Pharmacokinetic (PK) Study in Japanese Non-epileptic Renal Impaired Patients

UCB

Status and phase: Completed; Phase 4

Conditions: Healthy Subjects; Renal Impairments

Treatments: Drug: Levetiracetam 250 mg; Drug: Levetiracetam 500 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT01491113

N01373

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 patients

Sex: All

Ages: 20 to 80 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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30 participants in 5 patient groups

Group A: Normal renal function

Experimental group

Description:

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

Treatment:

Drug: Levetiracetam 500 mg

Group B: Mild renal impairment

Experimental group

Description:

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

Treatment:

Drug: Levetiracetam 500 mg

Group C: Moderate renal impairment

Experimental group

Description:

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

Treatment:

Drug: Levetiracetam 250 mg

Group D: Severe renal impairment

Experimental group

Description:

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

Treatment:

Drug: Levetiracetam 250 mg

Group E: End-stage renal disease

Experimental group

Description:

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: 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 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.

Treatment:

Drug: Levetiracetam 500 mg

Drug: Levetiracetam 250 mg