| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Narcolepsy with Cataplexy (Type 1) and Narcolepsy without Cataplexy (Type 2) |
| Narcolepsia con cataplejía ( tipo 1) y narcolepsia sin cataplejía ( tipo 2) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Narcolepsy with Cataplexy (Type 1) and Narcolepsy without Cataplexy (Type 2) |
| Narcolepsia con cataplejía ( tipo 1) y narcolepsia sin cataplejía ( tipo 2) |
|
| 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 |
|
| 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 long-term safety and tolerability of TAK-861. |
| Evaluar la seguridad y la tolerabilidad a largo plazo de TAK-861. |
|
| E.2.2 | Secondary objectives of the trial |
• To assess the effect of TAK-861 on excessive daytime sleepiness (EDS) as assessed by the mean sleep latency from the Maintenance of Wakefulness Test(MWT)
• To assess the effect of TAK-861 on EDS as measured by the Epworth Sleepiness Scale (ESS) total score.
• To assess the effect of TAK-861 on cataplexy as assessed by the weekly cataplexy rate (WCR) (participants with narcolepsy type 1
[NT1] only). |
• Evaluar el efecto de TAK-861 sobre la somnolencia diurna excesiva (SDE) según la evaluación de la latencia media del sueño en la prueba de mantenimiento de la vigilia (PMV).
• Evaluar el efecto de TAK-861 sobre la SDE determinado por la puntuación total de la escala de somnolencia de Epworth (ESE)
• Evaluar el efecto de TAK-861 sobre la cataplejía determinado por la tasa de cataplejía semanal (TCS) (participantes con narcolepsia tipo 1 [NT1] solamente). |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Informed Consent
1. Participant is willing and able to understand and fully comply with study procedures and requirements (including digital tools and applications), in the opinion of the investigator.
2. Participant has provided informed consent (that is, in writing, documented via a signed and dated informed consent form (ICF) and/or electronic consent [eConsent]) and any required privacy authorization before the initiation of any study procedures.
Type of Participant and Disease Characteristics
3. Participant with a diagnosis of narcolepsy who has completed a controlled study with TAK-861 (including participants diagnosed with NT1 or NT2) and for whom the investigator has no clinical objection to their enrollment. Additionally, a rare exception may be granted by the sponsor or designee for a participant who was unable to complete a previous TAK-861 controlled study conducted in participants with narcolepsy.
Contraception
4. The participant agrees to follow the birth control requirements |
Consentimiento informado
1.El participante está dispuesto y es capaz de comprender y cumplir plenamente con los procedimientos y requisitos del estudio (incluidas las herramientas y aplicaciones digitales), en opinión del investigador.
2.El participante ha proporcionado el consentimiento informado (es decir, por escrito, documentado a través de un documento de consentimiento informado [DCI] firmado y fechado y/o consentimiento electrónico) y cualquier autorización de privacidad necesaria antes del inicio de cualquier procedimiento del estudio.
Tipo de participante y características de la enfermedad seleccionada
3.Participante con un diagnóstico de narcolepsia que haya completado un estudio controlado con TAK-861 (incluidos los participantes diagnosticados con NT1 o NT2) y que, en opinión del investigador, no presenta ninguna objeción clínica para su inclusión. Además, el promotor o la persona designada pueden otorgar una rara excepción para un participante que no haya podido completar un estudio controlado con TAK-861 anterior realizado en participantes con narcolepsia.
Anticonceptivos
4.El participante acepta seguir los requisitos de anticoncepción |
|
| E.4 | Principal exclusion criteria |
Medical Conditions
1. Participant has a moderate or severe ongoing (TEAE) related to the study drug from the parent study or discontinued because of TEAEs in the parent study.
Prior/Concomitant Therapy
2. Participant used disallowed medication during the parent study and is unable to refrain from or anticipates using excluded medications.
Diagnostic Assessments
3. Participant has a (BP) >160 mm Hg (systolic) or >100 mm Hg (diastolic) at the final collection point in any prior controlled study without a dosing gap. The participant may have a history of hypertension and be on antihypertensive medication treatment as long as the BP values are below these criteria. BP measurements should be obtained after the participant has been semirecumbent (lying down with the head of the bed at 30 degrease) for a minimum of 5 minutes. BP will be repeated 3 times, with a minimum of 2 minutes between assessments. The median BP (of 3 assessments) obtained will be used for assessing participant eligibility.
4. Participant has a resting HR outside of the range of 40 to 100 beats per minute, confirmed on repeat testing within a maximum of 30 minutes at assessment at screening.
5. Participant has an ECG with a (QTcF) interval>450 ms (men) or >470 ms (women) at screening.
6. Participant has (ALT) and (AST) >1.5 times the (ULN) at multiple visits in the parent study and the findings are of clinical significance, per investigator or sponsor opinion, or ALT/AST >1.5 times ULN during the screening period for participants with a dosing gap.
7. Participant’s renal creatinine clearance is ≤50 mL/min.
8. Participant has a positive urine screen for drugs of abuse (findings confirmed) and/or positive alcohol test during any visit in their prior TAK-861 study, or during the screening period for participants with a dosing gap. Products containing cannabidiol are allowed throughout the study, at the discretion of the investigator.
9. Participant has a positive pregnancy test at screening or is a lactating/breastfeeding woman.
10. Participant has a risk of suicide according to endorsement of item 4 or 5 on the C-SSRS Since Last Visit (C-SSRS) on any visit in the prior study, or has positive answers on item 4 or 5 on the Screening/Baseline C-SSRS Lifetime (based on the past year) during the screening assessment for participants with a dosing gap.
Other Exclusion Criteria
11. Participant consumes excessive amounts of caffeine, defined as greater than 600 mg of caffeine of coffee, tea, cola, energy drinks, or other caffeinated beverages per day (1 cup of coffee is approximately 120 mg).
12. Participant is unwilling to refrain from drivingand/or operating dangerous or hazardous machinery during times of heightened sleepiness or fatigue as well as during times of medication weaning/changes, or is unwilling to adhere to local regulations and any PI guidance restricting driving.
Participants with a Dosing GapUp to 3 Months
Additional exclusion criteria for participants who have completed their parent study and who are not able to directly roll over into the current study (ie, for whom there is a dosing gap), are as follows:
13. Participant has participated in another investigational drug study, in which they received the investigational drug other than TAK-861, within 60 days (or 6 months if participant may have received an investigational biologic product). The interval window from the parent study will be derived from the date of the last study procedure in the parent study to the screening visit of TAK-861-2003.
14. Participant is unable to discontinue, or refrain from using excluded medications for the duration of the study, including those used for the treatment of narcolepsy. Participant must be willing to complete specified washout periods before the first dose of study drug
Medical Conditions
15. The participant has a current medical disorder, other than narcolepsy with or without cataplexy, associated with EDS.
a. Participants with NT1 with clinically significant, moderate-to-severe obstructive sleep apnea may be eligible if they are compliant with (PAP), defined as having at least 4 hours of PAP use per night on at least 70% of nights for approximately 1 month before Day 1 (assessed by machine tracking time) and have (AHI) ≤10 with PAP or other modes of positive airway pressure.
16. Participant has a known hypersensitivity to any component of the formulation of TAK-861 or related compounds.
17. Participant has current active major depressive episode (MDE) or has had an MDE in the past 6 months.
18. Participant has developed (within the last 6 months) gastrointestinal disease that is expected to influence the absorption of drugs (ie, a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis, frequent [more than once per week] occurrence of heartburn, or any surgical intervention).
For further exclusion criteria no 19-27 please refer to the protocol |
Afecciones médicas. 1.El participante presenta un acontecimiento adverso surgido durante el tratamiento (AAST) en curso moderado o grave relacionado con el fármaco del estudio original o suspendió el tratamiento debido a los AAST en el estudio original. Tratamiento previo/concomitante 2. El participante ha utilizado medicamentos no permitidos durante el estudio original y no puede abstenerse o anticipa usar medicamentos excluidos durante el estudio.
Evaluaciones diagnósticas. 3.El participante tiene una PA >160 mm Hg (sistólica) o >100 mm Hg (diastólica) en la recopilación de datos final de cualquier estudio controlado previo sin intervalo de dosificación. El participante puede tener antecedentes de hipertensión y estar en tratamiento con medicamentos antihipertensivos siempre que los valores de PA estén por debajo de estos criterios. Las mediciones de la PA deben obtenerse después de que el participante haya estado semirrecostado durante un mínimo de 5 minutos. La PA se medirá 3 veces, con un mínimo de 2 minutos entre cada medición. La PA media obtenida se utilizará para evaluar la elegibilidad de los participantes. 4.El participante tiene una frecuencia cardíaca en reposo fuera del rango de 40 a 100 latidos por minuto, confirmado en pruebas repetidas realizadas en un periodo máximo de 30 minutos en la selección. 5.El participante tiene un ECG con un intervalo QT corregido mediante QTcF de >450 ms (hombres) o >470 ms (mujeres) en la selección. 6.Los niveles ALT y AST del participante están 1,5 veces por encima del LSN visitas en el estudio original y los hallazgos son de importancia clínica, según la opinión del investigador o del promotor, o los niveles de ALT/AST están 1,5 veces por encima del LSN durante la selección para los participantes con un intervalo de dosificación. 7.El aclaramiento de creatinina renal del participante es ≤50 ml/min. 8.El participante da positivo en drogas adictivas en análisis de orina y/o prueba de alcohol positiva durante cualquier visita en su estudio TAK-861 anterior, o durante la selección para los participantes con un intervalo de dosificación. Los productos que contienen cannabidiol están permitidos durante todo el estudio, a discreción del investigador. 9.La participante da positivo en una prueba de embarazo en la selección o es una mujer en periodo de lactancia. 10.El participante tiene riesgo de suicidio basado en respuestas positivas en los ítems 4 o 5 de la escala de Columbia para evaluar el riesgo de suicidio desde la última visita (C-SSRS) en cualquier visita en el estudio anterior, o tiene respuestas positivas en los ítems 4 o 5 en la C-SSRS de la selección/momento basal (basado en el último año) durante la selección para participantes con un intervalo de dosificación.Otros criterios de exclusión. 11. El participante consume cantidades excesivas de cafeína, 12.El participante no está dispuesto a abstenerse de conducir y/o manejar maquinaria peligrosa durante los momentos de mayor somnolencia o cansancio, así como durante los momentos de retirada gradual/cambios de medicamentos o no está dispuesto a cumplir con las regulaciones locales y las instrucciones del IP sobre la restricción de la conducción. Participantes con un intervalo de dosificación de hasta 3 meses Los criterios de exclusión adicionales para los participantes que han completado su estudio original y que no pueden pasar directamente al estudio actual son los siguientes: 13.El participante ha participado en otro estudio con un fármaco en investigación, en el que recibió el fármaco en investigación distinto de TAK-861, dentro de los 60 días previos (o 6 meses si el participante puede haber recibido un producto biológico en investigación). 14.El participante no puede interrumpir o abstenerse de usar los medicamentos excluidos durante el estudio, incluidos los que se usan para el tratamiento de la narcolepsia. El participante debe estar dispuesto a completar los periodos de lavado especificados antes de la primera dosis del fármaco del estudio. Afecciones médicas. 15. El participante tiene un trastorno médico actual, que no sea narcolepsia con o sin cataplejía, asociado con SDE. a.Los participantes que padezcan NT1 con apnea obstructiva del sueño moderada o grave clínicamente significativa pueden ser elegibles si cumplen con la PAP, definida como tener al menos 4 horas de uso de PAP por noche en al menos el 70 % de las noches durante aproximadamente 1 mes antes del día 1 y tienen un IAH ≤10 con PAP u otros modos de presión positiva en las vías respiratorias. 16.El participante tiene una hipersensibilidad conocida a cualquier componente de la formulación de TAK-861 o compuestos relacionados. 17.El participante tiene actualmente un EDMo ha tenido un EDM en los últimos 6 meses. 18.El participante presenta una enfermedad gastrointestinal (en los 6 meses previos) que se espera que influya en la absorción de fármacos
Para conocer más criterios de exclusión n.º 19-27, consulte el protocolo |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| • Occurrence of at least 1 treatment-emergent adverse event (TEAE). |
| Aparición de al menos 1 acontecimiento adverso surgido durante el tratamiento (AAST). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Day 395, 425, 485, 515, 575, 605, 665, 695 |
| Dia 395, 425, 485, 515, 575, 605, 665, 695 |
|
| E.5.2 | Secondary end point(s) |
• Change from baseline in the parent study in MWT mean sleep latency.
• Change from baseline in the parent study in ESS total score
• Change from baseline in the parent study in WCR using the patient-reported cataplexy diary (participants with NT1 only) |
•Cambios en la latencia media del sueño en la PMV con respecto al valor basal en el estudio original.
•Cambios en la puntuación total de ESE con respecto al valor basal en el estudio original.
•Cambios en la TCS utilizando el diario de cataplejía cumplimentado por el paciente (participantes con NT1 solamente) con respecto al valor basal en el estudio original. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Day 182
- Day 14, 28, 56, 84, 182, 266, 364, 448, 546, 630. 728
- Day 69 to 84; 167 to 182; 251 to 266; 350to 364; 531 to 546; 715 to 728; 728 to 735 |
– Dia 182
– Dia 14, 28, 56, 84, 182, 266, 364, 448, 546, 630. 728
- Dia 69 a 84; 167 a 182; 251 a 266; 350 a 364; 531 a 546; 715 a728; 728 a 735 |
|
| 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 | No |
| 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 |
|
| 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) | 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 | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| 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 | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 30 |
| 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 |
| Australia |
| Japan |
| United States |
| Finland |
| France |
| Sweden |
| Netherlands |
| Spain |
| Switzerland |
| Germany |
| Italy |
| Norway |
|
| 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 defined as the final date on which data were or are expected to be collected, ie, the last visit of the last participant in the study |
| El final del estudio se define como la fecha final en la que se recogieron o se espera que se recopilen los datos, es decir, la última visita del último participante en el estudio. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 5 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
| E.8.9.2 | In all countries concerned by the trial days | 4 |
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