E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe levodopa induced dyskinesia in patients with Parkinson's disease |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10013916 |
E.1.2 | Term | Dyskinesia |
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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 safety and tolerability of AFQ056 in patients with PD-LID as assessed by •Incidence and severity of adverse events and serious adverse events •Changes in vital signs, laboratory assessments, and ECGs •Changes in cognitive function as measured by the MMSE •Changes in psychiatric symptoms as measured by the SCOPA-PC •Changes in underlying symptoms of PD as measured by the UPDRS part III, by the PD symptom items in the Clinical Global Impression of Change (CGIC) and Patient Global Impression of Change (PGIC), and by AEs potentially related to an exacerbation of the movement disorder of PD •Occurrence of rebound symptoms upon discontinuation of study drug
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E.2.2 | Secondary objectives of the trial |
To evaluate the anti-dyskinetic efficacy of AFQ056 treatment in patients with PD-LID on dyskinesia as assessed by •Change from baseline in mAIMS total score •Investigator and patient assessment of clinical changes in dyskinetic symptoms and disability due to dyskinesia compared to baseline, as measured by the corresponding CGIC and PGIC items respectively
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Group 1 patients 1.Must have been eligible for the core study i.e. must have met inclusion and not met any exclusion criteria at the time of entry into the core study 2.Have completed the core study 3.Female patients must be of non-childbearing potential, defined as all women physiologically not capable of becoming pregnant, and must have a negative pregnancy test at the last visit prior to taper-off of the core study. 4.Outpatients, residing in the community (nursing home patients are not allowed) 5.Provide written informed consent before any assessment is performed and before any open-label study drug is taken
6.Have a caregiver/family informant unless the investigator considers support not to be necessary
Group 2 patients 1.Must have been eligible for the core study i.e. must have met inclusion and not met any exclusion criteria at the time of entry into the core study 2.Have completed the core study 3.Female patients must be of non-childbearing potential, defined as all women physiologically not capable of becoming pregnant, and must have a negative pregnancy test at the screening visit of this study. 4.Outpatients, residing in the community (nursing home patients are not allowed) 5.Provide written informed consent before any assessment is performed and before any open-label study drug is taken 6.Have a caregiver/family informant unless the investigator considers support not to be necessary
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E.4 | Principal exclusion criteria |
Group 1 patients 1.A score of 5 in the "ON"-state on the Modified Hoehn and Yahr Staging (UPDRS Part V) assessment at baseline 2.Any advanced, severe or unstable disease (other than PD) that may interfere with the primary and secondary study outcome evaluations 3.Malignancy of any organ system (other than localized basal cell carcinoma of the skin or non-invasive, non-metastatic prostate cancer that has been effectively treated), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. 4.Evidence of dementia (or MMSE ≤ 26 at the baseline visit); untreated or ineffectively treated major depressive disorder; currently experiencing hallucinations/psychosis requiring antipsychotic treatment, and/or confusional states (DSM-IVR, Diagnostic and Statistical Manual of Mental Disorders, 4th edition, revised) 5.Lab values (at the last visit prior to the taper-off period of the respective core study or at any subsequent unscheduled visit prior to the baseline visit) that include AST, ALT, total bilirubin or creatinine ≥ 1.5 X ULN (upper limit of normal) for the central laboratory 6.Long QT syndrome or QTc > 450 msec for males and > 470 msec for females at the last visit prior to taper-off of the core study (Fridericia's corrections used) 7.Any patient unable or unwilling to participate in all study-related activities
Group 2 patients 1.A history of surgical treatment for PD, including deep brain stimulation 2.A score of 5 in the "ON"-state on the Modified Hoehn and Yahr Staging (UPDRS Part V) assessment at screening 3.Any advanced, severe or unstable disease (other than PD) that may interfere with the primary and secondary study outcome evaluations 4.Malignancy of any organ system (other than localized basal cell carcinoma of the skin or non-invasive, non-metastatic prostate cancer that has been effectively treated), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. 5.Evidence of dementia (or MMSE ≤ 26 at the screening visit); untreated or ineffectively treated major depressive disorder; currently experiencing hallucinations/psychosis requiring antipsychotic treatment, and/or confusional states (DSM-IVR, Diagnostic and Statistical Manual of Mental Disorders, 4th edition, revised) 6.Treatment with any of the following prior to baseline visit •current treatment with concomitant medications that are strong or moderate inhibitors or inducers of CYP3A4 within 1 week (see Appendix 2) •centrally acting anti-cholinergic medication within 3 days •amantadine within 3 days •metoclopramide within 3 days •typical or atypical neuroleptic agents within 1 week •other investigational drugs within 30 days or 5 half-lives of the BL visit, whichever is longer 7.Laboratory values at screening that include AST, ALT, total bilirubin or creatinine ≥ 1.5 X ULN (upper limit of normal) for the central laboratory 8.Long QT syndrome or QTc > 450 msec for males and > 470 msec for females at screening (Fridericia's corrections used) 9.Any patient unable or unwilling to participate in all study-related activities |
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate the safety, tolerability and efficacy of AFQ056 in patients with PD-LID as assessed by •Incidence and severity of adverse events and serious adverse events •Changes in vital signs, laboratory assessments, and ECGs •Changes in cognitive function as measured by the MMSE •Changes in psychiatric symptoms as measured by the SCOPA-PC •Changes in underlying symptoms of PD as measured by the UPDRS part III, by the PD symptom items in the Clinical Global Impression of Change (CGIC) and Patient Global Impression of Change (PGIC), and by AEs potentially related to an exacerbation of the movement disorder of PD •Occurrence of rebound symptoms upon discontinuation of study drug |
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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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 | Information not present in EudraCT |
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 |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |