Healthy Subjects, Renal Impairments
Conditions
Keywords
Levetiracetam, Oral administration, Japanese, Non-epileptic, Healthy, Renal impaired subjects
Brief summary
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.
Detailed description
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.
Interventions
Tablet containing Levetiracetam 250 mg
Tablet containing Levetiracetam 500 mg
Sponsors
Parexel
UCB Pharma
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy subjects with normal renal function * Subject is Japanese * Subjects with creatinine clearance within 1 of 3 Groups (CLcr\[mL/min/1.73 cm\^2\]: Group B: 50 - \<80, Group C: 30 - \<50, Group D: \<30), or for Group E, subjects with end-stage renal failure undergoing hemodialysis
Exclusion criteria
* Subjects has taken any drug treatment, disease or injury to influence Levetiracetam PK except for renal impairments
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Ucb L059 (LEV) for Groups A to D | From Baseline up to 144 hours post first dose | 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 |
| 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 | From Baseline up to 144 hours post first dose | 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 |
| Maximum Observed Plasma Concentration (Cmax) of Ucb L057 for Groups A to D | From Baseline up to 144 hours post first dose | 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 |
| Area Under the Concentration-time Curve (AUC(0-t)) of Ucb L057 From Baseline to the Last Quantifiable Concentration for Groups A to D | From Baseline up to 144 hours post first dose | 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 |
| Maximum Observed Plasma Concentration (Cmax) of Ucb L059 (LEV) for Group E During First Period | From Baseline to 44 hours post first dose | Cmax refers to the maximum observed concentration of ucb L059 (Levetiracetam). |
| Area Under the Concentration-time Curve (AUC(0-t)) of Ucb L059 (LEV) From Baseline to 44 Hours for Group E | From Baseline to 44 hours post first dose | AUC(0-t) refers to the area under the plasma concentration versus time curve, which provides information on the exposure. |
| Maximum Observed Plasma Concentration (Cmax) of Ucb L057 for Group E During First Period | From Baseline to 44 hours post first dose | Cmax refers to the maximum observed concentration of ucb L057. |
| Area Under the Concentration-time Curve (AUC(0-t)) of Ucb L057 From Baseline to 44 Hours for Group E | From Baseline to 44 hours post first dose | AUC(0-t) refers to the area under the plasma concentration versus time curve, which provides information on the exposure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach Maximum Plasma Concentration (Tmax) of Ucb L059 (LEV) for Groups A to D | From Baseline up to 144 hours post first dose | 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 |
| Area Under the Concentration-time Curve (AUC) of Ucb L059 (LEV) From Baseline to Infinite for Groups A to D | From Baseline up to 144 hours post first dose | 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 |
| Terminal Half-life (t1/2) of Ucb L059 (LEV) for Groups A to D | From Baseline up to 144 hours post first dose | 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 |
| Time to Reach Maximum Plasma Concentration (Tmax) of Ucb L057 for Groups A to D | From Baseline up to 144 hours post first dose | 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 |
| Area Under the Concentration-time Curve (AUC) of Ucb L057 From Baseline to Infinite for Groups A to D | From Baseline up to 144 hours post first dose | 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 |
| Terminal Half-life (t1/2) of Ucb L057 for Groups A to D | From Baseline up to 144 hours post first dose | 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 |
| Total Amount Excreted in Urine (Ae) of Ucb L059 (LEV) for Groups A to D | From Baseline up to 144 hours post first dose | 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 |
| Area Under the Concentration-time Curve (AUC) of Ucb L059 (LEV) From Baseline to Infinite for Group E | From Baseline to 140 hours post first dose | 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 %. |
| Terminal Half-life (t1/2) of Ucb L059 (LEV) for Group E During First Period | From Baseline to 44 hours post first dose | 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 %. |
| Time to Reach Maximum Plasma Concentration (Tmax) of Ucb L057 for Group E During First Period | From Baseline to 44 hours post first dose | tmax refers to the time to reach maximum plasma concentration (tmax). |
| Hemodialysis Clearance (CLD) of Ucb L059 (LEV) During First Dialysis for Group E | From 44 hours to 48 hours post first dose | Calculated by the Arterio - Venous difference method and cumulative dialysate method. |
| Ultrafiltration Clearance (CLUF) of Ucb L059 (LEV) During First Dialysis for Group E | From 44 hours to 48 hours post first dose | Calculated by the Arterio - Venous difference method and cumulative dialysate method. |
| Hemodialysis Clearance (CLHD) of Ucb L059 (LEV) During First Dialysis for Group E | From 44 hours to 48 hours post first dose | Calculated according: CLHD=CLD+CLUF. |
| Time to Reach Maximum Plasma Concentration (Tmax) of Ucb L059 (Levetiracetam) for Group E During First Period | From Baseline to 44 hours post first dose | tmax refers to the time to reach the maximum plasma concentration of ucb L059 (Levetiracetam). |
| Fraction of Dose Excreted in Urine (fe) of Ucb L059 (LEV) for Groups A to D | From Baseline up to 144 hours post first dose | 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 |
| Renal Clearance (CLR) of Ucb L059 (LEV) for Groups A to D | From Baseline up to 144 hours post first dose | 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 |
| Apparent Total Body Clearance (CL/F) of Ucb L059 (LEV) for Groups A to D | From Baseline up to 144 hours post first dose | 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 |
| Nonrenal Clearance (CLNR) of Ucb L059 (LEV) for Groups A to D | From Baseline up to 144 hours post first dose | 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 |
| Total Amount Excreted in Urine (Ae) of Ucb L057 for Groups A to D | From Baseline up to 144 hours post first dose | 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 |
| Renal Clearance (CLR) of Ucb L057 for Groups A to D | From Baseline up to 144 hours post first dose | 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 |
| Apparent Total Body Clearance (CL/F) of Ucb L059 (LEV) for Group E During First Period | From Baseline to 44 hours post first dose | 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 %. |
Countries
Japan
Participant flow
Recruitment details
The Participant Flow refers to the Safety Set population which includes all patients that received at least one dose of study medication.
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| 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.
* Blood samples for Pharmacokinetic (PK) analyses: Predose (Baseline), and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours postdose
* Urine samples for PK analyses: 0 - 6, 6 - 12, 12 - 24, 24 - 48, 48 - 72 hours postdose | 6 |
| Group B: Mild Renal Impairment Patients with mild renal impairment (50\<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 conducted through Day 5 during the Treatment Period, and safety follow-up assessments were performed on Day 8 according to the schedule of study assessments.
* Blood samples for Pharmacokinetics (PK) analyses: Predose (Baseline), and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 hours postdose
* Urine samples for PK analyses: 0 - 6, 6 - 12, 12 - 24, 24 - 48, 48 - 72, 72 - 96 hours postdose | 6 |
| Group C: Moderate Renal Impairment Patients with moderate renal impairment (30\<CLcr \< 50 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 6 during the Treatment Period, and safety follow-up assessments were performed on Day 8 according to the schedule of study assessments.
* Blood samples for Pharmacokinetic (PK) analyses: Predose (Baseline), and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose
* Urine samples for PK analyses: 0 - 6, 6 - 12, 12 - 24, 24 - 48, 48 - 72, 72 - 96, 96 -120 hours postdose | 6 |
| 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.
* Blood samples for Pharmacokinetic (PK) analyses: Predose (Baseline), and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144 hours postdose
* Urine samples for PK analyses: 0 - 6, 6 - 12, 12 - 24, 24 - 48, 48 - 72, 72 - 96, 96 -120, 120 - 144 hours postdose | 6 |
| 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:
1. Dialysis: 44 h to 48 h after the first dose (Day 3)
2. Dialysis: 92 h to 96 h after the first dose (Day 5)
3. Dialysis: 140 h after the first dose (Day 7)
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. | 6 |
| Total | 30 |
Baseline characteristics
| Characteristic | Group A: Normal Renal Function | Group B: Mild Renal Impairment | Group C: Moderate Renal Impairment | Group D: Severe Renal Impairment | Group E: End-stage Renal Disease | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 61.7 years STANDARD_DEVIATION 2.6 | 67.5 years STANDARD_DEVIATION 5 | 69.3 years STANDARD_DEVIATION 6.1 | 55.8 years STANDARD_DEVIATION 17.1 | 68.8 years STANDARD_DEVIATION 7.9 | 64.6 years STANDARD_DEVIATION 10 |
| Age, Customized 20 - <65 years | 5 participants | 3 participants | 1 participants | 4 participants | 2 participants | 15 participants |
| Age, Customized >=65 years | 1 participants | 3 participants | 5 participants | 2 participants | 4 participants | 15 participants |
| Height | 161.73 centimeters STANDARD_DEVIATION 9.05 | 165.65 centimeters STANDARD_DEVIATION 3.11 | 163.72 centimeters STANDARD_DEVIATION 5.64 | 164.50 centimeters STANDARD_DEVIATION 6.34 | 162.38 centimeters STANDARD_DEVIATION 3.41 | 163.60 centimeters STANDARD_DEVIATION 5.68 |
| Race/Ethnicity, Customized Asian | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 30 participants |
| Race/Ethnicity, Customized Japanese | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 30 participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 29 Participants |
| Weight | 60.95 kilogram STANDARD_DEVIATION 10.97 | 74.28 kilogram STANDARD_DEVIATION 4.14 | 63.07 kilogram STANDARD_DEVIATION 12.49 | 58.70 kilogram STANDARD_DEVIATION 6.1 | 62.20 kilogram STANDARD_DEVIATION 5.41 | 63.84 kilogram STANDARD_DEVIATION 9.62 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 6 | 2 / 6 | 0 / 6 | 1 / 6 | 2 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 1 / 6 |
Outcome results
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.
Time frame: From Baseline to 44 hours post first dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Normal Renal Function | Area Under the Concentration-time Curve (AUC(0-t)) of Ucb L057 From Baseline to 44 Hours for Group E | 230.4393 h*µg/mL | Geometric Coefficient of Variation 7.8 |
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
Time frame: From Baseline up to 144 hours post first dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Normal Renal Function | Area Under the Concentration-time Curve (AUC(0-t)) of Ucb L057 From Baseline to the Last Quantifiable Concentration for Groups A to D | 5.8607 h*µg/mL | Geometric Coefficient of Variation 9.7 |
| Group B: Mild Renal Impairment | Area Under the Concentration-time Curve (AUC(0-t)) of Ucb L057 From Baseline to the Last Quantifiable Concentration for Groups A to D | 22.5573 h*µg/mL | Geometric Coefficient of Variation 45.9 |
| Group C: Moderate Renal Impairment | Area Under the Concentration-time Curve (AUC(0-t)) of Ucb L057 From Baseline to the Last Quantifiable Concentration for Groups A to D | 18.6675 h*µg/mL | Geometric Coefficient of Variation 53.4 |
| Group D: Severe Renal Impairment | Area Under the Concentration-time Curve (AUC(0-t)) of Ucb L057 From Baseline to the Last Quantifiable Concentration for Groups A to D | 57.7773 h*µg/mL | Geometric Coefficient of Variation 57.3 |
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.
Time frame: From Baseline to 44 hours post first dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Normal Renal Function | Area Under the Concentration-time Curve (AUC(0-t)) of Ucb L059 (LEV) From Baseline to 44 Hours for Group E | 462.4883 h*µg/mL | Geometric Coefficient of Variation 10.5 |
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
Time frame: From Baseline up to 144 hours post first dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Normal Renal Function | 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 | 165.9996 h*µg/mL | Geometric Coefficient of Variation 16.5 |
| Group B: Mild Renal Impairment | 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 | 247.6430 h*µg/mL | Geometric Coefficient of Variation 16.9 |
| Group C: Moderate Renal Impairment | 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 | 169.3392 h*µg/mL | Geometric Coefficient of Variation 16.5 |
| Group D: Severe Renal Impairment | 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 | 212.1193 h*µg/mL | Geometric Coefficient of Variation 19.1 |
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.
Time frame: From Baseline to 44 hours post first dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Normal Renal Function | Maximum Observed Plasma Concentration (Cmax) of Ucb L057 for Group E During First Period | 8.8435 µg/mL | Geometric Coefficient of Variation 7 |
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
Time frame: From Baseline up to 144 hours post first dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Normal Renal Function | Maximum Observed Plasma Concentration (Cmax) of Ucb L057 for Groups A to D | 0.3620 µg/mL | Geometric Coefficient of Variation 9.4 |
| Group B: Mild Renal Impairment | Maximum Observed Plasma Concentration (Cmax) of Ucb L057 for Groups A to D | 0.7503 µg/mL | Geometric Coefficient of Variation 25.8 |
| Group C: Moderate Renal Impairment | Maximum Observed Plasma Concentration (Cmax) of Ucb L057 for Groups A to D | 0.5674 µg/mL | Geometric Coefficient of Variation 26 |
| Group D: Severe Renal Impairment | Maximum Observed Plasma Concentration (Cmax) of Ucb L057 for Groups A to D | 1.0640 µg/mL | Geometric Coefficient of Variation 29.3 |
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).
Time frame: From Baseline to 44 hours post first dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Normal Renal Function | Maximum Observed Plasma Concentration (Cmax) of Ucb L059 (LEV) for Group E During First Period | 18.6810 µg/mL | Geometric Coefficient of Variation 8.1 |
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
Time frame: From Baseline up to 144 hours post first dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Normal Renal Function | Maximum Observed Plasma Concentration (Cmax) of Ucb L059 (LEV) for Groups A to D | 21.9357 µg/mL | Geometric Coefficient of Variation 31.2 |
| Group B: Mild Renal Impairment | Maximum Observed Plasma Concentration (Cmax) of Ucb L059 (LEV) for Groups A to D | 15.5334 µg/mL | Geometric Coefficient of Variation 25.3 |
| Group C: Moderate Renal Impairment | Maximum Observed Plasma Concentration (Cmax) of Ucb L059 (LEV) for Groups A to D | 10.7767 µg/mL | Geometric Coefficient of Variation 24.3 |
| Group D: Severe Renal Impairment | Maximum Observed Plasma Concentration (Cmax) of Ucb L059 (LEV) for Groups A to D | 9.1754 µg/mL | Geometric Coefficient of Variation 30.4 |
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 %.
Time frame: From Baseline to 44 hours post first dose
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A: Normal Renal Function | Apparent Total Body Clearance (CL/F) of Ucb L059 (LEV) for Group E During First Period | 0.629 L/h |
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
Time frame: From Baseline up to 144 hours post first dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Normal Renal Function | Apparent Total Body Clearance (CL/F) of Ucb L059 (LEV) for Groups A to D | 2.9359 L/h | Geometric Coefficient of Variation 14.8 |
| Group B: Mild Renal Impairment | Apparent Total Body Clearance (CL/F) of Ucb L059 (LEV) for Groups A to D | 1.9826 L/h | Geometric Coefficient of Variation 16 |
| Group C: Moderate Renal Impairment | Apparent Total Body Clearance (CL/F) of Ucb L059 (LEV) for Groups A to D | 1.4362 L/h | Geometric Coefficient of Variation 15.3 |
| Group D: Severe Renal Impairment | Apparent Total Body Clearance (CL/F) of Ucb L059 (LEV) for Groups A to D | 1.1484 L/h | Geometric Coefficient of Variation 19.1 |
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
Time frame: From Baseline up to 144 hours post first dose
Population: 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.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Group A: Normal Renal Function | Area Under the Concentration-time Curve (AUC) of Ucb L057 From Baseline to Infinite for Groups A to D | 8.176 h*µg/mL | Full Range 0 |
| Group B: Mild Renal Impairment | Area Under the Concentration-time Curve (AUC) of Ucb L057 From Baseline to Infinite for Groups A to D | 32.401 h*µg/mL | — |
| Group C: Moderate Renal Impairment | Area Under the Concentration-time Curve (AUC) of Ucb L057 From Baseline to Infinite for Groups A to D | 27.441 h*µg/mL | — |
| Group D: Severe Renal Impairment | Area Under the Concentration-time Curve (AUC) of Ucb L057 From Baseline to Infinite for Groups A to D | 63.126 h*µg/mL | — |
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 %.
Time frame: From Baseline to 140 hours post first dose
Population: 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.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Group A: Normal Renal Function | Area Under the Concentration-time Curve (AUC) of Ucb L059 (LEV) From Baseline to Infinite for Group E | 794.588 h*µg/mL | Full Range 10.5 |
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
Time frame: From Baseline up to 144 hours post first dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Normal Renal Function | Area Under the Concentration-time Curve (AUC) of Ucb L059 (LEV) From Baseline to Infinite for Groups A to D | 170.3045 h*µg/mL | Geometric Coefficient of Variation 14.8 |
| Group B: Mild Renal Impairment | Area Under the Concentration-time Curve (AUC) of Ucb L059 (LEV) From Baseline to Infinite for Groups A to D | 252.1923 h*µg/mL | Geometric Coefficient of Variation 16 |
| Group C: Moderate Renal Impairment | Area Under the Concentration-time Curve (AUC) of Ucb L059 (LEV) From Baseline to Infinite for Groups A to D | 174.0764 h*µg/mL | Geometric Coefficient of Variation 15.3 |
| Group D: Severe Renal Impairment | Area Under the Concentration-time Curve (AUC) of Ucb L059 (LEV) From Baseline to Infinite for Groups A to D | 217.6854 h*µg/mL | Geometric Coefficient of Variation 19.1 |
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
Time frame: From Baseline up to 144 hours post first dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Normal Renal Function | Fraction of Dose Excreted in Urine (fe) of Ucb L059 (LEV) for Groups A to D | 60.9464 Percentage of Dose Administered | Geometric Coefficient of Variation 30.3 |
| Group B: Mild Renal Impairment | Fraction of Dose Excreted in Urine (fe) of Ucb L059 (LEV) for Groups A to D | 49.5312 Percentage of Dose Administered | Geometric Coefficient of Variation 12.5 |
| Group C: Moderate Renal Impairment | Fraction of Dose Excreted in Urine (fe) of Ucb L059 (LEV) for Groups A to D | 39.4873 Percentage of Dose Administered | Geometric Coefficient of Variation 11.9 |
| Group D: Severe Renal Impairment | Fraction of Dose Excreted in Urine (fe) of Ucb L059 (LEV) for Groups A to D | 29.7504 Percentage of Dose Administered | Geometric Coefficient of Variation 34.4 |
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.
Time frame: From 44 hours to 48 hours post first dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Normal Renal Function | Hemodialysis Clearance (CLD) of Ucb L059 (LEV) During First Dialysis for Group E | 113.9665 mL/min | Geometric Coefficient of Variation 8.5 |
Secondary
Hemodialysis Clearance (CLHD) of Ucb L059 (LEV) During First Dialysis for Group E
Calculated according: CLHD=CLD+CLUF.
Time frame: From 44 hours to 48 hours post first dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Normal Renal Function | Hemodialysis Clearance (CLHD) of Ucb L059 (LEV) During First Dialysis for Group E | 115.3702 mL/min | Geometric Coefficient of Variation 8.1 |
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
Time frame: From Baseline up to 144 hours post first dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Normal Renal Function | Nonrenal Clearance (CLNR) of Ucb L059 (LEV) for Groups A to D | 1.0712 L/h | Geometric Coefficient of Variation 50.6 |
| Group B: Mild Renal Impairment | Nonrenal Clearance (CLNR) of Ucb L059 (LEV) for Groups A to D | 0.9873 L/h | Geometric Coefficient of Variation 17.4 |
| Group C: Moderate Renal Impairment | Nonrenal Clearance (CLNR) of Ucb L059 (LEV) for Groups A to D | 0.8636 L/h | Geometric Coefficient of Variation 18.4 |
| Group D: Severe Renal Impairment | Nonrenal Clearance (CLNR) of Ucb L059 (LEV) for Groups A to D | 0.7848 L/h | Geometric Coefficient of Variation 17.9 |
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
Time frame: From Baseline up to 144 hours post first dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Normal Renal Function | Renal Clearance (CLR) of Ucb L057 for Groups A to D | 14.6937 L/h | Geometric Coefficient of Variation 18.3 |
| Group B: Mild Renal Impairment | Renal Clearance (CLR) of Ucb L057 for Groups A to D | 6.8015 L/h | Geometric Coefficient of Variation 32.6 |
| Group C: Moderate Renal Impairment | Renal Clearance (CLR) of Ucb L057 for Groups A to D | 4.6828 L/h | Geometric Coefficient of Variation 45.6 |
| Group D: Severe Renal Impairment | Renal Clearance (CLR) of Ucb L057 for Groups A to D | 1.6475 L/h | Geometric Coefficient of Variation 42 |
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
Time frame: From Baseline up to 144 hours post first dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Normal Renal Function | Renal Clearance (CLR) of Ucb L059 (LEV) for Groups A to D | 1.8622 L/h | Geometric Coefficient of Variation 27.4 |
| Group B: Mild Renal Impairment | Renal Clearance (CLR) of Ucb L059 (LEV) for Groups A to D | 0.9820 L/h | Geometric Coefficient of Variation 22.1 |
| Group C: Moderate Renal Impairment | Renal Clearance (CLR) of Ucb L059 (LEV) for Groups A to D | 0.5671 L/h | Geometric Coefficient of Variation 17.6 |
| Group D: Severe Renal Impairment | Renal Clearance (CLR) of Ucb L059 (LEV) for Groups A to D | 0.3417 L/h | Geometric Coefficient of Variation 49.3 |
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
Time frame: From Baseline up to 144 hours post first dose
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A: Normal Renal Function | Terminal Half-life (t1/2) of Ucb L057 for Groups A to D | 12.351 hours |
| Group B: Mild Renal Impairment | Terminal Half-life (t1/2) of Ucb L057 for Groups A to D | 19.030 hours |
| Group C: Moderate Renal Impairment | Terminal Half-life (t1/2) of Ucb L057 for Groups A to D | 20.303 hours |
| Group D: Severe Renal Impairment | Terminal Half-life (t1/2) of Ucb L057 for Groups A to D | 26.769 hours |
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 %.
Time frame: From Baseline to 44 hours post first dose
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A: Normal Renal Function | Terminal Half-life (t1/2) of Ucb L059 (LEV) for Group E During First Period | 34.669 hours |
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
Time frame: From Baseline up to 144 hours post first dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Normal Renal Function | Terminal Half-life (t1/2) of Ucb L059 (LEV) for Groups A to D | 7.6164 hours | Geometric Coefficient of Variation 6.9 |
| Group B: Mild Renal Impairment | Terminal Half-life (t1/2) of Ucb L059 (LEV) for Groups A to D | 12.6214 hours | Geometric Coefficient of Variation 11.3 |
| Group C: Moderate Renal Impairment | Terminal Half-life (t1/2) of Ucb L059 (LEV) for Groups A to D | 15.5033 hours | Geometric Coefficient of Variation 17.5 |
| Group D: Severe Renal Impairment | Terminal Half-life (t1/2) of Ucb L059 (LEV) for Groups A to D | 19.7320 hours | Geometric Coefficient of Variation 26.5 |
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).
Time frame: From Baseline to 44 hours post first dose
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A: Normal Renal Function | Time to Reach Maximum Plasma Concentration (Tmax) of Ucb L057 for Group E During First Period | 44.020 hours |
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
Time frame: From Baseline up to 144 hours post first dose
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A: Normal Renal Function | Time to Reach Maximum Plasma Concentration (Tmax) of Ucb L057 for Groups A to D | 5.000 hours |
| Group B: Mild Renal Impairment | Time to Reach Maximum Plasma Concentration (Tmax) of Ucb L057 for Groups A to D | 8.000 hours |
| Group C: Moderate Renal Impairment | Time to Reach Maximum Plasma Concentration (Tmax) of Ucb L057 for Groups A to D | 12.000 hours |
| Group D: Severe Renal Impairment | Time to Reach Maximum Plasma Concentration (Tmax) of Ucb L057 for Groups A to D | 24.000 hours |
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).
Time frame: From Baseline to 44 hours post first dose
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A: Normal Renal Function | Time to Reach Maximum Plasma Concentration (Tmax) of Ucb L059 (Levetiracetam) for Group E During First Period | 0.720 hours |
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
Time frame: From Baseline up to 144 hours post first dose
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A: Normal Renal Function | Time to Reach Maximum Plasma Concentration (Tmax) of Ucb L059 (LEV) for Groups A to D | 0.500 hours |
| Group B: Mild Renal Impairment | Time to Reach Maximum Plasma Concentration (Tmax) of Ucb L059 (LEV) for Groups A to D | 1.000 hours |
| Group C: Moderate Renal Impairment | Time to Reach Maximum Plasma Concentration (Tmax) of Ucb L059 (LEV) for Groups A to D | 0.500 hours |
| Group D: Severe Renal Impairment | Time to Reach Maximum Plasma Concentration (Tmax) of Ucb L059 (LEV) for Groups A to D | 0.500 hours |
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
Time frame: From Baseline up to 144 hours post first dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Normal Renal Function | Total Amount Excreted in Urine (Ae) of Ucb L057 for Groups A to D | 83.5936 mg | Geometric Coefficient of Variation 16.9 |
| Group B: Mild Renal Impairment | Total Amount Excreted in Urine (Ae) of Ucb L057 for Groups A to D | 169.3395 mg | Geometric Coefficient of Variation 19 |
| Group C: Moderate Renal Impairment | Total Amount Excreted in Urine (Ae) of Ucb L057 for Groups A to D | 93.1346 mg | Geometric Coefficient of Variation 14 |
| Group D: Severe Renal Impairment | Total Amount Excreted in Urine (Ae) of Ucb L057 for Groups A to D | 100.7489 mg | Geometric Coefficient of Variation 17.8 |
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
Time frame: From Baseline up to 144 hours post first dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Normal Renal Function | Total Amount Excreted in Urine (Ae) of Ucb L059 (LEV) for Groups A to D | 304.7321 mg | Geometric Coefficient of Variation 30.3 |
| Group B: Mild Renal Impairment | Total Amount Excreted in Urine (Ae) of Ucb L059 (LEV) for Groups A to D | 247.6562 mg | Geometric Coefficient of Variation 12.5 |
| Group C: Moderate Renal Impairment | Total Amount Excreted in Urine (Ae) of Ucb L059 (LEV) for Groups A to D | 98.7182 mg | Geometric Coefficient of Variation 11.9 |
| Group D: Severe Renal Impairment | Total Amount Excreted in Urine (Ae) of Ucb L059 (LEV) for Groups A to D | 74.3761 mg | Geometric Coefficient of Variation 34.4 |
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.
Time frame: From 44 hours to 48 hours post first dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Normal Renal Function | Ultrafiltration Clearance (CLUF) of Ucb L059 (LEV) During First Dialysis for Group E | 1.3271 mL/min | Geometric Coefficient of Variation 32.5 |