E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Leiomyoma |
Miomas uterinos |
|
E.1.1.1 | Medical condition in easily understood language |
Uterine fibroids, heavy menstrual bleeding |
Miomas uterinos, sangrado menstrual abundante |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
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 | 10046784 |
E.1.2 | Term | Uterine fibroids |
E.1.2 | System Organ Class | 100000004864 |
|
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 | 10016628 |
E.1.2 | Term | Fibroids |
E.1.2 | System Organ Class | 100000004864 |
|
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 | 10022794 |
E.1.2 | Term | Intramural leiomyoma of uterus |
E.1.2 | System Organ Class | 100000004864 |
|
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 |
To assess the efficacy of vilaprisan in subjects with uterine fibroids compared to placebo. |
Evaluar la eficacia de vilaprisán en comparación con el placebo en pacientes con miomas uterinos. |
|
E.2.2 | Secondary objectives of the trial |
To assess the efficacy of vilaprisan in subjects with uterine fibroids compared to ulipristal. To evaluate the safety of vilaprisan in subjects with uterine fibroids. |
Evaluar la eficacia de vilaprisán en comparación con ulipristal en pacientes con miomas uterinos. Evaluar la seguridad de vilaprisán en pacientes con miomas uterinos. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed and dated informed consent 2. Women, 18 to 50 years of age at the time of screening 3. Diagnosis of uterine fibroid(s) documented by transvaginal or abdominal ultrasound at screening with at least 1 fibroid with largest diameter >/=3.0 cm 4. Heavy menstrual bleeding (HMB) >80 mL documented by menstrual pictogram (MP) in a bleeding episode during the screening period Women who did not suffer from perceived HMB during the 3 months prior to Visit 1 due to any effective medical treatment, e.g. with a hormonal contraceptive, are not considered appropriate candidates and should not undergo further screening procedures. Women suffering from perceived HMB despite medical treatment, e.g. with a hormonal contraceptive, are appropriate candidates for further screening, if rules on stopping prior medication are followed. 5. Eligible to undergo surgical treatment for uterine fibroids at the end of study treatment 6. Good general health (except for findings related to uterine fibroids) as proven by medical history, physical and gynecological examinations, and laboratory test results 7. Normal or clinically insignificant cervical smear not requiring further follow-up. Human papilloma virus (HPV) testing in subjects with atypical squamous cells of undetermined significance (ASCUS) can be used as an adjunctive test. Subjects with ASCUS can be included if they are negative for high-risk HPV strains. 8. An endometrial biopsy performed during the screening period, without significant histological disorder such as endometrial hyperplasia (including simple hyperplasia) or other significant endometrial pathology. 9. Use of an acceptable nonhormonal method of contraception (i.e. either male condom, cap, diaphragm or sponge, each in combination with spermicide) starting at the bleeding episode following the screening visit 1 (Visit 1) until the end of the study. This is not required if safe contraception is achieved by a permanent method, such as bilateral fallopian tube blockage of the subject or vasectomy of the partner(s). |
1. Consentimiento informado firmado y fechado 2. Mujeres de edad comprendida entre 18 y 50 años en el momento de la selección 3. Diagnóstico de mioma(s) uterino(s) documentado mediante ecografía abdominal o transvaginal realizada en la selección, con al menos 1 mioma de >/= 3,0 cm en su diámetro máximo 4. Sangrado menstrual abundante (SMA) >80 ml documentado mediante pictograma menstrual durante el episodio de sangrado posterior a la visita de selección Las mujeres que no padezcan (SMA) durante los 3 meses previos a la visita 1 debido a un tratamiento médico efectivo, p.ej. Uso de anticonceptivos hormonales, no serán consideradas candidatas para entrar en el estudio y no deberían de ser seleccionadas. Las mujeres que padecen (SMA) aun siendo tratadas con un tratamiento médico, p.ej: anticonceptivos hormonales, serán candidatas para ser seleccionadas, si se siguen las reglas de finalización de medicación previa 5. Candidatas a recibir tratamiento quirúrgico al final del periodo de tratamiento debido a los miomas uterinos 6. Buen estado de salud general (exceptuando los signos relacionados con los miomas uterinos) confirmado mediante la anamnesis, una exploración física y ginecológica y los resultados de las pruebas analíticas 7. Citología vaginal normal o clínicamente no significativa, que no requiere seguimiento posterior En las pacientes que presenten células escamosas atípicas de significado indeterminado (ASCUS) se pueden realizar pruebas del virus del papiloma humano (VPH) a modo de análisis complementario. Puede incluirse a pacientes con ASCUS si dan negativo para las cepas del VPH de alto riesgo 8. Una biopsia endometrial realizada en la visita de selección, sin alteraciones histológicas significativas como hiperplasia endometrial (incluyendo hiperplasia simple) u otra patología endometrial importante. 9. Uso de un método anticonceptivo no hormonal aceptable (p. ej., preservativo o diafragma más espermicida), a partir del episodio de sangrado posterior a la visita de selección 1 (Visita 1) y hasta el final del estudio. Su uso no será necesario en caso de que se utilice un método anticonceptivo permanente, como la obstrucción bilateral de las trompas de Falopio de la paciente o la vasectomía de su(s) pareja(s). |
|
E.4 | Principal exclusion criteria |
1. Pregnancy or lactation (less than 3 months since delivery, abortion, or lactation before start of treatment) 2. Uterine fibroid with largest diameter >10.0 cm 3. Hypersensitivity to any ingredient of the study drugs 4. Hemoglobin values </= 6 g/dL or any condition requiring immediate blood transfusion (subjects with hemoglobin values </=10.9 g/dL will be offered iron supplementation). 5. Women with bleeding/spotting episodes lasting longer than 10 days should not be included. 6. Any diseases or conditions that can compromise the function of the body systems and could result in altered absorption, excessive accumulation, impaired metabolism, or altered excretion of the study drug 7. Any diseases or conditions that might interfere with the conduct of the study or the interpretation of the results 8. Abuse of alcohol, drugs, or medicines (e.g. laxatives) 9. Use of other treatments that might interfere with the conduct of the study or the interpretation of the results 10. Undiagnosed abnormal genital bleeding. |
1. Embarazo o lactancia (si han transcurrido menos de 3 meses desde el parto, aborto, o lactancia antes del inicio del tratamiento) 2. Mioma uterino con un diámetro máximo > 10.0 cm 3. Hipersensibilidad a cualquier componente de los fármacos del estudio 4. Concentración de hemoglobina </= 6 g/dl o cualquier trastorno que requiera una transfusión de sangre inmediata (las pacientes con niveles de hemoglobina </= 10,9 g/dl se les ofrecerá suplementos de hierro). 5. Mujeres con episodios de sangrado/manchado de duración superior a 10 días 6. Cualquier enfermedad o proceso que pueda alterar la función de los órganos, sistemas y aparatos corporales y pudiera ocasionar una acumulación excesiva o una alteración de la absorción, del metabolismo o de la excreción del fármaco del estudio 7. Cualquier enfermedad o proceso que pudiera interferir en la realización del estudio o la interpretación de los resultados 8. Abuso de alcohol, drogas o medicamentos (p. ej., laxantes) 9. Uso de otros tratamientos que pudieran interferir en la realización del estudio o la interpretación de los resultados. 10. Sangrado genital anormal no diagnosticado |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Amenorrhea (yes/no) Defined as no scheduled or unscheduled bleeding/spotting after end of the initial bleeding episode until the end of the respective treatment period |
Amenorrea (sí/no) definida como ausencia de sangrado/manchado programado o no programado después del final del episodio de sangrado inicial hasta el final del tratamiento. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
After end of the intial bleeding until treatment day 84 of each treatment period |
Después del final del primer sangrado hasta el día 84 de tratamiento para cada grupo de tratamiento. |
|
E.5.2 | Secondary end point(s) |
1. Number of bleeding days 2. Time to onset of controlled bleeding 3. Percent change in volume of largest fibroid compared to baseline 4. Endometrial histology (classical histology) 5. Endometrial thickness |
1. Número de días de sangrado 2. El tiempo hasta la aparición de sangrado 3. El porcentaje de cambio en el volumen del mioma de mayor tamaño con respecto al periodo basal 4. Estudio histológico endometrial (histología clásica) 5. Grosor endometrial |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. From start of treatment until the day before the next treatment period would start again 2. From baseline until end of treatment 3. From baseline until end of treatment 4. From baseline until end of follow-up period 5. From baseline until end of follow-up period |
1. Des del inicio del tratamiento hasta el día antes del inicio del siguiente período de tratamiento 2. Des del período basal hasta el final del tratamiento 3. Des del período basal hasta el final del tratamiento 4. Des del período basal hasta el final del período de seguimiento 5. Des del período basal hasta el final del período de seguimiento |
|
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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 |
Abierto para el control activo |
Open label active-controlled |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 7 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 64 |
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
|
LPLV (LVLS) |
último paciente última visita |
|
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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |