E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Depressive Disorder |
Trastorno depresivo |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10004940 |
E.1.2 | Term | Bipolar II disorder |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10057840 |
E.1.2 | Term | Major depression |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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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 this study is to assess whether the antidepressant response to IV ketamine can be maintained by minocycline compared to placebo. |
El objetivo principal de este estudio es determinar si la respuesta antidepresiva a la ketamina intravenosa puede mantenerse por la acción de la minociclina en comparación con un placebo. |
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E.2.2 | Secondary objectives of the trial |
To investigate the safety and tolerability of the administered study medications (i.e., ketamine and minocycline).
To investigate the effect of minocycline on symptoms of depression in ketamine non-responders. |
Los objetivos secundarios de este estudio son:
Investigar la seguridad y la tolerabilidad de los fármacos del estudio administrados (es decir, ketamina y minociclina).
Investigar el efecto de la minociclina en los síntomas de depresión en pacientes que no responden a la ketamina.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Diagnostic criteria for moderate to severe major depressive disorder (MDD), without mood incongruent psychotic features, or Bipolar Disorder Type II
- Patients should have an Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) total score ? 34 at Screening and at Day 1 (predose)
- Patients with major depressive disorder should have failed at least two adequate treatment courses (dose and duration) with antidepressant therapy, one of which is in the current episode
- Patients should not have received electroconvulsive therapy (ECT) in the current episode but could be those for whom ECT is considered
- Patients with bipolar depression (BPD) Type II must have been taking a stable dose of a mood-stabilizing medication (e.g., lithium, valproate, carbamazepine, lamotrigine, antipsychotic agents) for at least 4 weeks, dosed clinically to target the therapeutic range
- Patients currently taking an antidepressant(s) must have received at least 2 weeks of stable antidepressant therapy at the time of Screening
- Doses of current antidepressant therapies should remain the same for the duration of the study
- Women must be postmenopausal, surgically sterile, or if heterosexually active, practicing a highly effective method of birth control
- Men who are heterosexually active with a woman of childbearing potential must agree to use a double barrier method of birth control and to not donate sperm during the study and for 3 months after receiving the last dose of study drug |
- Criterio diagnóstico de trastorno depresivo mayor (TDM) moderado o severo, sin síntomas psicóticos incongruentes del ánimo, o trastorno bipolar tipo II.
- Los pacientes deben tener una puntuación total ≥ 34 en el Cuestionario de síntomas depresivos valorados por el médico (IDS-C30) en la visita de selección y el día 1 (antes de la administración).
- Los pacientes con TDM deben no haber respondido al menos a dos ciclos de tratamiento adecuados (dosis y duración) con un antidepresivo, uno de los cuales corresponde al episodio actual.
- No haber recibido TEC en el episodio actual, pero podría haberse considerado en ellos el uso del TEC.
- Los pacientes con TBP de tipo II deben haber estado tomando una dosis estable de un medicamento estabilizador del estado de ánimo (p. ej., litio, ácido valproico, carbamazepina, lamotrigina, antipsicóticos) durante al menos 4 semanas, en dosis clínicas para alcanzar el intervalo terapéutico.
- Los pacientes que estén recibiendo un antidepresivo deben haber recibido al menos 2 semanas de tratamiento antidepresivo estable en el momento de la selección
-Las dosis del antidepresivo actual deben ser las mismas durante todo el estudio.
- Las mujeres deben ser posmenopáusicas, estar esterilizadas quirúrgicamente, en caso de mantener relaciones heterosexuales, deben utilizar un método anticonceptivo eficaz.
- Los hombres que mantengan relaciones heterosexuales con una mujer con capacidad reproductiva deberán comprometerse a utilizar un método anticonceptivo de doble barrera y a no donar semen durante el estudio y durante 3 meses después de recibir la última dosis del fármaco del estudio.
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E.4 | Principal exclusion criteria |
- Has a current DSM-IV axis I diagnosis other than MDD or BPD Type II at screening (except for co-morbid anxiety disorders)
- Has a diagnosis of substance abuse or dependence within 6 months prior to screening evaluation (nicotine and caffeine dependence are not exclusionary)
- Patient is currently taking ? 4 psychotropic medications at Day 1 (predose)
- Has an autoimmune disorder such as Crohn?s disease, rheumatoid arthritis, psoriasis currently treated with/requiring treatment with immunomodulatory therapies
-Has any significant cardiovascular, respiratory, neurologic, renal, hepatic, endocrine, immunologic diseases, glaucoma, hypothyroidism or hyperthyroidism based on screening examination
- Has uncontrolled hypertension (diastolic blood pressure ? 90 mmHg), despite diet, exercise or a stable dose of an allowed antihypertensive treatment, at Screening or Day 1 (predose)
- Has planned vaccination within 2 weeks prior to the first dose of study medication through 2 weeks after the last dose of study medication
- Has an active infectious disease/current infection
- Has known allergies, hypersensitivity, or intolerance to minocycline or ketamine or its excipients
- Has contraindications to the use of minocycline or ketamine per local prescribing information |
-Tiene actualmente un diagnóstico del eje I del DSM-IV distinto de TDM o TBP tipo II (excepto trastornos de ansiedad comórbidos) en la visita de selección.
