Clinical Trials Register

Summary
EudraCT Number:	2010-019947-21
Sponsor's Protocol Code Number:	MIGRAPED01
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2011-11-03
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

2010-019947-21

A.3

Full title of the trial

Phase III study, multicenter, randomized, double-blind, parallel group measuring the efficacy and safety of flunarizine in the prevention of migraine in the pediatric population.

Estudio de Fase III, multicéntrico, aleatorizado, doble ciego, de grupos paralelos que mide la eficacia y seguridad de flunarizina para la prevención de las crisis de migraña en población pediátrica.

A.3.1

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

Study for prevention with flunarizine of migraine attacks in children

Estudio para la prevención con flunarizina de las crisis de migraña en población infantil

A.3.2

Name or abbreviated title of the trial where available

MIGRAPED

A.4.1

Sponsor's protocol code number

MIGRAPED01

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	CAIBER
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	CAIBER
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	CAIBER
B.5.2	Functional name of contact point	UCICEC CAIBER Albacete
B.5.3	Address:
B.5.3.1	Street Address	Hermanos Falcó nº 37
B.5.3.2	Town/ city	Albacete
B.5.3.3	Post code	02006
B.5.3.4	Country	Spain
B.5.4	Telephone number	34967597375
B.5.5	Fax number	34967597408
B.5.6	E-mail	lalajarin@sescam.jccm.es

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	FLURPAX cápsulas
D.2.1.1.2	Name of the Marketing Authorisation holder	TEOFARMA, S.R.L.
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.3.4	Pharmaceutical form	Capsule
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	FLUNARIZINA DIHIDROCLORURO
D.3.9.1	CAS number	30484-77-6
D.3.9.3	Other descriptive name	FLUNARIZINE DIHYDROCHLORIDE
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	5
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
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

Prevention of migraine attacks in pediatric population.

Prevención de las crisis de migraña en población pediátrica.

E.1.1.1

Medical condition in easily understood language

Prevention of migraine attacks in children

Prevención de crisis de migraña en niños.

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

Evaluate the efficacy of flunarizine versus placebo in preventing migraine in a pediatric population from 7 to 14 years, measured as the reduction in monthly frequency of attacks.

Evaluar la eficacia de la flunarizina frente a placebo en la prevención de migrañas en población pediátrica de 7 a 14 años, medida como reducción de la frecuencia de ataques mensuales.

E.2.2

Secondary objectives of the trial

- To evaluate the secondary efficacy of flunarizine versus placebo in the prevention of migraine in the pediatric population from 7 to 14 years, measured as the reduction of the duration of migraine attacks.
- To evaluate the secondary efficacy of flunarizine versus placebo in the prevention of migraine in the pediatric population from 7 to 14 years, measured as reduction in the intensity of migraines.
- Analyze the safety of flunarizine by monitoring and detection of adverse events occurring during the study period.
- Analyze the quality of life related to health (HRQOL) of these patients before and after preventive treatment, using the questionnaire PEDM.

- Evaluar la eficacia secundaria de flunarizina frente a placebo en la prevención de migrañas en población pediátrica de 7 a 14 años, medida como reducción de la duración de las crisis de migrañas.
- Evaluar la eficacia secundaria de flunarizina frente a placebo en la prevención de migrañas en población pediátrica de 7 a 14 años, medida como reducción de la intensidad de las migrañas.
?Analizar la seguridad de la flunarizina mediante la monitorización y detección de acontecimientos adversos que aparezcan durante el periodo del estudio.
?Analizar la calidad de vida relacionada con la salud (CVRS) de dichos pacientes antes y después del tratamiento preventivo, mediante el cuestionario Pedmidas.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-Patients aged from 7 to 14 years attended at Neuropediatrics outpatient clinic of the participating centers and diagnosed with migraine according to IHS criteria.
-Patients who had at least two migraine episodes per week in the last month.
-Informed consent signed (parent / legal representative and the patient in case of children aged 12-14 years).
-Assent of the child in case of children aged 7-11 years

-Pacientes de 7 a 14 años atendidos en las consultas de Neuropediatría de los centros participantes y diagnosticados de migraña, según los criterios de la IHS.
-Pacientes que presentaran al menos dos episodios de migraña por semana en el mes anterior.
-Consentimiento informado del estudio firmado (padre/madre o tutor legal y el propio paciente en caso de niños de 12-14 años).
-Asentimiento del menor en caso de niños de 7-11 años.

E.4

Principal exclusion criteria

·Previous treatment with flunarizine.
·Previous participation in other migraine clinical trials.
·Patients with lactose intolerance, since it is one of the excipients contained in both the drug and placebo.
·Contraindication of flunarizine according to study data sheet (eg, extrapyramidal symptoms, depressive syndrome), or according to the physician discretion.
·Patients taking hypnotics or sedatives, or who consume alcohol on a regular basis, as flunarizine may enhance their sedative effect.
·Patients treated with the following medication that cannot be suspended during the conduct of the trial (for having an indication other than migraine): calcium antagonists, beta-blockers, tricyclic antidepressants, and inhibitors of serotonin re-uptake, some antiepileptics (topiramate, zonisamide, valproic acid), or antiserotoninergic.

-Tratamiento previo con flunarizina.
-Haber participado previamente en otros ensayos clínicos de migraña.
-Pacientes con intolerancia a la lactosa, ya que es uno de los excipientes que contiene tanto el fármaco como el placebo.
-Pacientes en los que no se pueda prescribir la medicación del estudio por estar contraindicada según ficha técnica (ej.: sintomatología extrapiramidal, síndrome depresivo), o a criterio del médico responsable.
-Pacientes en tratamiento con hipnóticos o sedantes, o que consumen alcohol de manera habitual, ya que la flunarizina puede potenciar el efecto sedante de éstos.
-Pacientes en tratamiento con calcio-antagonistas, beta-bloqueantes, antidepresivos tricíclicos e inhibidores de la recaptación de serotonina, algunos antiepilépticos (topiramato, zonisamida, ácido valproico), o antiserotoninérgicos, cuya administración no pueda suspenderse durante la realización del ensayo (por tener una indicación diferente a migraña).

E.5 End points

E.5.1

Primary end point(s)

- Number of migraine attacks every 4 weeks.
The number of migraine attacks should be considered independently of its duration. An episode of migraine that remits temporarily but recurs within 72 hours after the start of the first episode should be considered as a single episode.

- Número de ataques de migraña por cada 4 semanas de tratamiento.
El número de ataques de migraña debe ser considerado independientemente de su duración. Un episodio de migraña que remite temporalmente pero recurre dentro de las 72 horas después del inicio del primer episodio debe ser considerado como un único episodio.

E.5.1.1

Timepoint(s) of evaluation of this end point

Every 4 weeks from the first visit.

Cada 4 semanas desde la primera visita.

E.5.2

Secondary end point(s)

- Response Rate. 50% improvement.
It is defined as "respondent" a patient with 50% or more reduction in seizure frequency during treatment compared to the number of attacks at baseline.
- Number of days with migraine every 4 weeks.
- Intensity of Migraine:
We will use the following scale:
1 = mild migraine, does not interfere with activities of daily living.
2 = moderate migraine, disturbed but does not completely interfere in the activities of daily living.
3 = severe migraine, precludes any activity, allowing only lying down or sleeping.
- Duration in hours.
It will be recorded for each migraine attack.
- Symptomatic treatment for acute attacks: 4 pain relievers groups allowed, describing the dose used, start date and end.
- Quality of life related to health (HRQOL): PEDM questionnaire at the screening visit and at the end of the treatment.
- Adherence to treatment: by counting the number of returned capsules medication.

Safety Variables
- Appearance of any serious adverse events.
- Weight gain of 7% or greater at study end.

- Tasa de Respuesta. 50% de mejora.
Se define como respondedor un paciente con un 50% o más de reducción en la frecuencia de ataques durante el tratamiento en comparación con el número de crisis en situación basal.
- Número de días con migraña: por cada 4 semanas de tratamiento.
- Intensidad de la Migraña:
Se utilizará la siguiente escala:
1 = migraña leve; no interfiere con las actividades de la vida diaria.
2 = migraña moderada; altera pero no interfiere por completo en las actividades de la vida diaria.
3 = migraña severa; impide realizar cualquier actividad, permite sólo estar tumbado o durmiendo.
- Duración en horas.
Se registrará para cada ataque de migraña.
- Tratamiento sintomático para ataques agudos: analgésicos de los 4 grupos permitidos, describiendo la dosis empleada, fecha de inicio y de fin.
- Calidad de vida relacionada con la salud (CVRS): mediante cuestionario Pedmidas en la visita de selección y al finalizar el tratamiento.
- Adherencia al tratamiento: mediante la contabilización del número de cápsulas de medicación devueltas.

Variables de seguridad
- Aparición de posibles acontecimientos adversos graves.
- Ganancia de peso del 7% o mayor al finalizar el estudio.

E.5.2.1

Timepoint(s) of evaluation of this end point

Number of days with migraine, intensity, duration, and symptomatic treatment, will be evaluated every 4 weeks from visit 1 to visit 5.
Quality of life related to health: in visits 1 and 5.
Adherence to treatment: visits 3, 4 and 5.
Occurrence of serious adverse events: from visit 1 to visit 6.
Weight gain: at visit 1 and visit 6.

Número de días con migraña, intensidad, duración y tratamiento sintomático serán evaluados cada 4 semanas desde la visita 1 a la visita 5.
Calidad de vida relacionada con la salud: en las visitas 1 y 5.
Adherencia al tratamiento: en las visitas 3, 4 y 5.
Aparición de acontecimientos adversos graves: desde la visita 1 a la visita 6.
Aumento de peso: en visita 1 y visita 6.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

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)

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.8.2.4

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

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

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:

180

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

112

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)

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

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

Yes

F.3.3.7.1

Details of other specific vulnerable populations

Population under 18 years

población menor de 18 años

F.4 Planned number of subjects to be included

F.4.1

In the member state

180

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)

After completion of the study, patients will continue the treatment and the follow up visits as recomended by the rutine clinical practice.

Tras la finalización del estudio los pacientes continuarán con el tratamiento y seguimiento correspondientes a la práctica clínica habitual.

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

2011-08-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-07-26

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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