Clinical Trials Register

Summary
EudraCT Number:	2009-013701-34
Sponsor's Protocol Code Number:	VMMET009
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2011-04-08
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2009-013701-34

A.3

Full title of the trial

Prophylactic treatment of vestibular migraine with metoprolol: a double-blind, placebo-
controlled trial

A.3.1

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

Prophylactic treatment of vertigo attacks as migrainous symptoms

A.3.2

Name or abbreviated title of the trial where available

PROVEMIG

A.4.1

Sponsor's protocol code number

VMMET009

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	Hospital of the University of Munich
B.1.3.4	Country	Germany
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	Deutsches Zentrum für Luft- und Raumfahrt (DLR)
B.4.2	Country	Germany
B.4.1	Name of organisation providing support	Bundesministerium für Bildung und Forschung (BMBF)
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	Hospital of the University of Munich
B.5.2	Functional name of contact point	DSGZ
B.5.3	Address:
B.5.3.1	Street Address	Marchioninistrasse 15
B.5.3.2	Town/ city	Munich
B.5.3.3	Post code	81377
B.5.3.4	Country	Germany
B.5.4	Telephone number	++498970953678
B.5.5	Fax number	++498970956673
B.5.6	E-mail	michael.strupp@med.uni-muenchen.de

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	Beloc-Zok
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	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	METOPROLOL SUCCINATE
D.3.9.1	CAS number	98418-47-4
D.3.9.4	EV Substance Code	SUB03274MIG
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	47.5
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.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	Beloc-Zok
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	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	METOPROLOL SUCCINATE
D.3.9.1	CAS number	98418-47-4
D.3.9.4	EV Substance Code	SUB03274MIG
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	95
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

vestibular migraine

E.1.1.1

Medical condition in easily understood language

vertigo, dizziness, headache, migraine

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10027599
E.1.2	Term	Migraine
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

Primary Objective:
To demonstrate the superiority of Metoprolol Succinate treatment regarding the number of vertigo attacks and the number of headache attacks per month compared to placebo.

E.2.2

Secondary objectives of the trial

Secondary Objective:
To analyze whether the superiority of Metoprolol Succinate treatment is kept up to three months after the last drug intake. To quantitatively describe and compare the median duration and severity of vertigo attacks, the number of headache days, neurological and neuro-orthoptic examination and the change of handicap / impairment due to vertigo or dizziness vs. placebo. To check for the occurrence of the adverse effects reported in the summary of the medical product characteristics (SmPC) of the drug.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subjects will only be included in the study if they meet all of the following
criteria:
· Patients male or female, aged 18 years or above,
· Patients with diagnosis of probable (1., 4., 5.) or definite (1., 2., 3., 5.) vestibular
migraine according to the criteria of Neuhauser (Neuhauser et al.
2001):
1. episodic vestibular symptoms of at least moderate severity (rotational
vertigo, other illusory self or object motion, positional vertigo, head motion
intolerance, i. e., sensation of imbalance or illusory self or object
motion that is provoked by head motion);
2. migraine according to the IHS criteria;
3. at least one of the following migrainous symptoms during at least two
vertiginous attacks: migrainous headache, photophobia, phonophobia,
visual or other auras;
4. at least one of the following: migraine according to the IHS criteria; migrainous
symptoms during vertigo as specified in 3.; migraine-specific
precipitants of vertigo, e. g. specific foods, sleep irregularities, hormonal
changes; response to antimigraine drugs
5. other causes ruled out by appropriate investigations;
· Between 6 and 30 attacks per 3 subsequent months;
· Subjects with the ability to follow study instructions and likely to attend and
complete all required visits;
· Written informed consent of the subject

E.4

Principal exclusion criteria

Subjects will not be included in the study if any of the following criteria applies:
· Patients not able to give consent;
· Other vestibular disorders such as Menière´s disease, phobic postural vertigo, benign paroxysmal positioning
vertigo, vestibular paroxysmia;
· Central disorders such as paroxysmal brainstem attacks, TIAs;
· Contraindications for the treatment with metoprolol such as
o known allergic reaction to the trial drug or other beta receptor blockers;
o shock, acidosis
o Any bronchospastic disease, e.g. bronchial asthma;
o Sick sinus syndrome, known SA-block, AV-block;
o Bradycardia < 50 bpm at rest, systolic blood pressure < 100 mmHg, end-grade peripheral arterial
disease;
o Known severe coronary heart disease or heart failure;
o Concurrend treatment with MAO-inhibitors, sympathomimetic drugs, Catecholamine-depleting
drugs, digitalis glycosides;
· Poorly controlled diabetes mellitus;
· Pheochromocytoma;
· Suspicion of developing thyrotoxicosis;
· Disorders of hemostasis;
· Porphyria;
· Psoriasis;
· Pregnancy or breast-feeding;
· Persistent hypertension with systolic blood pressure > 180 mmHg or diastolic BP > 110 mmHg (mean
of 3 consecutive arm-cuff readings over 20-30 minutes) that cannot be controlled by antihypertensive
therapy;
· Life expectancy < 12 months;
· Other serious illness, e.g., severe hepatic, cardiac, or renal failure, acute myocardial infarction, neoplasm
or a complex disease that may confound treatment assessment;
· Treatment with beta-blockers
· The patient has received any investigational medication within 30 days prior to administration of study
medication or is scheduled to receive an investigational drug up to 30 days after end of study;
· The patient was previously admitted to this trial or simultaneous participation in another clinical trial or
participation in any clinical trial involving an administration of investigational medicinal product.

E.5 End points

E.5.1

Primary end point(s)

Primary Endpoint:
• The number of vertigo attacks and the number of headache attacks during the last 3 months of the 6-month treatment period.

E.5.1.1

Timepoint(s) of evaluation of this end point

During the last 3 month of the 6-month treatment period.

E.5.2

Secondary end point(s)

Secondary Endpoints:
• The number of vertigo attacks and the number of headache attacks during the last 3 months of the total follow-up period of 9 months;
• the median duration and severity of vertigo attacks during the last 3 months of the 6-month treatment period and the last 3 months of the total follow-up period;
• the number of headache days per month during the last 3 months of the 6-month treatment period and the last 3 months of the total follow-up period;
• the changes in the neurological and neuro-orthoptic examination and handicap / impairment due to vertigo between baseline, 6-month visit and 9-month visit.

E.5.2.1

Timepoint(s) of evaluation of this end point

- During the last 3 months of total follow-up period of 9 month;
- During the last 3 months of 6-months treatment period;
- During the last 3 months of 6-months treatment and the last 3 months of total follow-up period of 9 month;

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

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)

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

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

The regular end of trial is defined as "Last Patient Last Visit".

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

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)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

200

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

266

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)

None

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2011-08-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-09-01

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2018-01-03

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials