometric Coefficient of Variation 42.7 |
Other Pre-specified
Half-life (t1/2) of Hydroxybupropion
Time frame: prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Half-life (t1/2) of Hydroxybupropion | 21.38 h | Geometric Coefficient of Variation 20.6 |
| Day 15 | Half-life (t1/2) of Hydroxybupropion | 20.97 h | Geometric Coefficient of Variation 20.3 |
| Day 22 | Half-life (t1/2) of Hydroxybupropion | 23.07 h | Geometric Coefficient of Variation 23.8 |
| Day 29 | Half-life (t1/2) of Hydroxybupropion | 22.89 h | Geometric Coefficient of Variation 16.8 |
Other Pre-specified
Peak Plasma Concentration (Cmax) of ASP2151
Time frame: prior to initial dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h after dosing on Day 15
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Peak Plasma Concentration (Cmax) of ASP2151 | 1409.8 ng/mL | Geometric Coefficient of Variation 33.7 |
Other Pre-specified
Peak Plasma Concentration (Cmax) of Hydroxybupropion
Time frame: prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Peak Plasma Concentration (Cmax) of Hydroxybupropion | 295.4 ng/mL | Geometric Coefficient of Variation 30.9 |
| Day 15 | Peak Plasma Concentration (Cmax) of Hydroxybupropion | 300.7 ng/mL | Geometric Coefficient of Variation 32.6 |
| Day 22 | Peak Plasma Concentration (Cmax) of Hydroxybupropion | 300.6 ng/mL | Geometric Coefficient of Variation 27.5 |
| Day 29 | Peak Plasma Concentration (Cmax) of Hydroxybupropion | 291.6 ng/mL | Geometric Coefficient of Variation 31.2 |
Other Pre-specified
Time of Peak Concentration (Tmax) of ASP2151
Time frame: prior to initial dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h after dosing on Day 15
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Day 1 | Time of Peak Concentration (Tmax) of ASP2151 | 3 h |
Other Pre-specified
Time of Peak Concentration (Tmax) of Bupropion
Time frame: prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Day 1 | Time of Peak Concentration (Tmax) of Bupropion | 3 h |
| Day 15 | Time of Peak Concentration (Tmax) of Bupropion | 3 h |
| Day 22 | Time of Peak Concentration (Tmax) of Bupropion | 3 h |
| Day 29 | Time of Peak Concentration (Tmax) of Bupropion | 3 h |
Other Pre-specified
Time of Peak Concentration (Tmax) of Hydroxybupropion
Time frame: prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Day 1 | Time of Peak Concentration (Tmax) of Hydroxybupropion | 8 h |
| Day 15 | Time of Peak Concentration (Tmax) of Hydroxybupropion | 8 h |
| Day 22 | Time of Peak Concentration (Tmax) of Hydroxybupropion | 8 h |
| Day 29 | Time of Peak Concentration (Tmax) of Hydroxybupropion | 8 h |
Other Pre-specified
Trough Plasma Concentration (Ctrough) of ASP2151
Time frame: Days 6-14 and at pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h after dosing on Day 15
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Day 1 | Trough Plasma Concentration (Ctrough) of ASP2151 | 0 ng/mL | Standard Deviation 0 |
| Day 15 | Trough Plasma Concentration (Ctrough) of ASP2151 | 244.95 ng/mL | Standard Deviation 104.63 |
| Day 22 | Trough Plasma Concentration (Ctrough) of ASP2151 | 245.83 ng/mL | Standard Deviation 122.39 |
| Day 29 | Trough Plasma Concentration (Ctrough) of ASP2151 | 219.17 ng/mL | Standard Deviation 105.83 |
| Day 10 | Trough Plasma Concentration (Ctrough) of ASP2151 | 185.31 ng/mL | Standard Deviation 84.66 |
| Day 11 | Trough Plasma Concentration (Ctrough) of ASP2151 | 199.16 ng/mL | Standard Deviation 105.72 |
| Day 12 | Trough Plasma Concentration (Ctrough) of ASP2151 | 197.05 ng/mL | Standard Deviation 99.95 |
| Day 13 | Trough Plasma Concentration (Ctrough) of ASP2151 | 192.66 ng/mL | Standard Deviation 102.29 |
| Day 14 | Trough Plasma Concentration (Ctrough) of ASP2151 | 188.46 ng/mL | Standard Deviation 95.75 |
| Day 15 | Trough Plasma Concentration (Ctrough) of ASP2151 | 178.93 ng/mL | Standard Deviation 87.78 |