E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The main objective of this study is to assess the efficacy of AFQ056 in reducing L-dopa induced dyskinesias. |
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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 anti-dyskinetic efficacy of multiple titrated doses of AFQ056 on moderate to severe L-dopa induced dyskinesias (LIDs) in patients with Parkinson’s disease using the Lang-Fahn Activities of Daily Living Dyskinesia Scale (LFADLDS). •To assess the potential anti-parkinsonian effect of multiple titrated doses of AFQ056 in combination with L-dopa in Parkinson’s patients with moderate to severe LIDs 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 moderate to severe LIDs.
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E.2.2 | Secondary objectives of the trial |
•To assess the anti-dyskinetic efficacy of multiple titrated doses of AFQ056 in combination with L-dopa in Parkinson’s patients with moderate to severe LIDs using the Abnormal Involuntary Movement Scale (AIMS) and UPDRS.
Exploratory objectives: •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 moderate to severe LIDs. •To explore the potential effect of multiple doses of AFQ056 on the mGlu5 receptor pathway in Parkinson’s patients with moderate to severe LIDs.
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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 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 amantadine within 15 days, and/or other anti-dyskinetic medication (i.e. antipsychotics) within 4 weeks before randomization and/or neuroleptics during 2 months before randomization, who is unable to perform the cognitive assessments at screening as determined by the neurocognitive test guidelines which is part of the CANTAB test battery. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Background, demographic and administrative assessments: •Physical examination •Hepatitis screen, HIV screen: Screening •Hoehn and Yahr assessment (part of inclusion/exclusion criteria): screening •Pregnancy test: Screening, Baseline (Day -4), Study Completion
Safety and tolerability assessments: •Vital signs and body measurements •ECG evaluation •Hematology; Blood chemistry; Urinalysis •Adverse events
Pharmacokinetic assessments: •PK parameters and evaluations
Efficacy assessments •Abnormal Involuntary Movement Scale (AIMS) •Unified Parkinson Disease Rating Scale (UPDRS – part III) •Unified Parkinson Disease Rating Scale (UPDRS – part IV) •Lang-Fahn Activities of Daily Living Dyskinesia Scale (LFADLDS, sum score) •Parkinson Disease Sleep Scale (PDSS) •Beck depression scale •Computerized CANTAB test battery including following cognitive functions tests
Exploratory biomarker assessments (optional) •Pharmacogenomics |
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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
| 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 | 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 | |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |