Clinical Trials Register

Summary
EudraCT Number:	2007-005439-27
Sponsor's Protocol Code Number:	SP902
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2008-11-18
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

Denmark - DHMA

A.2

EudraCT number

2007-005439-27

A.3

Full title of the trial

A Historical-controlled, Multicenter, Double-blind, Randomized Trial to Assess the Efficacy and Safety of Conversion to Lacosamide 400mg/day Monotherapy in Subjects with Partial-onset Seizures

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study to assess the efficacy and safety of conversion to Lacosamide (approved drug in Europe) 400mg/day monotherapy in people with partial-onset seizures

A.3.2

Name or abbreviated title of the trial where available

ALEX-MT (A Lacosamide EXchange to Monotherapy Trial)

A.4.1

Sponsor's protocol code number

SP902

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	UCB BIOSCIENCES, 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	UCB BIOSCIENCES GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	UCB BIOSCIENCES GmbH
B.5.2	Functional name of contact point	ClinTrial Reg & Results Disclosure
B.5.3	Address:
B.5.3.1	Street Address	Alfred-Nobel-Strasse 10
B.5.3.2	Town/ city	Monheim
B.5.3.3	Post code	40789
B.5.3.4	Country	Germany
B.5.4	Telephone number	+49217348 1515
B.5.5	Fax number	+49 217348 1572
B.5.6	E-mail	clinicaltrials@ucb.com

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	Yes
D.2.1.1.1	Trade name	Vimpat
D.2.1.1.2	Name of the Marketing Authorisation holder	UCB Pharma S.A.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Lacosamide
D.3.2	Product code	SPM 927
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
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	Lacosamide
D.3.9.1	CAS number	175481-36-4
D.3.9.2	Current sponsor code	SPM 927
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)	No
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	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
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	No
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	Yes
D.2.1.1.1	Trade name	Vimpat
D.2.1.1.2	Name of the Marketing Authorisation holder	UCB Pharma S.A.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Lacosamide
D.3.2	Product code	SPM 927
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
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	Lacosamide
D.3.9.1	CAS number	175481-36-4
D.3.9.2	Current sponsor code	SPM 927
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	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)	No
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	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
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	No
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	Film-coated 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

Partial-onset seizures (with or without secondary generalization)

E.1.1.1

Medical condition in easily understood language

Partial-onset seizures

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10040703
E.1.2	Term	Simple partial seizures
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10010145
E.1.2	Term	Complex partial seizures
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The objective of this trial is to demonstrate the efficacy and safety of conversion to LCM 400mg/day monotherapy for partial-onset seizures (with or without secondary generalization) in subjects 16 to 70 years of age who are withdrawn from 1 to 2 marketed AEDs.

E.2.2

Secondary objectives of the trial

There are no secondary objectives

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subject is informed and given ample time and opportunity to think about her/his participation and has given her/his written informed consent.
2. Subject is willing and able to comply with all trial requirements.
3. Subject is male or female between the age of 16 and 70 years of age, inclusive.
4. Subject has a diagnosis of epilepsy with simple partial seizures (motor component) and/or complex partial seizures (with or without secondary generalization) according to the International Classification of Epileptic Seizures, 1981.
5. Subject has been maintained on a stable dose of 1 or 2 marketed AEDs for at least 28 days prior to Visit 1 and during Baseline.
6. If a subject is on 2 AEDs, the second AED must be ≤50% of the minimum recommended maintenance dose per USA product label at Visit 1 and during Baseline when used as an adjunctive therapy.
7. The minimum required seizure frequency during the 8-week Baseline Phase is 2 partial-onset seizures (IA, IB, or IC) per 28 days. In the case of simple partial seizures, only those with motor signs (IA1) will be counted towards meeting this inclusion criterion. (See Section 15.2, International Classification of Epileptic Seizures, 1981.)
8. Subject has ≤ 40 partial seizures (ie, IA1, IA2, IA3, IA4, IB, IC) per 28 days during the 8-week Baseline Phase. (See Section 15.2, International Classification of Epileptic Seizures, 1981.)
9. Subject has had an electroencephalogram and a brain computerized tomography scan or magnetic resonance imaging exam of the brain consistent with the diagnosis of partial-onset epilepsy. If the electroencephalogram and brain computerised tomography scan or magnetic resonance imaging exam were not performed prior to Visit 1, it needs to be completed and results must be available prior to randomisation at Visit 3.

E.4

Principal exclusion criteria

1. Subject has previously participated in this trial, or subject has previously been assigned to treatment in a trial of the drug under investigation in this trial. Subjects who have previously received commercial LCM may be considered for participation if the treatment period was limited to a single iv administration for acute treatment. If the subject received a single iv administration of commercial LCM, it must have occurred earlier than 28 days prior to Visit 1. These cases must be discussed with the medical monitor prior to screening.
2. Subject is currently participating or has participated within the last 2 months in any trial of an investigational drug or experimental device.
3. Subject has a seizure disorder characterized primarily by isolated auras (ie, simple partial seizures without observable motor signs).
4. Subject has a history of primary generalized or unclassified seizures.
5. Subject has a history of status epilepticus within the 12-month period prior to Visit 1.
6. Subject has a history of cluster seizures, defined as bouts of increased seizures which cannot be reliably counted (but which do not represent status epilepticus) during the 8-week period prior to Visit 1 and during the 8-week Baseline Phase.
7. Subject has a seizure-free period ≥28 consecutive days during the 8-week Baseline Phase.
8. Subject has >5 seizures of any type, including isolated auras, on any day during 8-week Baseline Phase.
9. Subject has a current or previous diagnosis of pseudoseizures, conversion disorders, or other non-epileptic ictal events which could be confused with seizures.
10. Subject has an implanted VNS.
11. Subject has received treatment with benzodiazepines, phenobarbital, or primidone within 28 days prior to Visit 1 or during Baseline.
12. Subject is taking 1 or more of the following medications on a regular basis within 28 days prior to Visit 1 or during Baseline: neuroleptics, monoamine oxidase (MAO) inhibitors, barbiturates, or narcotic analgesics.
13. Subject has any medical or psychiatric condition, which in the opinion of the investigator, could jeopardize the subject’s health or would compromise the subject’s ability to participate in this trial.
14. Deleted and no longer applicable beginning with protocol amendment 6 (see protocol amendment details in Section 32).
15. Subject has a known hypersensitivity to any components of the investigational product(s) as stated in Section 4.4.2.
16. Subject has a medical condition that could reasonably be expected to interfere with drug absorption, distribution, metabolism or excretion.
17. Subject has any history of alcohol or drug abuse within the previous 2 years.
18. Subject has an acute or sub-acutely progressive central nervous system disease.
19. Subject with a known history of severe anaphylactic reaction or serious blood dyscrasias.
20. Subject weighs <40kg.
21. Subject has alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin levels ≥2 times the upper limit of normal (ULN) or has alkaline phosphatase levels ≥3 times the ULN at Visit 1.
22. Subject has impaired renal function, ie, creatinine clearance (CLCR) is lower than
50 mL/minute, at Visit 1. Creatinine clearance will be estimated by the central aboratory as follows:
Adult males: CLCR = (140-age) x weight in kg/(72 x serum creatinine in mg/dL)
Adult females: CLCR = [(140-age) x weight in kg/(72 x serum creatinine in mg/dL)] x 0.85.
23. removed
24. removed
25. Subject has sick sinus syndrome without a pacemaker, or second- or third-degree
atrioventricular (AV) block.
26. Subject has experienced a myocardial infarction in the last 3 months.
27. Subject has New York Heart Association Class III or Class IV heart failure.
28. removed
29. removed
30. Subject is a pregnant female, nursing woman and/or a female of childbearing potential who is not surgically sterile, 2 years postmenopausal, or does not practice 2 combined methods of contraception (unless sexually abstinent) for the duration of the trial.
31. Subject has ever received treatment with ethosuximide.
32. Subject is on a ketogenic diet.
33. Subject has been on felbamate after 1994.
34. Subject has been on vigabatrin after 1997, or subject has been on vigabatrin before 1997 and no visual fields examination report is available, including standard static (Humphrey or Octopus) or cinetic perimetry (Goldman), or if results of these examinations are abnormal. The visual fields examination report must be available no later than Visit 3 prior to randomisation.
35. Subject has a known sodium channelopathy, such as Brugada syndrome.
36. Subject has a lifetime history of suicide attempt (including an active attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response (Yes) to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening.

E.5 End points

E.5.1

Primary end point(s)

The percentage of subjects who are identified as meeting at least 1 of the following exit criteria by Day 112 relative to the start of the withdrawal of background AEDs is considered the primary efficacy variable.
1. A 2-fold or greater increase in average monthly (28-day) partial seizure frequency (motor and non-motor) compared to average monthly partial seizure frequency (motor and non-motor) during the Baseline Phase.
2. A 2-fold or greater increase in consecutive 2-day partial seizure frequency (motor and non-motor) versus the highest consecutive 2-day partial seizure frequency (motor and non-motor) that occurred during the Baseline Phase.
Note: if the highest consecutive 2-day partial seizure frequency during the Baseline Phase is 1, a 2-day partial seizure frequency of ≥3 is required to meet this exit criterion.
3. Occurrence of a single generalized tonic-clonic seizure if none had occurred in the 6 months prior to randomization.
4. A prolongation or worsening of overall seizure duration, frequency, type or pattern considered by the investigator as serious enough to warrant trial discontinuation.
5. Status epilepticus, or new onset of serial/cluster seizures.

E.5.1.1

Timepoint(s) of evaluation of this end point

112 Days

E.5.2

Secondary end point(s)

There are no secondary end points

E.5.2.1

Timepoint(s) of evaluation of this end point

There are no secondary end points

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

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

E.6.10

Pharmacogenetic

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

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Historical-controlled

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Lacosamide 300 mg/day and Historical Controlled Trials

E.8.2.4

Number of treatment arms in the trial

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

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

Australia

Canada

United States

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

Last visit of the last subject

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

Number of subjects for this age range:

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.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

338

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

104

F.4.2.2

In the whole clinical trial

451

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 either be enrolled in the open label extension trial SP904 (EudraCT number 2007-005440-25) or be treated by the investigator or their regular physician in accordance with current best clinical practise with existing treatments.

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

2008-12-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-05-04

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-12-06

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