E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Parkinson disease |
Enfermedad de Parkinson |
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E.1.1.1 | Medical condition in easily understood language |
Parkinson disease |
Enfermedad de Parkinson |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
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 compare the acute cognitive and affective effects of immediate-release oral LD (IR-LD) and continuous delivery of LCIG in patients with PD measured at baseline (-1 hour) and at time-points +1, +3 and +5 hour. Thus, as showed in the flow-chart section (pag. 15), cognitive and affective effects measures considered as main variables for statistical purposes will be collected at - 1hour (pre-dosing) and at +1 hour after initiating either IR-LD or LCIG and one hour after receiving either IR-LD or oral placebo (+3, +5 hour). |
Comparar los efectos cognitivos y afectivos agudos de IR-LD y de LCIG en pacientes con EP medidos basalmente (-1 hora) y en los puntos de tiempo +1, +3 y +5 horas. Así, como se muestra en el organigrama del estudio (pág.s 16-17), las variables cognitivas y afectivas -consideradas como las principales para propósitos estadísticos- serán recogidas a ? 1 hora (pre-dosis) y a +1 hora después de iniciar IR-LD o LCIG y una hora después de recibir IR-LD o placebo oral (+3, +5 horas). |
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E.2.2 | Secondary objectives of the trial |
To compare at six consecutive time-points ( -1, +1, +2, +3, +4, +5 hour): - Changes in LD plasma levels. - Motor and dyskinesia scores. - Changes on mood and anxiety levels. |
Comparar en seis tiempos consecutivos ( -1, +1, +2, +3, +4, +5 horas): - Cambios en los niveles plasmáticos de LD. - Puntuaciones motoras y de discinesias. - Cambios de humor y niveles de ansiedad. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female patients aged 40 to 80 years old with diagnosis of Idiopathic Parkinson?s Disease according to the London Brain Bank Criteria. [44] 2. Patients must be able and willing to provide informed consent to participate in the study. 3. Patients must be receiving optimized treatment with a stable dose of LCIG for at least four weeks before entering the study. 4. Patients must be experiencing motor fluctuations with a minimum of two hours/of OFF time during the awake day 5. Patients must have a Hoehn & Yahr stage between II and III in the ON condition [45]. |
1. Pacientes varones o mujeres de edades comprendidas entre 40 y 80 años de edad con diagnóstico de enfermedad de Parkinson idiopática de acuerdo con los Criterios del Brian Bank de Londres. 2. Los pacientes deben ser capaces de firmar el consentimiento informado para participar en el estudio. 3. Los pacientes deben estar recibiendo tratamiento optimizado con una dosis estable de LCIG durante al menos cuatro semanas antes de entrar en el estudio. 4. Los pacientes deben experimentar fluctuaciones motoras con un mínimo de dos horas de tiempo OFF durante el tiempo de vigilia 5. Los pacientes deben tener un estadio de Hoehn & Yahr entre II y III en el estado ON |
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E.4 | Principal exclusion criteria |
1. Any form of parkinsonism other than idiopathic Parkinson?s disease. 2. Patients with deep brain stimulation or history of neurosurgical procedure. 3. Untreated depressive disorder. 4. Patients with functional illiteracy or impossibility to perform any of the tests (i.e. cognitive, blood test) of the study. 5. Severe or ongoing unstable medical conditions (e.g. cardiac, hepatic, pulmonary, renal, metabolic or endocrine). 6. Imminent risk of self-harm based on Investigator?s clinical judgment, with a ?yes? answer on item 4 or 5 on the Columbia Suicide Severity Rating Scale (CSSRS)[50] at screening. 7. Parkinson?s Disease-Cognitive Rating Scale (PD-CRS) total score ? 64 and accomplishment of MDS criteria for dementia associated to PD at the time of screening [51, 52]. Patients with a PD-CRS total score ? 64, fulfilling diagnostic criteria for mild cognitive impairment in PD (PD-MCI) will be allowed to participate. [52, 53] 8. Patients with clinically significant apathetic symptoms as judged by both caregiver and neurologist and scoring > 14 on the Starkstein?s Apathy Evaluation Scale.[49] 9. Patients scoring ? 11 for anxiety and or depression on the Hospital Anxiety and Depression Scale (HADS). [37] 10. Previous history of any psychiatric condition as defined by the DSM-IV criteria based on the MINI International Neuropsychiatric Interview. [47, 54] 11. Patients with more than 30% of the day in off period and with dose failure episodes or unpredictable response to LD or severe dyskinesia that in opinion of the investigator could interfere with test performance or results. 12. Patients included in other clinical trial during the study period or 6 weeks before the study 13. Changes in psychotropic medication in the previous 4 weeks 14. Patients currently treated with: (i) Anticholinergic drugs; (ii) Typical neuroleptics, or any other drug which, in the opinion of the investigator, would interfere with the cognitive tests. Concomitant treatments with atypical neuroleptics (such as quetiapine, ziprasidone, or aripiprazole can be administered provided they remain at the lowest effective dose) 15. Permitted medications: anticholinesterase inhibitors and antidepressants initiated at least six weeks before study screening, or any other drug considered necessary for the safety and well-being of the patient are permitted during the study at the discretion of the investigator. |
1. Cualquier forma de parkinsonismo distinta de la enfermedad de Parkinson idiopática. 2. Pacientes con estimulación cerebral profunda o antecedentes de procedimiento neuroquirúrgico. 3. Trastorno depresivo significativo no tratado 4. Pacientes con analfabetismo funcional o imposibilidad de realizar cualquiera de las pruebas del estudio (por ejemplo, tests cognitivos, análisis de sangre) 5. Condiciones médicas severas o inestables (por ejemplo enfermedades cardíacas, hepáticas, pulmonares, renales, metabólicas o endocrinas). 6. Riesgo inminente de autolesión basado en el juicio clínico del investigador, con una respuesta "sí" en el ítem 4 o 5 en la Columbia Suicidio Gravedad Rating Scale (CssRS) en el sreening. 7. Puntuación total ? 64 en la Parkinson?s Disease -Cognitive Rating Scale (PD-CRS),y criterios de la MDS para la demencia asociada a la EP en el momento del screening. A los pacientes con una puntuación total PD-CRS ? 64 que cumplan criterios de diagnóstico para deterioro cognitivo leve en la EP (PD-MCI) se les permitirá participar. 8. Pacientes con apatía clínicamente significativa juzgada tanto por el cuidador y el neurólogo y con puntuación > 14 en la Escala de Evaluación de la Apatía del Starkstein. 9. Puntuación ? 11 en la Escala Hospitalaria de Depresión y Ansiedad (HADS). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary outcome measures will be the performance over time of different cognitive tasks: Wisconsin Card Sorting Test, Sternberg Test, phonetic and alternating verbal fluency and a reversal-learning task. |
Pruebas cognitivas: Wisconsin Card Sorting Test, Prueba de Sternberg, fluencias verbales fonética y alternante y un test de aprendizaje inverso. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Basal, +1 hour, +2 hours, +3 hours, +4 hours, +5 hours |
Basal, +1 hora, +2 horas, +3 horas, +4 horas, +5 horas |
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E.5.2 | Secondary end point(s) |
Motor function, mood and anxiety |
Función motora, y estado de ánimo y ansiedad |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Basal, +1 hour, +2 hours, +3 hours, +4 hours, +5 hours |
Basal, +1 hora, +2 horas, +3 horas, +4 horas, +5 horas |
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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 | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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LVLS |
Última visita del último 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 | 8 |
E.8.9.1 | In the Member State concerned days | |