Resumen

El propósito de este estudio es evaluar la eficacia de aticaprant en comparación con placebo como terapia adyuvante a un antidepresivo para mejorar los síntomas depresivos en participantes adultos con trastorno depresivo mayor (TDM) con anhedonia de moderada a grave (ANH+) que han tenido una respuesta inadecuada al tratamiento antidepresivo actual con un inhibidor selectivo de la recaptación de serotonina (ISRS) o un inhibidor de la recaptación de serotonina y norepinefrina (IRSN).

Descripción detallada

La depresión es un trastorno psiquiátrico frecuente y grave que es una de las principales causas de discapacidad en todo el mundo y se asocia con mayor mortalidad y riesgo de suicidio. Aticaprant (JNJ-67953964) es un antagonista del receptor opioide kappa (KOR) altamente selectivo de administración diaria única, con selectividad demostrada sobre el receptor opioide mu (MOR) y el receptor opioide delta (DOR), que está siendo desarrollado como tratamiento adyuvante del trastorno depresivo mayor (TDM) con anhedonia de moderada a grave (ANH+). El estudio consta de una fase de selección (hasta 30 días antes de la aleatorización), una fase de tratamiento doble ciego (43 días) y una fase de seguimiento (hasta 14 días). La duración total del estudio será de hasta 87 días. Las evaluaciones de seguridad, que incluyen eventos adversos, exámenes físicos, pruebas de drogas en orina, pruebas de aliento de alcohol y pruebas de laboratorio clínico, se realizarán en momentos específicos durante este estudio.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 74 YearsSexo: ALL

Criterios de inclusión

Be medically stable on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening and baseline
Have a Hamilton Depression Rating Scale 17 item (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
Meet Diagnostic and Statistical Manual of Mental Disorders-5th edition (DSM-5) diagnostic criteria for recurrent or single episode major depressive disorder (MDD), without psychotic features, based upon clinical assessment and confirmed by the structured clinical interview for DSM-5 Axis I disorders-clinical trials version (SCID-CT). 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 oral antidepressant treatment, administered at an adequate dose (at or above the minimum therapeutic dose per Massachusetts General Hospital Antidepressant Treatment Response Questionnaire \[MGH ATRQ\]) and duration (at least 6 weeks) in the current episode of depression. An inadequate response is defined as less than(\<) 50% reduction in depressive symptom severity but with some improvement (\>0%) (ie, there may be minimal to moderate symptomatic improvement since the initiation of treatment, but some of the initial symptoms are still present, troubling to the participant and affecting behavior and function), as assessed by the MGH ATRQ
Is currently receiving and tolerating well any one of the following selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) for depressive symptoms at screening, in any approved formulation and available in the participating country/territory: citalopram, duloxetine, escitalopram, fluvoxamine, fluoxetine, milnacipran, levomilnacipran, paroxetine, sertraline, venlafaxine, desvenlafaxine at a stable dose for at least 6 weeks. The current antidepressant cannot be the first antidepressant treatment for the first lifetime episode of depression
Participant's current major depressive episode, and antidepressant treatment response in the current depressive episode, must all be confirmed by the site independent qualification assessment

Criterios de exclusión

Have had in the current depressive episode, no response (treatment failure) to 5 or more antidepressant treatments including the current SSRI/SNRI (that is, the one presumed to be continued in the treatment phase) assessed using the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH ATRQ)
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 had in the current episode an inadequate response to adequate course of intravenous or intranasal ketamine or esketamine, electroconvulsive therapy, vagal nerve stimulation, or deep brain stimulation device
Has current, or a history (past 6 months), of seizures
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, per the investigator's clinical judgment or based on the Columbia Suicide Severity Rating Scale (C-SSRS), corresponding to a response of "Yes" on Item 4 or Item 5, or a history of suicidal behavior within the past 6 months prior to the start of the Screening Phase. Participants reporting suicidal ideation with intent to act or suicidal behavior at baseline should be excluded
Has one or more of the following diagnoses: a) 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; b) A current (in the past year) DSM-5 diagnosis of: obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), anorexia nervosa, bulimia nervosa; c) 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

Ubicaciones

Hospital Italiano

Buenos Aires, Argentina

STAT Research S A

Buenos Aires, Argentina

CIPREC

Buenos Aires, Argentina

CENydET - Centro Neurobiologico y de Stress Traumatico

Ciudad Autonoma Buenos Aires, Argentina

Fundacion Lennox

Córdoba, Argentina

CENPIA

La Plata, Argentina

Resolution

Mendoza, Argentina

Instituto Medico de La Fundacion Estudios Clinicos

Rosario, Argentina

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Aticaprant

Placebo

Ubicaciones

Hospital Italiano

STAT Research S A

CIPREC

CENydET - Centro Neurobiologico y de Stress Traumatico

Fundacion Lennox

CENPIA

Resolution

Instituto Medico de La Fundacion Estudios Clinicos

Patrocinadores