E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | Major Depressive Disorder (MDD) | Trastorno depresivo mayor (TDM) | |
E.1.1.1 | Medical condition in easily understood language | |
E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 | E.1.2 | Level | LLT | E.1.2 | Classification code | 10025453 | E.1.2 | Term | Major depressive disorder NOS | E.1.2 | System Organ Class | 100000004873 | |
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 long-term safety and tolerability of aticaprant | Evaluar la seguridad y la tolerabilidad a largo plazo de aticaprant | |
E.2.2 | Secondary objectives of the trial | To assess the long-term efficacy of aticaprant | Evaluar la eficacia a largo plazo de aticaprant | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria | Transferred patients: - Participants must have completed the Double Blind Treatment Phase of Study 67953964MDD3001 or Study 67953964MDD3002 study. - Participant must be medically stable on the basis of physical examination, medical history, vital signs (including blood pressure), and 12-lead ECG performed at baseline and prior to Open Label treatment initiation. Direct entry patients: - Male or female, aged 18 to 74 years of age, inclusive. - Be medically stable on the basis of physical examination, medical history, vital signs, and 12-lead ECG performed at screening and baseline - Be medically stable on the basis of clinical laboratory tests performed at screening - Meet DSM-5 diagnostic criteria for recurrent or single episode MDD, without psychotic features. Participants 65 years of age or older must have had the first onset of depression prior to 55 years of age. - Have had an inadequate response to at least 1 but no more than 3 antidepressants, administered at an adequate dose and duration in the current episode of depression. - Is receiving and tolerating well a SSRI/SNRI for depressive symptoms at screening, at a stable dose for at least 6 weeks - Have a HDRS-17 total score of 20 or higher at the first and second screening interviews and must not demonstrate a clinically significant improvement between the first and the second independent HDRS-17 assessments | Participantes de entrada transferida: - Los participantes tienen que haber completado el tratamiento doble ciego de las fases de los estudios MDD3001 o MDD3002. - El participante debe estar médicamente estable según el examen físico, el historial médico, los signos vitales (incluida la presión arterial) y el ECG de 12 derivaciones realizado al inicio y antes del inicio del tratamiento de etiqueta abierta. Participantes de entrada directa: - De sexo masculino o femenino, de 18 a 74 años, ambos inclusive. - Cumplir con los criterios diagnósticos de la 5.ª versión del Manual Diagnóstico y Estadístico de los Trastornos Mentales (DSM-5) para TDM recurrente o de episodio único, sin características psicóticas. Los participantes de 65 años o más deberán haber sufrido el primer episodio de depresión antes de los 55 años. - Haber tenido una respuesta inadecuada a un mínimo de 1, pero no más de 3 antidepresivos, administrados a una dosis adecuada y una duración adecuada en el episodio actual de depresión. - Estar recibiendo y tolerando bien un ISRS/IRSN para síntomas depresivos en la fase de selección, a una dosis adecuada durante al menos 6 semanas. - Tener una puntuación total de ≥ 20 en la primera y segunda entrevista de selección de la Escala de evaluación de la depresión de Hamilton de 17 elementos (HDRS-17) sin una mejora superior al 20 % de la primera a la segunda evaluación. | |
E.4 | Principal exclusion criteria | Transferred-entry participants: - Participant has been non-compliant with the study intervention administration in the Double Blind (DB) Treatment Phase in either of Studies 67953964MDD3001 or 67953964MDD3002 - The evaluation of the benefit versus risk of continued aticaprant treatment is not favorable for the participant in the opinion of the investigator. - Participant is reporting suicidal ideation with intent to act or suicidal behavior at baseline. - Participant has taken any prohibited therapies that would not permit dosing on Day 1, as noted in the pre-study and concomitant therapy section. - Participant has any condition or situation/circumstance for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol- specified assessments. Direct-entry participants: - Participant has lack of clinically meaningful improvement to the current SSRI/SNRI - Has a history or evidence of clinically meaningful noncompliance with current antidepressant therapy. - Has a history of moderate-to-severe substance use disorder including alcohol use disorder according to DSM-5 criteria within 6 months before screening - Has within the last 5 years received any prior antidepressant treatment with ketamine/esketamine, electroconvulsive therapy (i.e, at least 7 treatments), vagal nerve stimulation, or a deep brain stimulation device - Has a current homicidal ideation/intent, per the investigator’s clinical judgment, or has suicidal ideation with some intent to act within 3 months prior to the start of the screening phase | Participantes de entrada transferida: - El participante no cumplió con la administración de la intervención del estudio en la fase de tratamiento doble ciego (DB) en cualquiera de los estudios 67953964MDD3001 o 67953964MDD3002. - La evaluación del beneficio frente al riesgo de continuar el tratamiento con aticacaprant no es favorable para el participante en opinión del investigador. - El participante informa de ideas suicidas con intención de actuar o comportamiento suicida al inicio del estudio. - El participante ha tomado cualquier terapia prohibida que no permitiría la dosificación en el Día 1, como se indica en la sección de terapia previa al estudio y concomitante. - El participante tiene alguna condición o situación/circunstancia por la cual, en opinión del investigador, la participación no sería lo mejor para el participante (p. ej., comprometer el bienestar) o que podría impedir, limitar o confundir las evaluaciones especificadas en el protocolo. Participantes de entrada directa: - El participante carece de una mejora clínicamente significativa con respecto al ISRS/IRSN actual - Tiene antecedentes o evidencia de incumplimiento clínicamente significativo con la terapia antidepresiva actual. - Tiene antecedentes de trastorno por consumo de sustancias de moderado a grave, incluido el trastorno por consumo de alcohol según los criterios del DSM-5 en los 6 meses anteriores a la selección. - Ha recibido en los últimos 5 años algún tratamiento antidepresivo previo con ketamina/esketamina, terapia electroconvulsiva (es decir, al menos 7 tratamientos), estimulación del nervio vagal o un dispositivo de estimulación cerebral profunda - Tiene una idea/intención homicida actual, según el juicio clínico del investigador, o tiene ideas suicidas con alguna intención de actuar dentro de los 3 meses anteriores al inicio de la fase de selección. | |
E.5 End points |
E.5.1 | Primary end point(s) | * AEs including AEs of special interest (AESI) * Change from baseline in vital signs * Weight/body mass index (BMI) * Suicidality assessment using the Columbia Suicidality Severity Rating Scale (C-SSRS) * Laboratory parameters * 12-lead ECG * Change over time in patient-reported sexual functioning using Arizona Sexual Experiences Scale (ASEX) | •Acontecimientos adversos (AA), incluidos los AA de especial interés (AAEI). •Cambio con respecto al inicio en las constantes vitales. •Peso/índice de masa corporal (IMC). •Evaluación del riesgo de suicidio mediante la Escala Columbia de evaluación del riesgo de suicidio (Columbia Suicide Severity Rating Scale, C-SSRS). •Parámetros analíticos. •ECG de 12 derivaciones. •Cambio a lo largo del tiempo en los hábitos sexuales notificados por el paciente usando la Escala de experiencias sexuales de Arizona (Arizona Sexual Experiences Scale, ASEX). | |
E.5.1.1 | Timepoint(s) of evaluation of this end point | Throughout the study | A lo largo del estudio | |
E.5.2 | Secondary end point(s) | Depressive Symptoms, anhedonia symptoms, severity of depressive illness | Síntomas depresivos, síntomas de anhedonia, gravedad general de la enfermedad depresiva | |
E.5.2.1 | Timepoint(s) of evaluation of this end point | starting at baseline, ending at follow-up | Empezando por la fase de selección, terminando con la visita 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 | No |
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 | Yes |
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 | No |
E.8.1.1 | Randomised | No |
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 | No |
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 | No |
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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 101 |
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 | Argentina | Australia | Brazil | Canada | China | Japan | Korea, Republic of | Mexico | South Africa | Taiwan | United States | France | Poland | Sweden | Bulgaria | Spain | Czechia | Italy | Belgium | Hungary | Portugal | Slovakia | United Kingdom | Serbia | |
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 | The end of study is considered as the last scheduled study assessment shown in the schedule of assessments for the last participant in the study | El fin del estudio se considera la última evaluación programada del estudio que se ve en el calendario de actividades del último participante en el estudio. | |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 12 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
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 | 12 |