Clinical Trials Register

Summary
EudraCT Number:	2021-004868-95
Sponsor's Protocol Code Number:	FETEM
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-12-22
Trial 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

Spain - AEMPS

A.2

EudraCT number

2021-004868-95

A.3

Full title of the trial

AMANTADINE AND TRANSCRANIAL MAGNETIC STIMULATION FOR TREATING FATIGUE IN MULTIPLE SCLEROSIS: PHASE III STUDY, CONTROLLED, RANDOMIZED, CROSSED OVER AND DOUBLE BLIND

AMANTADINA Y ESTIMULACIÓN MAGNÉTICA TRANSCRANEAL PARA FATIGA EN LA ESCLEROSIS
MULTIPLE: ENSAYO FASE III, CONTROLADO, RANDOMIZADO, CRUZADO Y DOBLE CIEGO

A.3.1

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

AMANTADINE AND TRANSCRANIAL MAGNETIC STIMULATION FOR TREATING FATIGUE IN MULTIPLE SCLEROSIS

AMANTADINA Y ESTIMULACIÓN MAGNÉTICA TRANSCRANEAL PARA FATIGA EN LA ESCLEROSIS
MULTIPLE

A.3.2

Name or abbreviated title of the trial where available

FETEM

A.4.1

Sponsor's protocol code number

FETEM

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	Fundación para la Inv. Biomédica Hospital Clínico San Carlos
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	INSTITUTO CARLOS III
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Fundación para la Investigación Biomédica del Hospital Clínico San Carlos
B.5.2	Functional name of contact point	UICEC IdICSC
B.5.3	Address:
B.5.3.1	Street Address	C/ Prof Martin Lagos s/n
B.5.3.2	Town/ city	MADRID
B.5.3.3	Post code	28040
B.5.3.4	Country	Spain
B.5.4	Telephone number	+349133030007360
B.5.5	Fax number	+34913303515
B.5.6	E-mail	fibucicec.hcsc@salud.madrid.org

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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	Amantadine Level
D.2.1.1.2	Name of the Marketing Authorisation holder	Laboratorios ERN, S.A
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Amantadine
D.3.4	Pharmaceutical form	Capsule, hard
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	INN
D.3.9.1	CAS number	768-94-5
D.3.9.2	Current sponsor code	test1
D.3.9.3	Other descriptive name	AMANTADINE HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB00422MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	100 to 200
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	Capsule, hard
D.8.4	Route of administration of the placebo	Buccal use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Fatigue in multiple sclerosis

fatiga en esclerosis múltiple

E.1.1.1

Medical condition in easily understood language

Fatigue in multiple sclerosis

fatiga en esclerosis múltiple

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

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 assess the fatigue severity in patients with multiple sclerosis treated with amantadine, TMS or their combination in combination with placebo.

evaluar el cambio en la severidad de la fatiga en los pacientes con EM sometidos a tratamiento con amantadina, TMS y ambos en combinación, en comparación con placebo.

E.2.2

Secondary objectives of the trial

To assess the congnitive, depresion conditions and quality of live, a validated scale will be used for each aims. Thefore, it will be carried out a cost-effectivity and safety assement.

evaluarán cambios en cognición, depresión y calidad de vida. Para todo ello se utilizarán las escalas de referencia adecuadamente validadas para
cada uno de los objetivos. Asimismo, se realizara un análisis de seguridad y de coste-efectividad

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Expanded Disability Status Scale mark 1.5 - 4.5
2. Fatigue Severity Scale > 4
3. Beck Depression Inventory < 19
4. Drug washout period = 4 weeks for any fatigue aimed drug
5. No relapse for, at least, a month prior to screening

Criterios de inclusión: 1. Puntuación de escala de discapacidad (EDSS) en el momento del reclutamiento (1, 5 a 4,5 puntos). 2. Puntuación en la Fatigue Severity Scale (FSS) mayor a 4 puntos 3. Puntación en Beck Depression Inventory (BDI) menor de 19 puntos 4. Haberse realizado un lavado de cuatro semanas para cualquier fármaco relacionado con la fatiga: amantadina, modafinilo, metilfenidato, acetil-L-carnitina, cannabinol (delta-9-tetrahidrocannabinol y cannabidiol de Cannabis sativa L) y fampridina. 5. No haber presentado un brote de la enfermedad en, al menos, un mes antes del reclutamiento.

E.4

Principal exclusion criteria

1. Fatigue causing disease other than multiple sclerosis
2. Sleep apnea treated with CPAP devices
3. Other autoimmune disease which might cause fatigue
4. Cronic Fatigue Syndrome
5. Secondary Epilepsy or neuropathic cronic pain which requires continuous treatment.
6. High blood pressure out of control or cardiac condition.

1. Fatiga derivada de cualquier otra enfermedad diferente a esclerosis múltiple
2. Apnea del sueño tratada con dispositivo CPAP
3. Otras enfermedades autoinmunes las cuales causen fatiga
4. Síndrome de fatiga crónica
5. Epilepsia secundaria o dolor por neuropatía crónica los cuales requieren tratamiento continuado.
6. Presión sanguínea alta no controlada o alteración cardiaca.

E.5 End points

E.5.1

Primary end point(s)

Compare clinical response to amantadine, TMS or the combination

comparar la respuesta clínica de amantadine, TMS o su combinación

E.5.1.1

Timepoint(s) of evaluation of this end point

After 6 weeks of treatment

después de 6 semanas de tratamiento

E.5.2

Secondary end point(s)

1. Cognitive recovery measured by SDMT test
2. Depression measured with Beck's scale
3. Life quality measured with SF-12 scale.
4. Safety
5. Cost-effectiviness

1. Medidas de mejora congnitiva (test SDMT)
2. Medidas de depresión (Scala Beck)
3. Calidad de vida (Scala SF-12)
4. Seguridad
5- Costa/efectividad

E.5.2.1

Timepoint(s) of evaluation of this end point

After 6 weeks of treatment

Después de 6 semanas de tratamiento

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

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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

Yes

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

Yes

E.8.2.3.1

Comparator description

Transcranial magnetic stimulation

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

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

LVLS

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

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)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

144

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

144

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

Information not present in EudraCT

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

Information not present in EudraCT

F.4 Planned number of subjects to be included

F.4.1

In the member state

144

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)

Follow up as per clinical practice

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

2022-05-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-05-24

P. End of Trial
P.	End of Trial Status	Ongoing

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