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

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ClinicalTrials.gov Identifier: NCT01491113
Recruitment Status : Completed
First Posted : December 13, 2011
Results First Posted : January 10, 2014
Last Update Posted : February 10, 2014
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
UCB Pharma

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.

Condition or disease Intervention/treatment Phase
Healthy Subjects Renal Impairments Drug: Levetiracetam 250 mg Drug: Levetiracetam 500 mg Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
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)
Study Start Date : November 2011
Actual Primary Completion Date : November 2012
Actual Study Completion Date : November 2012

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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
Drug: Levetiracetam 500 mg
Tablet containing Levetiracetam 500 mg
Other Name: E-Keppra

Experimental: 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
Drug: Levetiracetam 500 mg
Tablet containing Levetiracetam 500 mg
Other Name: E-Keppra

Experimental: 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
Drug: Levetiracetam 250 mg
Tablet containing Levetiracetam 250 mg
Other Name: E-Keppra

Experimental: 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
Drug: Levetiracetam 250 mg
Tablet containing Levetiracetam 250 mg
Other Name: E-Keppra

Experimental: 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:

  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.

Drug: Levetiracetam 250 mg
Tablet containing Levetiracetam 250 mg
Other Name: E-Keppra

Drug: Levetiracetam 500 mg
Tablet containing Levetiracetam 500 mg
Other Name: E-Keppra




Primary Outcome Measures :
  1. Maximum Observed Plasma Concentration (Cmax) of Ucb L059 (LEV) for Groups A to D [ Time Frame: 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


  2. 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 [ Time Frame: 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


  3. Maximum Observed Plasma Concentration (Cmax) of Ucb L057 for Groups A to D [ Time Frame: 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


  4. Area Under the Concentration-time Curve (AUC(0-t)) of Ucb L057 From Baseline to the Last Quantifiable Concentration for Groups A to D [ Time Frame: 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


  5. Maximum Observed Plasma Concentration (Cmax) of Ucb L059 (LEV) for Group E During First Period [ Time Frame: From Baseline to 44 hours post first dose ]
    Cmax refers to the maximum observed concentration of ucb L059 (Levetiracetam).

  6. Area Under the Concentration-time Curve (AUC(0-t)) of Ucb L059 (LEV) From Baseline to 44 Hours for Group E [ Time Frame: 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.

  7. Maximum Observed Plasma Concentration (Cmax) of Ucb L057 for Group E During First Period [ Time Frame: From Baseline to 44 hours post first dose ]
    Cmax refers to the maximum observed concentration of ucb L057.

  8. Area Under the Concentration-time Curve (AUC(0-t)) of Ucb L057 From Baseline to 44 Hours for Group E [ Time Frame: 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 Outcome Measures :
  1. Total Amount Excreted in Urine (Ae) of Ucb L059 (LEV) for Groups A to D [ Time Frame: 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


  2. Fraction of Dose Excreted in Urine (fe) of Ucb L059 (LEV) for Groups A to D [ Time Frame: 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


  3. Renal Clearance (CLR) of Ucb L059 (LEV) for Groups A to D [ Time Frame: 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


  4. Apparent Total Body Clearance (CL/F) of Ucb L059 (LEV) for Groups A to D [ Time Frame: 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


  5. Nonrenal Clearance (CLNR) of Ucb L059 (LEV) for Groups A to D [ Time Frame: 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


  6. Total Amount Excreted in Urine (Ae) of Ucb L057 for Groups A to D [ Time Frame: 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


  7. Renal Clearance (CLR) of Ucb L057 for Groups A to D [ Time Frame: 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


  8. Apparent Total Body Clearance (CL/F) of Ucb L059 (LEV) for Group E During First Period [ Time Frame: 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 %.


  9. Time to Reach Maximum Plasma Concentration (Tmax) of Ucb L059 (LEV) for Groups A to D [ Time Frame: 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


  10. Area Under the Concentration-time Curve (AUC) of Ucb L059 (LEV) From Baseline to Infinite for Groups A to D [ Time Frame: 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


  11. Terminal Half-life (t1/2) of Ucb L059 (LEV) for Groups A to D [ Time Frame: 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


  12. Time to Reach Maximum Plasma Concentration (Tmax) of Ucb L057 for Groups A to D [ Time Frame: 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


  13. Area Under the Concentration-time Curve (AUC) of Ucb L057 From Baseline to Infinite for Groups A to D [ Time Frame: 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


  14. Terminal Half-life (t1/2) of Ucb L057 for Groups A to D [ Time Frame: 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


  15. Time to Reach Maximum Plasma Concentration (Tmax) of Ucb L059 (Levetiracetam) for Group E During First Period [ Time Frame: From Baseline to 44 hours post first dose ]
    tmax refers to the time to reach the maximum plasma concentration of ucb L059 (Levetiracetam).

  16. Area Under the Concentration-time Curve (AUC) of Ucb L059 (LEV) From Baseline to Infinite for Group E [ Time Frame: 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 %.


  17. Terminal Half-life (t1/2) of Ucb L059 (LEV) for Group E During First Period [ Time Frame: 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 %.


  18. Time to Reach Maximum Plasma Concentration (Tmax) of Ucb L057 for Group E During First Period [ Time Frame: From Baseline to 44 hours post first dose ]
    tmax refers to the time to reach maximum plasma concentration (tmax).

  19. Hemodialysis Clearance (CLD) of Ucb L059 (LEV) During First Dialysis for Group E [ Time Frame: From 44 hours to 48 hours post first dose ]
    Calculated by the Arterio - Venous difference method and cumulative dialysate method.

  20. Ultrafiltration Clearance (CLUF) of Ucb L059 (LEV) During First Dialysis for Group E [ Time Frame: From 44 hours to 48 hours post first dose ]
    Calculated by the Arterio - Venous difference method and cumulative dialysate method.

  21. Hemodialysis Clearance (CLHD) of Ucb L059 (LEV) During First Dialysis for Group E [ Time Frame: From 44 hours to 48 hours post first dose ]
    Calculated according: CLHD=CLD+CLUF.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   20 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01491113


Locations
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Japan
1
Fukuoka, Japan
2
Ibaraki, Japan
Sponsors and Collaborators
UCB Pharma
Parexel
Investigators
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Study Director: UCB Clinical Trial Call Center +1 877 822 9493 (UCB)

Additional Information:
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Responsible Party: UCB Pharma
ClinicalTrials.gov Identifier: NCT01491113     History of Changes
Other Study ID Numbers: N01373
First Posted: December 13, 2011    Key Record Dates
Results First Posted: January 10, 2014
Last Update Posted: February 10, 2014
Last Verified: January 2014
Keywords provided by UCB Pharma:
Levetiracetam
Oral administration
Japanese
Non-epileptic
Healthy
Renal impaired subjects
Additional relevant MeSH terms:
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Renal Insufficiency
Kidney Diseases
Urologic Diseases
Levetiracetam
Anticonvulsants
Nootropic Agents