E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Dyskinesia in advanced Parkinson's disease |
Discinesia en enfermedad de Parkinson avanzada. |
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E.1.1.1 | Medical condition in easily understood language |
Advanced Parkinson's disease |
Enfermedad de Parkinson avanzada. |
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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 | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10013113 |
E.1.2 | Term | Disease Parkinson's |
E.1.2 | System Organ Class | 100000004852 |
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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 of this interventional study is to examine the effect of LCIG treatment relative to that of Optimized Medical Treatment (OMT) on dyskinesia as measured by the Unified Dyskinesia Rating Scale (UDysRS) Total Score. |
El objetivo principal de este estudio intervencionista es examinar el efecto del tratamiento GILC en comparación con el tratamiento médico optimizado (TMO) en la discinesia, medida por la puntuación total de la Escala unificada de valoración de la discinesia (UDysRS). |
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E.2.2 | Secondary objectives of the trial |
The Secondary objective is to assess the effect of LCIG treatment relative to that of OMT on dyskinesia as measured by PD Diaries, motor symptoms, motor complications, safety, tolerability and health-related outcome measures. |
El objetivo secundario es evaluar el efecto del tratamiento con GILC en comparación con el TMO en la discinesia medida utilizando diarios de la EP, síntomas motores, complicaciones motoras, seguridad, tolerabilidad y medidas de resultados relacionados con la salud. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female subjects of at least 30 years old at the time of Visit 3. 2. Subject must have a diagnosis of idiopathic Parkinson's disease according to the United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank Criteria 3. Patients with advanced levodopa-responsive Parkinson's disease and persistent motor fluctuations who have not been controlled with optimized medical treatment. "Optimized medical treatment" is defined as the maximum therapeutic effect obtained with pharmacological antiparkinsonian therapies when no further improvement is expected regardless of any additional manipulations of levodopa and/or other antiparkinsonian medication. This will be based on the Investigator's clinical judgment. 4. UDysRS Total score ≥ 30 at Visit 3 based on Central Blinded Rater's score. 5. Subject (or subject's proxy/caregiver) must be able to complete both the Subject Dosing Diary and the PD Diary and must be able to demonstrate the ability to operate, manipulate, and care for the pump and tubing. 6. Subject must demonstrate at least 75% concordance with the Investigator's or qualified designee's assessment of symptoms on the Parkinson's Disease Diary following training at Screening Visit 1 with concordance on at least 1 time interval of "Off," concordance on at least 1 time interval of "ON regardless of dyskinesia" and at least 1 time interval of "ON with dyskinesia" irrespective of whether the dyskinesia are troublesome or not troublesome. 7. Subject is eligible to transfer to commercial treatment of Duodopa after completing the study based on local country requirements. |
1. Varones o mujeres de 30 o más años de edad en el momento de la visita 3. 2. El paciente tiene que tener diagnosticada la enfermedad idiopática de Parkinson, según los criterios del United Kingdom Parkinson’s Disease Society (UKPDS) Brain Bank. 3. Pacientes con Enfermedad de Parkinson avanzada que respondan a Levodopa, y con fluctuaciones motoras persistentes que no han sido controladas con un tratamiento médico optimizado. “Tratamiento Médico optimizado” se define como el efecto máximo terapéutico obtenido con terapias farmacológicas antiparkinsonianas cuando no se espera una mejoría mayor a pesar de cualquier manipulación adicional de levodopa y/u otra medicación antiparkinsoniana. Estará basado en el juicio del investigador clínico. 