E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Infertility. Assisted Reproductive Tecniques. |
Infertilidad. Técnica de Reprodución Asistida. |
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E.1.1.1 | Medical condition in easily understood language |
Assisted Reproductive Tecniques. |
Técnica de Reprodución Asistida. |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10073184 |
E.1.2 | Term | Embryo transfer |
E.1.2 | System Organ Class | 100000004865 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective of this study is to evaluate the effect on the clinical pregnancy rate at 4-5 weeks of gestation, using one of the two progesterone treatments with a different route of administration, either vaginal (Progeffik, 200 mg/8 h), or subcutaneous (Prolutex 25 mg/12 h), to support the luteal phase in subjects submitted to a frozen blastocyst embryo transfer. |
El objetivo de este estudio es evaluar el efecto sobre la tasa de embarazo clínico a las 4-5 semanas de gestación, utilizando uno de los dos tratamientos con progesterona con una vía de administración diferente, ya sea vaginal (Progeffik, 200 mg / 8 h), o subcutánea (Prolutex 25 mg / 12 h), para apoyar la fase lútea en sujetos sometidos a una transferencia de embriones de blastocistos congelados |
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E.2.2 | Secondary objectives of the trial |
Efficacy Assessments: •Serum progesterone levels in visits V2 and V3 •Frequency of uterine contractions (n of uterine contractions/min) on the day of the embryo transfer V2 •Positive serum β-hCG pregnancy test rate (V3) •Implantation rate (V4) •Ongoing pregnancy rate 9-11 weeks after progesterone treatment start (V5) Abortion rate.
In addition:
•Analyse if there is a relationship between serum progesterone levels on the day of em-bryo transfer and the ongoing pregnancy rate in each of the 2 groups. •Analyse if there is a relationship between serum progesterone levels on the day of em-bryo transfer and the frequency of uterine contractions before transfer. •Analyse if there is a relationship between the frequency of uterine contractions on the day of embryo transfer and the clinical and ongoing pregnancy rate. |
Evaluaciones de eficacia: •Niveles séricos de progesterona en las visitas V2 y V3. •Frecuencia de las contracciones uterinas (n de contracciones uterinas / min) en el día de la transferencia de embriones V2 •Tasa de prueba de embarazo β-hCG sérica positiva (V3) •Tasa de implantación (V4) •Tasa de embarazo en curso 9-11 semanas después del inicio del tratamiento con progesterona (V5) •Tasa de abortos. Adicionalmente: •Analizar si existe una relación entre los niveles de progesterona en suero en el día de la transferencia de embrio y la tasa de embarazo en curso en cada uno de los 2 grupos. •Analizar si existe una relación entre los niveles de progesterona en suero en el día de la transferencia de embrio y la frecuencia de las contracciones uterinas antes de la transferencia. •Analizar si existe una relación entre la frecuencia de las contracciones uterinas en el día de la transferencia de embriones y la tasa clínica y de embarazo en curso. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•18-49 years of age for subjects undergoing ET with donated oocytes (both inclusive); •18-37 years of age for subjects undergoing ET with autologous oocytes (both inclu-sive); •BMI <32 kg/m2; •Adequate endometrium preparation (Endometrial thickness > 7 mm) and E2 levels (>100 pg/ml) on the day progesterone treatment is started; •P4 levels <1.5 ng/ml on the day progesterone treatment is started; •Transfer of 1 or 2 frozen embryos at blastocyst stage; •Transfer of frozen embryos of quality A and/or B according to Gardner criteria1; •Semen from ejaculation either from the partner or from a bank; •≤ 3 previous ET (frozen and fresh) with no pregnancy; •Normal uterine cavity (i.e. no polyp or protruding sub-mucosal fibroid). |
18-49 años de edad para sujetos sometidos a ET con ovocitos donados (ambos inclusive); •18-37 años de edad para sujetos sometidos a ET con ovocitos autólogos (ambos inclusive); •IMC <32 kg / m2; •Preparación adecuada del endometrio (grosor endometrial> 7 mm) y niveles de E2 (> 100 pg / ml) el día en que se inicia el tratamiento con progesterona; •Niveles de P4 <1.5 ng / ml el día en que se inicia el tratamiento con progesterona; •Transferencia de 1 o 2 embriones congelados en la etapa de blastocisto; •Transferencia de embriones congelados de calidad A y / o B según los criterios de Gardner1; •Semen de eyaculación ya sea de la pareja o de un banco; •≤ 3 ET anteriores (congeladas y frescas) sin embarazo; •Cavidad uterina normal (es decir, sin pólipo o fibroma sub-mucosa saliente). |
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E.4 | Principal exclusion criteria |
•Presence of functional follicles > 10 mm of diameter on the day progesterone treatment is started; •Intramural uterine fibroids that distort the uterine cavity or polyps >1 cm; •Stage III or IV endometriosis (endometriomas); •Hydrosalpinx; •Pregnancy or lactation; •Malformations of the sexual organs incompatible with pregnancy; •Subjects affected by pathologies associated with any contraindication of being preg-nant; •Known allergy to progesterone preparations or their excipients; •Uncontrolled adrenal or thyroid dysfunction; •Undiagnosed vaginal haemorrhage; •History of, or current arterial disease; •Subjects with hepatic impairment; •Human Immunodeficiency Virus, Hepatitis B Virus or Hepatitis C Virus seropositive; •Neoplasias (current) or history of neoplasia that may be responsive to progesterone; •High grade cervical dysplasia; •Active thrombophlebitis or thromboembolic disorders, or a history of hormone-associated thrombophlebitis or thromboembolic disorders; •Currently dependent on alcohol, drugs or psychotropic drugs; •History of recurrent pregnancy loss defined as 3 or more spontaneous miscarriages wherein pregnancy developed to a minimum of a gestational sac on TVUS; •Participation in a concurrent clinical trial or another trial within the past 2 months; •Use of concomitant medications that might interfere with the study evaluation: hor-monal treatments other than those used in the study, except thyroid hormones. |
Presencia de folículos funcionales> 10 mm de diámetro en el día en que se inicia el tratamiento con progesterona; •Fibromas uterinos intramurales que distorsionan la cavidad uterina o los pólipos> 1 cm; •Endometriosis en etapa III o IV (endometriomas); •Hydrosalpinx; •Embarazo o lactancia; •Malformaciones de los órganos sexuales incompatibles con el embarazo; •Sujetos afectados por patologías asociadas a cualquier contraindicación de embarazo. •Alergia conocida a las preparaciones de progesterona o sus excipientes; •Disfunción suprarrenal o tiroidea no controlada; •Hemorragia vaginal no diagnosticada; •Historia de, o enfermedad arterial actual; •Sujetos con insuficiencia hepática; •Virus de inmunodeficiencia humana, virus de la hepatitis B o virus de la hepatitis C seropositivos; •Neoplasias (actuales) o antecedentes de neoplasia que pueden responder a la progesterona; •Displasia cervical de alto grado; •Tromboflebitis activa o trastornos tromboembólicos, o antecedentes de tromboflebitis asociada a hormonas o trastornos tromboembólicos; •Actualmente dependiente de alcohol, drogas o psicotrópicos; •Historial de pérdida recurrente de embarazo definida como 3 o más abortos espontáneos en los que el embarazo se desarrolló hasta un mínimo de un saco gestional en TVUS; •Participación en un ensayo clínico concurrente u otro ensayo en los últimos 2 meses; •Uso de medicamentos concomitantes que podrían interferir con la evaluación del estudio: tratamientos hormonales distintos a los utilizados en el estudio, excepto las hormonas tiroideas |
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E.5 End points |
E.5.1 | Primary end point(s) |
Clinical pregnancy rate |
Tasa de embarazo clínico |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
6 weeks of gestation |
6 semanas de gestación |
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E.5.2 | Secondary end point(s) |
-Serum progesterone levels at visits V2 and V3 -Frequency of uterine contractions (n of uterine contractions/min) on the day of the embryo transfer V2 -Positive pregnancy (serum β-hCG) test rate (V3) -Implantation rate (V4) -Ongoing pregnancy rate 9-11 weeks after progesterone treatment start (V5) -Abortion rate |
-Niveles séricos de progesterona en las visitas V2 y V3. -Frecuencia de las contracciones uterinas (n de contracciones uterinas / min) en el día de la transferencia de embriones V2 -Tasa de prueba positiva de embarazo (β-hCG) (V3) -Tasa de implantación (V4) -Tasa de embarazo en curso 9-11 semanas después del inicio del tratamiento con progesterona (V5) -Tasa de aborto |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
6 weeks of gestation |
6 semanas de gestación |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Estudio abierto de etiquetas. La evaluación de las contracciones uterinas se realizará a ciegas. |
Open label study. The assessment of the uterine contractions will be per-formed in a blind way |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
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 | 1 |