E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hipertensión Arterial Pulmonar Pulmonary Arterial Hypertension |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064911 |
E.1.2 | Term | Hipertensión arterial pulmonar |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065150 |
E.1.2 | Term | Hipertensión pulmonar arterial primaria asociada |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065151 |
E.1.2 | Term | Hipertensión pulmonar arterial primaria idiopática |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065152 |
E.1.2 | Term | Hipertensión pulmonar arterial primaria familiar |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064911 |
E.1.2 | Term | Hipertensión arterial pulmonar |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
El objetivo principal es la seguridad y la tolerabilidad a largo plazo de ambrisentan en la población de pediátrica con HAP (véase Seguridad). The primary objective is the safety and tolerability of ambrisentan in the paediatric PAH population. |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Subestudio de hemodinámica cardiopulmonar: Variación con respecto al periodo basal del estudio AMB112529 de los datos de evaluaciones hemodinámicas cardiopulmonares en sujetos en quienes los datos hemodinámicos se consideren parte de la asistencia habitual (véase el Apéndice 1 del protocolo). Cardiopulmonary Hemodynamic Sub-study (see Appendix 1 of protocol): The change from Study AMB112529 baseline in cardiopulmonary hemodynamic assessments data in subjects in whom hemodynamic data is consider |
|
E.3 | Principal inclusion criteria |
1. El paciente tendrá que haber participado en el estudio AMB112529 y haber cumplido el protocolo lo mejor posible, y deberá satisfacer uno de estos requisitos: a. Completó la visita de la semana 24 del estudio AMB112529; b. Necesitó tratamiento dirigido adicional para la HAP debido a una respuesta insuficiente al tratamiento que recibía o al empeoramiento de su estado clínico antes de la semana 24 en el estudio AMB112529; c. Precisó una reducción de la dosis del tratamiento basal específico para la HAP después de la adición de ambrisentan al régimen de tratamiento; d. En opinión del investigador, está justificado continuar el tratamiento con ambrisentan. 2. Una adolescente podrá para participar en este estudio, previa evaluación por el investigador, en caso de que: a. no sea potencialmente fértil (es decir, que fisiológicamente no pueda quedarse embarazada); o, b. si es potencialmente fértil, tenga un resultado negativo en una prueba de embarazo y no se encuentre en periodo de lactancia y, si es sexualmente activa, se comprometa a seguir usando dos métodos anticonceptivos fiables hasta la finalización del estudio y durante al menos 30 días después de recibir la última dosis del fármaco del estudio. 3. El sujeto (o su tutor legal) es capaz y está dispuesto a dar su consentimiento informado por escrito. Como parte del consentimiento, las pacientes en edad fértil serán informadas del riesgo de teratogenia y deberán recibir información, adecuada a su grado de madurez, acerca de la importancia de evitar el embarazo; los varones deberán ser informados del riesgo de sufrir atrofia de los túbulos testiculares y aspermia. 1. Have participated in and complied, to the best of their ability, with the protocol for AMB112529 and have met one of the following: a. Completed the Week 24 visit in AMB112529; b. Required additional targeted treatment for PAH due to inadequate response to the current treatment or worsening of their clinical condition prior to week 24 in AMB112529; c. Required reduction in dose of baseline targeted treatment for PAH after ambrisentan was added to the treatment regimen; d. In the opinion of the investigator, continued treatment with ambrisentan is warranted. 2. A female is eligible to participate in this study, as assessed by the investigator, if she is of: a. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant); or, b. Child-bearing potential - has a negative pregnancy test and is not lactating and, if sexually active, agrees to continue to use 2 reliable methods of contraception until study completion and for at least 30 days following the last dose of study drug 3. Subject or subject?s legal guardian is able and willing to give written informed consent. As part of the consent, female subjects of childbearing potential will be informed of the risk of teratogenicity and will need to be counselled in a developmentally appropriate manner on the importance of pregnancy prevention; and male subjects will need to be informed of potential risk of testicular tubular atrophy and aspermia. |
|
E.4 | Principal exclusion criteria |
1. Sujetos que dejaron de recibir ambrisentan en el estudio AMB112529. 2. Sujetos que no cumplieron el protocolo del estudio AMB112529. 3. Pacientes embarazadas o en periodo de lactancia. 4. Pacientes con insuficiencia renal grave (aclaramiento de creatinina calculado <30ml/min evaluado en los 45 días previos) en el momento de transición del estudio AMB112529 a este estudio. 5. Sujetos con retención de fluidos de importancia clínica en opinión del investigador. 6. Sujetos con anemia de importancia clínica en opinión del investigador. 7. Sujetos que vayan a participar en otro ensayo clínico o a recibir tratamiento con otro producto en investigación tras el estudio AMB112529. 1. Subjects who were withdrawn from ambrisentan in Study AMB112529; 2. Subjects who did not comply with the protocol in Study AMB112529; 3. Female subjects who are pregnant or breastfeeding; 4. Subjects with severe renal impairment (estimated creatinine clearance <30 mL/min assessed within the previous 45 days) at the point of transition from Study AMB112529 into this study; 5. Subject with clinically significant fluid retention in the opinion of the investigator; 6. Subject with clinically significant anaemia in the opinion of the investigator; 7. Subjects who are to enter another clinical trial or be treated with another investigational product after exiting Study AMB112529. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Acontecimientos adversos. - Acontecimientos adversos graves. - Parámetros de laboratorio clínico. - Exploración física (talla, peso, índice de masa corporal / superficie corporal, saturación de oxígeno, presión venosa yugular, tamaño hepático y presencia de edema periférico o ascitis). - Constantes vitales. - Desarrollo puberal (variación con respecto al periodo basal del estudio AMB112529 de las evaluaciones endocrinológicas realizadas cada seis meses y a los 20 años de edad). - Tiempo transcurrido hasta la modificación de la dosis de ambrisentan o de otros medicamentos específicos para la HAP (prostanoides, inhibidores de la PDE-5) debido a problemas de tolerabilidad (por ejemplo, acontecimientos adversos) Safety as assessed by: ?Adverse Events; ? Serious Adverse Events; ? Clinical laboratory parameters; ? Physical examination (including height, weight, body mass index / body surface area, oxygen saturation, jugular venous pressure, liver size, and presence of peripheral oedema and/or ascites); ? Vital Signs; ? Pubertal development (change from Study AMB112529 baseline in endocrinology assessments every six months and at 20 years of age); ? The time to change in dose of ambrisentan or other targeted PAH therapeutic agents (prostanoids, PDE-5 inhibitors) due to tolerability issues (e.g. adverse events). |
|
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 | Yes |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Diferent dose of same IMP |
|
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
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
|
Los sujetos podrán continuar en el estudio de extensión hasta se cumpla una de las condiciones siguientes: - El sujeto cumple 18 años - Se aprueba el producto y está disponible para usarse en el grupo en edad del sujeto - Se suspende el desarrollo del producto para uso en la población pediátrica. - El sujeto decide que no desea seguir participando en el estudio. - El investigador considera que lo más conveniente para el sujeto es dejar de recibir ambrisentan. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 12 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 12 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |