E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with Parkinson’s Disease with motor fluctuations |
Pacientes con enfermedad de Parkinson con fluctuaciones motoras |
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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 | 19.0 |
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 |
To determine the effect of ND0612 on daily “OFF” time using a subject completed home diary. |
Determinar el efecto del ND0612 en el tiempo en el que la medicación deja de hacer efecto |
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E.2.2 | Secondary objectives of the trial |
To determine the effect of ND0612 on daily “ON” time without troublesome dyskinesia (defined as the sum of "ON" time without dyskinesia and “ON” time with non-troublesome dyskinesia) using a subject completed home diary. |
Determinar el efecto del ND0612 en el tiempo en el que la medicación hace efecto ("ON") sin discinesia problemática (definido como la suma del tiempo "ON" sin discinesia y el tiempo "ON" con discinesia no problemática) usando un diario que el sujeto debe rellenar en casa. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female PD subjects of any race aged 30-80 years 2. PD diagnosis consistent with the UK Brain Bank Criteria. 3. Modified Hoehn & Yahr scale in “ON” state ≤3 4. Subjects must experience motor fluctuations and experience an average of at least 2 hours daily in the “OFF” state 5. Taking at least 4 doses/day of IR LD/DDI (or at least 3 doses/day of Rytary) and taking, or having taken therapeutic doses of at least 2 other classes of anti-PD medications. 6. Subjects must be on stable doses of all their anti-PD medications for at least 28 days before Baseline (Day 1). 7. Subject and/or study partner must demonstrate ability to keep accurate diary entries of PD symptoms (“ON-OFF” diaries) with at least 75% concordance with the study rater by the end of the diary training session at the end of the screening period. 8. Mini Mental State Examination (MMSE) score >26. 9. Female subjects must be surgically sterile (hysterectomy, bilateral oophorectomy, or tubal ligation), postmenopausal (defined as cessation of menses for at least 1 year), or willing to practice a highly effective method of contraception. |
1. Sujetos con EP de sexo masculino o femenino, de cualquier raza, de entre 30-80 años 2. Diagnóstico de EP conforme a los Criterios del Banco de Cerebros del Reino Unido. 3. Escala de Hoehn y Yahr modificada en estado “ON” de ≤ 3 4. Los sujetos deben experimentar fluctuaciones motoras y una media de al menos 2 horas diariamente en estado "OFF" 5. Tomar al menos 4 dosis/día de LD/IDD de LI (o al menos 3 dosis/día de Rytary) y tomar, o haber tomado, dosis terapéuticas de al menos 2 tipos de medicamentos anti-EP. 6. Los sujetos deben haber tomado dosis estables de todos los medicamentos anti-EP durante al menos 28 días antes del periodo basal (día 1). 7. Los sujetos y/o compañeros de estudio deben demostrar la capacidad de registrar los síntomas de EP (diarios "ON-OFF") de manera exacta con al menos el 75 % de concordancia con el evaluador del estudio al finalizar la sesión de formación del diario al término del periodo de selección. 09. Los sujetos de sexo femenino deben haberse sometido a una esterilización quirúrgica (histerectomía, ovariectomía bilateral o ligadura de trompas), estar en la posmenopausia (definida como cese de la menstruación durante al menos 1 año) o estar dispuestas a utilizar un método anticonceptivo altamente eficaz. |
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E.4 | Principal exclusion criteria |
1. Atypical or secondary parkinsonism. 2. Psychosis or hallucinations in past 6 months. 3. Subjects with a clinically significant or unstable medical, surgical, psychiatric condition or laboratory abnormalities which, in the opinion of the Investigator or the EAC, represents a safety risk, makes the subject unsuitable for study entry or potentially unable to complete all aspects of the study. 4. Clinically significant ECG abnormalities. 5. Renal or liver dysfunction that may alter drug metabolism including Screening visit serum levels of creatinine >1.3 mg/dL, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2x upper limit of normal (ULN), total bilirubin >2.5 mg/dL. 6. Positive serum serology for Hepatitits B Virus (HBV), Hepatitits C Virus (HCV) or Human Immunodeficiency Virus (HIV) at the Screening visit 7. Any malignancy in the 5 years prior to randomization excluding basal cell carcinoma of the skin or cervical carcinoma in situ that have been successfully treated 8. Use of prohibited medications as per protocol 9. Subjects who have previously undergone treatment for PD with a neurosurgical intervention (e.g., pallidotomy, thalamotomy, transplantation, deep brain stimulation procedures), Duodopa/Duopa, or continuous dopaminergic or apomorphine infusion. |
1. Parkinsonismo atípico o secundario. 2. Psicosis o alucinaciones los últimos 6 meses. 3. Sujetos con una afección médica, quirúrgica, psiquiátrica clínicamente significativa o inestable o anomalías analíticas que, en opinión del investigador o del CAI, representen un riesgo para la seguridad o hagan que el sujeto no sea apto para participar en el estudio o potencialmente incapaz de cumplir todos los aspectos del estudio. 4. Anormalidades de ECG clínicamente significativas. 5. Trastorno renal o hepático que pueda alterar el metabolismo del fármaco, incluidos los niveles séricos de creatinina > 1,3 mg/dl en la visita de selección, aspartato aminotransferasa (AST) o alanina aminotransferasa (ALT) > 2x el límite superior de normalidad (LSN) y bilirrubina total > 2,5 mg/dl. 6. Prueba sérica positiva para el virus de la hepatitis B (VHB), el virus de la hepatitis C (VHC) o el virus de la inmunodeficiencia humana (VIH) en la visita de selección 7. Cualquier neoplasia maligna en los 5 años anteriores a la aleatorización, excluidos el carcinoma basocelular de la piel o el carcinoma cervical localizado tratado con éxito. 8. El uso de medicamentos prohibidos según el protocol. 9. Sujetos que se hayan sometido con anterioridad a un tratamiento para la EP con intervención neuroquirúrgica (p. ej. palidotomía, talamectomía, trasplante, procedimientos de estimulación cerebral profunda), Duodopa/Duopa o perfusiones continuas de dopaminérgicos o apomorfina. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the change from Baseline to Week 16 in the mean percentage of “OFF” time during waking hours, based on patient's home diary assessments on 3 consecutive days before the visit. The “OFF” time will also be presented as hours normalized to 16 waking hours. |
El criterio principal de valoración es el cambio entre el periodo basal y la semana 16 en el porcentaje medio del tiempo "OFF" durante las horas de vigilia, basándose en las evaluaciones del diario domiciliario del paciente en los 3 días consecutivos antes de la visita. Además, el tiempo "OFF" debe presentarse como horas normalizadas a 16 horas de vigilia. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 16 visit |
Visita Semana 16 |
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E.5.2 | Secondary end point(s) |
The key secondary efficacy endpoint is the change from Baseline to Week 16 in the mean percentage of “ON” time without troublesome dyskinesia during waking hours, based on patient's home diary assessments on the 3 consecutive days before the visit. "ON" time without troublesome dyskinesia is defined as the sum of "ON" time without dyskinesia and “ON” time with non-troublesome dyskinesia. |
El criterio secundario de valoración clave es el cambio entre el periodo basal y la semana 16 en el porcentaje medio del tiempo "ON" sin discinesia problemática durante las horas de vigilia, basándose en las evaluaciones del diario domiciliario del paciente en los 3 días consecutivos antes de la visita. El tiempo "ON" sin discinesia problemática se define como la suma del tiempo "ON" sin discinesia y del tiempo "ON" con discinesia no problemática. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 16 visit |
Visita Semana 16 |
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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 | 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 | Yes |
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 | 19 |
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 |
Belgium |
Canada |
Denmark |
France |
Israel |
Netherlands |
Spain |
Sweden |
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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LVLS |
Última visita de ultimo paciente |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |