An Open Label Study of Levetiracetam in Japanese Pediatric Patients With Partial Seizures

• ClinicalTrials.gov Identifier: NCT01063764
• Recruitment Status: Completed
• First Posted: February 5, 2010
• Results First Posted: June 19, 2012
• Last Update Posted: March 5, 2015
• Sponsor: UCB Japan Co. Ltd.
• Information provided by (Responsible Party): UCB Pharma ( UCB Japan Co. Ltd. )

Study Description

Brief Summary:

Objective of the First Period: To evaluate the efficacy of Levetiracetam dry syrup at doses up to a maximum of 60 mg/kg/day or 3000 mg/day used as an adjunctive therapy in Japanese pediatric patients (4 to 16 years) with uncontrolled partial seizures despite treatment with 1 or 2 anti-epileptic drug(s).

Condition or disease	Intervention/treatment	Phase
Epilepsy; Partial Seizures	Drug: Levetiracetam	Phase 3

Detailed Description:

Objectives of the Second Period: To provide the Levetiracetam treatment to subjects who are judged by the investigators to benefit from the long-term treatment and who are willing to continuously receive this drug. To continuously evaluate the safety of the Levetiracetam long-term administration at doses ranging from 20 mg/kg/day or 1000 mg/day to 60 mg/kg/day or 3000 mg/day in subjects who completed the First Period of this study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 73 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label, Single-Arm, Multi-Center Study on the Efficacy, Safety and Pharmacokinetics of Levetiracetam in Pediatric Patients (4 to 16 Years) With Partial Seizures Despite Treatment With 1 or 2 Anti-Epileptic Drugs
• Study Start Date: January 2010
• Actual Primary Completion Date: April 2011
• Actual Study Completion Date: October 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Levetiracetam; Open-label, single-arm	Drug: Levetiracetam; First Period: Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks. Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.; Other Name: Keppra

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Partial Seizure Frequency Per Week Over the 14-weeks Treatment Period [ Time Frame: From Baseline (Week 0-8) to the 14-weeks Treatment Period (First Period: 4 weeks Up-titration (Week 8-12) and 10 weeks Evaluation (Week 12-22)); Week 0-22 ]

   The change in partial seizure frequency from Baseline (B) over the Treatment Period (T) is given as a percentage reduction computed as:

   (B values- T values) / B values x 100.

   Positive values in percent reduction mean that the value decreased from Baseline during the first 14-week Period.

   Frequency per week of partial seizures = (Total number of partial seizures in a certain Period/number of observation days in the Period) x 7.

   Partial seizures can be classified into:

   • Simple partial seizures
   • Complex partial seizures
   • Partial seizures evolving to secondarily generalized seizures.
2. Incidence of Treatment-Emergent Adverse Events (TEAEs) During the Second Period (up to Three Years Until the Time of Approval Granted) [ Time Frame: During the second Period from Visit 8 (Week 22) to the end of the Follow-up Period (up to three years until the time of approval granted) ]
   An Adverse Event (AE) is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product which does not necessarily have a causal relationship with the pharmaceutical product. Incidence of treatment-emergent AEs is reported by the percentage of subjects with at least one treatment-emergent AE.

Secondary Outcome Measures :

1. Change From Baseline in Partial Seizure Frequency Per Week Over the 10-week Evaluation Period [ Time Frame: From Baseline (Week 0-8) to the 10-weeks Evaluation Period (Part of the first Period: Week 12 to Week 22) ]

   The change in partial seizure frequency from Baseline (B) over the Evaluation Period (E) is given as a percentage reduction computed as:

   (B values- E values) / B values x 100. Positive values in percent reduction mean that the value decreased from Baseline to the 10-week Evaluation Period.

   Frequency per week of partial seizures = (Total number of partial seizures in a certain Period/number of observation days in the Period) x 7.

   Partial seizures can be classified into:

   • Simple partial seizures
   • Complex partial seizures
   • Partial seizures evolving to secondarily generalized seizures.
2. Partial Seizure Frequency Per Week Over the 14-weeks Treatment Period [ Time Frame: 14-weeks Treatment Period (First Period: 4 weeks Up-titration (Week 8-12) and 10 weeks Evaluation (Week 12-22)) ]

   The seizure frequency per week was calculated as:

   Frequency per week of partial seizures = (Total number of partial seizures in the Treatment Period/number of days for observation in the Treatment Period) x 7. Partial seizures can be classified into one of the following three groups:

   • Simple partial seizures
   • Complex partial seizures
   • Partial seizures evolving to secondarily generalized seizures.
3. Partial Seizure Frequency Per Week Over the 10-weeks Evaluation Period [ Time Frame: 10-weeks Evaluation Period (Part of the first Period: Week 12 to Week 22) ]

   The seizure frequency per week was calculated as:

   Frequency per week of partial seizures = (Total number of partial seizures in the Evaluation Period/number of days for observation in the Evaluation Period) x 7. Partial seizures can be classified into one of the following three groups:

   • Simple partial seizures
   • Complex partial seizures
   • Partial seizures evolving to secondarily generalized seizures.
4. Percentage of Partial Seizures 50 % Responders Over the 14-weeks Treatment Period [ Time Frame: 14-weeks Treatment Period (First Period: 4 weeks Up-titration (Week 8-12) and 10 weeks Evaluation (Week 12-22)) ]

   50 % responders are those subjects which have a 50 % or more reduction in the frequency of partial seizures from Baseline to the Treatment Period. The results show the percentage of participants that are 50 % responders.

