E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Parkinson´s Disease |
Enfermedad de Parkinson |
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E.1.1.1 | Medical condition in easily understood language |
Parkinson´s Disease |
Enfermedad de Parkinson |
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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 | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061536 |
E.1.2 | Term | Parkinson's disease |
E.1.2 | System Organ Class | 10029205 - Nervous system 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 efficacy objective of this study is to demonstrate the efficacy of the A2a receptor antagonist tozadenant in the treatment of levodopa-treated PD patients experiencing end-of-dose "wearing-off", based on the change from Baseline to Week 24 in the number of hours per day spent in the OFF state. |
Demostrar la eficacia del antagonista del receptor de A2a tozadenant en el tratamiento de pacientes con EP tratados con levodopa que experimenten esfumación de la respuesta, a través del cambio producido desde el momento inicial hasta la semana 24 en el número de horas al día transcurridas en estado sin efecto (OFF). |
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E.2.2 | Secondary objectives of the trial |
The key secondary efficacy objectives of this study are: 1. To evaluate the effect of tozadenant on good ON time (defined as the sum of ON time without dyskinesia and ON time with non-troublesome dyskinesia). 2. To evaluate the effect of tozadenant on UPDRS Parts II (Activities of Daily Living [ADL] subscale) + III (motor subscale) total scores. |
Objetivos secundarios claves de eficacia (parte A): 1. Evaluar el efecto del tozadenant sobre el tiempo bueno con efecto (ON) (definido como la suma del tiempo ON sin discinesia y el tiempo ON con discinesia no problemática). 2. Evaluar el efecto del tozadenant sobre las puntuaciones totales en la escala unificada para la evaluación de la enfermedad de Parkinson (Unified Parkinson's Disease Rating Scale, UPDRS), partes II (subescala de Actividades de la vida cotidiana [AVC]) + III (subescala motora). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
? Patient understands study requirements and has given his/her written informed consent on an Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approved consent form. ? Parkinson's disease diagnosis consistent with UK Parkinson's Disease Society Brain Bank Diagnostic criteria ? Minimum of 3 years since diagnosis. ? Meet Hoehn and Yahr PD stage ? Good response to levodopa ? Stable regimen of anti-PD medications ? Patients must have been taking a levodopa-containing anti-PD medication continuously for at least the previous 12 months ? Patient has documented a minimum amount of Off time. ? If of childbearing potential (male and female) must use an acceptable method of contraception |
? El paciente entiende los requisitos del estudio y ha otorgado su consentimiento informado en un formulario de consentimiento aprobado por la junta de revisión institucional (JRI) o el comité de ética de investigación clínica (CEIC). ? Diagnóstico de enfermedad de Parkinson de acuerdo con los criterios diagnósticos del Banco de Cerebros de la Sociedad de la Enfermedad de Parkinson del Reino Unido. ? Mínimo de 3 años desde el diagnóstico. ? Cumplir el estadio de Hoehn y Yahr para EP. ? Buena respuesta a levodopa. ? Pauta estable de medicamentos antiparkinsonianos. ? Los pacientes deben haber tomado de forma continua medicación antiparkinsoniana que contenga levodopa, al menos durante los 12 meses anteriores. ? Verificación de que el paciente tiene una cantidad mínima de tiempo en Off. ? Los pacientes (hombres y mujeres) en edad fértil deben utilizar un método anticonceptivo aceptable. |
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E.4 | Principal exclusion criteria |
? Previous tozadenant study participation ? Current or recent participation in another study. ? Secondary or atypical parkinsonism ? Neurosurgical intervention for PD ? Patient is taking apomorphine, budipine, istradefylline, tolcapone, or DUOPA?/Duodopa® ? Treatment with excluded medications ? Untreated or uncontrolled hyperthyroidism or hypothyroidism ? Clinically significant out-of-range laboratory ? MMSE out of range ? Current episode of major depression (stable treatment for depression is permitted). ? Recent suicide attempt or suicidal ideation type 4 or type 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) ? Women lactating or pregnant ? Hypersensitivity to any components of tozadenant or excipients ? Abnormal findings on the physical or neurological examination, or medical history that would make the patient unsuitable for the study ? History of hepatitis or cholangitis |
? Participación en el estudio anterior de tozadenant. ? Participación actual o reciente en otro estudio. ? Parkinsonismo secundario o atípico. ? Intervención neuroquirúrgica por EP. ? El paciente está tomando apomorfina, budipina, istradefilina, tolcapona o DUOPA?/Duodopa®. ? Tratamiento con medicamentos excluidos. ? Hipertiroidismo o hipotiroidismo no tratado o no controlado. ? Parámetros analíticos de importancia clínica fuera de su rango. ? MMSE fuera de rango. ? Episodio actual de depresión grave (se permite el tratamiento estable de la depresión). ? Intento reciente de suicidio o ideas de suicidio de tipo 4 o tipo 5 en la escala de valoración de la gravedad del suicidio de Columbia (C-SSRS). ? Mujeres embarazadas o en periodo de lactancia. ? Hipersensibilidad a cualquier componente de tozadenant o a los excipientes. ? Hallazgos anómalos en la exploración física o neurológica o antecedentes médicos que hagan que el paciente no sea adecuado para el estudio. ? Antecedentes de hepatitis o de colangitis. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint (Part A): The primary efficacy endpoint will be the change from Baseline to Week 24 in the number of hours per day spent in the OFF state, as assessed by patient-completed PD diaries and averaged over 3 consecutive days. |
Criterio de valoración principal de la eficacia (parte A): El criterio de valoración principal de la eficacia será el cambio producido entre el momento inicial y la semana 24 en el número de horas al día transcurridas en estado OFF, evaluado mediante diarios de la EP rellenados por el paciente y hallando la media de 3 días consecutivos. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Analysis of the Primary Efficacy Variable The primary efficacy variable will be the change from Baseline to Week 24 in the number of hours per day spent in the OFF state, as assessed by patient-completed PD diaries and averaged over 3 consecutive days. |
Análisis de la variable principal de eficacia La variable principal de eficacia será el cambio producido entre el momento inicial y la semana 24 en el número de horas al día transcurridas en estado OFF, evaluado mediante diarios de la EP rellenados por el paciente y hallando la media de 3 días consecutivos |
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E.5.2 | Secondary end point(s) |
Key Secondary Efficacy Endpoints (Part A): 1. Change from Baseline to Week 24 in the number of hours per day spent in good ON time, defined as the sum of ON time without dyskinesia and ON time with non-troublesome dyskinesia. 2. Change from Baseline to Week 24 on UPDRS Parts II (ADL subscale) + III (motor subscale) total scores. |
Criterios de valoración de la eficacia secundarios claves (parte A): 1. Cambio producido entre el momento inicial y la semana 24 en el número de horas transcurridas al día con tiempo bueno ON, definido como la suma del tiempo ON sin discinesia y el tiempo ON con discinesia no problemática. 2. Cambio producido entre el momento inicial y la semana 24 en las puntuaciones totales de las partes II (subescala AVC) + III (subescala motora) de la UPDRS. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Analysis of the key Secondary Efficacy Endpoints (Part A): 1. Change from Baseline to Week 24 in the number of hours per day spent in good ON time, defined as the sum of ON time without dyskinesia and ON time with non-troublesome dyskinesia. 2. Change from Baseline to Week 24 on UPDRS Parts II (ADL subscale) + III (motor subscale) total scores. |
Análisis de los criterios de valoración de la eficacia secundarios claves (parte A): 1. Cambio producido entre el momento inicial y la semana 24 en el número de horas transcurridas al día con tiempo bueno ON, definido como la suma del tiempo ON sin discinesia y el tiempo ON con discinesia no problemática. 2. Cambio producido entre el momento inicial y la semana 24 en las puntuaciones totales de las partes II (subescala AVC) + III (subescala motora) de la UPDRS. |
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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 | 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 | 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 | 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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
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 |
European Union |
United States |
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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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The end of the study is defined as the date of the last visit of the last patient in the study. |
El final del estudio se define como la fecha de la última visita del último paciente en el estudio. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 15 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |