Healthy Japanese Participants
Conditions
Keywords
Padsevonil, CYP2C19, Healthy Japanese Participants, Pharmacokinetics
Brief summary
The purpose of the study is to investigate the pharmacokinetics (PK) of padesevonil in CYP2C19 genotyped healthy male Japanese study participants.
Interventions
DRUGPadsevonil
Padsevonil will be administered in predefined dosages.
Sponsors
UCB Biopharma S.P.R.L.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
20 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* The study participant must be 20 to 55 years of age inclusive, at the time of signing the informed consent * The study participant is overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring * The study participant is of Japanese descent as evidenced by appearance and verbal confirmation of familial heritage * The study participant has a body weight ≥50 kg and body mass index within the range \[18 to 30\] kg/m\^2 (inclusive) * The study participant is male
Exclusion criteria
* The study participant has any medical or psychiatric condition that, in the opinion of the Investigator, could jeopardize or would compromise the study participant's ability to participate in this study, such as a history of schizophrenia, or other psychotic disorder, bipolar disorder, or severe unipolar depression. The presence of potential psychiatric
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) of a Single Dose Padsevonil | Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose (up to Day 3) | Cmax is the maximum plasma drug concentration of PSL observed from pharmacokinetic samples taken at predefined time points. |
| Area Under the Curve From 0 to t (AUC(0-t)) of a Single Dose Padsevonil | Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose (up to Day 3) | AUC(0-t) is the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration. |
| Area Under the Curve From Time 0 to Infinity (AUC) of a Single Dose Padsevonil | Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose (up to Day 3) | AUC is the area under the plasma concentration-time curve from time zero to infinity. |
| Terminal Half-life (t1/2) of a Single Dose Padsevonil | Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose (up to Day 3) | The t1/2 is the apparent terminal half-life. Geometric Means and Geometric Coefficient of Variations were only calculated if at least 2/3 of the parameters were properly determined parameters (i.e. non-calculated and non-flagged). |
| Time to Reach the Maximum Plasma Concentration (Tmax) of a Single Dose Padsevonil | Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose (up to Day 3) | The tmax is the time to reach maximum plasma concentration. |
| Maximum Plasma Concentration (Cmax) of Padsevonil at Steady-state (ss) | Day 10: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after the morning dose | Cmax, ss is the maximum plasma concentration of PSL observed from pharmacokinetic samples, taken at predefined time point at a steady-state. |
| Area Under the Curve Over a Dosing Interval (AUCtau) of Multiple Doses Padsevonil | Day 10: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after the morning dose | AUCtau is the area under the plasma concentration time curve over a dosing interval. |
| Terminal Half-life (t1/2) of Multiple Doses Padsevonil | Day 10: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after the morning dose | The t1/2 is the apparent terminal half-life. |
| Time to Reach Maximum Concentration (Tmax) for Padsevonil at Steady-state (ss) | Day 10: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after the morning dose | The tmax, ss is the time of observed maximum plasma concentration at a steady-state. |
| Percentage of Participants With Treatment Emergent Adverse Events During the Study | From Baseline until the Safety Follow-up Visit (up to Day 21) | An Adverse Event (AE) is any untoward medical occurrence in a participant or trial participant that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage. |
Countries
Japan
Participant flow
Recruitment details
The study started to enroll patients in September 2019 and concluded in December 2019.
Pre-assignment details
Participant flow refers to the Safety Set.
Participants by arm
| Arm | Count |
|---|---|
| Extensive Metabolizers Extensive metabolizers (Participants confirmed with genotype \*1/\*1) received a single oral dose of padsevonil (PSL) 200 mg in the morning on Day 1 of the Single-dose Period. During the Multiple-dose Period, participants received PSL 100 mg twice a day (BID) on Day 6, PSL 200 mg BID from Day 7 to Day 9, PSL 200 mg in the morning on Day 10; PSL 100 mg in the evening on Day 10, and PSL 100 mg BID from Day 11 to Day 12 orally. | 13 |
| Intermediate Metabolizers Intermediate metabolizers (Participants confirmed with genotype \*1/\*2,\*1/\*3) received a single oral dose of PSL 200 mg in the morning on Day 1 of the Single-dose Period. During the Multiple-dose Period, participants received PSL 100 mg BID on Day 6, PSL 200 mg BID from Day 7 to Day 9, PSL 200 mg in the morning on Day 10; PSL 100 mg in the evening on Day 10, and PSL 100 mg BID from Day 11 to Day 12 orally. | 13 |
| Poor Metabolizers Poor metabolizers (Participants confirmed with genotype \*2/\*2, \*2/\*3, \*3/\*3) received a single oral dose of PSL 200 mg in the morning on Day 1 of the Single-dose Period. During the Multiple-dose Period, participants received PSL 100 mg BID on Day 6, PSL 200 mg BID from Day 7 to Day 9, PSL 200 mg in the morning on Day 10; PSL 100 mg in the evening on Day 10, and PSL 100 mg BID from Day 11 to Day 12 orally. | 13 |
| Total Title | 39 |
| Total | 78 |
Baseline characteristics
| Characteristic | Intermediate Metabolizers | Poor Metabolizers | Extensive Metabolizers | Total Title |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 13 Participants | 13 Participants | 39 Participants |
| Age, Continuous | 32.5 years STANDARD_DEVIATION 5.9 | 32.5 years STANDARD_DEVIATION 7.7 | 27.5 years STANDARD_DEVIATION 6.6 | 30.9 years STANDARD_DEVIATION 7 |
| Race/Ethnicity, Customized Asian | 13 Participants | 13 Participants | 13 Participants | 39 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 13 Participants | 13 Participants | 13 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 13 | 0 / 13 | 0 / 13 | 0 / 13 | 0 / 13 |
| other Total, other adverse events | 13 / 13 | 13 / 13 | 13 / 13 | 13 / 13 | 13 / 13 | 13 / 13 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 | 0 / 13 | 0 / 13 | 0 / 13 | 0 / 13 |
Outcome results
Primary
Area Under the Curve From 0 to t (AUC(0-t)) of a Single Dose Padsevonil
AUC(0-t) is the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration.
Time frame: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose (up to Day 3)
Population: The Pharmacokinetic Per-protocol Set (PK-PPS) was a subset of the Safety Set, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Poor Metabolizers (PK-PPS) | Area Under the Curve From 0 to t (AUC(0-t)) of a Single Dose Padsevonil | 5988 h*ng/mL |
| Intermediate Metabolizers (PK-PPS) | Area Under the Curve From 0 to t (AUC(0-t)) of a Single Dose Padsevonil | 4645 h*ng/mL |
| Extensive Metabolizers (PK-PPS) | Area Under the Curve From 0 to t (AUC(0-t)) of a Single Dose Padsevonil | 2823 h*ng/mL |
Comparison: Point estimates for the geometric least squares (LS) means ratio and the respective 2-sided 90% CIs were computed using the LS means and the root mean squares of error, based on of the log-transformed data with subsequent exponential transformation.90% CI: [1.706, 2.638]ANOVA
Comparison: Point estimates for the geometric least squares (LS) means ratio and the respective 2-sided 90% CIs were computed using the LS means and the root mean squares of error, based on of the log-transformed data with subsequent exponential transformation.90% CI: [1.037, 1.603]ANOVA
Comparison: Point estimates for the geometric least squares (LS) means ratio and the respective 2-sided 90% CIs were computed using the LS means and the root mean squares of error, based on of the log-transformed data with subsequent exponential transformation.90% CI: [1.323, 2.046]ANOVA
Primary
Area Under the Curve From Time 0 to Infinity (AUC) of a Single Dose Padsevonil
AUC is the area under the plasma concentration-time curve from time zero to infinity.
Time frame: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose (up to Day 3)
Population: The Pharmacokinetic Per-protocol Set (PK-PPS) was a subset of the Safety Set, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Poor Metabolizers (PK-PPS) | Area Under the Curve From Time 0 to Infinity (AUC) of a Single Dose Padsevonil | 6024 h*ng/mL |
| Intermediate Metabolizers (PK-PPS) | Area Under the Curve From Time 0 to Infinity (AUC) of a Single Dose Padsevonil | 4666 h*ng/mL |
| Extensive Metabolizers (PK-PPS) | Area Under the Curve From Time 0 to Infinity (AUC) of a Single Dose Padsevonil | 2837 h*ng/mL |
Comparison: Point estimates for the geometric least squares (LS) means ratio and the respective 2-sided 90% CIs were computed using the LS means and the root mean squares of error, based on of the log-transformed data with subsequent exponential transformation.90% CI: [1.709, 2.639]ANOVA
Comparison: Point estimates for the geometric least squares (LS) means ratio and the respective 2-sided 90% CIs were computed using the LS means and the root mean squares of error, based on of the log-transformed data with subsequent exponential transformation.90% CI: [1.039, 1.604]ANOVA
Comparison: Point estimates for the geometric least squares (LS) means ratio and the respective 2-sided 90% CIs were computed using the LS means and the root mean squares of error, based on of the log-transformed data with subsequent exponential transformation.90% CI: [1.324, 2.044]ANOVA
Primary
Area Under the Curve Over a Dosing Interval (AUCtau) of Multiple Doses Padsevonil
AUCtau is the area under the plasma concentration time curve over a dosing interval.
