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 evaluate the efficacy of aticaprant 10 mg compared with placebo as adjunctive therapy to an antidepressant in improving depressive symptoms in adult participants with MDD with moderate-to-severe anhedonia (ANH+) who have had an inadequate response to current antidepressant therapy with an SSRI or SNRI. | Evaluar la eficacia de aticaprant 10 mg en comparación con placebo como tratamiento complementario a un antidepresivo en la mejoría de los síntomas depresivos en participantes con TDM con anhedonia de moderada a grave (ANH+) que han tenido una respuesta insuficiente al tratamiento antidepresivo actual con ISRS o un IRSN. | |
E.2.2 | Secondary objectives of the trial | To evaluate the efficacy of adjunctive aticaprant 10 mg compared with placebo in improving anhedonia in adult participants with MDD ANH+ who have had an inadequate response to current antidepressant therapy with an SSRI or SNRI | •Evaluar la eficacia de aticaprant 10 mg en comparación con placebo como tratamiento complementario en la mejoría de la anhedonia en participantes adultos con TDM ANH+ que han tenido una respuesta insuficiente al tratamiento antidepresivo actual con un ISRS o un IRSN. | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria | - 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 (therapeutic dose per MHH ATRQ) and duration (at least 6 weeks) in the current episode of depression. - Is currently 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 | - Hombre o mujer, de 18 a 74 años de edad, ambos inclusive. - Estar médicamente estable sobre la base del examen físico, el historial médico, los signos vitales y el ECG de 12 derivaciones realizado en la selección y al inicio. - Estar médicamente estable sobre la base de las pruebas de laboratorio clínico realizadas en la selección - Cumplir con los criterios diagnósticos del DSM-5 para TDM recurrente o de episodio único, sin características psicóticas. Los participantes de 65 años o más deben haber tenido el primer inicio de depresión antes de los 55 años. - Haber tenido una respuesta inadecuada a al menos 1 pero no más de 3 antidepresivos, administrados a una dosis adecuada (dosis terapéutica por MHH ATRQ) y duración (al menos 6 semanas) en el episodio actual de depresión. | |
E.4 | Principal exclusion criteria | - Participant has lack of clinically meaningful improvement (≤25% improvement) to the current SSRI/SNRI (ie, the one presumed to be continued in the treatment phase) assessed using the MGH ATRQ. - Has one or more of the following diagnoses: *A DSM-5 diagnosis (which has been the primary focus of psychiatric treatment within the past 2 years)of any of the following: panic disorder, generalized anxiety disorder, social anxiety disorder, specific phobia. * current (in the past year) DSM-5 diagnosis of: obsessive-compulsive disorder, post-traumatic stress disorder, anorexia nervosa, bulimia nervosa * A current or prior (lifetime) DSM-5 diagnosis of: a psychotic disorder or MDD with psychotic features, bipolar or related disorders, intellectual disability, autism spectrum disorder, borderline personality disorder, antisocial personality disorder, histrionic personality disorder, narcissistic personality disorders, somatoform disorders. - 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 | El participante carece de una mejoría clínicamente significativa (mejora ≤25 %) con respecto al ISRS/IRSN actual (es decir, el que se supone que continuará en la fase de tratamiento) evaluado mediante el MGH ATRQ. - Tiene uno o más de los siguientes diagnósticos: *Un diagnóstico DSM-5 (que ha sido el enfoque principal del tratamiento psiquiátrico en los últimos 2 años) de cualquiera de los siguientes: trastorno de pánico, trastorno de ansiedad generalizada, trastorno de ansiedad social, fobia específica. * diagnóstico actual (en el último año) DSM-5 de: trastorno obsesivo-compulsivo, trastorno de estrés postraumático, anorexia nerviosa, bulimia nerviosa * Un diagnóstico DSM-5 actual o previo (de por vida) de: un trastorno psicótico o TDM con características psicóticas, trastornos bipolares o relacionados, discapacidad intelectual, trastorno del espectro autista, trastorno límite de la personalidad, trastorno antisocial de la personalidad, trastorno histriónico de la personalidad, trastornos narcisistas de la personalidad, trastornos somatomorfos. - 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/s-ketamina, terapia electroconvulsiva (es decir, al menos 7 tratamientos), estimulación del nervio vago o un dispositivo de estimulación cerebral profunda - Tiene una idea/intención homicida actual, según el juicio clínico del investigador, o tiene ideación suicida 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) | Change from baseline to Day 43 in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score | Cambio desde el inicio (es detercir, día 1 antes de la aleatorización y, en adelante, denominado “inicio”) hasta el día 43 en la puntuación total de la escala de valoración de la depresión de Montgomery-Åsberg (Montgomery-Åsberg Depression Rating Scale, MADRS). | |
E.5.1.1 | Timepoint(s) of evaluation of this end point | Day 1, Day 15, Day 29, Day 43 | Día 1, Día 15, Día 29, Día 43 | |
E.5.2 | Secondary end point(s) | Change from baseline to Day 43 in Dimensional Anhedonia Rating Scale (DARS) total score. | Cambio con respecto al inicio hasta el día 43 en la puntuación total de la Escala de valoración de la anhedonia dimensional (DARS). | |
E.5.2.1 | Timepoint(s) of evaluation of this end point | Day 1, Day 15, Day 29, Day 43 | Día 1, Día 15, Día 29, Día 43 | |
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 | 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 | 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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 51 |
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 | United States | Poland | Sweden | Bulgaria | Spain | Czechia | Italy | Belgium | Hungary | Portugal | |
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 | Se considera que el ensayo termina en la última visita que aparece en el calendario de actividades del último paciente en el ensayo. | |
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 | 9 |
E.8.9.1 | In the Member State concerned days | |
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 | 9 |