Clinical Trials Register

Summary
EudraCT Number:	2014-001809-40
Sponsor's Protocol Code Number:	MER001
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:	2015-06-22
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

2014-001809-40

A.3

Full title of the trial

Scheduling of GnRH antagonist FIV-ICSI cycles with estrogen or contraceptive oral pills in previous luteal phase. Comparison of results against no treatment.

PROGRAMACIÓN DE CICLOS FIV-ICSI CON ESTRÓGENOS O ANTICONCEPTIVOS ORALES EN FASE LÚTEA EN PROTOCOLO CON ANTAGONISTA. COMPARACIÓN DE RESULTADOS FRENTE A NO TRATAMIENTO

A.3.1

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

Scheduling of GnRH antagonist FIV-ICSI cycles with estrogen or contraceptive oral pills in previous luteal phase. Comparison of results against no treatment.

PROGRAMACIÓN DE CICLOS FIV-ICSI CON ESTRÓGENOS O ANTICONCEPTIVOS ORALES EN FASE LÚTEA EN PROTOCOLO CON ANTAGONISTA. COMPARACIÓN DE RESULTADOS FRENTE A NO TRATAMIENTO

A.3.2

Name or abbreviated title of the trial where available

Comparison of results in GnRh antagonist FIV-ICSI cycles pre treated with steroid hormones

A.4.1

Sponsor's protocol code number

MER001

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	IDIPAZ
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	Sara Fernandez Prada/ Onica Armijo Suarez
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	Servicio de Reproduccion Humana- H. la Paz
B.5.2	Functional name of contact point	Sara Fernandez
B.5.3	Address:
B.5.3.1	Street Address	Paseo Castellana 261
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28046
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34606823685
B.5.6	E-mail	sara_ferpra@hotmail.com

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	OVOPLEX
D.2.1.1.2	Name of the Marketing Authorisation holder	WYETH FARMA, 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	Ovoplex
D.3.2	Product code	52574
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	LEVONORGESTREL
D.3.9.1	CAS number	797-63-7
D.3.9.4	EV Substance Code	SUB08483MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ETHINYLESTRADIOL
D.3.9.1	CAS number	57-63-6
D.3.9.4	EV Substance Code	SUB07277MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
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	MERIESTRA
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Farmaceutica, 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	Meriestra
D.3.2	Product code	60207
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	ESTRADIOL VALERATE
D.3.9.1	CAS number	979-32-8
D.3.9.2	Current sponsor code	60.207
D.3.9.4	EV Substance Code	SUB07245MIG
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	4
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Sterility

Esterilidad

E.1.1.1

Medical condition in easily understood language

Sterility

Esterilidad

E.1.1.2

Therapeutic area

Body processes [G] - Reproductive physiologi cal processes [G08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.0
E.1.2	Level	LLT
E.1.2	Classification code	10042012
E.1.2	Term	Sterility
E.1.2	System Organ Class	100000004872

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Comparing gestational outcomes like pregnancy rate, clinical pregnancy rate, miscarriage rate or live birth rate between patients pretreated with estrogen pills, contraceptive pills and no pretreated .

Comparar la tasa de gestación, aborto y recién nacido vivo observadas en los grupos pre tratados y el no pre tratado en pacientes sometidas a ciclo de FIV en protocolo con antagonistas.

E.2.2

Secondary objectives of the trial

-To evaluate cancellation rate in order to insufficient ovarian stimulation in each group
-To evaluate adverse effects like hyperstimulation ovarian syndrome in each group
-To evaluate the number of ovarian follicles observed by US and the number of ovocytes obtained after puncture, as well as ovocyte quality in the different study groups.
-To observe hormonal basal values of FSH and estradiol before to ovarian stimulation and the possible effect over gestational outcomes.
-To observe hormonal values of E2 and Progesterone previously to ovulation induction, and the potential effect over endometrial receptiveness and implantation rates
-To evaluate treatment days and gonadotropin total doses necessary to get ovarian stimulation in each group.

- Valorar la tasa de cancelación de los ciclos por estimulación ovárica insuficiente obtenida en los diferentes grupos
- Valorar el hallazgo de posibles complicaciones como la hiperestimulación ovárica observada en los diferentes grupos.
- Valorar el número de folículos ováricos observados ecográficamente y el número de ovocitos obtenidos determinando la calidad ovocitaria de los mismos en los diferentes grupos a estudio.
9
- Observar los valores hormonales de FSH y estradiol al inicio de la estimulación, de estradiol pico, de progesterona el día de inducción de la ovulación con HCG por la posible implicación en la receptividad endometrial por alteración de los receptores hormonales a este nivel y por tanto, en el resultado gestacional.
- Valorar el grosor y el patrón endometrial previo a la transferencia por su posible relación con el resultado gestacional.
- Valorar los días necesarios para la estimulación ovárica y las dosis de gonadotropinas administradas en los grupos.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-Patients belong to La Paz University Hospital, Human reproductive service that begin a GnRH antagonist FIV-ICSI cycle.
-Patients between 18-40 years diagnosed of primary sterility for several causes like male factor, tubal factor, endometriosis of low grade and low ovarian reserve.
-Patients with a BMI < 30kg/m2
-Regular ovulation cycles (each 26-35 days)
-Patients with less than 3 FIV-ICSI cycles performed
-Hormonal basal values of FSH <14 UI/ml and Estradiol < 80 pg/ml.
-Patients who signed the informed consent.
-Presence of both ovaries.

-Pacientes del servicio de Reproducción del Hospital Universitario La Paz que inicien un tratamiento FIV-ICSI con protocolo de estimulación ovárica con antagonistas de la GnRH.
- Pacientes entre 18 y 40 años con esterilidad primaria previa por diversas causas como factor masculino, factor tubárico, endometriosis grado I-II, baja reserva ovárica o esterilidad primaria de origen desconocido.
- Pacientes con un IMC < 30Kg/m2
- Presencia de ciclos ovulatorios regulares (cada 26-35 días)
- Realización de < 3 ciclos FIV-ICSI
- Pacientes con valores hormonales basales el 3º día del ciclo de FSH < 14 IU/ml y estradiol < 80 pg/ml.
- Pacientes que otorguen el consentimiento informado.
- Presencia de ambos ovarios

E.4

Principal exclusion criteria

-Endometriosis high grade
-Endometrial pathology or uterine malformations previously diagnosed
-Ovarian polycystic syndrome according to Rotterdam criteria
-Presence of hydrosalpinx
-Intolerance or allergy to some drug
-Severe male factor (<100.000 REM or severe oligoasthenozoospermia)

-Endometriosis grado III-IV
- Patología endometrial o malformación uterina diagnosticada previamente
- Síndrome de ovario poliquístico de acuerdo con los criterios de Rotterdam
- Presencia de hidrosalpinx no extirpados
- Intolerancia o alergia a alguno de los fármacos
- Factor masculino severo (< 100.000 REM o semen de biopsia testicular o oligoastenozoospermias severas)

E.5 End points

E.5.1

Primary end point(s)

Gestational outcomes like pregnancy rate per cycle, clinical pregnancy rate per cycle, clinical miscarriage rate per cycle, live birth rate per cycle.

Obtención o ausencia de gestación, la consecución de gestación con recién nacido vivo o la interrupción de la gestación antes de la semana 22, además de la tasa de cancelación y síndrome de hiperestimulación en los diferentes grupos a estudio

E.5.1.1

Timepoint(s) of evaluation of this end point

2 months

2 meses

E.5.2

Secondary end point(s)

-Cancellation rate
-Hyperstimulation ovarian syndrome
-Hormonal basal values of FSH and Estradiol
-Hormonal values of E2 and Progesterone previously to ovulation induction
-Ovarian follicles observed after ovarian stimulation
-Ovocytes obtained after puncture, number of embryo complex and embryo quality
-Gonadotropin total doses used to get ovarian stimulation
-Total treatment days with gonadotropins
-Endometrial thickness before the embryo transfer.

- valores hormonales (FSH y E2 al inicio del ciclo y E2 y progesterona previa a la inducción de la ovulación)
- folículos ováricos observados ecográficamente tras la estimulación ovárica
- ovocitos obtenidos tras punción y calidad embrionaria
- las dosis de gonadotropinas utilizadas
- los días de estimulación
- el grosor y patrón endometrial previo a la transferencia embrionaria.

E.5.2.1

Timepoint(s) of evaluation of this end point

2 months

2 meses

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

brazo sin tratamiento

no treatment

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the 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

Yes

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:

150

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

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

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

150

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

Ninguno

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

2015-09-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-11-28

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

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