Time frame: Day 10: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after the morning dose
Population: The Pharmacokinetic Per-protocol Set (PK-PPS) was a subset of the Safety Set, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Poor Metabolizers (PK-PPS) | Area Under the Curve Over a Dosing Interval (AUCtau) of Multiple Doses Padsevonil | 6482 h*ng/mL |
| Intermediate Metabolizers (PK-PPS) | Area Under the Curve Over a Dosing Interval (AUCtau) of Multiple Doses Padsevonil | 6488 h*ng/mL |
| Extensive Metabolizers (PK-PPS) | Area Under the Curve Over a Dosing Interval (AUCtau) of Multiple Doses Padsevonil | 4824 h*ng/mL |
Comparison: Point estimates for the geometric least squares (LS) means ratio and the respective 2-sided 90% CIs were computed using the LS means and the root mean squares of error, based on of the log-transformed data with subsequent exponential transformation.90% CI: [1.092, 1.653]ANOVA
Comparison: Point estimates for the geometric least squares (LS) means ratio and the respective 2-sided 90% CIs were computed using the LS means and the root mean squares of error, based on of the log-transformed data with subsequent exponential transformation.90% CI: [0.812, 1.229]ANOVA
Comparison: Point estimates for the geometric least squares (LS) means ratio and the respective 2-sided 90% CIs were computed using the LS means and the root mean squares of error, based on of the log-transformed data with subsequent exponential transformation.90% CI: [1.093, 1.655]ANOVA
Primary
Maximum Plasma Concentration (Cmax) of a Single Dose Padsevonil
Cmax is the maximum plasma drug concentration of PSL observed from pharmacokinetic samples taken at predefined time points.
Time frame: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose (up to Day 3)
Population: The Pharmacokinetic Per-protocol Set (PK-PPS) was a subset of the Safety Set, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Poor Metabolizers (PK-PPS) | Maximum Plasma Concentration (Cmax) of a Single Dose Padsevonil | 1029 ng/mL |
| Intermediate Metabolizers (PK-PPS) | Maximum Plasma Concentration (Cmax) of a Single Dose Padsevonil | 833.6 ng/mL |
| Extensive Metabolizers (PK-PPS) | Maximum Plasma Concentration (Cmax) of a Single Dose Padsevonil | 721.3 ng/mL |
Comparison: Point estimates for the geometric least squares (LS) means ratio and the respective 2-sided 90% Confidence Intervals (CIs) were computed using the LS means and the root mean squares of error, based on of the log-transformed data with subsequent exponential transformation.90% CI: [1.112, 1.83]ANOVA
Comparison: Point estimates for the geometric least squares (LS) means ratio and the respective 2-sided 90% CIs were computed using the LS means and the root mean squares of error, based on of the log-transformed data with subsequent exponential transformation.90% CI: [0.9619, 1.584]ANOVA
Comparison: Point estimates for the geometric least squares (LS) means ratio and the respective 2-sided 90% CIs were computed using the LS means and the root mean squares of error, based on of the log-transformed data with subsequent exponential transformation.90% CI: [0.9008, 1.483]ANOVA
Primary
Maximum Plasma Concentration (Cmax) of Padsevonil at Steady-state (ss)
Cmax, ss is the maximum plasma concentration of PSL observed from pharmacokinetic samples, taken at predefined time point at a steady-state.
Time frame: Day 10: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after the morning dose
Population: The Pharmacokinetic Per-protocol Set (PK-PPS) was a subset of the Safety Set, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Poor Metabolizers (PK-PPS) | Maximum Plasma Concentration (Cmax) of Padsevonil at Steady-state (ss) | 1375 ng/mL |
| Intermediate Metabolizers (PK-PPS) | Maximum Plasma Concentration (Cmax) of Padsevonil at Steady-state (ss) | 1318 ng/mL |
| Extensive Metabolizers (PK-PPS) | Maximum Plasma Concentration (Cmax) of Padsevonil at Steady-state (ss) | 1263 ng/mL |
Comparison: Point estimates for the geometric least squares (LS) means ratio and the respective 2-sided 90% CIs were computed using the LS means and the root mean squares of error, based on of the log-transformed data with subsequent exponential transformation.90% CI: [0.8859, 1.339]ANOVA
Comparison: Point estimates for the geometric least squares (LS) means ratio and the respective 2-sided 90% CIs were computed using the LS means and the root mean squares of error, based on of the log-transformed data with subsequent exponential transformation.90% CI: [0.8489, 1.283]ANOVA
Comparison: Point estimates for the geometric least squares (LS) means ratio and the respective 2-sided 90% CIs were computed using the LS means and the root mean squares of error, based on of the log-transformed data with subsequent exponential transformation.90% CI: [0.8489, 1.283]ANOVA
Primary
Percentage of Participants With Treatment Emergent Adverse Events During the Study
An Adverse Event (AE) is any untoward medical occurrence in a participant or trial participant that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage.
Time frame: From Baseline until the Safety Follow-up Visit (up to Day 21)
Population: The Safety Set (SS) consisted of all study participants who had received at least 1 dose of padsevonil.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Poor Metabolizers (PK-PPS) | Percentage of Participants With Treatment Emergent Adverse Events During the Study | 100 percentage of participants |
| Intermediate Metabolizers (PK-PPS) | Percentage of Participants With Treatment Emergent Adverse Events During the Study | 100 percentage of participants |
| Extensive Metabolizers (PK-PPS) | Percentage of Participants With Treatment Emergent Adverse Events During the Study | 100 percentage of participants |
| Extensive Metabolizers Multiple Dose (SS) | Percentage of Participants With Treatment Emergent Adverse Events During the Study | 100 percentage of participants |
| Intermediate Metabolizers Multiple Dose (SS) | Percentage of Participants With Treatment Emergent Adverse Events During the Study | 100 percentage of participants |
| Poor Metabolizers Multiple Dose (SS) | Percentage of Participants With Treatment Emergent Adverse Events During the Study | 100 percentage of participants |
Primary
Terminal Half-life (t1/2) of a Single Dose Padsevonil
The t1/2 is the apparent terminal half-life. Geometric Means and Geometric Coefficient of Variations were only calculated if at least 2/3 of the parameters were properly determined parameters (i.e. non-calculated and non-flagged).
Time frame: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose (up to Day 3)
Population: The Pharmacokinetic Per-protocol Set (PK-PPS) was a subset of the Safety Set, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Poor Metabolizers (PK-PPS) | Terminal Half-life (t1/2) of a Single Dose Padsevonil | 5.018 hours | Geometric Coefficient of Variation 22.2 |
| Intermediate Metabolizers (PK-PPS) | Terminal Half-life (t1/2) of a Single Dose Padsevonil | 5.904 hours | Geometric Coefficient of Variation 21.3 |
| Extensive Metabolizers (PK-PPS) | Terminal Half-life (t1/2) of a Single Dose Padsevonil | 6.138 hours | Geometric Coefficient of Variation 24.1 |
Primary
Terminal Half-life (t1/2) of Multiple Doses Padsevonil
The t1/2 is the apparent terminal half-life.
Time frame: Day 10: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after the morning dose
Population: The Pharmacokinetic Per-protocol Set (PK-PPS) was a subset of the Safety Set, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Poor Metabolizers (PK-PPS) | Terminal Half-life (t1/2) of Multiple Doses Padsevonil | NA hours |
| Intermediate Metabolizers (PK-PPS) | Terminal Half-life (t1/2) of Multiple Doses Padsevonil | NA hours |
| Extensive Metabolizers (PK-PPS) | Terminal Half-life (t1/2) of Multiple Doses Padsevonil | NA hours |
Primary
Time to Reach Maximum Concentration (Tmax) for Padsevonil at Steady-state (ss)
The tmax, ss is the time of observed maximum plasma concentration at a steady-state.
Time frame: Day 10: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after the morning dose
Population: The Pharmacokinetic Per-protocol Set (PK-PPS) was a subset of the Safety Set, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Poor Metabolizers (PK-PPS) | Time to Reach Maximum Concentration (Tmax) for Padsevonil at Steady-state (ss) | 1.500 hours |
| Intermediate Metabolizers (PK-PPS) | Time to Reach Maximum Concentration (Tmax) for Padsevonil at Steady-state (ss) | 2.000 hours |
| Extensive Metabolizers (PK-PPS) | Time to Reach Maximum Concentration (Tmax) for Padsevonil at Steady-state (ss) | 1.500 hours |
Primary
Time to Reach the Maximum Plasma Concentration (Tmax) of a Single Dose Padsevonil
The tmax is the time to reach maximum plasma concentration.
Time frame: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose (up to Day 3)
Population: The Pharmacokinetic Per-protocol Set (PK-PPS) was a subset of the Safety Set, consisting of those study participants who had no important protocol deviations affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Poor Metabolizers (PK-PPS) | Time to Reach the Maximum Plasma Concentration (Tmax) of a Single Dose Padsevonil | 2.000 hours |
| Intermediate Metabolizers (PK-PPS) | Time to Reach the Maximum Plasma Concentration (Tmax) of a Single Dose Padsevonil | 3.000 hours |
| Extensive Metabolizers (PK-PPS) | Time to Reach the Maximum Plasma Concentration (Tmax) of a Single Dose Padsevonil | 3.000 hours |