E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Obsessive Compulsive Disorder |
Trastorno Obsesivo-Compulsivo |
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E.1.1.1 | Medical condition in easily understood language |
Obsessive Compulsive Disorder (OCD) |
Tastorno Obsesivo-Compulsivo (TOC) |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Behavioral Disciplines and Activities [F04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10002860 |
E.1.2 | Term | Anxiety disorder NEC |
E.1.2 | System Organ Class | 100000004873 |
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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 |
The primary objective of the study is to evaluate the efficacy of troriluzole as adjunctive therapy compared to placebo in subjects with OCD who have had an inadequate response to their current OCD treatment based on the change in their Y-BOCS score |
El objetivo principal del estudio es evaluar la eficacia del troriluzol como tratamiento complementario en comparación con placebo en pacientes con TOC con una respuesta insuficiente a su tratamiento actual para el TOC basándose en el cambio en su puntuación de Y BOCS. |
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E.2.2 | Secondary objectives of the trial |
•To assess the safety and tolerability of troriluzole, relative to placebo, in subjects with OCD •Evaluate the efficacy of troriluzole compared to placebo on functional disability as measured by the Sheehan Disability Scale (SDS) •Evaluate the efficacy of troriluzole compared to placebo on global clinical condition as measured by the Clinical Global Impression- Severity Scale (CGI-S) |
•Evaluar la seguridad y tolerabilidad del troriluzol en comparación con el placebo en pacientes con TOC. •Evaluar la eficacia del troriluzol en comparación con el placebo en la discapacidad funcional medida mediante la escala de discapacidad de Sheehan (Sheehan Disability Scale, SDS). •Evaluar la eficacia del troriluzol en comparación con el placebo en el estado clínico global medida mediante la escala de intensidad de la impresión clínica global (Clinical Global Impression-Severity, CGI S). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Primary diagnosis of OCD as per Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition as confirmed by the MINI at Screening; The duration of the subject’s illness must be ≥ 1 year; 2.Subjects must be currently experiencing non-response or inadequate response to their current SOC medication defined as: Subjects Y-BOCS total score must be ≥ 22 at Screening and Baseline, reflecting moderate or severe OCD symptoms. 3.Subjects must currently be on an SSRI (with the exception of fluvoxamine, see Section 1.1.3), or clomipramine, venlafaxine or desvenlafaxine monotherapy treatment for an adequate duration and at an adequate dose defined as clinical trial protocol 4.Subjects must be on stable doses of other psychotropic medication (with exclusions specified below) for at least 12 weeks prior to screening; 5.CGI-S score of ≥ 4 at screening and baseline; 6.It is required that all women of child-bearing potential (WOCBP) who are sexually active agree to use two methods of contraception for the duration of the study (i.e. beginning 30 days prior to baseline and extending to 30 days after the last dose of study drug). 7.It is required that men who are sexually active with WOCBP agree to use two methods of contraception for the duration of the study (beginning at first treatment and extending to 90 days after the last dose of study drug). |
1.Diagnóstico primario de TOC según el Manual Diagnóstico y Estadístico de los Trastornos Mentales, Quinta Edición, confirmado por un MINI en la selección. La duración de la enfermedad del sujeto debe ser ≥ 1 año; 2. Los sujetos deben estar experimentando fracaso o una respuesta insuficiente a su TdR actual, definida por una puntuación de la Escala de trastorno obsesivo compulsivo de Yale-Brown de 22 o superior en la selección y al momento del inicio, presentando síntomas de TOC de moderados a graves. 3.Los sujetos deben estar en tratamiento con un ISRS (con la excepción de fluvoxamina, véase la sección 1.1.3), clomipramina, venlafaxina o desvenlafaxina como tratamiento monoterápico durante un período de tiempo adecuado y a dosis adecuadas definidas en el protocolo. 4.Los sujetos deben estar tomando dosis estables del resto de su medicación psicotrópica (con las exclusiones especificadas en el protocolo) durante al menos 12 semanas antes de la selección. 5.Puntuación ≥ 4 en la escala de intensidad de la impresión clínica global (CGI-S) en la selección y el momento del inicio. 6.Todas las mujeres en edad fértil que sean sexualmente activas deberán aceptar utilizar dos métodos anticonceptivos durante la duración del estudio (desde 30 días antes del inicio hasta 30 días después de la última dosis del fármaco del estudio). 7.Los hombres que sean sexualmente activos con mujeres en edad fértil deberán aceptar utilizar dos métodos anticonceptivos durante la duración del estudio (desde el primer día de tratamiento hasta 90 días después de la última dosis del fármaco del estudio). |
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E.4 | Principal exclusion criteria |
1.Subjects with a history of more than two (2) previous failed or inadequate treatment trials of SSRIs, clomipramine, venlafaxine, or desvenlafaxine, (not including the current SSRI trial) given for an adequate duration at an adequate dose. 2.Subjects should be excluded at screening or baseline if any medical or psychiatric condition other than OCD, as specified in the inclusion criteria, could predominantly explain or contribute significantly to the subjects’ symptoms or that could confound assessment of OCD symptoms; 3.Current or prior history, per DSM-5 criteria, of bipolar I or II disorder, schizophrenia or other psychotic disorders, schizoaffective disorder, autism or autistic spectrum disorders, borderline personality disorder, antisocial personality disorder, body dysmorphic disorder, hoarding disorder (symptoms of hoarding disorder as part of the OCD diagnosis are allowed, but a primary diagnosis of hoarding disorder is excluded); a current diagnosis of Tourette’s disorder is also excluded; 4.Any eating disorder within the last 12 months; 5.Primary active major depressive episode or primary active anxiety disorder within the past 6 months. 6.Acute suicidality or suicide attempt or self-injurious behavior in the last 12 months. 7.Any positive ("yes") C-SSRS response to questions 1-5 in last 6 months at screening and/or (before dosing) baseline 8.Total BABS score >17 at screening and baseline; 9.Subjects who may have received a non-biological investigational agent in any clinical trial within 30 days or a biological agent within 90 days prior to screening; 10.History of psychosurgery, Deep Brain Stimulation (DBS) or Electroconvulsive Therapy (ECT). 11.History of substance use disorder (drug or alcohol) in the last 12 months, with the exception of tobacco, as defined by DSM-5 criteria; 12.Positive urine drug screening for cannabis (both medical and recreational use of cannabis are prohibited; subjects will be expected to refrain from use during the period of the study), amphetamines (including MDMA/ecstasy), cocaine, barbiturate, PCP, and/or opiates at screening. |
1.Sujetos con un historial de más de dos (2) intentos de tratamiento fallidos o inadecuados con ISRSs, clomipramina, venlafaxina o desvenlafaxina (sin incluir el intento actual) probados durante un período de tiempo adecuado y en una dosis adecuada. 2. Los sujetos podrán ser excluidos en la selección o el momento del inicio si otra condición médica o psiquiátrica diferente del TOC, como se explica en los criterios de inclusión, pudiera explicar predominantemente o contribuir significativamente a los síntomas del paciente o confundir la evaluación de los síntomas del TOC. 3.Historial actual o pasado, en base al DSM-5, de trastorno bipolar I o II, esquizofrenia u otros trastornos psiquiátricos, trastorno esquizoafectivo, autismo o trastorno del espectro autista, trastorno límite de la personalidad, trastorno de personalidad antisocial, trastorno dismórfico corporal, trastorno de acumulación compulsiva (se permiten síntomas de acaparamiento como parte del diagnóstico de TOC, pero quedaría excluido un diagnóstico primario de trastorno de acumulación); también quedaría excluido un diagnóstico actual de síndrome de Tourette; 4.Un trastorno alimenticio en los últimos 12 meses; 5.Episodio primario de depresión activa o trastorno primario de ansiedad en los últimos 6 meses; 6.Tendencias suicidas o intentos de suicidio o comportamiento autolesivo en los últimos 12 meses; 7.Una respuesta positiva (“sí”) en cualquiera de las preguntas 1-5 de la escala C-SSRS en los últimos 6 meses en el momento de la selección y/o el inicio (previa a la primera dosis); 8.Puntuación total en la escala BABS >17 en la selección y el momento del inicio; 9.Sujetos que hayan recibido un agente no-biológico en investigación en un ensayo clínico en los 30 días previos o, en caso de un agente biológico, en los 90 días previos a la selección; 10.Historial de psicocirugía, Estimulación Cerebral Profunda (DBS) o Terapia Electroconvulsiva (ECT). 11.Historial de abuso de sustancias (drogas o alcohol) en los últimos 12 meses, a excepción del tabaco, definido por los criterios del DSM-5; 12.Test de orina positivo para cannabis (el uso tanto médico como recreacional del cannabis está prohibido), anfetaminas (incluyendo MDMA/éxtasis), cocaína, barbitúricos, PCP y/u opiáceos en la selección. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Improvement in obsessive-compulsive symptomatology is assessed using the Y-BOCS change from baseline in the total score |
La mejora de la sintomatología obsesiva-compulsiva se evalúa utilizando el cambio en la puntuación total de la escala Y-BOCS desde el inicio |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Screening, Baseline, Week 4, Week 8 and Week 10 |
Selección, Inicio, Semana 4, Semana 8 y Semana 10 |
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E.5.2 | Secondary end point(s) |
The change from baseline on the SDS total score and the CGI Severity score |
El cambio desde el inicio en la puntuación total de las escalas SDS y CGI-S |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Screening, Baseline, Week 4, Week 8 and Week 10 |
Selección, Inicio, Semana 4, Semana 8 y Semana 10 |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
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) | 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 | Yes |
E.8.1.7.1 | Other trial design description |
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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 | 6 |
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 | 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 |
Canada |
United States |
Italy |
Netherlands |
Spain |
United Kingdom |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 21 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |