E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Parkinson's disease patients with refractory visual hallucinations |
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E.1.1.1 | Medical condition in easily understood language |
Parkinson's disease patients with visual hallucinations |
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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 evaluate the efficacy of continuous subcutaneous apomorphine infusion compared to placebo in Parkinson's disease patients with refractory visual hallucinations. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of continuous subcutaneous apomorphine infusion compared to placebo in Parkinson's disease patients with refractory visual hallucinations on "bottom-up" and "top-down" visual processing.
To evaluate the efficacy of continuous subcutaneous apomorphine infusion compared to placebo in Parkinson's disease patients with refractory visual hallucinations on quality of life.
To evaluate the efficacy of continuous subcutaneous apomorphine infusion compared to placebo in Parkinson's disease patients with refractory visual hallucinations on cognition, neuropsychiatric symptoms, and motor symptoms. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Female and male subjects aged ≥30;
- Diagnosis of established PD, defined by the MDS-PD criteria (Postuma et al., 2015);
- Presence of visual severe hallucinations defined as more than 3 times a week (van Laar et al., 2010);
- Visual hallucinations must have developed after PD diagnosis;
- Visual hallucinations must have been optimally treated with reduction of dopamine agonists if possible, and prescription of clozapine and/or cholinesterase inhibitors if needed;
- Female subjects must complaint with a highly effective contraceptive method (oral hormonal contraception alone is not considered highly effective and must be used in combination with a barrier method) during the study, if sexually active;
- Subjects should be able and capable of adhering to the protocol, visit schedules, and medication intake according to the judgement of the investigator. |
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E.4 | Principal exclusion criteria |
- Symptomatic, clinically relevant and medically uncontrolled orthostatic hypotension;
- Patients with a prolonged QT interval corrected for heart rate according to Bazett’s formula (QTc) of >450 ms for male and >470 ms for female at screening, or history of a long QT syndrome;
- PD medication change (i.e., dopamine-agonists, amantadine, MAO-B inhibitor, anticholinergics and cholinesterase inhibitors) in last month prior to initiation (van Laar et al., 2010);
- Active psychosis or a history of significant psychosis;
- Any medical condition that is likely to interfere with an adequate participation in the study including e.g. current diagnosis of unstable epilepsy, clinically relevant cardiac dysfunction and/or myocardial infarction or stroke within the last 12 months. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in clinical global impression of severity of visual hallucinations |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary end points are change in visual hallucinations, neuropsychiatric symptoms, cognition, sleeping problems, apathy, depression, anxiety, motor symptoms, motor complications, "bottom-up" perception, "top-down" attention, and quality of life.
Safety end points are change in blood pressure and the occurrence of adverse events. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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) | 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 | 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
| 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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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 | |
E.8.9.1 | In the Member State concerned days | |