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| Name | Class |
|---|---|
| Parexel | INDUSTRY |
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This is a human pharmacology, single-dose study to investigate the pharmacokinetics of orally administered Levetiracetam (LEV) in Japanese subjects with normal renal function and in Japanese subjects with various degrees of impaired renal function.
The primary objective of this study is to evaluate the plasma and urine PK of Levetiracetam (ucb L059) and its metabolite (ucb L057) after a single dose of LEV 250 mg or LEV 500 mg in Japanese subjects with normal renal function and in Japanese subjects with various degrees of renal impairment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A: Normal renal function | Experimental | Subjects who have normal renal function (CLcr >80 mL/min/1.73 m^2). Subjects will be orally administered Levetiracetam (LEV) 500 mg once. After LEV administration, safety assessments and blood and urine samplings will be taken through to Day 4 during the Treatment Period, and safety follow-up assessments will be performed on Day 8 according to the schedule of study assessments.
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| Group B: Mild renal impairment | Experimental | Patients who have mild renal impairment (50\ |
|
| Group C: Moderate renal impairment | Experimental | Patients who have moderate renal impairment (30\ |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Levetiracetam 250 mg | Drug | Tablet containing Levetiracetam 250 mg |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Ucb L059 (LEV) for Groups A to D | Cmax refers to the maximum observed concentration of L059 (Levetiracetam). Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | From Baseline up to 144 hours post first dose |
| Area Under the Concentration-time Curve (AUC(0-t)) of Ucb L059 (LEV) From Baseline to the Last Quantifiable Concentration for Groups A to D | AUC(0-t) refers to the area under the plasma concentration versus time curve, which provides information on the exposure. Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | From Baseline up to 144 hours post first dose |
| Maximum Observed Plasma Concentration (Cmax) of Ucb L057 for Groups A to D | Cmax refers to the maximum observed concentration of ucb L057. Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | From Baseline up to 144 hours post first dose |
| Area Under the Concentration-time Curve (AUC(0-t)) of Ucb L057 From Baseline to the Last Quantifiable Concentration for Groups A to D | AUC(0-t) refers to the area under the plasma concentration versus time curve, which provides information on the exposure. Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | From Baseline up to 144 hours post first dose |
| Maximum Observed Plasma Concentration (Cmax) of Ucb L059 (LEV) for Group E During First Period | Cmax refers to the maximum observed concentration of ucb L059 (Levetiracetam). |
| Measure | Description | Time Frame |
|---|---|---|
| Total Amount Excreted in Urine (Ae) of Ucb L059 (LEV) for Groups A to D | Ae refers to the total amount of ucb L059 (Levetiracetam) excreted in urine. Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | From Baseline up to 144 hours post first dose |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| UCB Clinical Trial Call Center | +1 877 822 9493 (UCB) | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1 | Fukuoka | Japan | ||||
| 2 |
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| Label | URL |
|---|---|
| FDA Safety Alerts and Recalls | View source |
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About 30 (28 to 30) subjects were planned to be enrolled for 5 groups (A to E) according to their renal function based on the value of creatinine clearance (CLCr).
The Participant Flow refers to the Safety Set population which includes all patients that received at least one dose of study medication.
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| ID | Title | Description |
|---|---|---|
| FG000 | Group A: Normal Renal Function | Subjects with normal renal function (CLcr >80 mL/min/1.73 m^2). Subjects were orally administered Levetiracetam (LEV) 500 mg once. After LEV administration, safety assessments and blood and urine samplings were taken through to Day 4 during the Treatment Period, and safety follow-up assessments were performed on Day 8 according to the schedule of study assessments.
|
| FG001 | Group B: Mild Renal Impairment | Patients with mild renal impairment (50\ |
| FG002 | Group C: Moderate Renal Impairment | Patients with moderate renal impairment (30\ |
| FG003 | Group D: Severe Renal Impairment | Patients with severe renal impairment (CLcr <30 mL/min/1.73 m^2). Subjects were orally administered Levetiracetam (LEV) 250 mg once. After LEV administration, safety assessments and blood and urine samplings were conducted through Day 7 during the Treatment Period, and safety follow-up assessments were performed on Day 8 according to the schedule of study assessments.
|
| FG004 | Group E: End-stage Renal Disease | Group E received Levetiracetam (LEV) 500 mg orally on Day 1, 44 hours (h) before the first hemodialysis. As a supplementary dose LEV 250 mg was administered 1 h after the end of the first hemodialysis on Day 3. The 4-h Hemodialysis was scheduled as follows:
Safety assessments and blood samplings were conducted until Day 7. Safety follow-up assessments were performed on Day 10. Blood samples for Pharmacokinetics (PK): Predose (Baseline), and 0.5, 1, 2, 4, 6, 8, 12, 24, 30, 44*, 44.25*, 44.5*, 45*, 46*, 47*, 48*, 49, 49.5, 50, 51, 53, 55, 57, 61, 73, 92, 96, 120, 140 hours post first dosing. 49 h-sample was taken before the additional dose. The 44 h, 92 h, and 140 h samples were taken before the start of the hemodialysis. *Inflow blood, outflow blood, and dialysate fluid were collected. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
The Baseline Analysis Population refers to the Pharmacokinetic Per Protocol Set (PK-PPS) which consists of all subjects included in the Safety Set (SS), who also had a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the PK parameters.
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| ID | Title | Description |
|---|---|---|
| BG000 | Group A: Normal Renal Function | Subjects with normal renal function (CLcr >80 mL/min/1.73 m^2). Subjects were orally administered Levetiracetam (LEV) 500 mg once. After LEV administration, safety assessments and blood and urine samplings were taken through to Day 4 during the Treatment Period, and safety follow-up assessments were performed on Day 8 according to the schedule of study assessments.
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| 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, Continuous | Mean |
| 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 Ucb L059 (LEV) for Groups A to D | Cmax refers to the maximum observed concentration of L059 (Levetiracetam). Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | µg/mL | From Baseline up to 144 hours post first dose |
|
Treatment-Emergent Adverse Events were reported from Day 1 up to Day 8 (+2 days) for Group A to D and from Day 1 up to Day 10 (+2 days) for Group E.
Treatment-Emergent Adverse Events (TEAEs) were reported. TEAEs are defined as those adverse events that either start or worsen in intensity on or after the date/time of first dose of study treatment.
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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 | Group A: Normal Renal Function | Subjects with normal renal function (CLcr >80 mL/min/1.73 m^2). Subjects were orally administered Levetiracetam (LEV) 500 mg once. After LEV administration, safety assessments and blood and urine samplings were taken through to Day 4 during the Treatment Period, and safety follow-up assessments were performed on Day 8 according to the schedule of study assessments.
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA 14.1 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gingivitis | Gastrointestinal disorders | MedDRA 14.1 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| UCB Clinical Trials Call Center | UCB | +1 877 822 9493 |
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| ID | Term |
|---|---|
| D000077287 | Levetiracetam |
| ID | Term |
|---|---|
| D000081 | Acetamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000085 | Acetates |
| D000144 |
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| Group D: Severe renal impairment | Experimental | Patients who have severe renal impairment (CLcr <30 mL/min/1.73 m^2). Subjects will be orally administered Levetiracetam (LEV) 250 mg once. After LEV administration, safety assessments and blood and urine samplings will be conducted through Day 7 during the Treatment Period, and safety follow-up assessments will be performed on Day 8 according to the schedule of study assessments.
|
|
| Group E: End-stage renal disease | Experimental | Group E will receive Levetiracetam (LEV) 500 mg on Day 1, 44 hours (h) before the first hemodialysis. As a supplementary dose LEV 250 mg will be administered 1 h after the end of the first hemodialysis on Day 3. The 4-h Hemodialysis are scheduled as follows:
Safety assessments and blood samplings will be conducted until Day 7. Safety follow-up assessments will be performed on Day 10. Blood samples for Pharmacokinetics (PK): Predose (Baseline), and 0.5, 1, 2, 4, 6, 8, 12, 24, 30, 44*, 44.25*, 44.5*, 45*, 46*, 47*, 48*, 49, 49.5, 50, 51, 53, 55, 57, 61, 73, 92, 96, 120, 140 hours post first dosing. 49 h-sample should be taken before the additional dose. The 44 h, 92 h, and 140 h sample should be taken before the start of the hemodialysis. *Inflow blood, outflow blood, and dialysate fluid will be collected. |
|
|
| Levetiracetam 500 mg | Drug | Tablet containing Levetiracetam 500 mg |
|
|
| From Baseline to 44 hours post first dose |
| Area Under the Concentration-time Curve (AUC(0-t)) of Ucb L059 (LEV) From Baseline to 44 Hours for Group E | AUC(0-t) refers to the area under the plasma concentration versus time curve, which provides information on the exposure. | From Baseline to 44 hours post first dose |
| Maximum Observed Plasma Concentration (Cmax) of Ucb L057 for Group E During First Period | Cmax refers to the maximum observed concentration of ucb L057. | From Baseline to 44 hours post first dose |
| Area Under the Concentration-time Curve (AUC(0-t)) of Ucb L057 From Baseline to 44 Hours for Group E | AUC(0-t) refers to the area under the plasma concentration versus time curve, which provides information on the exposure. | From Baseline to 44 hours post first dose |
| Fraction of Dose Excreted in Urine (fe) of Ucb L059 (LEV) for Groups A to D |
fe refers to the fraction of dose excreted in urine of L059 (Levetiracetam). Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours |
| From Baseline up to 144 hours post first dose |
| Renal Clearance (CLR) of Ucb L059 (LEV) for Groups A to D | Renal clearance describes the removal of drug from a volume of plasma in a given unit of time by the kidneys. Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | From Baseline up to 144 hours post first dose |
| Apparent Total Body Clearance (CL/F) of Ucb L059 (LEV) for Groups A to D | Clearance (expressed as volume/time) describes the removal of drug from a volume of plasma in a given unit of time (drug loss from the body). It indicates the volume of plasma (or blood) from which the drug is completely removed, or cleared, in a given time period. Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | From Baseline up to 144 hours post first dose |
| Nonrenal Clearance (CLNR) of Ucb L059 (LEV) for Groups A to D | The Non-Renal Clearance (CLNR) describes the removal of drug by organs other than the kidneys. Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | From Baseline up to 144 hours post first dose |
| Total Amount Excreted in Urine (Ae) of Ucb L057 for Groups A to D | Ae refers to the total amount of ucb L057 excreted in urine. Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | From Baseline up to 144 hours post first dose |
| Renal Clearance (CLR) of Ucb L057 for Groups A to D | Renal clearance describes the removal of drug from a volume of plasma in a given unit of time by the kidneys. Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | From Baseline up to 144 hours post first dose |
| Apparent Total Body Clearance (CL/F) of Ucb L059 (LEV) for Group E During First Period | Clearance (expressed as volume/time) describes the removal of drug from a volume of plasma in a given unit of time (drug loss from the body). It indicates the volume of plasma (or blood) from which the drug is completely removed, or cleared, in a given time period. Geometric mean and Coefficient of Variation (CV) was not calculated since the extrapolated part of the AUC was greater than 20 %. | From Baseline to 44 hours post first dose |
| Time to Reach Maximum Plasma Concentration (Tmax) of Ucb L059 (LEV) for Groups A to D | tmax refers to the time to reach maximum plasma concentration of ucb L059 (Levetiracetam). Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | From Baseline up to 144 hours post first dose |
| Area Under the Concentration-time Curve (AUC) of Ucb L059 (LEV) From Baseline to Infinite for Groups A to D | AUC(0-t) refers to the area under the plasma concentration versus time curve, which provides information on the exposure. Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | From Baseline up to 144 hours post first dose |
| Terminal Half-life (t1/2) of Ucb L059 (LEV) for Groups A to D | Terminal half-life refers to the time it takes for the concentrations to decrease by half. Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | From Baseline up to 144 hours post first dose |
| Time to Reach Maximum Plasma Concentration (Tmax) of Ucb L057 for Groups A to D | tmax refers to the time to reach maximum plasma concentration (tmax). Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | From Baseline up to 144 hours post first dose |
| Area Under the Concentration-time Curve (AUC) of Ucb L057 From Baseline to Infinite for Groups A to D | AUC(0-t) refers to the area under the plasma concentration versus time curve, which provides information on the exposure. Geometric mean and CV was not calculated since the extrapolated part of the AUC was greater than 20 %. Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | From Baseline up to 144 hours post first dose |
| Terminal Half-life (t1/2) of Ucb L057 for Groups A to D | Terminal half-life refers to the time it takes for the concentrations to decrease by half. Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | From Baseline up to 144 hours post first dose |
| Time to Reach Maximum Plasma Concentration (Tmax) of Ucb L059 (Levetiracetam) for Group E During First Period | tmax refers to the time to reach the maximum plasma concentration of ucb L059 (Levetiracetam). | From Baseline to 44 hours post first dose |
| Area Under the Concentration-time Curve (AUC) of Ucb L059 (LEV) From Baseline to Infinite for Group E | AUC(0-t) refers to the area under the plasma concentration versus time curve, which provides information on the exposure. Geometric mean and CV was not calculated since the extrapolated part of the AUC was greater than 20 %. | From Baseline to 140 hours post first dose |
| Terminal Half-life (t1/2) of Ucb L059 (LEV) for Group E During First Period | Terminal half-life refers to the time it takes for the concentrations to decrease by half. Geometric mean and CV was not calculated since the extrapolated part of the AUC was greater than 20 %. | From Baseline to 44 hours post first dose |
| Time to Reach Maximum Plasma Concentration (Tmax) of Ucb L057 for Group E During First Period | tmax refers to the time to reach maximum plasma concentration (tmax). | From Baseline to 44 hours post first dose |
| Hemodialysis Clearance (CLD) of Ucb L059 (LEV) During First Dialysis for Group E | Calculated by the Arterio - Venous difference method and cumulative dialysate method. | From 44 hours to 48 hours post first dose |
| Ultrafiltration Clearance (CLUF) of Ucb L059 (LEV) During First Dialysis for Group E | Calculated by the Arterio - Venous difference method and cumulative dialysate method. | From 44 hours to 48 hours post first dose |
| Hemodialysis Clearance (CLHD) of Ucb L059 (LEV) During First Dialysis for Group E | Calculated according: CLHD=CLD+CLUF. | From 44 hours to 48 hours post first dose |
| Ibaraki |
| Japan |
| BG001 | Group B: Mild Renal Impairment | Patients with mild renal impairment (50\ |
| BG002 | Group C: Moderate Renal Impairment | Patients with moderate renal impairment (30\ |
| BG003 | Group D: Severe Renal Impairment | Patients with severe renal impairment (CLcr <30 mL/min/1.73 m^2). Subjects were orally administered Levetiracetam (LEV) 250 mg once. After LEV administration, safety assessments and blood and urine samplings were conducted through Day 7 during the Treatment Period, and safety follow-up assessments were performed on Day 8 according to the schedule of study assessments.
|
| BG004 | Group E: End-stage Renal Disease | Group E received Levetiracetam (LEV) 500 mg orally on Day 1, 44 hours (h) before the first hemodialysis. As a supplementary dose LEV 250 mg was administered 1 h after the end of the first hemodialysis on Day 3. The 4-h Hemodialysis was scheduled as follows:
Safety assessments and blood samplings were conducted until Day 7. Safety follow-up assessments were performed on Day 10. Blood samples for Pharmacokinetic (PK) analyses: Predose (Baseline), and 0.5, 1, 2, 4, 6, 8, 12, 24, 30, 44*, 44.25*, 44.5*, 45*, 46*, 47*, 48*, 49, 49.5, 50, 51, 53, 55, 57, 61, 73, 92, 96, 120, 140 hours post first dosing. 49 h-sample was taken before the additional dose. The 44 h, 92 h, and 140 h samples were taken before the start of the hemodialysis. *Inflow blood, outflow blood, and dialysate fluid were collected. |
| BG005 | Total | Total of all reporting groups |
| years |
|
| Age, Customized | Number | participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Weight | Mean | Standard Deviation | kilogram |
|
| Height | Mean | Standard Deviation | centimeters |
|
| OG001 | Group B: Mild Renal Impairment | Patients with mild renal impairment (50\ |
| OG002 | Group C: Moderate Renal Impairment | Patients with moderate renal impairment (30\ |
| OG003 | Group D: Severe Renal Impairment | Patients with severe renal impairment (CLcr <30 mL/min/1.73 m^2). Subjects were orally administered Levetiracetam (LEV) 250 mg once. After LEV administration, safety assessments and blood and urine samplings were conducted through Day 7 during the Treatment Period, and safety follow-up assessments were performed on Day 8 according to the schedule of study assessments.
|
|
|
| Primary | Area Under the Concentration-time Curve (AUC(0-t)) of Ucb L059 (LEV) From Baseline to the Last Quantifiable Concentration for Groups A to D | AUC(0-t) refers to the area under the plasma concentration versus time curve, which provides information on the exposure. Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*µg/mL | From Baseline up to 144 hours post first dose |
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|
| Primary | Maximum Observed Plasma Concentration (Cmax) of Ucb L057 for Groups A to D | Cmax refers to the maximum observed concentration of ucb L057. Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | µg/mL | From Baseline up to 144 hours post first dose |
|
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|
| Primary | Area Under the Concentration-time Curve (AUC(0-t)) of Ucb L057 From Baseline to the Last Quantifiable Concentration for Groups A to D | AUC(0-t) refers to the area under the plasma concentration versus time curve, which provides information on the exposure. Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*µg/mL | From Baseline up to 144 hours post first dose |
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|
| Primary | Maximum Observed Plasma Concentration (Cmax) of Ucb L059 (LEV) for Group E During First Period | Cmax refers to the maximum observed concentration of ucb L059 (Levetiracetam). | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | µg/mL | From Baseline to 44 hours post first dose |
|
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| Primary | Area Under the Concentration-time Curve (AUC(0-t)) of Ucb L059 (LEV) From Baseline to 44 Hours for Group E | AUC(0-t) refers to the area under the plasma concentration versus time curve, which provides information on the exposure. | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*µg/mL | From Baseline to 44 hours post first dose |
|
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|
| Primary | Maximum Observed Plasma Concentration (Cmax) of Ucb L057 for Group E During First Period | Cmax refers to the maximum observed concentration of ucb L057. | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | µg/mL | From Baseline to 44 hours post first dose |
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| Primary | Area Under the Concentration-time Curve (AUC(0-t)) of Ucb L057 From Baseline to 44 Hours for Group E | AUC(0-t) refers to the area under the plasma concentration versus time curve, which provides information on the exposure. | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*µg/mL | From Baseline to 44 hours post first dose |
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| Secondary | Total Amount Excreted in Urine (Ae) of Ucb L059 (LEV) for Groups A to D | Ae refers to the total amount of ucb L059 (Levetiracetam) excreted in urine. Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | mg | From Baseline up to 144 hours post first dose |
|
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| Secondary | Fraction of Dose Excreted in Urine (fe) of Ucb L059 (LEV) for Groups A to D | fe refers to the fraction of dose excreted in urine of L059 (Levetiracetam). Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | Percentage of Dose Administered | From Baseline up to 144 hours post first dose |
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| Secondary | Renal Clearance (CLR) of Ucb L059 (LEV) for Groups A to D | Renal clearance describes the removal of drug from a volume of plasma in a given unit of time by the kidneys. Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/h | From Baseline up to 144 hours post first dose |
|
|
|
| Secondary | Apparent Total Body Clearance (CL/F) of Ucb L059 (LEV) for Groups A to D | Clearance (expressed as volume/time) describes the removal of drug from a volume of plasma in a given unit of time (drug loss from the body). It indicates the volume of plasma (or blood) from which the drug is completely removed, or cleared, in a given time period. Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/h | From Baseline up to 144 hours post first dose |
|
|
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| Secondary | Nonrenal Clearance (CLNR) of Ucb L059 (LEV) for Groups A to D | The Non-Renal Clearance (CLNR) describes the removal of drug by organs other than the kidneys. Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/h | From Baseline up to 144 hours post first dose |
|
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| Secondary | Total Amount Excreted in Urine (Ae) of Ucb L057 for Groups A to D | Ae refers to the total amount of ucb L057 excreted in urine. Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | mg | From Baseline up to 144 hours post first dose |
|
|
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| Secondary | Renal Clearance (CLR) of Ucb L057 for Groups A to D | Renal clearance describes the removal of drug from a volume of plasma in a given unit of time by the kidneys. Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/h | From Baseline up to 144 hours post first dose |
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| Secondary | Apparent Total Body Clearance (CL/F) of Ucb L059 (LEV) for Group E During First Period | Clearance (expressed as volume/time) describes the removal of drug from a volume of plasma in a given unit of time (drug loss from the body). It indicates the volume of plasma (or blood) from which the drug is completely removed, or cleared, in a given time period. Geometric mean and Coefficient of Variation (CV) was not calculated since the extrapolated part of the AUC was greater than 20 %. | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Median | Full Range | L/h | From Baseline to 44 hours post first dose |
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| Secondary | Time to Reach Maximum Plasma Concentration (Tmax) of Ucb L059 (LEV) for Groups A to D | tmax refers to the time to reach maximum plasma concentration of ucb L059 (Levetiracetam). Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Median | Full Range | hours | From Baseline up to 144 hours post first dose |
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| Secondary | Area Under the Concentration-time Curve (AUC) of Ucb L059 (LEV) From Baseline to Infinite for Groups A to D | AUC(0-t) refers to the area under the plasma concentration versus time curve, which provides information on the exposure. Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*µg/mL | From Baseline up to 144 hours post first dose |
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| Secondary | Terminal Half-life (t1/2) of Ucb L059 (LEV) for Groups A to D | Terminal half-life refers to the time it takes for the concentrations to decrease by half. Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | From Baseline up to 144 hours post first dose |
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| Secondary | Time to Reach Maximum Plasma Concentration (Tmax) of Ucb L057 for Groups A to D | tmax refers to the time to reach maximum plasma concentration (tmax). Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Median | Full Range | hours | From Baseline up to 144 hours post first dose |
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| Secondary | Area Under the Concentration-time Curve (AUC) of Ucb L057 From Baseline to Infinite for Groups A to D | AUC(0-t) refers to the area under the plasma concentration versus time curve, which provides information on the exposure. Geometric mean and CV was not calculated since the extrapolated part of the AUC was greater than 20 %. Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Median | Full Range | h*µg/mL | From Baseline up to 144 hours post first dose |
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| Secondary | Terminal Half-life (t1/2) of Ucb L057 for Groups A to D | Terminal half-life refers to the time it takes for the concentrations to decrease by half. Group A: Baseline to 72 hours; Group B: Baseline to 96 hours; Group C: Baseline to 120 hours; Group D: Baseline to 144 hours | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Median | Full Range | hours | From Baseline up to 144 hours post first dose |
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| Secondary | Time to Reach Maximum Plasma Concentration (Tmax) of Ucb L059 (Levetiracetam) for Group E During First Period | tmax refers to the time to reach the maximum plasma concentration of ucb L059 (Levetiracetam). | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Median | Full Range | hours | From Baseline to 44 hours post first dose |
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| Secondary | Area Under the Concentration-time Curve (AUC) of Ucb L059 (LEV) From Baseline to Infinite for Group E | AUC(0-t) refers to the area under the plasma concentration versus time curve, which provides information on the exposure. Geometric mean and CV was not calculated since the extrapolated part of the AUC was greater than 20 %. | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Median | Full Range | h*µg/mL | From Baseline to 140 hours post first dose |
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| Secondary | Terminal Half-life (t1/2) of Ucb L059 (LEV) for Group E During First Period | Terminal half-life refers to the time it takes for the concentrations to decrease by half. Geometric mean and CV was not calculated since the extrapolated part of the AUC was greater than 20 %. | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Median | Full Range | hours | From Baseline to 44 hours post first dose |
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| Secondary | Time to Reach Maximum Plasma Concentration (Tmax) of Ucb L057 for Group E During First Period | tmax refers to the time to reach maximum plasma concentration (tmax). | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Median | Full Range | hours | From Baseline to 44 hours post first dose |
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| Secondary | Hemodialysis Clearance (CLD) of Ucb L059 (LEV) During First Dialysis for Group E | Calculated by the Arterio - Venous difference method and cumulative dialysate method. | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/min | From 44 hours to 48 hours post first dose |
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| Secondary | Ultrafiltration Clearance (CLUF) of Ucb L059 (LEV) During First Dialysis for Group E | Calculated by the Arterio - Venous difference method and cumulative dialysate method. | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/min | From 44 hours to 48 hours post first dose |
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| Secondary | Hemodialysis Clearance (CLHD) of Ucb L059 (LEV) During First Dialysis for Group E | Calculated according: CLHD=CLD+CLUF. | The Analysis Population refers to the Pharmacokinetic Per Protocol Set which consists of all subjects included in the Safety Set, who also have a sufficient number of bioanalytical assessments (plasma or urine) to calculate reliable estimates for the Pharmacokinetic parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/min | From 44 hours to 48 hours post first dose |
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| 0 |
| 6 |
| 0 |
| 6 |
| EG001 | Group B: Mild Renal Impairment | Patients with mild renal impairment (50\ | 0 | 6 | 2 | 6 |
| EG002 | Group C: Moderate Renal Impairment | Patients with moderate renal impairment (30\ | 0 | 6 | 0 | 6 |
| EG003 | Group D: Severe Renal Impairment | Patients with severe renal impairment (CLcr <30 mL/min/1.73 m^2). Subjects were orally administered Levetiracetam (LEV) 250 mg once. After LEV administration, safety assessments and blood and urine samplings were conducted through Day 7 during the Treatment Period, and safety follow-up assessments were performed on Day 8 according to the schedule of study assessments.
| 0 | 6 | 1 | 6 |
| EG004 | Group E: End-stage Renal Disease | Group E received Levetiracetam (LEV) 500 mg orally on Day 1, 44 hours (h) before the first hemodialysis. As a supplementary dose LEV 250 mg was administered 1 h after the end of the first hemodialysis on Day 3. The 4-h Hemodialysis was scheduled as follows:
Safety assessments and blood samplings were conducted until Day 7. Safety follow-up assessments were performed on Day 10. Blood samples for Pharmacokinetic (PK) analyses: Predose (Baseline), and 0.5, 1, 2, 4, 6, 8, 12, 24, 30, 44*, 44.25*, 44.5*, 45*, 46*, 47*, 48*, 49, 49.5, 50, 51, 53, 55, 57, 61, 73, 92, 96, 120, 140 hours post first dosing. 49 h-sample was taken before the additional dose. The 44 h, 92 h, and 140 h samples were taken before the start of the hemodialysis. *Inflow blood, outflow blood, and dialysate fluid were collected. | 1 | 6 | 2 | 6 |
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 14.1 | Non-systematic Assessment |
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| Shunt malfunction | Injury, poisoning and procedural complications | MedDRA 14.1 | Non-systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA 14.1 | Non-systematic Assessment |
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| Pyrexia | General disorders | MedDRA 14.1 | Non-systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 14.1 | Non-systematic Assessment |
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| Postoperative wound complication | Injury, poisoning and procedural complications | MedDRA 14.1 | Non-systematic Assessment |
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| White blood cell count increased | Investigations | MedDRA 14.1 | Non-systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 14.1 | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 14.1 | Non-systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 14.1 | Non-systematic Assessment |
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| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 14.1 | Non-systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA 14.1 | Non-systematic Assessment |
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Not provided
| Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D011760 | Pyrrolidinones |
| D011759 | Pyrrolidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |