| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| L-dopa induced dyskinesias in Parkinson’s patients with severe motor complications |
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| 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 assess the potential anti-dyskinetic efficacy of multiple titrated doses of AFQ056 in Parkinson’s patients with severe L-dopa induced dyskinesias using the Abnormal Involuntary Movement Scale (AIMS).
•To assess the potential anti-parkinsonian effect of multiple titrated doses of AFQ056 in combination with L-dopa in Parkinson’s patients with severe L-dopa induced dyskinesias using the Unified Parkinson’s Disease Rating Scale (UPDRS) – part III.
•To assess the safety and tolerability of multiple titrated doses of AFQ056 in combination with L-dopa in Parkinson’s patients with severe L-dopa induced dyskinesias .
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| E.2.2 | Secondary objectives of the trial |
•To assess the potential anti-dyskinetic efficacy of multiple titrated doses of AFQ056 in Parkinson’s patients with severe L-dopa induced dyskinesias using the Lang-Fahn Activities of Daily Living Dyskinesia Scale (LFADLDS) and UPDRS(32-33).
•To explore the potential relationship between the exposure of AFQ056 and the efficacy assessments after multiple dose treatment with AFQ056 in Parkinson’s patients with severe L-dopa induced dyskinesias
•To explore the potential effect of multiple doses of AFQ056 on the mGlu5 receptor pathway in Parkinson’s patients with severe L-dopa induced dyskinesias .
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| Patients who are eligible for enrollment in the study will be males and females, aged between 30 and 85 years of age (both inclusive), non-smokers, with idiopathic Parkinson’s disease (diagnosed by UK Parkinson’s disease Society Brain Bank criteria), with an AIMS score of 18 or greater, with L-dopa induced dyskinesia greater than 20% (UPDRS item of 32, rating ≥1) of moderate to severe (complete disabling) intensity (UPDRS item 33 rating ≥ 2), with dyskinesias for at least 3 months before randomization, and who are on L-dopa treatment for at least 3 years prior to randomization; L-dopa treatment has to be stable for at least 1 month prior to randomization (i.e. the total daily dose and dosing regimen can vary among patients but will be the same for individual patients). Other concomitant anti-parkinsonian medication is allowed but the total daily dose and dosing regimen has to be stable for at least one month prior to randomization. Female patients must be without childbearing potential (post-menopausal or surgically sterilized); for safety reasons they have to use a double-barrier local contraception (e.g., intra-uterine device plus condom) during the entire study from screening up to the study completion visit. Male patients must be using a double-barrier local contraception for the entire duration of the study (from screening up to the study completion visit), and refrain from fathering a child in the 3 months following last study drug administration. Patients must be able to provide written informed consent prior to study participation. |
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| E.4 | Principal exclusion criteria |
| Following patients will be excluded from the study: smokers, with a prior surgery for Parkinson’s Disease, with a Hoehn and Yahr score of 5 when ‘off’, with cognitive impairment (MMSE less than 24), with atypical Parkinson’s disease (Progressive Supranuclear Palsy (PSP), Multi Systemic Atrophy (MSA)), with history or presence of psychosis and/or confusional states, with a history or presence of nephrolithiasis, renal impairment, and/or liver disease, who participated in an anti-dyskinetic clinical study within the 6 months before randomization, who are under deep brain stimulation, who received anti-dyskinetic medication (i.e. antipsychotics, amantadine) within 15 days before randomization and/or neuroleptics during 2 months before randomization, who is unable to perform cognitive assessments (scheduled at screening) as determined by the neurocognitive test guidelines. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
•Abnormal Involuntary Movement Scale (AIMS): screening; baseline (Day -4 and Day -3): in the morning* and once in the afternoon between 12:00 and 18:00**; on Days 1, 4, 8, 12, 16 and 20: at 2 h after the morning dose of the study medication and once in the afternoon between 12:00 and 18:00**; Study completion.
* on Days -4 and -3, the morning and afternoon assessment should be performed at the similar day time as the scheduled time points during the multiple dose treatment.
** the time point in the afternoon (being patient specific as depending on the dosing regimen) will be identified on Day -4 based on the occurrence of dyskinesias. On the following days (Day -3 and Day 1 to 20), the assessment should be done at the similar day time as the time point identified on Day -4.
For all scheduled AIMS time points a time window ± 1 h is acceptable.
The AIMS should be done by the same neurologist for individual patients.
•Unified Parkinson Disease Rating Scale (UPDRS – part III): screening; baseline (Day -4 and Day -3): in the morning* and once in the afternoon between 12:00 and 18:00**; on Days 1, 4, 8, 12, 16 and 20: at 2 h after the morning dose of the study medication and once in the afternoon between 12:00 and 18:00**; Study completion
* on Days -4 and -3, the morning and afternoon assessment should be performed at the similar day time as the scheduled time points during the multiple dose treatment.
** the time point in the afternoon (being patient specific as depending on the dosing regimen) will be identified on Day -4 based on the occurrence of dyskinesias. On the following days (Day -3 and Day 1 to 20) the assessment should be done at the similar day time as the time point identified on Day -4.
For all scheduled UPDRS time points a time window ± 1 h is acceptable.
The UPDRS should be done by the same neurologist for individual patients.
•Unified Parkinson Disease Rating Scale (UPDRS – part IV): screening; baseline (Day -4 and Day -3): in the morning*; on Days 1, 4, 8, 12, 16 and 20: at 2 h after the morning dose of the study medication; Study completion.
* on Days -4 and -3, the morning assessment should be performed at the similar day time as the scheduled time points during the multiple dose treatment.
For all scheduled UPDRS time points a time window ± 1 h is acceptable.
The UPDRS should be done by the same neurologist for individual patients.
•Lang-Fahn Activities of Daily Living Dyskinesia Scale (LFADLDS, sum score): screening; baseline (Day -4 and Day -3): in the morning*; on Days 1, 4, 8, 12, 16 and 20: at 2 h after the morning dose of the study medication; Study completion
* on Days -4 and -3, the morning assessment should be performed at the similar day time as the scheduled time points during the multiple dose treatment.
For all scheduled LFADLDS time points a time window ± 1 h is acceptable.
•Computerized CANTAB test battery including following cognitive functions tests:
•Motor/visual control task, visual memory, attention and reaction time, decision making and response control, executive function: Screening*, Day -4 (half of the test battery)**, Day -3 (remaining half of the test battery)**: in the morning at similar day time as the scheduled time points on Day 15 and 16; Day 15 (half of the test battery as on Day -4)** and Day 16 (remaining half of the test battery as one Day -3)**: at approximately 2.5 h after the morning dose of the study medication
* screening assessment to ensure optimal performance at baseline assessments, as well as to test if the patient can perform the test as determined by the neurocognitive test guidelines (part of the inclusion/exclusion criteria).
** due to the long duration of the test battery (lasting about 70 to 85 minutes), the tests will be split over 2 days (over Day -4 and Day -3 as well as over Day 15 and Day 16)
Intra-extra dimensional set shift (as part of executive function)*: Day 16: at approximately 2.5 h after the morning dose of the study medication
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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 | Yes |
| 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 | Yes |
| 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) | No |
| 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.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
| 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 | 5 |
| 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 | Information not present in EudraCT |
| 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 | 0 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
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