4. Puntuación total de UDyRS ≥ 30 en la visita 3 basada en la puntuación de un evaluador central enmascarado. 5. Paciente (o los cuidadores de los pacientes) tienen que ser capaces de completar tanto el diario de dosificación del paciente como el diario de EP, y tienen que ser también capaces de demostrar la habilidad de manejar, manipular y cuidar la bomba y la sonda. 6. Los pacientes deberán demostrar una concordancia mínima del 75% con la evaluación de los síntomas realizada por el investigador o por otra persona cualificada en el diario de la enfermedad de Parkinson tras recibir instrucción en la visita 1 de selección, con concordancia en al menos 1 intervalo de tiempo "off", concordancia en al menos 1 intervalo de tiempo "on" con o sin discinesia y al menos un intervalo de tiempo "on" con discinesia, independientemente de que la discinesia sea o no problemática. 7. El paciente cumple los requisitos locales de su país para pasar a recibir tratamiento comercial con Duodopa una vez completado el estudio. |
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E.4 | Principal exclusion criteria |
1. Predominantly di-phasic dyskinesia, as per Investigator discretion. 2. Patients who were treated with LCIG before 3. Patients who have had previous surgery for PD including, but not limited to deep brain stimulation (DBS) or cell transplantation. 4. A Mini-Mental State Examination (MMSE) score of < 24 at Visit 1 or significant cognitive impairment that, in the opinion of the Investigator, could impact the subject's ability to participate in the trial 5. Current primary psychiatric diagnosis of uncontrolled acute psychotic disorder or primary psychiatric diagnoses of bipolar disorder, schizophrenia, obsessive compulsive disorder or currently experiencing a major depressive episode with psychotic features per Diagnostic and Statistical Manual of Mental Disorders Fifth Edition, Text Revision (DSM V-TR). 6. Subject experiencing clinically significant sleep attacks or clinically significant impulsive behavior (e.g., pathological gambling, hypersexuality) at any point during the three months prior to the Screening evaluation as judged by the Investigator. 7. Current diagnosis or history of drug or alcohol abuse (DSM-V-TR criteria) within 12 months prior to screening visit. 8. Participation in a concurrent interventional or observational study. 9. Lack of motivation or insufficient language skills to complete the study questionnaires. 10. Subject's PD diagnosis is unclear or there is a suspicion that the subject has a parkinsonian syndrome such as secondary parkinsonism (e.g., caused by drugs, toxins, infectious agents, vascular disease, trauma, brain neoplasm), atypical Parkinson Syndrome (e.g., Multiple System Atrophy, Progressive supranuclear Palsy, Diffuse Lewy Body disease) or other neurodegenerative disease that might mimic the symptoms of PD. |
1. Discinesia predominantemente bifásica, a criterio del investigador. 2. Pacientes tratados anteriormente con GILC. 3. Pacientes que se hayan sometido previamente a un procedimiento quirúrgico para la EP, entre otros, estimulación cerebral profunda (ECP) o trasplante de células. 4. Puntuación menor de 24 en el Miniexamen del estado mental (MMSE) en la visita 1 o deterioro cognitivo importante que, en opinión del investigador, pudiera afectar a la capacidad del sujeto para participar en el ensayo. 5. Diagnóstico psiquiátrico primario de trastorno psicótico agudo y no controlado o de trastorno bipolar, esquizofrenia o trastorno obsesivo-compulsivo, o episodio actual de depresión mayor con manifestaciones psicóticas según el Manual diagnóstico y estadístico de los trastornos mentales, quinta edición, texto revisado (DSM-V-TR). 6. Pacientes que experimenten ataques significantes durante el sueño, o impulsos de conducta clínicos significativos (ej.: hipersexualidad, problemas de juego) en cualquier momento durante los 3 meses antes a la evaluación de screening a juicio del investigador. 7. Diagnóstico actual o antecedentes de alcoholismo o drogadicción (según los criterios del DSM-V-TR) en los 12 meses anteriores a la visita de selección. 8. Participar en un estudio intervencionista u observacional concurrente. 