Clinical Trials Register

Summary
EudraCT Number:	2004-000199-14
Sponsor's Protocol Code Number:	N01009
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2005-08-05
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Belgium - FPS Health-DGM

A.2

EudraCT number

2004-000199-14

A.3

Full title of the trial

A double-blind, randomized, multicenter, placebo-controlled, in-patients maximum 34 day study of levetiracetam oral solution (20-50 mg/kg/day) as adjunctive treatment of refractory partial onset seizures in pediatric epileptic subjects ranging in age from 1 month to less than 4 years of age

A.3.2

Name or abbreviated title of the trial where available

Pediatric Exclusivity Efficacy

A.4.1

Sponsor's protocol code number

N01009

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	UCB S.A. Pharma Sector
B.1.3.4	Country	Belgium
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point
B.Sponsor: 2
B.1.1	Name of Sponsor	UCB Pharma Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Information not present in EudraCT
D.2.1.1.1	Trade name	Keppra
D.2.1.1.2	Name of the Marketing Authorisation holder	UCB S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Levetiracetam
D.3.2	Product code	ucb L059
D.3.4	Pharmaceutical form	Oral solution
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Levetiracetam
D.3.9.1	CAS number	102767-28-2
D.3.9.2	Current sponsor code	ucb L059
D.3.9.3	Other descriptive name	S-enantiomer of α-ethyl-2-oxo-1- pyrrolidine acetamide
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	Information not present in EudraCT
D.3.11.8	Extractive medicinal product	Information not present in EudraCT
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Oral solution
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Epilepsy - Refractory Partial Onset Seizures

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	7.0
E.1.2	Level	LLT
E.1.2	Classification code	10061334

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the efficacy and safety of levetiracetam (LEV) used as adjunctive treatment in pediatric subjects age 1 month to less than 4 years with refractory partial onset seizures.

E.2.2

Secondary objectives of the trial

Not Applicable

E.2.3

Trial contains a sub-study

Information not present in EudraCT

E.3

Principal inclusion criteria

Before any study procedures are initiated for any subject in this study, an IRB/IEC approved written informed consent form will be properly executed and documented. To be eligible to participate in the study, a subject must meet each of the following criteria.
• The subject’s parent(s) or legally authorized representative(s) must give consent and sign and date the IRB/IEC approved written informed consent form.
• Subject must have a diagnosis of epilepsy with refractory partial onset seizures (i.e., seizures of focal onset), whether or not secondarily generalized.
• Subject must be male or female from 1 month to less than 4 years of age.
• Must be a subject for whom the Investigator believes that past or current anti-epileptic drug (AED) treatment is unsatisfactory in terms of efficacy and/or safety.
• Must be a subject for whom alternative treatment with levetiracetam may be of benefit.
• Subject must be on a stable regimen of one or a maximum of two other AEDs for the Selection and Evaluation periods of the study.
• Minor adjustments to the dose of current AEDs are allowed only prior to Day -8.
• Subject has no additions of new AEDs or deletions of current AEDs that have been
observed for at least 2 weeks prior to Day -8.
• Subject may have Vagus Nerve Stimulation (VNS) which has been implanted for at
least 6 months prior to Day -8; the settings must be stable for at least 2 months prior to Day -8. Activated VNS must be counted as one of the two AEDs.
• Subject must have experienced at least two partial onset seizures (i.e., seizures of focal onset), with or without secondary generalization during each 7-day period during the 2 weeks prior to Day -8.
• Subjects 1 month to less than 6 months of age must experience at least two, partial onset seizures (i.e., seizures of focal onset), whether or not secondarily generalized during the 48-hour video-EEG performed prior to randomization on Day 1. These seizures do not need to be accompanied by a corresponding clinical event.
• Subjects 6 months to less than 1 year of age, subjects 1 year to less than 2 years of age and subjects 2 years to less than 4 years of age must experience at least two partial onset seizures (i.e., seizures of focal onset), whether or not secondarily generalized, during the 48-hour video-EEG performed prior to randomization on Day 1. These seizures must be accompanied by a corresponding clinical event as noted on either video or as reported by a qualified observer, such as a medical doctor or a nurse with significant neurology training and experience.
• If epilepsy surgery has been performed prior to study entry, then the subjects must have a documented failed epilepsy surgery outcome at least 4 weeks prior to Day -8.
• The use of intermittent benzodiazepines is allowed as long as the frequency is not
greater than one single administration per week for at least 2 weeks prior to Day -8 and throughout study participation.
• If benzodiazepines are used more than once a week, they must be considered as one of the AEDs.

E.4

Principal exclusion criteria

Subjects must be excluded if they meet any of the following criteria:
• Subject is taking any medication (other than their concomitant AED(s)) that influences the central nervous system (CNS) for which they have not been on a stable regimen for at least 1 month prior to Day -8.
• Subject is taking any medication that may interfere with the absorption, distribution, metabolism, or excretion of the concomitant AEDs or levetiracetam during the course of the study.
• Subject has received any investigational medication or device within thirty (30) days prior to Day -8.
• Subject has taken levetiracetam prior to the study.
• Subjects using felbamate who have presented with clinically significant abnormalities with WBC’s, RBC’s, platelets, and/or hepatic function during felbamate treatment, and subjects who are taking felbamate less than one year from the date of Day -8.
• Subject has a treatable seizure etiology, (i.e., febrile seizures).
• Subject has a history of status epilepticus requiring hospitalization during the 1 month prior to Day -8, except for status epilepticus occurring during the first 10 days of life.
• Subject has a current diagnosis of Lennox-Gastaut syndrome.
• Subject is on a ketogenic diet (currently or within 30 days prior to Day -8).
• Subject has epilepsy secondary to a progressing cerebral disease or any other
progressively neurodegenerative disease, such as Rasmussen and Landau-Kleffner
diseases.
• Subject has clinically significant deviations from reference range values for renal
function or any of the other laboratory parameters required for this study, as determined by the Investigator.
• Subject has any clinically significant acute or chronic illness (as determined during the physical examination or from other information available to the Investigator).
• Subject has an allergy to pyrrolidine derivatives or a history of multiple drug allergies.
• Subject is known to have a terminal illness.
• Subject has a disorder or condition that may interfere with the absorption, distribution, metabolism, or excretion of medications.
• Subject has a history of or presence of pseudoseizures.
• Subject has any medical condition that might interfere with the subject’s study
participation (i.e., serious infection, scheduled elective surgery, severe scalp eczema,
etc).

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy analyses will be based on mITT and PP populations.
The primary efficacy variable, Responder Rate, for total partial onset seizures for subjects in all age groups is defined as the number of subjects with a ≥ 50% reduction in their average daily frequency (ADF) of partial onset seizures recorded on the 48-hour Evaluation video-EEG compared to the 48-hour Selection video-EEG.

Safety parameters will be: physical and neurological examinations, adverse events, vital signs, and laboratory tests, including blood chemistry, levetiracetam (LEV) levels, and hematology.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Information not present in EudraCT

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.5

The trial involves multiple Member States

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

E.8.7

Trial has a data monitoring committee

Information not present in EudraCT

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of the trial is defined as the date of Database Lock as, at that time, interactions between the Sponsor and the Investigator with possible impact on subjects data have ended.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

Yes

F.1.1.5

Children (2-11years)

Yes

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Information not present in EudraCT

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Information not present in EudraCT

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Pediatric Population

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

220

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Subjects will have the opportunity to enter in the Open-label, Long-term, Follow-up study N01148(Sponsor's protocol code number), EudraCT number 2004-000200-40.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2004-12-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2004-08-24

P. End of Trial
P.	End of Trial Status	Completed

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IMP with orphan designation in the indication
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