Clinical Trials Register

Summary
EudraCT Number:	2007-002667-28
Sponsor's Protocol Code Number:	MK0974-031
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2008-09-22
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2007-002667-28

A.3

Full title of the trial

Multicenter, Double-Blind, Placebo-Controlled, Parallel Group Multiple Attacks Study
to Compare the Efficacy and Safety of Oral MK-0974 With Placebo for the Acute
Treatment of Migraine With or Without Aura.

titolo del piano clinico generale: Studio multicentrico in doppio cieco, controllato con Placebo a gruppi paralleli per valutare su attacchi multipli la sicurezza, la tollerabilita` e l`efficacia di MK-0974 per via orale con placebo nel trattamento dell`attacco acuto di emicrania con o senza aura.

A.4.1

Sponsor's protocol code number

MK0974-031

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	MERCK & CO., 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
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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	NA
D.3.2	Product code	MK0974
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	Other antimigraine preparations
D.3.9.2	Current sponsor code	MK0974
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.3	Concentration number	140
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	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

Patient has had a history of migraine with or without aura > 1 year with ≥ 1 and ≤ 8 moderate or severe migraine attacks per month in the 2 months prior to screening that typically last between 4 to 72 hours untreated

Paziente con una storia di emicrania con o senza aura da piu' di 1 anno con attacchi di emicrania moderati o severi da 1 ad 8 al mese nei 2 mesi precedenti la visita di screening e della durata di 2 ore

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	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

1) To evaluate the efficacy and safety of MK-0974 compared to placebo in the treatment
of acute migraine.
2) To evaluate the safety and the consistency of efficacy of MK-0974 across multiple
migraine attacks.

1) valutare la sicurezza e la tollerabilita' di MK-0974 rispetto a placebo nel trattamento
dell'attacco acuto di emicrania.
2) Valutare la sicurezza e la consistenza dell'efficacia di MK-0974 in attacchi multipli di
emicrania.

E.2.2

Secondary objectives of the trial

1) To evaluate the efficacy of MK-0974 (280 mg and 140 mg) compared to placebo in
the treatment of acute migraine, as measured using sustained pain freedom from 2-24 hours and 2-48 hours post-dose and total migraine freedom at 2 hours and from 2-24 hours postdose (first attack only).

1) Valutare l'efficacia di MK-0974 (280 mg e 140 mg) rispetto a placebo nel trattamento
dell'attacco acuto di emicrania,valutando il parametro 'di liberta' prolungata dal
dolore' da 2 a 24 ore e da 2 a 48 ore dopo la somministrazione e di liberta' assoluta dall'emicrania a 2 e da 2 a 24 ore dopo la prima somministrazione.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patient is ≥18 years of age at screening.
2. Patient has had a history of migraine with or without aura > 1 year with ≥ 1 and ≤ 8
moderate or severe migraine attacks per month in the 2 months prior to screening that
typically last between 4 to 72 hours untreated (see Appendix 6.1 and ICHD II
Attachment for IHS migraine definitions).
3. Patient is either:
a. of reproductive potential and agrees to maintain true abstinence* or use (or have
their partner use) one of the listed highly effective methods of birth control within
the projected duration of the study: hormonal contraceptives, intrauterine device
0974, Protocol 031-00 Issue Date: 10-Mar-2008 15
Product: MK-0974 7
Protocol/Amendment No.: 031-00
0974_031-00_ProtCore VERSION 6.0 APPROVED 10-Mar-2008
Worldwide Restricted Confidential Limited Access
(IUD), condoms, diaphragm, cervical cap, vasectomy. The use of barrier
contraceptive (condom, diaphragm, or cervical cap) should always be
supplemented with the use of a spermicide. Complete details regarding
contraceptive requirements are specified in protocol Section 3.2.3.2.
OR
b. not of reproductive potential. The following definitions apply:
A female patient who is not of reproductive potential is defined as:
one who has either 1) reached natural menopause (defined as age 46 or older
with a) 12 months spontaneous amenorrhea or b) 6 months of spontaneous
amenorrhea with serum FSH levels in the postmenopausal range as
determined by the central laboratory), 2) 6 weeks post surgical bilateral
oophorectomy 3) hysterectomy, or 4) bilateral tubal ligation.
A male patient who is not of reproductive potential is defined as:
one who has undergone a successful vasectomy. A successful vasectomy is
defined as: 1) microscopic documentation of azoospermia, or 2) a vasectomy
more than 2 years ago with no resultant pregnancy despite sexual activity post
vasectomy.
* If abstinence is not a locally acceptable method of contraception, then another highly
effective birth control method must be used.
4. Patient understands the study procedures, alternative treatments available, and risks
involved with the study, and voluntarily agrees to participate by giving written
informed consent.
5. Patient is able to complete the study questionnaire(s) and paper diary.

1. Paziente con piu' di 18 anni al momento dello screening.
2. Paziente con una storia di emicrania con o senza aura da piu' di 1 anno con attacchi di
emicrania moderati o severi da 1 ad 8 al mese nei 2 mesi precedenti la visita di
screening e della durata di 2 ore (vedere Appendice 6.1 per la definizione di emicrania
secondo la IHS).
3. Il paziente e':
a) in eta' fertile pertanto si consiglia astinenza* dai rapporti o l'uso di due metodi
accettabili di controllo delle nascite per tutta la durata dello studio (oppure avere un
partner che utilizza tali metodi). I metodi accettabili di contraccezione sono: il
dispositivo intrauterino (IUD), il diaframma con lo spermicida, la spugna
contraccettiva, i preservativi, la vasectomia. Per completare le informazioni riguardanti
i contraccettivi vedere la sezione 3.2.2.2. del protocollo
oppure
b) non in eta' fertile.Secondo le seguenti definizioni:
o Una paziente donna non in eta' fertile viene definita tale se presenta 1)
menopausa naturale (definita come 6 mesi di amenorrea spontanea con
Merck Sharp & Dohme Italia Spa
Principio attivo: MK0974
Protocollo No.: 031-00
Page 5 of 8
livelli sierici di FSH postmenopausali determinati dal laboratorio
centrale, o 12 mesi si amenorrea spontanea, 2) 6 settimane da
un'ovariectomia chirurgica bilaterale, 3) isterectomia, o 4) legatura
bilaterale delle tube.
o paziente maschio non potenzialmente riproduttivo e' definito tale se
presenta una vasectomia di successo. Una vasectomia di successo e'
definita tale se e' presente: 1) documentazione microscopica di
azoospermia, o 2) vasectomia eseguita da piu' di 2 anni e nessuna
gravidanza postvasectomia nonostante attivita' sessuale.
* Se l'astinenza non e' un metodo localmente accettabile di contraccezione, allora un
altro metodo di controllo valido deve essere usato.
4. Il paziente ad opinione dell'investigatore e' in buone condizioni di salute riferendosi
alle valutazioni effettuate durante lo screening inclusi anamnesi, esame obiettivo ed
esami di laboratorio effettuati entro 2 mesi dall'inizio dello studio
5. Il paziente capisce le procedure dello studio, le terapie alternative disponibili, ed i
rischi dello studio, e consente di partecipare dando volontariamente consenso informato
scritto.
6. Il paziente e' in grado di completare il/i questionario/i dello studio ed il diario.

E.4

Principal exclusion criteria

1. Patient is pregnant (positive serum pregnancy test at pre-study) or breast-feeding, or
is a female expecting to conceive within the projected duration of the study.
2. Patient has difficulty distinguishing his/her migraine attacks from tension headaches.
3. Patient has a history of predominantly mild migraine attacks or migraines that usually
resolve spontaneously in less than 2 hours.
4. Patient has basilar or hemiplegic migraine headache.
0974, Protocol 031-00 Issue Date: 10-Mar-2008 16
Product: MK-0974 8
Protocol/Amendment No.: 031-00
0974_031-00_ProtCore VERSION 6.0 APPROVED 10-Mar-2008
Worldwide Restricted Confidential Limited Access
5. Patient has more than 15 headache-days per month or has taken medication for acute
headache on more than 10 days per month in any of the 3 months prior to screening.
6. Patient is taking migraine prophylactic medication where the prescribed daily dose
has changed during the 3 months prior to screening.
7. Patient was > 50 years old at age of migraine onset.
8. Patient has clinical, laboratory, or ECG evidence of uncontrolled hypertension
(defined as SBP of ≥150 mm Hg and/or DBP of ≥95 mm Hg), uncontrolled diabetes,
HIV disease, or significant pulmonary,

1. paziente incinta (test ß-hCG sierico positivo al prestudy) o allatta al seno, o e' intenzionata a
concepire una gravidanza entro la durata prevista dello studio.
2. paziente con difficolta' a distinguere i propri attacchi di emicrania dalla cefalea tensiva o da
intervallo.
3. paziente con una storia di attacchi di emicrania prevalentemente lieve che si risolvono di
solito spontaneamente in meno di 2 ore.
4. paziente con emicrania basilare o emiplegica .
5. paziente con piu' di 15 giorni di cefalea al mese o che ha intrapreso terapie per cefalea acuta
per piu' di 10 giorni al mese nei 3 mesi precedenti lo screening.
6. paziente che assume terapia profilattica per l'emicrania il cui dosaggio quotidiano e' stato
modificato durante i 3 mesi precedenti lo screening.
7. paziente con piu' di 50 anni al momento di insorgenza dell' emicrania.
8. paziente con una storia clinica e di laboratorio od evidenze ECG di ipertensione non
controllata (definita come PAS > 150 mm Hg e/o PAD > 95 mm Hg), diabete non controllato,
malattia HIV, o significative malattie polmonari, renali, epatiche, endocrine,, o di altri sistemi,
a discrezione del ricercatore.

E.5 End points

E.5.1

Primary end point(s)

2-hour pain
relief, pain freedom, and associated symptoms (photophobia, phonophobia, and nausea)

sollievo dal dolore a 2 ore (endpoint primario), assenza del dolore a 2 ore e anche per quanto riguarda i sintomi associati all'emicrania (fotofobia, fonofobia, and nausea)

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

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

Yes

E.8.2.3.1

Comparator description

- Stesso farmaco ad altro dosaggio

- same IMP used at different dosage

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

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

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	No
F.1.1	Number of subjects for this age range:	0
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
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	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2008-09-22.	Yes
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	75
F.4.2	For a multinational trial
F.4.2.1	In the EEA	744
F.4.2.2	In the whole clinical trial	1800

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

2008-11-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2008-07-14

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2009-03-27

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