-Tiene antecedentes de abuso o dependencia del alcohol o de sustancias conforme a los criterios del Manual diagnóstico y estadístico de los trastornos mentales (4.a edición) (DSM-IV), excepto nicotina y cafeína, en los 6 meses previos a la visita de selección.
-Está tomando ≥ 4 psicofármacos el día 1 (antes de la administración).
-Tiene un trastorno autoinmunitario tal como la enfermedad de Crohn, artritis reumatoide o psoriasis tratado actualmente con inmunomoduladores o que requiere inmunomoduladores.
-Tiene una enfermedad cardiovascular, respiratoria, neurológica, renal, hepática, endocrina, inmunológica importante, glaucoma, hipotiroidismo o hipertiroidismo conforme a la exploración de selección.
-Padece hipertensión no controlada (presión arterial diastólica ≥ 90 mm Hg), a pesar de controlar la dieta, hacer ejercicio o tomar una dosis estable de un antihipertensivo permitido, en la visita de selección o el día 1 (antes de la administración).
-Tiene previsto vacunarse desde 2 semanas antes de la primera dosis de la medicación del estudio hasta 2 semanas después de la última dosis de la medicación del estudio.
-Tiene una enfermedad infecciosa activa/infección actual.
-Padece alergias, hipersensibilidad o intolerancia conocidas a la minociclina, a la ketamina o a sus excipientes.
-Tiene contraindicaciones para el uso de minociclina o ketamina conforme a la ficha técnica local.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be the proportion of subjects who survive relapse-free (among responders). |
El criterio de valoración principal de la eficacia será la proporción de pacientes que sobrevivan sin recaídas (entre los pacientes con respuesta) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 54 (Week 6) of the 6-week blinded treatment period. |
Dia 54 (Semana 6) de las 6 semanas de tratamiento ciego |
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E.5.2 | Secondary end point(s) |
1. The change in MADRS total score among non-responders from pre-randomization to end-of-study.
2. Change in the MADRS total score from baseline during the IV ketamine treatment phase.
3. Change in the MADRS total score from baseline after IV ketamine treatment phase.
4. Response (reduction ? 50% in MADRS total score relative to baseline) rate during the IV ketamine treatment phase.
5. Time to relapse (among responders) following completion of the IV ketamine infusion schedule .
6. Change in Columbia Suicide Severity Rating Scale (C-SSRS). |
1 Cambio de la puntuación total de la escala MADRS entre los pacientes que no respondan desde pre-aleatorización hasta el final del estudio.
2 Cambio de la puntuación total de la escala MADRS con respecto al valor basal (día 1 antes de la administración) durante la fase de tratamiento con ketamina intravenosa.
3 Cambio de la puntuación total de la escala MADRS con respecto al valor basal (día 1 antes de la administración) después de la fase de tratamiento con ketamina intravenosa.
4 Tasa de respuesta (reducción ≥ 50% de la puntuación total de la escala MADRS con respecto al valor basal) durante la fase de tratamiento con ketamina intravenosa.
5 Tiempo hasta la recaída (entre los pacientes con respuesta) después de la finalización de la pauta de infusión de ketamina intravenosa.
6 Efectos sobre la escala de valoración de la gravedad de la conducta suicida de Columbia (C-SSRS)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. From Day 12 to Day 54.
2. Days 1, 3, 5, 8, 10, and 12.
3. Days 1, 20, 27, 34, 41, 48, and 54.
3. Days 1, 3, 5, 8, 10 and 12.
4. Day 12 to Day 54.
5. Day 1, 12 & 54. |
1. Desde día 12 a día 54
2. Días 1, 3, 5, 8, 10, y 12.
3. Días 1, 20, 27, 34, 41, 48, y 54.
3. Días 1, 3, 5, 8, 10 y 12.
4. Día 12 a día 54.
5. Día 1, 12 y 54. |
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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 | 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 | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarker Marker Analysis |
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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 | 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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 |
Belgium |
France |
Moldova, Republic of |
Netherlands |
Spain |
Romania |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 25 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 25 |