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

Healthy Subjects Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01491113
• Other study ID #: N01373
• Status: Completed
• Phase: Phase 4
• First received: December 9, 2011
• Last updated: January 13, 2014
• Start date: November 2011
• Est. completion date: November 2012

Study information

• Verified date: January 2014
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 20 Years to 80 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy Subjects
• Renal Impairments
• Renal Insufficiency

Intervention

Drug:
• Levetiracetam 250 mg
Tablet containing Levetiracetam 250 mg
• Levetiracetam 500 mg
Tablet containing Levetiracetam 500 mg

Locations

Country	Name	City	State
Japan	1	Fukuoka
Japan	2	Ibaraki

Sponsors (2)

Lead Sponsor	Collaborator
UCB Pharma	Parexel

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	From Baseline up to 144 hours post first dose	No
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	From Baseline up to 144 hours post first dose	No
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	From Baseline up to 144 hours post first dose	No
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	From Baseline up to 144 hours post first dose	No
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).	From Baseline to 44 hours post first dose	No
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.	From Baseline to 44 hours post first dose	No
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.	From Baseline to 44 hours post first dose	No
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.	From Baseline to 44 hours post first dose	No
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	From Baseline up to 144 hours post first dose	No
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	From Baseline up to 144 hours post first dose	No
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	From Baseline up to 144 hours post first dose	No
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	From Baseline up to 144 hours post first dose	No
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	From Baseline up to 144 hours post first dose	No
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	From Baseline up to 144 hours post first dose	No
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	From Baseline up to 144 hours post first dose	No
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 %.	From Baseline to 44 hours post first dose	No
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	From Baseline up to 144 hours post first dose	No
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	From Baseline up to 144 hours post first dose	No
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	From Baseline up to 144 hours post first dose	No
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	From Baseline up to 144 hours post first dose	No
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	From Baseline up to 144 hours post first dose	No
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	From Baseline up to 144 hours post first dose	No
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).	From Baseline to 44 hours post first dose	No
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 %.	From Baseline to 140 hours post first dose	No
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 %.	From Baseline to 44 hours post first dose	No
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).	From Baseline to 44 hours post first dose	No
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.	From 44 hours to 48 hours post first dose	No
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.	From 44 hours to 48 hours post first dose	No
Secondary	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	No

External Links

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