Pharmacokinetics
Conditions
Keywords
Padsevonil
Brief summary
The purpose of this study is to evaluate and compare the Pharmacokinetics (PK) of concomitant administration of Padsevonil (PSL) in the presence and absence of erythromycin in healthy study participants.
Interventions
DRUGPadsevonil (UCB0942)
* Pharmaceutical Form: film-coated tablet * Route of Administration: Oral use
DRUGErythromycin
* Pharmaceutical Form: film-coated tablet * Route of Administration: Oral use
Sponsors
UCB Biopharma S.P.R.L.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Study participant is male or female and between 18 and 55 years of age (inclusive) * Study participant is of a body weight of at least 50 kg for males and 45 kg for females, as determined by a body mass index (BMI) between 18 and 30 kg/m\^2 * Female study participants use an efficient form of contraception for the duration of the study (unless menopausal). Hormonal contraception may be susceptible to an interaction with the Investigational Medicinal Product (IMP), which may reduce the efficacy of the contraception method. The potential for reduced efficacy of any hormonal contraception methods requires that a barrier method (preferably male condom) also be used * Study participant has clinical laboratory test results within the local reference ranges or values are considered as not clinically relevant by the investigator and approved by the UCB Study Physician * Study participant has Blood Pressure (BP) and pulse rate within normal range in supine position after 10 minutes of rest * Male study participant agrees that, during the study period, when having sexual intercourse with a woman of childbearing potential, he will use an efficient barrier contraceptive (condom plus spermicide) AND that the respective partner will use an additional efficient contraceptive method
Exclusion criteria
* Study participant has previously received Investigational Medicinal Product (IMP) in this study * Study participant has participated in another study of an IMP (or a medical device) within the previous 3 months before Screening (or within 5 half-lives for the IMP, whichever is longer) or is currently participating in another study of an IMP (or a medical device) * Study participant has a history of drug or alcohol dependency within the previous 6 months or tests positive for alcohol (breath test) and/or drugs of abuse (urine test) at the Screening Visit or at any time during confinement * Study participant has made a blood or plasma donation or has had a comparable blood loss (\>400 mL) within the last 3 months prior to the Screening Visit * Study participant smokes more than 5 cigarettes per day (or equivalent) or has done so within 6 months prior to the Screening Visit * Study participant is taking any concomitant medication currently or within 2 weeks prior to the first day of dosing with the exception of paracetamol (acetaminophen) * Study participant has any clinically relevant Electrocardiogram (ECG) finding at the Screening Visit or confinement * Study participant has a history within the last 5 years or present condition of malignancy, with the exception of basal cell carcinoma * Female study participant tests positive for pregnancy, plans to get pregnant during the participation in the study, or who is breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Padsevonil for Single Dose | Predose and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1, 12, and 26 | Cmax: The maximum observed plasma concentration of padsevonil for single dose . Cmax was expressed in nanograms per milliliter (ng/mL). |
| Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours (AUC(0-12)) of Padsevonil for Single Dose | Predose and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1, 12, and 26 | AUC(0-12): The area under the plasma concentration-time curve from time zero to 12 hours of padsevonil for single dose . AUC(0-12) was expressed in hours times nanograms per milliliter (hours\*ng/mL). |
| Maximum Observed Steady-state Plasma Concentration (Cmax, ss) of Padsevonil for Multiple Doses | Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3) | Cmax, ss: The maximum observed steady-state plasma concentration of padsevonil for multiple doses. Cmax, ss was expressed in nanograms per millilitre (ng/mL). |
| Area Under the Plasma Concentration-time Curve Over a Dosing Interval (12 Hours) (AUCtau) of Padsevonil for Multiple Doses | Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3) | AUCtau: The area under the plasma concentration-time curve over a dosing interval (12 hours) of padsevonil for multiple doses. AUC(tau) was expressed in hours times nanograms per millilitre (hours\*ng/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Predose Observed Plasma Concentration (Ctrough) of Padsevonil for Multiple Doses | Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3) | Ctrough: The predose observed plasma concentration of padsevonil for multiple doses. Ctrough was expressed in nanograms per millilitre (ng/mL). |
| Apparent Total Clearance at Steady-state (CL/Fss) of Padsevonil for Multiple Doses in Plasma | Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3) | CL/Fss: The apparent total clearance at steady-state of padsevonil for multiple doses in plasma. CL/Fss was expressed in milliliters per hour (mL/hour). |
| Apparent Elimination Rate Constant (Lambdaz) of Padsevonil for Multiple Doses in Plasma | Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3) | lambdaz: The apparent elimination rate constant of padsevonil for multiple doses in plasma. Lambdaz was expressed in liters per hour (l/hour). |
| Maximum Observed Plasma Concentration (Cmax) of Padsevonil Metabolites (1 and 2) for Single Dose | Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period | Cmax: The maximum plasma concentration of padsevonil metabolites (1 and 2) for single dose. Cmax was expressed in nanograms per milliliter (ng/mL). |
| Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours (AUC(0-12)) of Padsevonil Metabolites (1 and 2) for Single Dose | Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period | AUC(0-12): The area under the plasma concentration-time curve from time zero to 12 hours of padsevonil metabolites (1 and 2) for single dose. AUC(0-12) was expressed in hours times nanograms per milliliter (hours\*ng/mL). |
| Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Multiple Doses | Urine samples were taken 0 to 12 hours, 12 to 24 hours,and 24 to 48 hours post last PSL dose during Treatment Period 1 and 2; 0 to 12 hours, 12 to 24 hours, 24 to 48 hours, 48 to 72 hours, and 72 to 96 hours post last dose of PSL during Treatment Period 3 | CLform: The formation clearance of padsevonil metabolites (1, 2, and 3) in the urine for multiple doses. CLform was expressed in milliliters per hour (mL/hour). |
| Area Under the Plasma Concentration-time Curve Over a Dosing Interval (12 Hours) (AUCtau) of Padsevonil Metabolites (1 and 2) for Multiple Doses | Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3) | AUCtau: The area under the plasma concentration-time curve over a dosing interval (12 hours) of padsevonil metabolites (1 and 2) for multiple doses. AUCtau was expressed in hours times nanograms per milliliter (hours\*ng/mL). |
| Maximum Observed Steady-state Plasma Concentration (Cmax, ss) of Padsevonil Metabolites (1 and 2) for Multiple Doses | Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3) | Cmax, ss: The maximum observed steady-state plasma concentration of padsevonil metabolites (1 and 2) for multiple doses. Cmax, ss was expressed in nanograms per millilitre (ng/mL). |
| Metabolite-to-parent Ratio for Cmax of Padsevonil Metabolites (1 and 2) in Plasma | Blood samples were taken at specific time points from pre-dose to 12 hours post dose of Padsevonil for each Treatment Period | Metabolite-to-parent ratio calculated as: Cmax of padsevonil metabolites (1 and 2) divided by Cmax of padsevonil following a single dose in plasma. Metabolite-to-parent ratio for Cmax was expressed as ratio. |
| Metabolite-to-parent Ratio for AUC(0-12) of Padsevonil Metabolites (1 and 2) in Plasma | Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period | Metabolite-to-parent ratio calculated as: AUC(0-12)of padsevonil metabolites (1 and 2) divided by AUC(0-12) of padsevonil following a single dose in plasma. Metabolite-to-parent ratio for AUC(0-12) was expressed as ratio. |
| Time of Maximum Plasma Concentration (Tmax) of Padsevonil for Single Dose | Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period | Tmax: The time of maximum plasma concentration of padsevonil for single dose. Tmax was expressed in hours (h). |
| Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Single Dose in Urine | Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment Period | CLr: The renal clearance of padsevonil and its metabolites (1 and 2) for single dose in urine. CLr was expressed in milliliters per hour (mL/hour). |
| Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Multiple Doses in Urine | Urine samples were taken 0 to 12 hours, 12 to 24 hours,and 24 to 48 hours post last PSL dose during Treatment Period 1 and 2; 0 to 12 hours, 12 to 24 hours, 24 to 48 hours, 48 to 72 hours, and 72 to 96 hours post last dose of PSL during Treatment Period 3 | CLr: The renal clearance of padsevonil and its metabolites (1 and 2) for multiple doses in urine. CLr was expressed in milliliters per hour (mL/hour). |
| Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose | Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment Period | Ae: The cumulative amount of padsevonil and its metabolites (1, 2, and 3) excreted into the urine for single dose. Ae was expressed in milligrams (mg). |
| Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses | Urine samples were taken 0 to 12 hours, 12 to 24 hours,and 24 to 48 hours post last PSL dose during Treatment Period 1 and 2; 0 to 12 hours, 12 to 24 hours, 24 to 48 hours, 48 to 72 hours, and 72 to 96 hours post last dose of PSL during Treatment Period 3 | Ae: The cumulative amount of padsevonil and its metabolites (1, 2, and 3) excreted into the urine for multiple doses. Ae was expressed in milligrams (mg). |
| Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose | Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment Period | fe: The fraction of padsevonil or metabolites (1, 2, and 3) excreted into the urine for single dose. fe was expressed in percentage (%). |
| Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses | Urine samples were taken 0 to 12 hours, 12 to 24 hours,and 24 to 48 hours post last PSL dose during Treatment Period 1 and 2; 0 to 12 hours, 12 to 24 hours, 24 to 48 hours, 48 to 72 hours, and 72 to 96 hours post last dose of PSL during Treatment Period 3 | fe: The fraction of padsevonil and its metabolites (1, 2, and 3) excreted into the urine for multiple doses. fe was expressed in percentage (%). |
| Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Single Dose | Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment Period | CLform: The formation clearance of padsevonil metabolites (1, 2, and 3) in the urine for single dose. CLform was expressed in milliliters per hour (mL/hour). |
| Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs) During the Study | From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to 48 days ) | An SAE is any untoward medical occurrence that at any dose: * Results in death * Is life-threatening * Requires in patient hospitalization or prolongation of existing hospitalization * Is a congenital anomaly or birth defect * Is an infection that requires treatment parenteral antibiotics * Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above. |
| Percentage of Participants Experiencing Treatment-Emergent Non-serious Adverse Events (AEs) During the Study | From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to 48 days ) | Treatment-emergent Adverse Events (TEAEs) were defined as those events which started on or after the date of first dose of UP0057 IMP, or events in which severity worsened on or after the date of first dose of UP0057 study medication. |
| Metabolite-to-parent Ratio for AUCtau of Padsevonil Metabolites (1 and 2) in Plasma | Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3) | Metabolite-to-parent ratio calculated as: AUCtau of padsevonil metabolites (1 and 2) divided by AUCtau of padsevonil following multiple dosing in plasma. Metabolite-to-parent ratio for AUCtau was expressed as ratio. |
| Minimum Observed Plasma Concentration (Cmin) of Padsevonil for Single Dose | Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period | Cmin: The minimum observed plasma concentration of padsevonil for single dose. Cmin was expressed in nanograms per millilitre (ng/mL). |
| Time of Maximum Plasma Concentration (Tmax) of Padsevonil for Multiple Doses | Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3) | Tmax: The time of maximum plasma concentration of padsevonil for multiple doses. Tmax was expressed in hours (h). |
| Apparent Terminal Elimination Half-life at Steady-state (t1/2,ss) of Padsevonil for Multiple Doses in Plasma | Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3) | t½,ss: The apparent terminal elimination half-life at steady-state of padsevonil for multiple doses in plasma. t1/2, ss was expressed in hours (h). |
Countries
United Kingdom
Participant flow
Recruitment details
The study started to enroll patients in March 2018 and concluded in August 2018.
Pre-assignment details
Participant Flow refers to the Full Analysis Set (FAS).
Participants by arm
| Arm | Count |
|---|---|
| Padsevonil and/or Erythromycin The study participants received treatment as follows:
Treatment Period 1: From Day 1 to Day 11:
* Padsevonil 100 mg twice daily (bid) on Day 1 to Day 4
* Padsevonil 100 mg single dose on Day 5
* 1 week of wash-out (from evening of Day 5 to Day 11).
Treatment Period 2: From Day 12 to Day 22:
* Padsevonil 100 mg bid on Day 12 to Day 15
* Padsevonil 100 mg single dose on Day 16
* 1 week of wash-out (from evening of Day 16 to Day 22). Treatment Period 3: From Day 23 to 37
Treatment Period 3a:
-Erythromycin 500 mg bid on Day 23 to Day 25.
Treatment Period 3b:
* Padsevonil 100 mg bid and erythromycin 500 mg bid on Day 26 to Day 32
* Padsevonil 100 mg single dose on Day 33
* Erythromycin 500 mg bid on Day 33.
Treatment Period 3c:
\- Erythromycin 500 mg bid on Day 34 to Day 37. | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Padsevonil and Erythromycin (Period 3b) | Un-cooperative behaviour | 1 |
| Padsevonil (Period 2) | Consent withdrawal by subject | 1 |
Baseline characteristics
| Characteristic | Padsevonil and/or Erythromycin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants |
| Age, Continuous | 36.7 years STANDARD_DEVIATION 8.3 |
| Race/Ethnicity, Customized Asian | 2 Participants |
| Race/Ethnicity, Customized Black | 1 Participants |
| Race/Ethnicity, Customized Missing | 1 Participants |
| Race/Ethnicity, Customized White | 24 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 25 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 / 28 | 0 / 27 | 0 / 27 | 0 / 26 |
| other Total, other adverse events | 28 / 28 | 0 / 27 | 25 / 27 | 2 / 26 |
| serious Total, serious adverse events | 0 / 28 | 0 / 27 | 0 / 27 | 0 / 26 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours (AUC(0-12)) of Padsevonil for Single Dose
AUC(0-12): The area under the plasma concentration-time curve from time zero to 12 hours of padsevonil for single dose . AUC(0-12) was expressed in hours times nanograms per milliliter (hours\*ng/mL).
Time frame: Predose and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1, 12, and 26
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, 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. As per the planned analysis, data was summarized by treatment periods.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Padsevonil (Period 1) (PK-PPS) | Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours (AUC(0-12)) of Padsevonil for Single Dose | 1428 hours*ng/mL | Geometric Coefficient of Variation 40.7 |
| Padsevonil (Period 2) (PK-PPS) | Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours (AUC(0-12)) of Padsevonil for Single Dose | 1571 hours*ng/mL | Geometric Coefficient of Variation 41.8 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours (AUC(0-12)) of Padsevonil for Single Dose | 2576 hours*ng/mL | Geometric Coefficient of Variation 47 |
Comparison: The analysis of variance model included the fixed effects period (1, 2 or 3b) and participant as a random effect.90% CI: [1.5, 2.17]ANOVA
Comparison: The analysis of variance model included the fixed effects period (1, 2 or 3b) and participant as a random effect.90% CI: [1.36, 1.97]ANOVA
Primary
Area Under the Plasma Concentration-time Curve Over a Dosing Interval (12 Hours) (AUCtau) of Padsevonil for Multiple Doses
AUCtau: The area under the plasma concentration-time curve over a dosing interval (12 hours) of padsevonil for multiple doses. AUC(tau) was expressed in hours times nanograms per millilitre (hours\*ng/mL).
Time frame: Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, 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. As per the planned analysis, data was summarized by treatment periods. Here, number of participants were included who were evaluable for the assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Padsevonil (Period 1) (PK-PPS) | Area Under the Plasma Concentration-time Curve Over a Dosing Interval (12 Hours) (AUCtau) of Padsevonil for Multiple Doses | 2049 hours*ng/mL | Geometric Coefficient of Variation 41.1 |
| Padsevonil (Period 2) (PK-PPS) | Area Under the Plasma Concentration-time Curve Over a Dosing Interval (12 Hours) (AUCtau) of Padsevonil for Multiple Doses | 2274 hours*ng/mL | Geometric Coefficient of Variation 47.1 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Area Under the Plasma Concentration-time Curve Over a Dosing Interval (12 Hours) (AUCtau) of Padsevonil for Multiple Doses | 5073 hours*ng/mL | Geometric Coefficient of Variation 55.9 |
Comparison: The analysis of variance model included the fixed effects period (1, 2 or 3b) and participant as a random effect.90% CI: [2.02, 3.03]ANOVA
Comparison: The analysis of variance model included the fixed effects period (1, 2 or 3b) and participant as a random effect.90% CI: [1.82, 2.73]ANOVA
Primary
Maximum Observed Plasma Concentration (Cmax) of Padsevonil for Single Dose
Cmax: The maximum observed plasma concentration of padsevonil for single dose . Cmax was expressed in nanograms per milliliter (ng/mL).
Time frame: Predose and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose on Day 1, 12, and 26
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, 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. As per the planned analysis, data was summarized by treatment periods.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Padsevonil (Period 1) (PK-PPS) | Maximum Observed Plasma Concentration (Cmax) of Padsevonil for Single Dose | 366.6 ng/mL | Geometric Coefficient of Variation 38.8 |
| Padsevonil (Period 2) (PK-PPS) | Maximum Observed Plasma Concentration (Cmax) of Padsevonil for Single Dose | 385.3 ng/mL | Geometric Coefficient of Variation 40.9 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Maximum Observed Plasma Concentration (Cmax) of Padsevonil for Single Dose | 697.4 ng/mL | Geometric Coefficient of Variation 46.9 |
Comparison: The analysis of variance model included the fixed effects period (1, 2 or 3b) and participant as a random effect.90% CI: [1.59, 2.27]ANOVA
Comparison: The analysis of variance model included the fixed effects period (1, 2 or 3b) and participant as a random effect.90% CI: [1.51, 2.16]ANOVA
Primary
Maximum Observed Steady-state Plasma Concentration (Cmax, ss) of Padsevonil for Multiple Doses
Cmax, ss: The maximum observed steady-state plasma concentration of padsevonil for multiple doses. Cmax, ss was expressed in nanograms per millilitre (ng/mL).
Time frame: Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, 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. As per the planned analysis, data was summarized by treatment periods. Here, number of participants were included who were evaluable for the assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Padsevonil (Period 1) (PK-PPS) | Maximum Observed Steady-state Plasma Concentration (Cmax, ss) of Padsevonil for Multiple Doses | 475.0 ng/mL | Geometric Coefficient of Variation 38.4 |
| Padsevonil (Period 2) (PK-PPS) | Maximum Observed Steady-state Plasma Concentration (Cmax, ss) of Padsevonil for Multiple Doses | 473.9 ng/mL | Geometric Coefficient of Variation 43.7 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Maximum Observed Steady-state Plasma Concentration (Cmax, ss) of Padsevonil for Multiple Doses | 1010 ng/mL | Geometric Coefficient of Variation 45.7 |
Comparison: The analysis of variance model included the fixed effects period (1, 2 or 3b) and participant as a random effect.90% CI: [1.77, 2.55]ANOVA
Comparison: The analysis of variance model included the fixed effects period (1, 2 or 3b) and participant as a random effect.90% CI: [1.78, 2.56]ANOVA
Secondary
Apparent Elimination Rate Constant (Lambdaz) of Padsevonil for Multiple Doses in Plasma
lambdaz: The apparent elimination rate constant of padsevonil for multiple doses in plasma. Lambdaz was expressed in liters per hour (l/hour).
Time frame: Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, 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. As per the planned analysis, data was summarized by treatment periods. Here, number of participants were included who were evaluable for the assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Padsevonil (Period 1) (PK-PPS) | Apparent Elimination Rate Constant (Lambdaz) of Padsevonil for Multiple Doses in Plasma | 0.1049 l\hour | Geometric Coefficient of Variation 27.9 |
| Padsevonil (Period 2) (PK-PPS) | Apparent Elimination Rate Constant (Lambdaz) of Padsevonil for Multiple Doses in Plasma | 0.1006 l\hour | Geometric Coefficient of Variation 36.2 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Apparent Elimination Rate Constant (Lambdaz) of Padsevonil for Multiple Doses in Plasma | 0.07975 l\hour | Geometric Coefficient of Variation 34.5 |
Secondary
Apparent Terminal Elimination Half-life at Steady-state (t1/2,ss) of Padsevonil for Multiple Doses in Plasma
t½,ss: The apparent terminal elimination half-life at steady-state of padsevonil for multiple doses in plasma. t1/2, ss was expressed in hours (h).
Time frame: Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, 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. As per the planned analysis, data was summarized by treatment periods. Here, number of participants were included who were evaluable for the assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Padsevonil (Period 1) (PK-PPS) | Apparent Terminal Elimination Half-life at Steady-state (t1/2,ss) of Padsevonil for Multiple Doses in Plasma | 6.465 hours |
| Padsevonil (Period 2) (PK-PPS) | Apparent Terminal Elimination Half-life at Steady-state (t1/2,ss) of Padsevonil for Multiple Doses in Plasma | 6.649 hours |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Apparent Terminal Elimination Half-life at Steady-state (t1/2,ss) of Padsevonil for Multiple Doses in Plasma | 8.548 hours |
Secondary
Apparent Total Clearance at Steady-state (CL/Fss) of Padsevonil for Multiple Doses in Plasma
CL/Fss: The apparent total clearance at steady-state of padsevonil for multiple doses in plasma. CL/Fss was expressed in milliliters per hour (mL/hour).
Time frame: Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, 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. As per the planned analysis, data was summarized by treatment periods. Here, number of participants were included who were evaluable for the assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Padsevonil (Period 1) (PK-PPS) | Apparent Total Clearance at Steady-state (CL/Fss) of Padsevonil for Multiple Doses in Plasma | 48810 mL/hour | Geometric Coefficient of Variation 41.1 |
| Padsevonil (Period 2) (PK-PPS) | Apparent Total Clearance at Steady-state (CL/Fss) of Padsevonil for Multiple Doses in Plasma | 43970 mL/hour | Geometric Coefficient of Variation 47.1 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Apparent Total Clearance at Steady-state (CL/Fss) of Padsevonil for Multiple Doses in Plasma | 19710 mL/hour | Geometric Coefficient of Variation 55.9 |
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours (AUC(0-12)) of Padsevonil Metabolites (1 and 2) for Single Dose
AUC(0-12): The area under the plasma concentration-time curve from time zero to 12 hours of padsevonil metabolites (1 and 2) for single dose. AUC(0-12) was expressed in hours times nanograms per milliliter (hours\*ng/mL).
Time frame: Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, 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. As per the planned analysis, data was summarized by treatment periods.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Padsevonil (Period 1) (PK-PPS) | Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours (AUC(0-12)) of Padsevonil Metabolites (1 and 2) for Single Dose | Metabolite 1 | 828.3 hours*ng/mL | Geometric Coefficient of Variation 24.2 |
| Padsevonil (Period 1) (PK-PPS) | Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours (AUC(0-12)) of Padsevonil Metabolites (1 and 2) for Single Dose | Metabolite 2 | 596.5 hours*ng/mL | Geometric Coefficient of Variation 39 |
| Padsevonil (Period 2) (PK-PPS) | Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours (AUC(0-12)) of Padsevonil Metabolites (1 and 2) for Single Dose | Metabolite 1 | 824.3 hours*ng/mL | Geometric Coefficient of Variation 25.5 |
| Padsevonil (Period 2) (PK-PPS) | Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours (AUC(0-12)) of Padsevonil Metabolites (1 and 2) for Single Dose | Metabolite 2 | 534.4 hours*ng/mL | Geometric Coefficient of Variation 43.9 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours (AUC(0-12)) of Padsevonil Metabolites (1 and 2) for Single Dose | Metabolite 1 | 905.6 hours*ng/mL | Geometric Coefficient of Variation 29.7 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours (AUC(0-12)) of Padsevonil Metabolites (1 and 2) for Single Dose | Metabolite 2 | 599.5 hours*ng/mL | Geometric Coefficient of Variation 49.5 |
Secondary
Area Under the Plasma Concentration-time Curve Over a Dosing Interval (12 Hours) (AUCtau) of Padsevonil Metabolites (1 and 2) for Multiple Doses
AUCtau: The area under the plasma concentration-time curve over a dosing interval (12 hours) of padsevonil metabolites (1 and 2) for multiple doses. AUCtau was expressed in hours times nanograms per milliliter (hours\*ng/mL).
Time frame: Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, 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. As per the planned analysis, data was summarized by treatment periods. Here, number of participants were included who were evaluable for the assessment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Padsevonil (Period 1) (PK-PPS) | Area Under the Plasma Concentration-time Curve Over a Dosing Interval (12 Hours) (AUCtau) of Padsevonil Metabolites (1 and 2) for Multiple Doses | Metabolite 1 | 1748 hours*ng/mL | Geometric Coefficient of Variation 35.1 |
| Padsevonil (Period 1) (PK-PPS) | Area Under the Plasma Concentration-time Curve Over a Dosing Interval (12 Hours) (AUCtau) of Padsevonil Metabolites (1 and 2) for Multiple Doses | Metabolite 2 | 775.1 hours*ng/mL | Geometric Coefficient of Variation 37.4 |
| Padsevonil (Period 2) (PK-PPS) | Area Under the Plasma Concentration-time Curve Over a Dosing Interval (12 Hours) (AUCtau) of Padsevonil Metabolites (1 and 2) for Multiple Doses | Metabolite 1 | 1993 hours*ng/mL | Geometric Coefficient of Variation 40.8 |
| Padsevonil (Period 2) (PK-PPS) | Area Under the Plasma Concentration-time Curve Over a Dosing Interval (12 Hours) (AUCtau) of Padsevonil Metabolites (1 and 2) for Multiple Doses | Metabolite 2 | 813.1 hours*ng/mL | Geometric Coefficient of Variation 40.5 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Area Under the Plasma Concentration-time Curve Over a Dosing Interval (12 Hours) (AUCtau) of Padsevonil Metabolites (1 and 2) for Multiple Doses | Metabolite 1 | 2625 hours*ng/mL | Geometric Coefficient of Variation 46.1 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Area Under the Plasma Concentration-time Curve Over a Dosing Interval (12 Hours) (AUCtau) of Padsevonil Metabolites (1 and 2) for Multiple Doses | Metabolite 2 | 799.0 hours*ng/mL | Geometric Coefficient of Variation 38.5 |
Secondary
Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses
Ae: The cumulative amount of padsevonil and its metabolites (1, 2, and 3) excreted into the urine for multiple doses. Ae was expressed in milligrams (mg).
Time frame: Urine samples were taken 0 to 12 hours, 12 to 24 hours,and 24 to 48 hours post last PSL dose during Treatment Period 1 and 2; 0 to 12 hours, 12 to 24 hours, 24 to 48 hours, 48 to 72 hours, and 72 to 96 hours post last dose of PSL during Treatment Period 3
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, 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. As per the planned analysis, data was summarized by treatment periods. Here, number of participants were included who were evaluable for the assessment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Padsevonil (Period 1) (PK-PPS) | Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses | Padsevonil | 0.05825 milligrams | Geometric Coefficient of Variation 57.2 |
| Padsevonil (Period 1) (PK-PPS) | Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses | Metabolite 1 | 0.6188 milligrams | Geometric Coefficient of Variation 45.3 |
| Padsevonil (Period 1) (PK-PPS) | Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses | Metabolite 2 | 15.03 milligrams | Geometric Coefficient of Variation 45.8 |
| Padsevonil (Period 1) (PK-PPS) | Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses | Metabolite 3 | 70.83 milligrams | Geometric Coefficient of Variation 30.7 |
| Padsevonil (Period 2) (PK-PPS) | Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses | Metabolite 3 | 65.30 milligrams | Geometric Coefficient of Variation 34 |
| Padsevonil (Period 2) (PK-PPS) | Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses | Padsevonil | 0.05741 milligrams | Geometric Coefficient of Variation 58.6 |
| Padsevonil (Period 2) (PK-PPS) | Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses | Metabolite 2 | 15.07 milligrams | Geometric Coefficient of Variation 46.9 |
| Padsevonil (Period 2) (PK-PPS) | Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses | Metabolite 1 | 0.6657 milligrams | Geometric Coefficient of Variation 45 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses | Metabolite 3 | 81.36 milligrams | Geometric Coefficient of Variation 30.7 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses | Metabolite 1 | 0.8797 milligrams | Geometric Coefficient of Variation 46.8 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses | Metabolite 2 | 13.67 milligrams | Geometric Coefficient of Variation 41.4 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses | Padsevonil | 0.1274 milligrams | Geometric Coefficient of Variation 62.3 |
Secondary
Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose
Ae: The cumulative amount of padsevonil and its metabolites (1, 2, and 3) excreted into the urine for single dose. Ae was expressed in milligrams (mg).
Time frame: Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment Period
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, 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. As per the planned analysis, data was summarized by treatment periods.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Padsevonil (Period 1) (PK-PPS) | Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose | Padsevonil | 0.03914 milligrams | Geometric Coefficient of Variation 57.5 |
| Padsevonil (Period 1) (PK-PPS) | Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose | Metabolite 1 | 0.2101 milligrams | Geometric Coefficient of Variation 43.2 |
| Padsevonil (Period 1) (PK-PPS) | Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose | Metabolite 2 | 10.53 milligrams | Geometric Coefficient of Variation 42.5 |
| Padsevonil (Period 1) (PK-PPS) | Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose | Metabolite 3 | 29.11 milligrams | Geometric Coefficient of Variation 39.3 |
| Padsevonil (Period 2) (PK-PPS) | Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose | Metabolite 3 | 27.44 milligrams | Geometric Coefficient of Variation 42.3 |
| Padsevonil (Period 2) (PK-PPS) | Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose | Padsevonil | 0.04054 milligrams | Geometric Coefficient of Variation 75 |
| Padsevonil (Period 2) (PK-PPS) | Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose | Metabolite 2 | 9.423 milligrams | Geometric Coefficient of Variation 45.5 |
| Padsevonil (Period 2) (PK-PPS) | Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose | Metabolite 1 | 0.2333 milligrams | Geometric Coefficient of Variation 52.1 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose | Metabolite 3 | 26.09 milligrams | Geometric Coefficient of Variation 40.6 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose | Metabolite 1 | 0.2309 milligrams | Geometric Coefficient of Variation 45.8 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose | Metabolite 2 | 9.764 milligrams | Geometric Coefficient of Variation 53.1 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Cumulative Amount (Ae) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose | Padsevonil | 0.04987 milligrams | Geometric Coefficient of Variation 74.6 |
Secondary
Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Multiple Doses
CLform: The formation clearance of padsevonil metabolites (1, 2, and 3) in the urine for multiple doses. CLform was expressed in milliliters per hour (mL/hour).
Time frame: Urine samples were taken 0 to 12 hours, 12 to 24 hours,and 24 to 48 hours post last PSL dose during Treatment Period 1 and 2; 0 to 12 hours, 12 to 24 hours, 24 to 48 hours, 48 to 72 hours, and 72 to 96 hours post last dose of PSL during Treatment Period 3
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, 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. As per the planned analysis, data was summarized by treatment periods. Here, number of participants were included who were evaluable for the assessment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Padsevonil (Period 1) (PK-PPS) | Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Multiple Doses | Metabolite 2 | 7331 mL/h | Geometric Coefficient of Variation 80.5 |
| Padsevonil (Period 1) (PK-PPS) | Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Multiple Doses | Metabolite 1 | 295.3 mL/h | Geometric Coefficient of Variation 63.2 |
| Padsevonil (Period 1) (PK-PPS) | Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Multiple Doses | Metabolite 3 | 25150 mL/h | Geometric Coefficient of Variation 44.7 |
| Padsevonil (Period 2) (PK-PPS) | Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Multiple Doses | Metabolite 2 | 6622 mL/h | Geometric Coefficient of Variation 90.9 |
| Padsevonil (Period 2) (PK-PPS) | Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Multiple Doses | Metabolite 1 | 294.6 mL/h | Geometric Coefficient of Variation 58.9 |
| Padsevonil (Period 2) (PK-PPS) | Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Multiple Doses | Metabolite 3 | 20890 mL/h | Geometric Coefficient of Variation 48.1 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Multiple Doses | Metabolite 1 | 166.4 mL/h | Geometric Coefficient of Variation 63.8 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Multiple Doses | Metabolite 3 | 11170 mL/h | Geometric Coefficient of Variation 58.7 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Multiple Doses | Metabolite 2 | 2593 mL/h | Geometric Coefficient of Variation 93.9 |
Secondary
Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Single Dose
CLform: The formation clearance of padsevonil metabolites (1, 2, and 3) in the urine for single dose. CLform was expressed in milliliters per hour (mL/hour).
Time frame: Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment Period
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, 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. As per the planned analysis, data was summarized by treatment periods.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Padsevonil (Period 1) (PK-PPS) | Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Single Dose | Metabolite 3 | 14820 mL/hour | Geometric Coefficient of Variation 60.5 |
| Padsevonil (Period 1) (PK-PPS) | Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Single Dose | Metabolite 2 | 7365 mL/hour | Geometric Coefficient of Variation 80.2 |
| Padsevonil (Period 1) (PK-PPS) | Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Single Dose | Metabolite 1 | 151.9 mL/hour | Geometric Coefficient of Variation 67.3 |
| Padsevonil (Period 2) (PK-PPS) | Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Single Dose | Metabolite 2 | 5994 mL/hour | Geometric Coefficient of Variation 87.8 |
| Padsevonil (Period 2) (PK-PPS) | Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Single Dose | Metabolite 1 | 153.4 mL/hour | Geometric Coefficient of Variation 75.8 |
| Padsevonil (Period 2) (PK-PPS) | Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Single Dose | Metabolite 3 | 12700 mL/hour | Geometric Coefficient of Variation 59.9 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Single Dose | Metabolite 1 | 92.59 mL/hour | Geometric Coefficient of Variation 80.8 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Single Dose | Metabolite 3 | 7367 mL/hour | Geometric Coefficient of Variation 72 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Formation Clearance (CLform) of Padsevonil Metabolites (1, 2, and 3) in the Urine for Single Dose | Metabolite 2 | 3788 mL/hour | Geometric Coefficient of Variation 107.5 |
Secondary
Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses
fe: The fraction of padsevonil and its metabolites (1, 2, and 3) excreted into the urine for multiple doses. fe was expressed in percentage (%).
Time frame: Urine samples were taken 0 to 12 hours, 12 to 24 hours,and 24 to 48 hours post last PSL dose during Treatment Period 1 and 2; 0 to 12 hours, 12 to 24 hours, 24 to 48 hours, 48 to 72 hours, and 72 to 96 hours post last dose of PSL during Treatment Period 3
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, 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. As per the planned analysis, data was summarized by treatment periods. Here, number of participants were included who were evaluable for the assessment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Padsevonil (Period 1) (PK-PPS) | Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses | Padsevonil | 0.05825 percentage excreted | Geometric Coefficient of Variation 57.2 |
| Padsevonil (Period 1) (PK-PPS) | Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses | Metabolite 1 | 0.6049 percentage excreted | Geometric Coefficient of Variation 45.6 |
| Padsevonil (Period 1) (PK-PPS) | Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses | Metabolite 2 | 15.02 percentage excreted | Geometric Coefficient of Variation 45.8 |
| Padsevonil (Period 1) (PK-PPS) | Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses | Metabolite 3 | 51.52 percentage excreted | Geometric Coefficient of Variation 30.7 |
| Padsevonil (Period 2) (PK-PPS) | Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses | Metabolite 3 | 47.50 percentage excreted | Geometric Coefficient of Variation 34 |
| Padsevonil (Period 2) (PK-PPS) | Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses | Padsevonil | 0.05741 percentage excreted | Geometric Coefficient of Variation 58.6 |
| Padsevonil (Period 2) (PK-PPS) | Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses | Metabolite 2 | 15.06 percentage excreted | Geometric Coefficient of Variation 46.9 |
| Padsevonil (Period 2) (PK-PPS) | Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses | Metabolite 1 | 0.6700 percentage excreted | Geometric Coefficient of Variation 44.6 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses | Metabolite 3 | 56.69 percentage excreted | Geometric Coefficient of Variation 38 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses | Metabolite 1 | 0.8443 percentage excreted | Geometric Coefficient of Variation 45.3 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses | Metabolite 2 | 13.15 percentage excreted | Geometric Coefficient of Variation 37.9 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Multiple Doses | Padsevonil | 0.1274 percentage excreted | Geometric Coefficient of Variation 62.3 |
Secondary
Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose
fe: The fraction of padsevonil or metabolites (1, 2, and 3) excreted into the urine for single dose. fe was expressed in percentage (%).
Time frame: Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment Period
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, 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. As per the planned analysis, data was summarized by treatment periods.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Padsevonil (Period 1) (PK-PPS) | Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose | Padsevonil | 0.03914 percentage excreted | Geometric Coefficient of Variation 57.5 |
| Padsevonil (Period 1) (PK-PPS) | Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose | Metabolite 1 | 0.2170 percentage excreted | Geometric Coefficient of Variation 43.2 |
| Padsevonil (Period 1) (PK-PPS) | Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose | Metabolite 2 | 10.52 percentage excreted | Geometric Coefficient of Variation 42.5 |
| Padsevonil (Period 1) (PK-PPS) | Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose | Metabolite 3 | 21.17 percentage excreted | Geometric Coefficient of Variation 39.3 |
| Padsevonil (Period 2) (PK-PPS) | Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose | Metabolite 3 | 19.96 percentage excreted | Geometric Coefficient of Variation 42.3 |
| Padsevonil (Period 2) (PK-PPS) | Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose | Padsevonil | 0.04054 percentage excreted | Geometric Coefficient of Variation 75 |
| Padsevonil (Period 2) (PK-PPS) | Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose | Metabolite 2 | 9.419 percentage excreted | Geometric Coefficient of Variation 45.5 |
| Padsevonil (Period 2) (PK-PPS) | Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose | Metabolite 1 | 0.2410 percentage excreted | Geometric Coefficient of Variation 52.1 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose | Metabolite 3 | 18.98 percentage excreted | Geometric Coefficient of Variation 40.6 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose | Metabolite 1 | 0.2385 percentage excreted | Geometric Coefficient of Variation 45.8 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose | Metabolite 2 | 9.760 percentage excreted | Geometric Coefficient of Variation 53.1 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Fraction (fe) of Padsevonil and Metabolites (1, 2, and 3) Excreted Into the Urine for Single Dose | Padsevonil | 0.04987 percentage excreted | Geometric Coefficient of Variation 74.6 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Padsevonil Metabolites (1 and 2) for Single Dose
Cmax: The maximum plasma concentration of padsevonil metabolites (1 and 2) for single dose. Cmax was expressed in nanograms per milliliter (ng/mL).
Time frame: Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, 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. As per the planned analysis, data was summarized by treatment periods.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Padsevonil (Period 1) (PK-PPS) | Maximum Observed Plasma Concentration (Cmax) of Padsevonil Metabolites (1 and 2) for Single Dose | Metabolite 1 | 166.6 ng/mL | Geometric Coefficient of Variation 29.1 |
| Padsevonil (Period 1) (PK-PPS) | Maximum Observed Plasma Concentration (Cmax) of Padsevonil Metabolites (1 and 2) for Single Dose | Metabolite 2 | 110.5 ng/mL | Geometric Coefficient of Variation 33.4 |
| Padsevonil (Period 2) (PK-PPS) | Maximum Observed Plasma Concentration (Cmax) of Padsevonil Metabolites (1 and 2) for Single Dose | Metabolite 1 | 158.7 ng/mL | Geometric Coefficient of Variation 34.5 |
| Padsevonil (Period 2) (PK-PPS) | Maximum Observed Plasma Concentration (Cmax) of Padsevonil Metabolites (1 and 2) for Single Dose | Metabolite 2 | 94.47 ng/mL | Geometric Coefficient of Variation 44.2 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Maximum Observed Plasma Concentration (Cmax) of Padsevonil Metabolites (1 and 2) for Single Dose | Metabolite 1 | 189.5 ng/mL | Geometric Coefficient of Variation 29.8 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Maximum Observed Plasma Concentration (Cmax) of Padsevonil Metabolites (1 and 2) for Single Dose | Metabolite 2 | 108.3 ng/mL | Geometric Coefficient of Variation 49.6 |
Secondary
Maximum Observed Steady-state Plasma Concentration (Cmax, ss) of Padsevonil Metabolites (1 and 2) for Multiple Doses
Cmax, ss: The maximum observed steady-state plasma concentration of padsevonil metabolites (1 and 2) for multiple doses. Cmax, ss was expressed in nanograms per millilitre (ng/mL).
Time frame: Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, 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. As per the planned analysis, data was summarized by treatment periods. Here, number of participants were included who were evaluable for the assessment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Padsevonil (Period 1) (PK-PPS) | Maximum Observed Steady-state Plasma Concentration (Cmax, ss) of Padsevonil Metabolites (1 and 2) for Multiple Doses | Metabolite 1 | 232.3 ng/mL | Geometric Coefficient of Variation 27.1 |
| Padsevonil (Period 1) (PK-PPS) | Maximum Observed Steady-state Plasma Concentration (Cmax, ss) of Padsevonil Metabolites (1 and 2) for Multiple Doses | Metabolite 2 | 118.6 ng/mL | Geometric Coefficient of Variation 29.3 |
| Padsevonil (Period 2) (PK-PPS) | Maximum Observed Steady-state Plasma Concentration (Cmax, ss) of Padsevonil Metabolites (1 and 2) for Multiple Doses | Metabolite 1 | 258.3 ng/mL | Geometric Coefficient of Variation 32.3 |
| Padsevonil (Period 2) (PK-PPS) | Maximum Observed Steady-state Plasma Concentration (Cmax, ss) of Padsevonil Metabolites (1 and 2) for Multiple Doses | Metabolite 2 | 113.3 ng/mL | Geometric Coefficient of Variation 36.8 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Maximum Observed Steady-state Plasma Concentration (Cmax, ss) of Padsevonil Metabolites (1 and 2) for Multiple Doses | Metabolite 1 | 310.3 ng/mL | Geometric Coefficient of Variation 46 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Maximum Observed Steady-state Plasma Concentration (Cmax, ss) of Padsevonil Metabolites (1 and 2) for Multiple Doses | Metabolite 2 | 101.8 ng/mL | Geometric Coefficient of Variation 37.1 |
Secondary
Metabolite-to-parent Ratio for AUC(0-12) of Padsevonil Metabolites (1 and 2) in Plasma
Metabolite-to-parent ratio calculated as: AUC(0-12)of padsevonil metabolites (1 and 2) divided by AUC(0-12) of padsevonil following a single dose in plasma. Metabolite-to-parent ratio for AUC(0-12) was expressed as ratio.
Time frame: Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, 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. As per the planned analysis, data was summarized by treatment periods.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Padsevonil (Period 1) (PK-PPS) | Metabolite-to-parent Ratio for AUC(0-12) of Padsevonil Metabolites (1 and 2) in Plasma | Metabolite 1 | 0.5799 ratio | Geometric Coefficient of Variation 39.7 |
| Padsevonil (Period 1) (PK-PPS) | Metabolite-to-parent Ratio for AUC(0-12) of Padsevonil Metabolites (1 and 2) in Plasma | Metabolite 2 | 0.4176 ratio | Geometric Coefficient of Variation 70 |
| Padsevonil (Period 2) (PK-PPS) | Metabolite-to-parent Ratio for AUC(0-12) of Padsevonil Metabolites (1 and 2) in Plasma | Metabolite 1 | 0.5246 ratio | Geometric Coefficient of Variation 42.8 |
| Padsevonil (Period 2) (PK-PPS) | Metabolite-to-parent Ratio for AUC(0-12) of Padsevonil Metabolites (1 and 2) in Plasma | Metabolite 2 | 0.3401 ratio | Geometric Coefficient of Variation 78.7 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Metabolite-to-parent Ratio for AUC(0-12) of Padsevonil Metabolites (1 and 2) in Plasma | Metabolite 1 | 0.3515 ratio | Geometric Coefficient of Variation 48.9 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Metabolite-to-parent Ratio for AUC(0-12) of Padsevonil Metabolites (1 and 2) in Plasma | Metabolite 2 | 0.2327 ratio | Geometric Coefficient of Variation 97.1 |
Secondary
Metabolite-to-parent Ratio for AUCtau of Padsevonil Metabolites (1 and 2) in Plasma
Metabolite-to-parent ratio calculated as: AUCtau of padsevonil metabolites (1 and 2) divided by AUCtau of padsevonil following multiple dosing in plasma. Metabolite-to-parent ratio for AUCtau was expressed as ratio.
Time frame: Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, 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. As per the planned analysis, data was summarized by treatment periods. Here, number of participants were included who were evaluable for the assessment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Padsevonil (Period 1) (PK-PPS) | Metabolite-to-parent Ratio for AUCtau of Padsevonil Metabolites (1 and 2) in Plasma | Metabolite 1 | 0.8533 ratio | Geometric Coefficient of Variation 34.9 |
| Padsevonil (Period 1) (PK-PPS) | Metabolite-to-parent Ratio for AUCtau of Padsevonil Metabolites (1 and 2) in Plasma | Metabolite 2 | 0.3783 ratio | Geometric Coefficient of Variation 63.4 |
| Padsevonil (Period 2) (PK-PPS) | Metabolite-to-parent Ratio for AUCtau of Padsevonil Metabolites (1 and 2) in Plasma | Metabolite 1 | 0.8766 ratio | Geometric Coefficient of Variation 38.7 |
| Padsevonil (Period 2) (PK-PPS) | Metabolite-to-parent Ratio for AUCtau of Padsevonil Metabolites (1 and 2) in Plasma | Metabolite 2 | 0.3576 ratio | Geometric Coefficient of Variation 75.5 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Metabolite-to-parent Ratio for AUCtau of Padsevonil Metabolites (1 and 2) in Plasma | Metabolite 1 | 0.5174 ratio | Geometric Coefficient of Variation 48.2 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Metabolite-to-parent Ratio for AUCtau of Padsevonil Metabolites (1 and 2) in Plasma | Metabolite 2 | 0.1575 ratio | Geometric Coefficient of Variation 88.5 |
Secondary
Metabolite-to-parent Ratio for Cmax of Padsevonil Metabolites (1 and 2) in Plasma
Metabolite-to-parent ratio calculated as: Cmax of padsevonil metabolites (1 and 2) divided by Cmax of padsevonil following a single dose in plasma. Metabolite-to-parent ratio for Cmax was expressed as ratio.
Time frame: Blood samples were taken at specific time points from pre-dose to 12 hours post dose of Padsevonil for each Treatment Period
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, 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. As per the planned analysis, data was summarized by treatment periods.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Padsevonil (Period 1) (PK-PPS) | Metabolite-to-parent Ratio for Cmax of Padsevonil Metabolites (1 and 2) in Plasma | Metabolite 1 | 0.4544 ratio | Geometric Coefficient of Variation 40.6 |
| Padsevonil (Period 1) (PK-PPS) | Metabolite-to-parent Ratio for Cmax of Padsevonil Metabolites (1 and 2) in Plasma | Metabolite 2 | 0.3015 ratio | Geometric Coefficient of Variation 66.8 |
| Padsevonil (Period 2) (PK-PPS) | Metabolite-to-parent Ratio for Cmax of Padsevonil Metabolites (1 and 2) in Plasma | Metabolite 1 | 0.4119 ratio | Geometric Coefficient of Variation 45.5 |
| Padsevonil (Period 2) (PK-PPS) | Metabolite-to-parent Ratio for Cmax of Padsevonil Metabolites (1 and 2) in Plasma | Metabolite 2 | 0.2452 ratio | Geometric Coefficient of Variation 77.1 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Metabolite-to-parent Ratio for Cmax of Padsevonil Metabolites (1 and 2) in Plasma | Metabolite 1 | 0.2717 ratio | Geometric Coefficient of Variation 49.5 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Metabolite-to-parent Ratio for Cmax of Padsevonil Metabolites (1 and 2) in Plasma | Metabolite 2 | 0.1552 ratio | Geometric Coefficient of Variation 94.3 |
Secondary
Minimum Observed Plasma Concentration (Cmin) of Padsevonil for Single Dose
Cmin: The minimum observed plasma concentration of padsevonil for single dose. Cmin was expressed in nanograms per millilitre (ng/mL).
Time frame: Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, 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. As per the planned analysis, data was summarized by treatment periods.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Padsevonil (Period 1) (PK-PPS) | Minimum Observed Plasma Concentration (Cmin) of Padsevonil for Single Dose | 2.857 ng/mL | Geometric Coefficient of Variation 100.9 |
| Padsevonil (Period 2) (PK-PPS) | Minimum Observed Plasma Concentration (Cmin) of Padsevonil for Single Dose | 5.643 ng/mL | Geometric Coefficient of Variation 147.8 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Minimum Observed Plasma Concentration (Cmin) of Padsevonil for Single Dose | 4.286 ng/mL | Geometric Coefficient of Variation 172.5 |
Secondary
Percentage of Participants Experiencing Treatment-Emergent Non-serious Adverse Events (AEs) During the Study
Treatment-emergent Adverse Events (TEAEs) were defined as those events which started on or after the date of first dose of UP0057 IMP, or events in which severity worsened on or after the date of first dose of UP0057 study medication.
Time frame: From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to 48 days )
Population: The FAS consisted of all study participants who have signed the Informed Consent form ICF and received IMP. The analysis of this outcome measure was performed according to the treatment the participants actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Padsevonil (Period 1) (PK-PPS) | Percentage of Participants Experiencing Treatment-Emergent Non-serious Adverse Events (AEs) During the Study | 100 percentage of participants |
| Padsevonil (Period 2) (PK-PPS) | Percentage of Participants Experiencing Treatment-Emergent Non-serious Adverse Events (AEs) During the Study | 11.1 percentage of participants |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Percentage of Participants Experiencing Treatment-Emergent Non-serious Adverse Events (AEs) During the Study | 96.3 percentage of participants |
| Erythromycin (Period 3c) (FAS) | Percentage of Participants Experiencing Treatment-Emergent Non-serious Adverse Events (AEs) During the Study | 19.2 percentage of participants |
Secondary
Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs) During the Study
An SAE is any untoward medical occurrence that at any dose: * Results in death * Is life-threatening * Requires in patient hospitalization or prolongation of existing hospitalization * Is a congenital anomaly or birth defect * Is an infection that requires treatment parenteral antibiotics * Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above.
Time frame: From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to 48 days )
Population: The Full Analysis Set (FAS) consisted of all study participants who have signed the Informed Consent form (ICF) and received investigational medicinal product (IMP). The analysis of this outcome measure was performed according to the treatment the participants actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Padsevonil (Period 1) (PK-PPS) | Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs) During the Study | 0 percentage of participants |
| Padsevonil (Period 2) (PK-PPS) | Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs) During the Study | 0 percentage of participants |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs) During the Study | 0 percentage of participants |
| Erythromycin (Period 3c) (FAS) | Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs) During the Study | 0 percentage of participants |
Secondary
Predose Observed Plasma Concentration (Ctrough) of Padsevonil for Multiple Doses
Ctrough: The predose observed plasma concentration of padsevonil for multiple doses. Ctrough was expressed in nanograms per millilitre (ng/mL).
Time frame: Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, 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. As per the planned analysis, data was summarized by treatment periods. Here, number of participants were included who were evaluable for the assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Padsevonil (Period 1) (PK-PPS) | Predose Observed Plasma Concentration (Ctrough) of Padsevonil for Multiple Doses | 57.03 ng/mL | Geometric Coefficient of Variation 69 |
| Padsevonil (Period 2) (PK-PPS) | Predose Observed Plasma Concentration (Ctrough) of Padsevonil for Multiple Doses | 68.57 ng/mL | Geometric Coefficient of Variation 85.1 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Predose Observed Plasma Concentration (Ctrough) of Padsevonil for Multiple Doses | 182.6 ng/mL | Geometric Coefficient of Variation 95.5 |
Secondary
Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Multiple Doses in Urine
CLr: The renal clearance of padsevonil and its metabolites (1 and 2) for multiple doses in urine. CLr was expressed in milliliters per hour (mL/hour).
Time frame: Urine samples were taken 0 to 12 hours, 12 to 24 hours,and 24 to 48 hours post last PSL dose during Treatment Period 1 and 2; 0 to 12 hours, 12 to 24 hours, 24 to 48 hours, 48 to 72 hours, and 72 to 96 hours post last dose of PSL during Treatment Period 3
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, 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. As per the planned analysis, data was summarized by treatment periods. Here, number of participants were included who were evaluable for the assessment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Padsevonil (Period 1) (PK-PPS) | Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Multiple Doses in Urine | Metabolite 1 | 335.0 mL/hours | Geometric Coefficient of Variation 50.2 |
| Padsevonil (Period 1) (PK-PPS) | Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Multiple Doses in Urine | Padsevonil | 28.43 mL/hours | Geometric Coefficient of Variation 58 |
| Padsevonil (Period 1) (PK-PPS) | Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Multiple Doses in Urine | Metabolite 2 | 19390 mL/hours | Geometric Coefficient of Variation 24.9 |
| Padsevonil (Period 2) (PK-PPS) | Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Multiple Doses in Urine | Metabolite 1 | 325.4 mL/hours | Geometric Coefficient of Variation 40.8 |
| Padsevonil (Period 2) (PK-PPS) | Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Multiple Doses in Urine | Padsevonil | 25.24 mL/hours | Geometric Coefficient of Variation 59.7 |
| Padsevonil (Period 2) (PK-PPS) | Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Multiple Doses in Urine | Metabolite 2 | 18530 mL/hours | Geometric Coefficient of Variation 20.7 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Multiple Doses in Urine | Padsevonil | 25.12 mL/hours | Geometric Coefficient of Variation 56.1 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Multiple Doses in Urine | Metabolite 2 | 16470 mL/hours | Geometric Coefficient of Variation 27.6 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Multiple Doses in Urine | Metabolite 1 | 311.4 mL/hours | Geometric Coefficient of Variation 51.7 |
Secondary
Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Single Dose in Urine
CLr: The renal clearance of padsevonil and its metabolites (1 and 2) for single dose in urine. CLr was expressed in milliliters per hour (mL/hour).
Time frame: Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment Period
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, 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. As per the planned analysis, data was summarized by treatment periods.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Padsevonil (Period 1) (PK-PPS) | Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Single Dose in Urine | Metabolite 1 | 253.7 mL/hour | Geometric Coefficient of Variation 47.8 |
| Padsevonil (Period 1) (PK-PPS) | Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Single Dose in Urine | Padsevonil | 27.40 mL/hour | Geometric Coefficient of Variation 54.3 |
| Padsevonil (Period 1) (PK-PPS) | Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Single Dose in Urine | Metabolite 2 | 17640 mL/hour | Geometric Coefficient of Variation 19.6 |
| Padsevonil (Period 2) (PK-PPS) | Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Single Dose in Urine | Metabolite 1 | 283.0 mL/hour | Geometric Coefficient of Variation 60.1 |
| Padsevonil (Period 2) (PK-PPS) | Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Single Dose in Urine | Padsevonil | 25.80 mL/hour | Geometric Coefficient of Variation 73 |
| Padsevonil (Period 2) (PK-PPS) | Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Single Dose in Urine | Metabolite 2 | 17630 mL/hour | Geometric Coefficient of Variation 21.2 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Single Dose in Urine | Padsevonil | 19.36 mL/hour | Geometric Coefficient of Variation 60.2 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Single Dose in Urine | Metabolite 2 | 16290 mL/hour | Geometric Coefficient of Variation 20.7 |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Renal Clearance (CLr) of Padsevonil and Metabolites (1 and 2) for Single Dose in Urine | Metabolite 1 | 255.0 mL/hour | Geometric Coefficient of Variation 53.9 |
Secondary
Time of Maximum Plasma Concentration (Tmax) of Padsevonil for Multiple Doses
Tmax: The time of maximum plasma concentration of padsevonil for multiple doses. Tmax was expressed in hours (h).
Time frame: Blood samples were taken at specific time points from pre-dose to 72 hours post last dose of Padsevonil (PSL) (Treatment Period 1 and 2); from pre-dose to 120 hours post last dose of PSL (Treatment Period 3)
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, 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. As per the planned analysis, data was summarized by treatment periods. Here, number of participants were included who were evaluable for the assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Padsevonil (Period 1) (PK-PPS) | Time of Maximum Plasma Concentration (Tmax) of Padsevonil for Multiple Doses | 1.750 hours |
| Padsevonil (Period 2) (PK-PPS) | Time of Maximum Plasma Concentration (Tmax) of Padsevonil for Multiple Doses | 1.500 hours |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Time of Maximum Plasma Concentration (Tmax) of Padsevonil for Multiple Doses | 2.000 hours |
Secondary
Time of Maximum Plasma Concentration (Tmax) of Padsevonil for Single Dose
Tmax: The time of maximum plasma concentration of padsevonil for single dose. Tmax was expressed in hours (h).
Time frame: Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the FAS, 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. As per the planned analysis, data was summarized by treatment periods.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Padsevonil (Period 1) (PK-PPS) | Time of Maximum Plasma Concentration (Tmax) of Padsevonil for Single Dose | 3.000 hours |
| Padsevonil (Period 2) (PK-PPS) | Time of Maximum Plasma Concentration (Tmax) of Padsevonil for Single Dose | 1.500 hours |
| Padsevonil and Erythromycin (Period 3b) (PK-PPS) | Time of Maximum Plasma Concentration (Tmax) of Padsevonil for Single Dose | 1.500 hours |