   Partial seizures can be classified into one of the following three groups:

   • Simple partial seizures
   • Complex partial seizures
   • Partial seizures evolving to secondarily generalized seizures.
5. Percentage of Partial Seizures 50 % Responders Over the 10-weeks Evaluation Period [ Time Frame: 10-weeks Evaluation Period (Part of the first Period: Week 12 to Week 22) ]

   50 % responders are those subjects which have a 50 % or more reduction in the frequency of partial seizures from Baseline to the Evaluation Period. The results show the percentage of participants that are 50 % responders.

   Partial seizures can be classified into one of the following three groups:

   • Simple partial seizures
   • Complex partial seizures
   • Partial seizures evolving to secondarily generalized seizures.
6. Number of Seizure-free Subjects Over the 14-weeks Treatment Period [ Time Frame: 14-weeks Treatment Period (First Period: 4 weeks Up-titration (Week 8-12) and 10 weeks Evaluation (Week 12-22)) ]

   Seizure-free means not having a seizure of type I (Partial seizure).

   Partial seizures can be classified into one of the following three groups:

   • Simple partial seizures
   • Complex partial seizures
   • Partial seizures evolving to secondarily generalized seizures.
7. Number of Seizure-free Subjects Over the 10-weeks Evaluation Period [ Time Frame: 10-weeks Evaluation Period (Part of the first Period: Week 12 to Week 22) ]

   Seizure-free means not having a seizure of type I (Partial seizure).

   Partial seizures can be classified into one of the following three groups:

   • Simple partial seizures
   • Complex partial seizures
   • Partial seizures evolving to secondarily generalized seizures.
8. Incidence of Treatment-emergent Adverse Drug Reactions (ADRs) During the Second Period (up to Three Years Until the Time of Approval Granted) [ Time Frame: During the second Period from Visit 8 (Week 22) to the end of the Follow-up Period (up to three years until the time of approval granted) ]
   An Adverse Drug Reaction (ADR) is an Adverse Event for which a causal relationship between the product and the occurrence is suspected. Incidence of ADRs is reported by the number of subjects with at least one ADR.
9. Change From Baseline in Partial Seizure Frequency Per Week for the Second Period (up to Three Years From Informed Consent Until the Time of Approval Granted) [ Time Frame: From Baseline (Week 0-8) until the time of approval granted (up to three years from date of informed consent (Week 0); without 6-weeks Withdrawal Period) ]

   The outcome was also calculated for each 3-month Period but here only the result for the total Second Evaluation Period (Second Period without following 6-weeks Withdrawal Period for withdrawers) is presented.

   Change in partial seizure frequency from Baseline (B) over Second Evaluation Period (E) is given as a percentage reduction computed as:

   (B values- E values) / B values x 100. Positive values in percent reduction show a decrease from Baseline. Frequency per week of partial seizures = (Total number of partial seizures in a certain Period/number of observation days in the Period) x 7.

Eligibility Criteria

• Ages Eligible for Study: 4 Years to 16 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• The patient has partial Epilepsy and the diagnosis must be confirmed in the last 6 months
• The patients must be on a stable 1 or 2 anti-epileptic drug(s) treatment during the 4 weeks prior to Baseline and must have at least 8 partial seizures during the 8-week prospective Baseline Period
• Patient at the age of 4 to 16 years, and at the body weight of 11 to 82 kg

Exclusion Criteria:

• The patient has a treatable seizure etiology
• The patient has Epilepsy secondary to a progressive cerebral disease or any other progressively neurodegenerative disease, including Rasmussen and Landau-Kleffner diseases
• The patient has a history of status Epilepticus during the 3 months prior to Visit 1
• The patient has a past and present history of pseudo seizures
• The patient has a current diagnosis of Lennox-Gastaut syndrome

Contacts and Locations

Locations

Japan

21

Chuo, Japan

12

Hakodate, Japan

22

Hamamatsu, Japan

28

Hiroshima, Japan

7

Izumi, Japan

9

Kobe, Japan

3

Kodaira, Japan

30

Koga, Japan

10

Koushi, Japan

31

Kurume, Japan

23

Kyoto, Japan

2

Nagaoka, Japan

5

Nagoya, Japan

6

Nagoya, Japan

8

Neyagawa, Japan

1

Niigata, Japan

27

Okayama, Japan

24

Osaka, Japan

25

Osaka, Japan

11

Sapporo, Japan

13

Sendai, Japan

4

Shizuoka, Japan

26

Takatsuki, Japan

16

Tokyo, Japan

17

Tokyo, Japan

15

Yachiyo, Japan

14

Yamagata, Japan

19

Yokohama, Japan

20

Yokohama, Japan

Sponsors and Collaborators

UCB Japan Co. Ltd.

Investigators

• Study Director: UCB Clinical Trial Call Center; +1 877 822 9493 (UCB)

More Information

Additional Information:

FDA Safety Alerts and Recalls 

Publications of Results:

Nakamura H, Osawa M, Yokoyama T, Yoshida K, Suzuki A. [Efficacy and safety of levetiracetam as adjunctive therapy in Japanese children with uncontrolled partial-onset seizures: multicenter and open-label study (N01223), short term evaluation]. Brain Nerve. 2013 Sep;65(9):1083-92. Japanese.

• Responsible Party: UCB Japan Co. Ltd.
• ClinicalTrials.gov Identifier: NCT01063764
• Other Study ID Numbers: N01223; 2014-004335-39 ( EudraCT Number )
• First Posted: February 5, 2010
• Results First Posted: June 19, 2012
• Last Update Posted: March 5, 2015
• Last Verified: February 2015

Keywords provided by UCB Pharma ( UCB Japan Co. Ltd. ):

Keppra; Levetiracetam; Children; Epilepsy; Partial Seizures

Additional relevant MeSH terms:

Epilepsy; Seizures; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Levetiracetam; Anticonvulsants; Nootropic Agents