E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Narcolepsy With Cataplexy |
Narcolepsia con Cataplejía |
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E.1.1.1 | Medical condition in easily understood language |
Extreme sleepiness with episodes of sudden muscle weakness |
Somnolencia extrema con episodios de debilidad muscular repentina. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028713 |
E.1.2 | Term | Narcolepsy |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to evaluate the safety and tolerability of TAK-994 in the active drug extension period of the study over a period of up to 8 weeks. |
El objetivo principal es evaluar la seguridad y la tolerabilidad del TAK-994 en el período de ampliación con fármaco activo del estudio durante un máximo de 8 semanas. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to evaluate the safety and tolerability of TAK-994 versus placebo in the randomized withdrawal period of the study over a period of up to 4 weeks. |
El objetivo secundario es evaluar la seguridad y la tolerabilidad del TAK-994 en comparación con el placebo en el período de retirada aleatorizado del estudio durante un período máximo de 4 semanas. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subject eligibility is determined according to the following criteria before entry into the study: 1. Subject with a diagnosis of NT1 who has completed TAK-994-1501 Part B before enrollment (which will occur immediately following the final TAK-994-1501 assessments), and for whom the investigator has no clinical objection they be enrolled. 2. Subject is capable of understanding and complying with protocol requirements. 3. Male subject who is not sterilized and sexually active with a female partner of childbearing potential, must use barrier contraception from signing of informed consent until 5 half-lives of TAK-994 plus 90 days after the last dose of study drug. In addition, they must be advised not to donate sperm during this period. 4. Female subject of childbearing potential who is sexually active with a male partner who is not sterilized, must agree to use highly effective methods of contraception from signing of informed consent until 5 half-lives of TAK-994 plus 30 days after the last dose of study drug. In addition, they must be advised not to donate ova during this period. 5. Subject must agree to participate by providing written informed consent. |
Se determina la idoneidad de la participación de los pacientes en el estudio con arreglo a los siguientes criterios previos a la entrada en el estudio: 1. Paciente con diagnóstico de NT1 que haya completado la parte B del TAK-994-1501 antes de la inscripción (que se producirá inmediatamente después de las evaluaciones finales del TAK-994-1501) y para la que el investigador no tenga objeciones clínicas. 2. El paciente puede entender y cumplir los requisitos del protocolo. 3. Los pacientes varones que no estén esterilizados y sean sexualmente activos con una pareja de sexo femenino en edad fértil deben usar anticonceptivos de barrera desde la firma del consentimiento informado hasta 5 semividas del TAK-994 más 90 días después de la última dosis del fármaco del estudio. Además, se les debe advertir que no deben donar esperma durante este período. 4. Las pacientes en edad fértil, sexualmente activas con una pareja de sexo masculino que no esté esterilizada deben aceptar utilizar métodos anticonceptivos altamente eficaces desde la firma del consentimiento informado hasta 5 semividas del TAK-994 más 30 días después de la última dosis del fármaco del estudio. Además, se les debe advertir que no donen óvulos durante este período. 5. El paciente debe aceptar participar otorgando su consentimiento informado por escrito. |
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E.4 | Principal exclusion criteria |
1. Subject has a clinically significant moderate or severe ongoing adverse event (AE) related to the study drug from the prior study. 2. Subject has used/uses disallowed concomitant medication. 3. Subject, in the opinion of the investigator, is unlikely to comply with the clinical study protocol or is unsuitable for any reason. 4. The subject is an employee of the sponsor or study site or an immediate family member (eg, spouse, parent, child, sibling) of an employee of the sponsor or study site who is directly involved in the conduct of the study. 5. The subject has a known hypersensitivity to any component of the formulation of TAK-994 or related compounds. 6. The subject has a positive pregnancy test or is a lactating/breastfeeding woman. 7. The subject had major surgery or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks before Baseline I (excluding samples taken as part of TAK-994-1501). 8. The subject’s renal creatinine clearance is <=50 mL/min. 9. Has liver function tests (alanine aminotransferase, aspartate aminotransferase) higher than 1.5 times the upper limit of normal at any visit in TAK-994-1501. 10. The subject has a risk of suicide according to endorsement of Item 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS) at any visit during TAK-994-1501 and/or has made a suicide attempt during TAK-994-1501. |
1. El paciente presenta un acontecimiento adverso (AA) moderado o grave persistente clínicamente significativo relacionado con el fármaco del estudio originado en el estudio anterior. 2. El paciente ha utilizado/utiliza medicamentos concomitantes prohibidos. 3. En opinión del investigador, es poco probable que el paciente cumpla el protocolo del estudio clínico o no es apto por cualquier motivo. 4. El paciente es empleado del promotor o del centro del estudio o un familiar directo (p. ej., cónyuge, progenitor, hijo/a o hermano/a) de un empleado del promotor o del centro del estudio que interviene directamente en la realización del estudio. 5. El paciente tiene hipersensibilidad conocida a cualquier componente de la formulación del TAK-994 o a compuestos relacionados. 6. La paciente da positivo en una prueba del embarazo o está en período de lactancia. 7. El paciente se ha sometido a una cirugía mayor o ha donado o perdido 1 unidad de sangre (aproximadamente 500 ml) en las 4 semanas previas al Valor inicial I (excluidas las muestras obtenidas como parte del TAK-994-1501). 8. El aclaramiento renal de la creatinina del paciente es <=50 ml/min. 9. Presenta pruebas de la función hepática (alanina aminotransferasa, aspartato aminotransferasa) con valores 1,5 veces mayores que el límite superior de la normalidad en cualquier visita del TAK-994-1501. 10. El paciente presenta riesgo de suicidio según la aprobación del elemento 4 o 5 de la escala Columbia para evaluar el riesgo de suicidio (Columbia Suicide Severity Rating Scale, C-SSRS) en cualquier visita durante el TAK-994-1501 o ha tenido intento de suicidio durante el estudio TAK-994-1501. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Subjects with at least 1 treatment-emergent adverse event (TEAE) during the active drug extension period of the study. Subjects with at least 1 markedly abnormal value (MAV) for postdose laboratory values during the active drug extension period of the study. Subjects with at least 1 MAV for postdose vital signs during the active drug extension period of the study. Subjects with at least 1 MAV for postdose ECG parameters during the active drug extension period of the study. |
• Pacientes con al menos 1 acontecimiento adverso surgido durante el tratamiento (AAST) durante el período de ampliación con el fármaco activo del estudio. • Pacientes con al menos 1 valor notablemente anómalo (VNA) de los valores analíticos posteriores a la administración durante el período de ampliación con el fármaco activo del estudio. • Pacientes con al menos 1 VNA de las constantes vitales después de la administración durante el período de ampliación con el fármaco activo del estudio. • Pacientes con al menos 1 VNA de los parámetros del ECG posteriores a la administración durante el período de ampliación con el fármaco activo del estudio. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Active drug extension period of the study |
Período de ampliación del fármaco activo de este estudio. |
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E.5.2 | Secondary end point(s) |
Subjects with at least 1 TEAE during the randomized withdrawal period of the study. Subjects with at least 1 MAV for postdose laboratory values during the randomized withdrawal period of the study. Subjects with at least 1 MAV for postdose vital signs during the randomized withdrawal period of the study. Subjects with at least 1 MAV for postdose ECG parameters during the randomized withdrawal period of the study. |
• Pacientes con al menos 1 AAST durante el período de retirada aleatorizado del estudio. • Pacientes con al menos 1 VNA de los valores analíticos posteriores a la administración durante el período de retirada aleatorizado del estudio. • Pacientes con al menos 1 VNA de las constantes vitales después de la administración durante el período de retirada aleatorizado del estudio. • Pacientes con al menos 1 VNA de los parámetros del ECG posteriores a la administración durante el período de retirada aleatorizado del estudio. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Randomized withdrawal period of the study. |
Período de retirada aleatorizado de este estudio |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | 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) | 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 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 |
Japan |
Korea, Republic of |
United States |
Czechia |
Finland |
France |
Hungary |
Italy |
Netherlands |
Spain |
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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
|
The study ends when the last subject completes the last planned or follow-up visit/interaction associated with a planned visit (this can be a phone contact), withdraws from the study, or is lost to follow-up (ie, the investigator is unable to contact the subject). |
El estudio finaliza cuando el último sujeto completa la última visita / interacción planificada o de seguimiento asociada con una visita planificada (puede ser un contacto telefónico), se retira del estudio o se pierde durante el seguimiento (es decir, el investigador está incapaz de contactar con el sujeto). |
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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 | |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 10 |