9. Falta de motivación o capacidades lingüísticas insuficientes para cumplimentar los cuestionarios del estudio. 10. El diagnóstico de enfermedad de Parkinson es dudoso o se sospecha que el sujeto presenta un síndrome parkinsoniano, como parkinsonismo secundario (por ejemplo, por fármacos, toxinas, agentes infecciosos, enfermedad vascular, traumatismo, neoplasia cerebral), síndrome de Parkinson atípico (por ejemplo, atrofia multisistémica, parálisis supranuclear progresiva, enfermedad difusa con cuerpos de Lewy) u otra enfermedad neurodegenerativa que pueda imitar los síntomas de la enfermedad de Parkinson. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline to week 12 in Unified Dyskinesia Rating Scale (UDysRS) Total Score. |
Cambio desde la visita basal a la semana 12 en el resultado total de la escala unificada para la discinesia (UDysRS). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline, Week 2, Week 4, Week 8, Week 12/Early termination visit |
Visita basal, visita semana 2, visita semana 4, visita semana 8, visita semana 12/visita de terminación temprana |
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E.5.2 | Secondary end point(s) |
Secondary endpoints (with hierarchical analysis)
• ON time without troublesome dyskinesia as measured by the PD Diary • PDQ-8 Summary Index • CGI-C • UPDRS Part II Score • OFF time as measured by PD Diary • UPDRS Part III Score
Additional Efficacy Endpoints are: ● UDysRS Historical Score, Objective Score and Parts 1 through 4 Scores ● ON time with troublesome dyskinesia and ON time without dyskinesia as measured by PD Diary ● mAIMS
Additional Health Outcome Endpoints: ● King's PD Pain Scale |
-Tiempo “on” con discinesia problemática medida por el Diario de EP -Puntuación global de PDQ-8 -CGI-C -Puntuación de UPDRS, parte II - Tiempo “off” medido por el diario de EP Evaluaciones de eficacia adicional: - Puntuación histórica de UDysRS, puntuación objetiva y puntuaciones de las partes 1 a 4 -Tiempo “on” con discinesia problemática a y tiempo “on” sin discinesia medida por el diario de EP -mAIMS Evaluaciones de resultados adicionales de salud: -Escala de dolor en la EP del King’s College Hospital |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Baseline, Week 2, Week 4, Week 8, Week 12/Early termination visit 2. Baseline, Week 8, Week 12/Early termination visit 3. Week 2, Week 4, Week 8, Week 12/Early termination visit 4. Screening, Baseline, Week 2, Week 4, Week 8, Week 12/Early termination visit 5. Baseline, Week 2, Week 4, Week 8, Week 12/Early termination visit 6. Screening, Baseline, Week 2, Week 4, Week 8, Week 12/Early termination visit 7. Baseline, Week 2, Week 4, Week 8, Week 12/Early termination visit 8. Baseline, Week 2, Week 4, Week 8, Week 12/Early termination visit 9. Baseline, Week 2, Week 4, Week 8, Week 12/Early termination visit 10. Baseline, Week 4, Week 8, Week 12/Early termination visit |
1. Visita basal, visit sem 2, visit sem 4, visit sem 8, visit sem 12/visit de terminación temprana 2. Visita basal, visit sem 8, visit sem 12/visit de terminación temprana 3. visita semana 2, visit sem 4, visit sem 8, visit sem 12/ visit de terminación temprana 4. visita de selección, visita basal, visit sem 2, visit sem 4, visit sem 8, visit sem 12/ visit de terminación temprana 7. Visita basal, visit sem 2, visit sem 4 visit sem 8, visit sem 12/ visit de terminación temprana 8. Visita basal, visit sem 2, visit sem 4, visit sem 8, visit sem 12/visit de terminación temprana. 9. Visita basal, visit sem 2, visit sem 4, visit sem 8, visit sem 12/visit de terminación temprana. 10. Visita basal, visit sem 4, visit sem 8, visit sem 12/visit de terminación temprana |
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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 | Yes |
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 | No |
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 |
Optimized medical treatment |
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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 | 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 |
European Union |
United States |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |