Clinical Trials Register

Summary
EudraCT Number:	2017-004083-35
Sponsor's Protocol Code Number:	2017-53
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-02-09
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

France - ANSM

A.2

EudraCT number

2017-004083-35

A.3

Full title of the trial

A double-blind, randomized, multicenter study evaluating 200 mg versus 600 mg of Mifepristone on pain in voluntary abortion by drug prior to 7 SA. DoMy Study

Etude multicentrique randomisée en double aveugle évaluant 200 mg versus 600 mg de Mifepristone sur la douleur dans l’interruption volontaire de grossesse par voie médicamenteuse avant 7 SA. Etude DoMy

A.3.1

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

A double-blind, randomized, multicenter study evaluating 200 mg versus 600 mg of Mifepristone on pain in voluntary abortion by drug prior to 7 SA. DoMy Study

A.3.2

Name or abbreviated title of the trial where available

DoMy

A.4.1

Sponsor's protocol code number

2017-53

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	Assistance Publique Hôpitaux de Marseille
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor
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	Yes
D.2.1.1.1	Trade name	MIFEPRISTONE 200MG
D.2.1.1.2	Name of the Marketing Authorisation holder	EXELGYN
D.2.1.2	Country which granted the Marketing Authorisation	France
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	MIFEGYNE
D.3.2	Product code	MIFEPRISTONE
D.3.4	Pharmaceutical form	Cachet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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	Cachet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Cachet
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 of 18 years or more, wishing an abortion with medication before 7 weeks of amenorrhea

patiente de 18 ans ou plus désirant une interruption volontaire de grossesse par voie médicamenteuse avant 7 Semaines d'aménorrhée (SA)

E.1.1.1

Medical condition in easily understood language

patient of 18 years or more, wishing an abortion with medication before 7 weeks of amenorrhea

patiente de 18 ans ou plus désirant une interruption volontaire de grossesse par voie médicamenteuse avant 7 Semaines d'aménorrhée

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

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

The main objective of this research is to compare the efficacy in reducing the pain of two doses of Mifegyne during medicinal abortion before 7 Weeks of amenorrhea (600 versus 200 mg).

L’objectif principal de cette recherche est de comparer l’efficacité dans la réduction de la douleur de deux doses de Mifegyne lors de l’IVG médicamenteuse avant 7 SA (600 vs 200 mg).

E.2.2

Secondary objectives of the trial

The secondary objectives of this research are to compare the 2 dosages of Mifegyne (600 vs 200 mg) in terms of:
• Pain within days of taking misoprostol
• Pain between taking Mifegyne and misprostol
• Failed method
• Additional consultations and gestures following IVG4 consultation
• Tolerance of drug-induced abortion
• Abortion experience documented by the EVAN-LR self-questionnaire
• Impact on the degree of anxiety of the subjects by the questionnaire STAI of anxiety
• Patient satisfaction with an EVA scale and the SF12 questionnaire

Les objectifs secondaires de cette recherche sont de comparer les 2 dosages de Mifegyne (600 vs 200 mg) en termes de:
• Douleur dans les jours suivant la prise de misoprostol
• Douleurs entre la prise de Mifegyne et de misprostol
• Echec de la méthode
• Consultations et gestes supplémentaires après la consultation IVG4
• Tolérance de l’IVG médicamenteuse
• Vécu de l’IVG documenté par l’auto-questionnaire EVAN-LR
• Impact sur le degré d’anxiété des sujets par le questionnaire STAI d’anxiété
• Satisfaction des patientes par une échelle EVA et le questionnaire SF12

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Female aged 18 or over.
Female with a single intrauterine pregnancy, the term of which is less than 7 weeks on the day of mifegyne intake, estimated by ultrasound with a cranio-caudal length measurement less than or equal to 10 millimeters.
Woman seeking medical abortion in hospital.
A woman who has signed a written informed consent and agrees to abide by the protocol.

Femme âgée de 18 ans ou plus.
Femme présentant une grossesse intra-utérine unique, dont le terme est inférieur à 7 SA le jour de la prise de mifégyne, estimé par échographie avec une mesure de la longueur crânio-caudale inférieure ou égale à 10 millimètres.
Femme désirant une IVG médicamenteuse en milieu hospitalier.
Femme ayant signé un consentement éclairé écrit et s'engageant à respecter les instructions du protocole.

E.4

Principal exclusion criteria

Minor woman.
Female with multiple pregnancy, uterine malformation (cloisonné uterus, bicorn, fibroma) or coagulation disorder defined by biological parameters (TP <70%, TCA patient / control ratio <1.20).
Female with a contraindication to mifepristone: chronic adrenal insufficiency, severe asthma not controlled by treatment, hereditary porphyria, known allergy to the active substance or to any of the excipients.
Women with a contraindication to misoprostol: hypersensitivity to the active substance, to any of the excipients or to other prostaglandins;
Female with contraindication to one of the analgesics used in the study (nefopam, paracetamol, opium, caffeine).
Female not affiliated to the social security system.
Wife with no informed consent.

Femme mineure.
Femme présentant une grossesse multiple, malformation utérine (utérus cloisonné, bicorne, fibrome) ou un trouble de la coagulation défini par des paramètres biologiques (TP<70%, TCA rapport patient/témoin<1,20).
Femme présentant une contre-indication à la mifepristone : insuffisance surrénale chronique, asthme sévère non contrôlé par traitement, porphyrie héréditaire, allergie connue à la substance active ou à l'un des excipients.
Femme présentant une contre-indication au misoprostol : hypersensibilité à la substance active, à l'un des excipients ou à d'autres prostaglandines ;
Femme présentant une contre-indication à l’un des antalgiques utilisés dans l’étude (nefopam, paracétamol, opium, caféine).
Femme n’étant pas affiliée au régime de sécurité sociale.
Femme n’ayant pas signé de consentement éclairé.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of efficacy is the hourly pain for 5 hours after taking misoprostol. The measurement is simple, reproducible, performed with an EN on the side of 0 to 10 (0 absence of pain, 10 maximum of pains felt). The ladder will be explained to the patient. The question asked will be: what is your pain now?

Le critère de jugement principal d’efficacité est représenté par la douleur horaire pendant 5 heures suivant la prise de misoprostol. La mesure est simple, reproductible, effectuée à l’aide d’une EN cotée de 0 à 10 (0 absence de douleurs, 10 maximum de douleurs ressenties). L’échelle sera expliquée à la patiente. La question posée sera la suivante : actuellement quelle est votre douleur ?.

E.5.1.1

Timepoint(s) of evaluation of this end point

Patients will be assessed for consultation with the 2 abortion (IVG 2) prior to taking Mifegyne (J1), the next day (D2), IVG3 before taking misoprostol (J3) and the follow-up visit (IVG4) on a digital scale

E.5.2

Secondary end point(s)

Pains will be assessed at the consultation of voluntary termination of pregnancy 2 (IVG2)
before taking Mifegyne (J1), the next day (D2), IVG3 prior to taking misoprostol (J3) and IVG4 on an EN. The questions will be as follows:
At the consultation IVG1: "currently, what is your pain? "
At the IVG2 consultation before taking misoprostol: "yesterday, what was the maximum pain felt? "And" currently, what is your pain?
At IVG4: "The day after taking misoprostol and the day after, what was the maximum pain felt in the day? "And" currently, what is your pain? and "since the day after taking misoprostol and so far, what was the maximum pain and how many days have you had trouble"
- The use of painkillers on the day of taking misoprostol and the following days, specifying the duration and quantity of ibuprofen and other analgesics taken.

- Failed method
Failure is defined by the ultrasound presence of a progressive pregnancy at the IVG4 or IVG5 consultation. The means used to enable the diagnosis of the failure will be those used by the investigating centers.

- Additional consultations and gestures
Additional consultations are planned over a one-month period after taking misoprostol (IVG5 and higher) if the physician deems it necessary to review the patient in relation to the medicinal abortion. It will be specified if it is a simple consultation or the realization of an uterine gesture for retention. The indication of consultation or additional gesture will be carried out according to the habits of the investigating centers.

- Tolerance
Tolerance will be assessed by the questioning before the end of hospitalization for misoprostol (IVG3). The following signs will be carefully collected: nausea, vomiting, fever, diarrhea, abdominal pain, other (to be specified by the patient).

- Experience and Anxiety
Assessment of anxiety will be assessed by passing the Anxiety Task Inventory (STAI). The STAI is a self-questionnaire developed by Spielberger (Spielberger, 1983) and validated in French (Gauthier & Bouchard, 1993). It consists of 20 questions, assessing the usual emotional state of the subject. A score is calculated, a high score indicating the presence
anxiety. The experience of the abortion will be done by the EVAN-LR self-questionnaire. This assessment
at IVG2 and IVG consultation 4.

- Satisfaction
The satisfaction of the subjects will be assessed using an EVA, graduated from 0 to 10, completed by the patient at the IVG4 consultation as well as the questionnaire SF12 completed at the consultation IVG2 and IVG4.

- Les douleurs seront évaluées à la consultation IVG 2 avant prise de Mifegyne (J1), le lendemain (J2) , le jour de la consultation IVG3 avant la prise de misoprostol (J3) et à la visite de contrôle (IVG4) sur une EN. Les questions posées seront les suivantes :
A la consultation IVG1 : « actuellement, quelle est votre douleur ? »
A la consultation IVG2 avant prise de misoprostol : « hier, quelle a été la douleur maximale ressentie ? » et «actuellement, quelle est votre douleur ?
A la consultation IVG4 : « le jour suivant la prise de misoprostol et le jour d’aprés, quelle a été la douleur ressentie maximale dans la journée ? » et « actuellement, quelle est votre douleur ? et « depuis le jour suivant la prise de misoprostol et jusqu’à ce jour, quelle a été la douleur maximale et combien de jours avez-vous eu mal »
- La prise d’antalgiques le jour de la prise de misoprostol et les jours suivants en précisant la durée et la quantité d’ibuproféne et d’autres antalgiques pris.

- Echec de la méthode
L’échec est défini par la présence échographique d’une grossesse évolutive à la consultation IVG4 ou IVG5. Les moyens mis en œuvre pour permettre le diagnostic de l’échec seront ceux utilisés classiquement par les centres investigateurs.

- Consultations et gestes supplémentaires
Il est prévu des consultations supplémentaires sur une période de un mois après la prise de misoprostol (IVG5 et plus) si le médecin juge qu’il est nécessaire de revoir la patiente en rapport avec l’IVG médicamenteuse. Il sera précisé s’il s’agit d’une consultation simple ou la réalisation d’un geste endo utérin pour rétention. L’indication de consultation ou geste supplémentaire sera réalisée selon les habitudes des centres investigateurs.

- Tolérance
La tolérance sera appréciée par l’interrogatoire avant la fin d’hospitalisation pour la prise de misoprostol (IVG3). Les signes suivants seront minutieusement recueillis : nausées, vomissements, fièvre, diarrhée, douleurs abdominales, autres (à préciser par la patiente).

- Vécu et Anxiété
L’évaluation de l’anxiété sera appréciée par la passation de l’Inventaire de trait d’anxiété (STAI). Le STAI est un auto-questionnaire, développé par Spielberger (Spielberger, 1983) et validé en français (Gauthier & Bouchard, 1993). Il comporte 20 questions, évaluant l’état émotionnel habituel du sujet. Un score est calculé, un score élevé indiquant la présence
d’anxiété. Le vécu de l’IVG se fera par l’auto-questionnaire d’EVAN-LR. Cette évaluation se fera à la consultation IVG2 et IVG 4.

- Satisfaction
La satisfaction des sujets sera appréciée à l’aide d’une EVA, graduée de 0 à 10, remplie par la patiente à la consultation IVG4 ainsi que le questionnaire SF12 rempli à la consultation IVG2 et IVG4.

E.5.2.1

Timepoint(s) of evaluation of this end point

The average pain level on the initial time (primary endpoint) will be compared between the 2 groups (Student's t-test or Mann Whitney's test as a function of the parameter distribution). The maximum pain value over the first 5 hours will be compared between the 2 groups, but in secondary analysis.
For the secondary endpoints, qualitative variables will be compared between the 2 groups using the exact chi-2 or Fisher test and the continuous variables will be compared is Student's t or Mann Whitney's test depending on the distribution of parameter.

La moyenne du niveau de douleur sur les 5 temps horaires initiaux (critère de jugement principal) sera comparée entre les 2 groupes (test t de Student ou test de Mann Whitney en fonction de la distribution du paramètre). La valeur maximale de douleur sur les 5 1ères heures sera comparée entre les 2 groupes, mais en analyse secondaire.
Pour les critères de jugement secondaires, les variables qualitatives seront comparées entre les 2 groupes à l'aide du test de chi-2 ou Fisher exact et les variables continues seront comparées est t de Student ou test de Mann Whitney en fonction de la distribution du paramètre.

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

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

Dernière visite du dernier sujet en cours de participation dans l'étude

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:

320

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

Yes

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

Yes

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.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

Aucun

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

2018-03-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-03-27

P. End of Trial
P.	End of Trial Status	Completed

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