Single-Dose Pharmacokinetics of Orally Administered Levetiracetam (LEV) in Japanese Subjects With Normal Renal Function and Various Degrees of Renal Impairment Using a Dosing Regimen Adjusted to Renal Function (250 mg or 500 mg)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- UCB Pharma
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Maximum Observed Plasma Concentration (Cmax) of Ucb L057 for Groups A to D
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •Subjects has taken any drug treatment, disease or injury to influence Levetiracetam PK except for renal impairments
研究组 & 干预措施
Group A: Normal renal function
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.
- Blood samples for Pharmacokinetics (PK): Predose (Baseline), and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours postdose
- Urine samples for PK: 0 - 6, 6 - 12, 12 - 24, 24 - 48, 48 - 72 hours postdose
干预措施: Levetiracetam 500 mg (Drug)
Group B: Mild renal impairment
Patients who have mild renal impairment (50<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 conducted through Day 5 during the Treatment Period, and safety follow-up assessments will be performed on Day 8 according to the schedule of study assessments.
- Blood samples for Pharmacokinetics (PK): Predose (Baseline), and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96 hours postdose
- Urine samples for PK: 0 - 6, 6 - 12, 12 - 24, 24 - 48, 48 - 72, 72 - 96 hours postdose
干预措施: Levetiracetam 500 mg (Drug)
Group C: Moderate renal impairment
Patients who have moderate renal impairment (30<CLcr < 50 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 6 during the Treatment Period, and safety follow-up assessments will be performed on Day 8 according to the schedule of study assessments.
- Blood samples for Pharmacokinetics (PK): Predose (Baseline), and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose
- Urine samples for PK: 0 - 6, 6 - 12, 12 - 24, 24 - 48, 48 - 72, 72 - 96, 96 -120 hours postdose
干预措施: Levetiracetam 250 mg (Drug)
Group D: Severe renal impairment
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.
- Blood samples for Pharmacokinetics (PK): Predose (Baseline), and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144 hours postdose
- Urine samples for PK: 0 - 6, 6 - 12, 12 - 24, 24 - 48, 48 - 72, 72 - 96, 96 -120, 120 - 144 hours postdose
干预措施: Levetiracetam 250 mg (Drug)
Group E: End-stage renal disease
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:
- Dialysis: 44 h to 48 h after the first dose (Day 3)
- Dialysis: 92 h to 96 h after the first dose (Day 5)
- Dialysis: 140 h after the first dose (Day 7)
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.
干预措施: Levetiracetam 250 mg (Drug)
Group E: End-stage renal disease
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:
- Dialysis: 44 h to 48 h after the first dose (Day 3)
- Dialysis: 92 h to 96 h after the first dose (Day 5)
- Dialysis: 140 h after the first dose (Day 7)
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.
干预措施: Levetiracetam 500 mg (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax) of Ucb L057 for Groups A to D
时间窗: 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
Maximum Observed Plasma Concentration (Cmax) of Ucb L059 (LEV) for Groups A to D
时间窗: 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
时间窗: 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
Area Under the Concentration-time Curve (AUC(0-t)) of Ucb L057 From Baseline to the Last Quantifiable Concentration for Groups A to D
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- Total Amount Excreted in Urine (Ae) of Ucb L057 for Groups A to D(From Baseline up to 144 hours post first dose)
- Total Amount Excreted in Urine (Ae) of Ucb L059 (LEV) for Groups A to D(From Baseline up to 144 hours post first dose)
- 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)
- 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)
- 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)
- Terminal Half-life (t1/2) of Ucb L059 (LEV) for Groups A to D(From Baseline up to 144 hours post first dose)
- Time to Reach Maximum Plasma Concentration (Tmax) of Ucb L057 for Groups A to D(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(From Baseline up to 144 hours post first dose)
- Terminal Half-life (t1/2) of Ucb L057 for Groups A to D(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(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(From Baseline to 140 hours post first dose)
- Renal Clearance (CLR) of Ucb L059 (LEV) for Groups A to D(From Baseline up to 144 hours post first dose)
- Nonrenal Clearance (CLNR) of Ucb L059 (LEV) for Groups A to D(From Baseline up to 144 hours post first dose)
- Apparent Total Body Clearance (CL/F) of Ucb L059 (LEV) for Groups A to D(From Baseline up to 144 hours post first dose)
- Renal Clearance (CLR) of Ucb L057 for Groups A to D(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(From Baseline to 44 hours post first dose)
- Terminal Half-life (t1/2) of Ucb L059 (LEV) for Group E During First Period(From Baseline to 44 hours post first dose)
- Time to Reach Maximum Plasma Concentration (Tmax) of Ucb L057 for Group E During First Period(From Baseline to 44 hours post first dose)
- Hemodialysis Clearance (CLD) of Ucb L059 (LEV) During First Dialysis for Group E(From 44 hours to 48 hours post first dose)
- Ultrafiltration Clearance (CLUF) of Ucb L059 (LEV) During First Dialysis for Group E(From 44 hours to 48 hours post first dose)
- Hemodialysis Clearance (CLHD) of Ucb L059 (LEV) During First Dialysis for Group E(From 44 hours to 48 hours post first dose)