E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ulcerative colitis |
Colitis ulcerosa |
|
E.1.1.1 | Medical condition in easily understood language |
A form of inflammatory bowel disease |
Un tipo de enfermedad inflamatoria intestinal |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
E.1.2 | System Organ Class | 100000004856 |
|
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 evaluate the long-term safety and tolerability of APD334 in patients with ulcerative colitis who have completed the APD334-03 study. |
Evaluar la seguridad y tolerabilidad a largo plazo de APD334 en pacientes con colitis ulcerosa que han completado el estudio APD334-003. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the effect of APD334 on achieving and maintaining clinical response and/or remission in patients with ulcerative colitis after 52 weeks of treatment. |
Evaluar el efecto de APD334 para alcanzar y mantener la respuesta clínica y/o la remisión en pacientes con colitis ulcerosa después de 52 semanas de tratamiento. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Evidence of a personally signed and dated informed consent document 2. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures and is deemed an appropriate candidate for participation in this long-term extension study 3. Eligible female patients must be: a. non-pregnant, evidenced by a negative urine dipstick pregnancy test at Week 12 of study APD334-003 b. non-lactating c. sexually abstinent, surgically sterile, postmenopausal, or agree to continue to use an accepted method of birth control during and for at least 30 days after last study medication administration. Acceptable methods of birth control are: - hormonal contraceptives (patients should be consistently taking the hormonal contraceptive for at least 3 months [90 days] prior to screening); - double barrier method (condom or occlusive cap [diaphragm or cervical cap] with spermicide); - an intrauterine device; - surgical sterility for at least 6 months prior to screening for tubal ligation performed laparoscopically, hysterectomy and/or bilateral oophorectomy; and/or postmenopausal (defined as at least 2 years without menses). Contraceptive measures such as Plan B (used after unprotected sex) are not acceptable methods of contraception for this study. 4. Eligible male patients will either be: - Surgically sterile (i.e., vasectomy), for at least 3 months (90 days) prior to screening or - Agree to use a condom with spermicide when sexually active with a female partner who is not using an acceptable method of birth control during the study and for 30 days after last study medication administration 5. Eligible male and female patients must agree not to participate in a conception process (i.e. active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization) for 30 days after the last dose of study drug 6. Fulfillment of all eligibility criteria for APD334-003 and completion the study as planned |
1. Confirmación del documento de consentimiento informado firmado y fechado personalmente. 2. Disposición y capacidad de cumplir con las visitas, el plan de tratamiento, los análisis de laboratorio y todos los demás procedimientos del estudio programados, además de ser considerado un candidato idóneo para la participación en este estudio de extensión a largo plazo. 3. Las mujeres idóneas tienen que: a. no estar embarazadas, demostrado por una prueba de embarazo en orina con tira reactiva negativa en la semana 12 del estudio APD334-003; b. no estar dando el pecho; c. mantener abstinencia sexual, ser quirúrgicamente estériles, posmenopáusicas o aceptar utilizar un método anticonceptivo aceptado durante el estudio y al menos en los 30 días siguientes a la última administración del medicamento del estudio. Los métodos anticonceptivos aceptables son: - anticonceptivos hormonales (las pacientes deben tomar sistemáticamente el anticonceptivo hormonal durante al menos 3 meses [90 días] antes de la selección); - método de doble barrera (preservativo o capuchón oclusivo [diafragma o capuchón cervical/vaginal] con espermicida); - dispositivo intrauterino; - esterilidad por métodos quirúrgicos durante al menos 6 meses antes de la selección en caso de ligadura de trompas realizada mediante laparoscopia, histerectomía y/u ooforectomía bilateral, y/o posmenopausia (definida como al menos 2 años sin menstruación). Los métodos anticonceptivos como el Plan B (utilizado después de mantener relaciones sexuales sin protección) no son métodos anticonceptivos aceptables para este estudio. 4. Los pacientes varones idóneos tienen que: - ser estériles por métodos quirúrgicos (es decir, vasectomía), durante al menos 3 meses (90 días) antes de la selección; o - acordar usar un preservativo con espermicida cuando mantengan relaciones con una pareja femenina que no esté utilizando un método anticonceptivo aceptable durante el estudio y en los 30 días siguientes a la última administración del medicamento del estudio. 5. los pacientes idóneos de ambos sexos tienen que estar de acuerdo en no participar en un proceso de concepción (es decir, un intento activo de quedarse embarazada o de dejar embarazada a su pareja, donación de esperma o fertilización in vitro) durante 30 días después de recibir la última dosis del fármaco del estudio. 6. Cumplir todos los criterios de idoneidad del estudio APD334-003 y completar el estudio tal como está programado. |
|
E.4 | Principal exclusion criteria |
1. Patients who were withdrawn from study drug treatment due to any AE or SAE, or patients who did not complete the APD334-003 study 2. Female patients who wish to become pregnant 3. Other severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study |
1. Pacientes que suspendieron el tratamiento con el fármaco del estudio debido a AA o AAG o que no completaron el estudio APD334-003. 2. Pacientes que desean quedarse embarazadas. 3. Cualquier otra anomalía analítica o médica de carácter agudo grave o crónico que pueda aumentar el riesgo asociado a la participación en el estudio o a la administración del producto en investigación o interferir en la interpretación de los resultados del estudio y, en opinión del investigador, convertir al paciente en inadecuado para la participación en este estudio. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for the study is long-term safety. The safety of APD334 will be monitored throughout the study with safety endpoints being as follows: - Treatment-emergent adverse events (AEs) up to 30 days following discontinuation of the study drug. - Treatment-emergent serious adverse events (SAEs) up to 30 days following discontinuation of the study drug. |
El criterio de valoración principal del estudio es la seguridad a largo plazo. La seguridad de APD334 se vigilará durante todo el estudio, siendo los criterios de valoración de la seguridad los siguientes: - Acontecimientos adversos (AA) aparecidos durante el tratamiento hasta 30 días después de la suspensión del fármaco del estudio. - Acontecimientos adversos graves (AAG) aparecidos durante el tratamiento hasta 30 días después de la suspensión del fármaco del estudio. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Monitored throughout study up to 30 days after discontinuation of study drug |
Monitorizado a lo largo del estudio hasta hasta 30 días después de la suspensión del fármaco del estudio. |
|
E.5.2 | Secondary end point(s) |
In responders who transitioned from study APD334-003 to APD334-005: - The proportion of patients who maintain clinical response [defined as a decrease in 3-component Mayo Clinic score of >= 2 points and at least 30% with either a decrease of rectal bleeding of >= 1 or rectal bleeding score of 0 or 1] at Week 52 compared to APD334-003 baseline - The proportion of patients who achieve clinical remission [defined as individual subscores of the 3-component Mayo Clinic score as follows: an endoscopy score (using flexible proctosigmoidoscopy) of 0 or 1, a rectal bleeding score of 0, and a stool frequency score of 0 or 1 with a decrease of >= 1 point from baseline at Week 52 compared to APD334-003 baseline |
En los pacientes que respondan que pasen del estudio APD334-003 al estudio APD334-005: - La proporción de pacientes que mantengan la respuesta clínica (definida como una disminución >= 2 puntos en la puntuación de 3 componentes de la Clínica Mayo y al menos del 30 %, con una disminución de rectorragia >= 1 o una puntuación de rectorragia de 0 o 1) en la semana 52 en comparación con el valor inicial del estudio APD334-003. - La proporción de pacientes que alcancen la remisión clínica (definida como subescalas individuales de la puntuación de 3 componentes de la Clínica Mayo, de la siguiente forma: puntuación de endoscopia [utilizando proctosigmoidoscopia flexible] de 0 o 1, puntuación de rectorragia de 0 y puntuación de frecuencia de deposiciones de 0 o 1, con descenso >= 1 punto respecto al valor inicial en la semana 52 en comparación con el valor inicial del estudio APD334-003). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Screening and Week 52 |
Selección a semana 52 |
|
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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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) | 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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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 | No |
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 |
Australia |
Belgium |
Bulgaria |
Canada |
Czech Republic |
France |
Germany |
Hungary |
Israel |
Latvia |
Lithuania |
New Zealand |
Poland |
Romania |
Russian Federation |
Spain |
Ukraine |
United Kingdom |
United States |
|
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
|
Last visit of the last subject |
Última visita del último paciente |
|
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 | 12 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 5 |