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

NCT01491113 | Completed Phase 4 Results

• 1 other identifier: N01373
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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.

Conditions

Healthy Subjects; Renal Impairments

Keywords

Levetiracetam; Oral administration; Japanese; Non-epileptic; Healthy; Renal impaired subjects

Outcome Measures

Primary Outcomes (8)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

Secondary Outcomes (21)

• 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

• Renal Clearance (CLR) 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

• Nonrenal Clearance (CLNR) of Ucb L059 (LEV) for Groups A to D

  From Baseline up to 144 hours post first dose

Study Arms (5)

Group A: Normal renal function

EXPERIMENTAL

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

Group B: Mild renal impairment

EXPERIMENTAL

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

Group C: Moderate renal impairment

EXPERIMENTAL

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

Group D: Severe renal impairment

EXPERIMENTAL

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

Group E: End-stage renal disease

EXPERIMENTAL

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; Drug: Levetiracetam 500 mg

Interventions

Levetiracetam 250 mg DRUG

Tablet containing Levetiracetam 250 mg

Also known as: E-Keppra

Group C: Moderate renal impairment; Group D: Severe renal impairment; Group E: End-stage renal disease

Levetiracetam 500 mg DRUG

Tablet containing Levetiracetam 500 mg

Also known as: E-Keppra

Group A: Normal renal function; Group B: Mild renal impairment; Group E: End-stage renal disease

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Subjects has taken any drug treatment, disease or injury to influence Levetiracetam PK except for renal impairments

Sponsors & Collaborators

• UCB Pharma: lead
• Parexel: collaborator

Study Sites (2)

1

Fukuoka, Japan

Location

2

Ibaraki, Japan

Location

Related Links

• FDA Safety Alerts and Recalls

MeSH Terms

Interventions

Levetiracetam

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: UCB Clinical Trials Call Center
• Organization: UCB

+1 877 822 9493

Study Officials

• UCB Clinical Trial Call Center

  +1 877 822 9493 (UCB)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2011
• First Posted: December 13, 2011
• Study Start: November 1, 2011
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: February 10, 2014
• Results First Posted: January 10, 2014

Record last verified: 2014-01

Locations

JP (2)