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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-004694-13 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Padsevonil and Erythromycin | Experimental | Treatment Period 1 (Day 1 to Day 11):
Treatment Period 2 (Day 12 to 22):
Treatment Period 3 (Day 23 to Day 38):
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Padsevonil (UCB0942) | Drug |
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| Measure | Description | Time Frame |
|---|---|---|
| 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). | 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 |
| 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). | 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 |
| 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). | 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) |
| 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). | 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| UCB Cares | 001 844 599 2273 (UCB) | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Up0057 001 | London | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38932723 | Derived | Chanteux H, MacPherson M, Kramer H, Otoul C, Okagaki T, Rospo C, De Bruyn S, Watling M, Bani M, Sciberras D. Overview of preclinical and clinical studies investigating pharmacokinetics and drug-drug interactions of padsevonil. Expert Opin Drug Metab Toxicol. 2024 Aug;20(8):841-855. doi: 10.1080/17425255.2024.2373108. Epub 2024 Jul 9. |
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Participant Flow refers to the Full Analysis Set (FAS).
The study started to enroll patients in March 2018 and concluded in August 2018.
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| ID | Title | Description |
|---|---|---|
| FG000 | Padsevonil and/or Erythromycin | The study participants received treatment as follows: Treatment Period 1: From Day 1 to Day 11:
Treatment Period 2: From Day 12 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:
Treatment Period 3c: - Erythromycin 500 mg bid on Day 34 to Day 37. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Padsevonil (Period 1) |
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| Padsevonil (Period 2) |
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| Erythromycin (Period 3a) |
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| Padsevonil and Erythromycin (Period 3b) |
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| Erythromycin (Period 3c) |
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Baseline Characteristics refer to the Full Analysis Set (FAS) which consisted of all study participants who have signed the Informed Consent Form (ICF) and received the investigational medicinal product (IMP).
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| ID | Title | Description |
|---|---|---|
| BG000 | Padsevonil and/or Erythromycin | The study participants received treatment as follows: Treatment Period 1: From Day 1 to Day 11:
Treatment Period 2: From Day 12 to Day 22:
Treatment Period 3a: -Erythromycin 500 mg bid on Day 23 to Day 25. Treatment Period 3b:
Treatment Period 3c: - Erythromycin 500 mg bid on Day 34 to Day 37. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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 |
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From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to Day 48)
FAS consisted of all study participants who have signed the ICF and received the IMP. The analysis was performed according to the treatment the participants actually received.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Padsevonil (Period 1+2) (FAS) | Treatment Period 1 (Day 1 to Day 11):
Treatment Period 2 (Day 12 to 22):
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Medical device site reaction | General disorders | MedDRA21.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| UCB | Cares | +1844 599 | 2273 | UCBCares@ucb.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 26, 2018 | Apr 23, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 15, 2018 | Apr 23, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| C000708857 | padsevonil |
| D004917 | Erythromycin |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D061065 | Polyketides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
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| Erythromycin | Drug |
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| 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). |
| Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period |
| 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). | 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) |
| 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). | 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) |
| 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). | 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) |
| 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). | 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) |
| 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). | 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) |
| 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). | Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period |
| 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). | Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period |
| 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). | 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) |
| 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). | 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 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. | 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 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. | 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 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. | 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) |
| 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). | Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment Period |
| 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). | 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 |
| 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). | Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment Period |
| 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). | 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 |
| 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 (%). | Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment Period |
| 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 (%). | 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 |
| 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). | Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment Period |
| 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). | 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 |
| Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs) During the Study | An SAE is any untoward medical occurrence that at any dose:
| From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to 48 days ) |
| 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. | From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to 48 days ) |
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| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| OG001 | Padsevonil (Period 2) (PK-PPS) | The study participants, of a single cohort, received Padsevonil during the Treatment Period 2 as follows: From Day 12 to Day 22:
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| OG002 | Padsevonil and Erythromycin (Period 3b) (PK-PPS) | The study participants, of a single cohort, received Padsevonil and Erythromycin during the second part of the Treatment Period 3b as follows:
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| 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours*ng/mL | 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 |
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| 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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) |
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| 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours*ng/mL | 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) |
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| 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). | 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. | Posted | Median | Full Range | hours | Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period |
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| 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period |
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| 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). | 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. | Posted | Median | Full Range | hours | 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) |
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| 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). | 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. | Posted | Median | Full Range | hours | 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) |
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| 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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) |
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| 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/hour | 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) |
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| 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | l\hour | 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) |
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| 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period |
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| 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours*ng/mL | Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period |
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| 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours*ng/mL | 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) |
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| 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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) |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Blood samples were taken at specific time points from pre-dose to 12 hours post dose of Padsevonil for each Treatment Period |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Blood samples were taken at specific time points from pre-dose to 12 hours post first dose of Padsevonil for each Treatment Period |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | 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) |
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| 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/hour | Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment Period |
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| 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/hours | 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 |
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| 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | milligrams | Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment Period |
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| 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | milligrams | 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 |
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| 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 (%). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | percentage excreted | Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment Period |
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| 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 (%). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | percentage excreted | 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 |
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| 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/hour | Urine samples were taken 0 to 12 hours post first dose of Padsevonil during each Treatment Period |
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| 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/h | 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 |
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| 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:
| 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. | Posted | Number | percentage of participants | From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to 48 days ) |
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| 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. | 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. | Posted | Number | percentage of participants | From beginning of the first Treatment Period (Day 1) to the Safety Follow-up Visit (up to 48 days ) |
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| 0 |
| 28 |
| 0 |
| 28 |
| 28 |
| 28 |
| EG001 | Erythromycin (Period 3a) (FAS) | Study participants received Erythromycin in Treatment Period 3a as follows: 500 mg bid on Day 23 to Day 25. Study participants formed the FAS. | 0 | 27 | 0 | 27 | 0 | 27 |
| EG002 | Padsevonil and Erythromycin (Period 3b) (FAS) | Study participants received Padsevonil and Erythromycin in Treatment Period 3b as follows:
| 0 | 27 | 0 | 27 | 25 | 27 |
| EG003 | Erythromycin (Period 3c) (FAS) | Study participants received Erythromycin in Treatment Period 3c as follows: 500 mg bid on Day 34 to Day 37. Study participants formed the FAS. | 0 | 26 | 0 | 26 | 2 | 26 |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA21.0 | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA21.0 | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA21.0 | Non-systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA21.0 | Non-systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA21.0 | Non-systematic Assessment |
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| Depressed mood | Psychiatric disorders | MedDRA21.0 | Non-systematic Assessment |
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| Euphoric mood | Psychiatric disorders | MedDRA21.0 | Non-systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA21.0 | Non-systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | MedDRA21.0 | Non-systematic Assessment |
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Not provided
| ANOVA |
| AUC Estimate Ratio |
| 1.64 |
| 2-Sided |
| 90 |
| 1.36 |
| 1.97 |
| Other |
| ANOVA |
| Cmax,ss Estimate Ratio |
| 2.13 |
| 2-Sided |
| 90 |
| 1.78 |
| 2.56 |
| Other |
| ANOVA |
| AUCtau Estimate Ratio |
| 2.23 |
| 2-Sided |
| 90 |
| 1.82 |
| 2.73 |
| Other |
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| Metabolite 2 |
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| Metabolite 2 |
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| Metabolite 2 |
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| Metabolite 3 |
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| Metabolite 2 |
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| Metabolite 3 |
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| Metabolite 2 |
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| Metabolite 3 |
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| Metabolite 2 |
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| Metabolite 3 |
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| Metabolite 3 |
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| Metabolite 3 |
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