Clinical Trials Register

Summary
EudraCT Number:	2006-000169-12
Sponsor's Protocol Code Number:	N01187
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2006-09-28
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

Netherlands - Competent Authority

A.2

EudraCT number

2006-000169-12

A.3

Full title of the trial

A multicenter, randomized, double-blind, placebo-controlled, parallel study to evaluate the efficacy and safety of brivaracetam used as adjunctive treatment for 12 weeks in adolescent and adult patients (≥16 years) with genetically ascertained Unverricht-Lundborg disease.

A.4.1

Sponsor's protocol code number

N01187

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.
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

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	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/05/315
D.3 Description of the IMP
D.3.1	Product name	Brivaracetam
D.3.2	Product code	ucb 34714
D.3.4	Pharmaceutical form	Tablet
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	brivaracetam
D.3.9.1	CAS number	357336-20-0
D.3.9.2	Current sponsor code	ucb 34714
D.3.9.3	Other descriptive name	(2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl] butanamide
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
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	No
D.3.11.8	Extractive medicinal product	No
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.IMP: 2
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	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/05/315
D.3 Description of the IMP
D.3.1	Product name	Brivaracetam
D.3.2	Product code	ucb 34714
D.3.4	Pharmaceutical form	Tablet
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	brivaracetam
D.3.9.1	CAS number	357336-20-0
D.3.9.2	Current sponsor code	ucb 34714
D.3.9.3	Other descriptive name	(2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl] butanamide
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
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	No
D.3.11.8	Extractive medicinal product	No
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	Tablet
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

Patients with genetically ascertained Unverricht-Lundborg disease (ULD).

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	8.1
E.1.2	Level	LLT
E.1.2	Classification code	10054894
E.1.2	Term	Unverricht-Lundborg disease

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of the study is to compare the efficacy of brivaracetam 50 and
150mg/d in b.i.d. administration with placebo, on the symptom relief of action myoclonus in patients with ULD.

E.2.2

Secondary objectives of the trial

The secondary objectives are to compare the efficacy of brivaracetam 50 and 150mg/d in b.i.d. administration with placebo on the functional disability and on the symptom relief as evaluated by the Myoclonus Patient Questionnaire in patients with ULD. The secondary objectives are also to evaluate the dose/clinical response relationship, to assess the safety and tolerability of Brivaracetam (BRV) in this patient population as well as to assess the effect of BRV on the global evaluation of the disease evolution (assessed by the investigator) of these ULD patients.
The exploratory objectives are to evaluate the effect of BRV on the mood, on the health related quality of life and on the global evaluation of the evolution of the disease (assessed by the patients) of these ULD patients.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.) Subjects with diagnosed ULD ascertained by appropriate genetic testing for a
homozygous or compound heterozygous mutation in the CSTB gene.

2.) Subjects with moderate to severe myoclonus documented by an Action Myoclonus
sum score of ≥ 30 (evaluation by investigator).

3.) Subjects currently being or having been treated with clonazepam up to the maximum recommended daily dose of 20 mg or up to their individual optimal dose as assessed by the investigator.

4.) Subjects currently being or having been treated with valproate up to the maximum
recommended daily dose 60 mg/kg or serum levels of 100 mcg/ml or up to their individual optimal dose as specified by the investigator.

E.4

Principal exclusion criteria

1.) Subjects currently on felbamate or having been on felbamate within less than 18
months prior to visit 1.

2.) Subjects currently treated with phenytoin or having been on phenytoin in the last
month prior to visit 1.

3.) Subjects currently on vigabatrine. Subjects having been on vigabatrine if no visual
fields examination report available including standard static (Humphrey or Octopus)
or cinetic perimetry (Goldman).

4.) Subject taking any drug with possible CNS effects.

5.) Subjects taking any drug that may significantly influence the metabolism of BRV
(CYP2C or CYP3A potent inducers/inhibitors).

6.) Known clinically significant acute or chronic illness or illness which may impair
reliable participation in the trial, necessitate the use of medication not allowed by
protocol or represent a safety risk in the Investigator’s opinion.

7.) Subjects with history of severe adverse hematological reaction to any drug.

8.) Impaired hepatic function: ALAT/SGPT, ASAT/SGOT, alkaline phosphatase, GGT
value of more than three times the upper limit of the reference range.

9.) History of suicide attempt during the last 5 years.

10.) Subject with suicidal ideations within the last year or at risk of suicide attempt
unless cleared by written confirmation from a psychiatrist and approved by the UCB
physician.

11.) Ongoing psychiatric disorder other than mild controlled disorder.

E.5 End points

E.5.1

Primary end point(s)

The least-square means of the percent reduction from baseline on the Action Myoclonus will be estimated at every post-randomization visit in each treatment arm.

95% confidence limits on the difference between the least-square means of the Action Myoclonus score at the scheduled end of the treatment phase (V7) will be presented. The population for primary efficacy analysis is the ITT population.

The effect on the treatment difference because of concomitant use of Levetiracetam and/or Piracetam will be investigated through an interaction term with treatment and
randomization stratum in the model.

A descriptive analysis will be performed on the categorized percent reduction from
baseline at end of treatment on the action myoclonus. The defined categories are <- 25%, [-25% , 0], [0 , 25%[ , [25% , 50%[ , [50% , 75%[ , [75% , 100%[ and 100%.

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

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

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

Yes

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.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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

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

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

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)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.2

Adults (18-64 years)

Yes

F.1.3

Elderly (>=65 years)

Yes

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

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

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

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

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)

A LTFU trial (trial N01125) will allow subjects to continue on open brivaracetam treatment, until European approval has been obtained or until UCB decides to stop brivaracetam drug development.

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

2006-09-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2006-12-27

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2007-10-15

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