| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| L-dopa induced dyskinesias in patients with Parkinson's disease |
| discinesie indotte da L-dopa in pazienti affetti da malattia di Parkinson |
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| E.1.1.1 | Medical condition in easily understood language |
| Parkinson's Patients with L-dopa induced dyskinesias |
| Pazienti con Parkinson con discinesie daL-dopa |
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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 | 14.1 |
| E.1.2 | Level | HLT |
| E.1.2 | Classification code | 10013929 |
| E.1.2 | Term | Dyskinesias and movement disorders NEC |
| 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 assess how titration of modified release AFQ056 at 2-week intervals to a target dose of 200 mg b.i.d. or 150 mg b.i.d. versus placebo affects the tolerability profile in patients with moderate to severe PD-LID. To demonstrate the anti-dyskinetic efficacy, as measured by change from baseline to Week 12 in the modified AIMS (Abnormal Involuntary Movement Scale) total score, of titration of modified release AFQ056 at 2-week intervals to a target dose of 200 mg b.i.d. or 150 mg b.i.d. versus placebo in patients with moderate to severe PD-LID. |
| • Valutare come AFQ056 nella formulazione a rilascio modificato, somministrato con dose incrementale ad intervalli di due settimane fino a raggiungere il dosaggio finale di di 200 mg b.i.d. o 150 mg b.i.d, influenza il profilo di tollerabilità in pazienti con PD-LID di grado da moderato a severo rispetto a placebo. • Dimostrare l’efficacia anti-discinetica, misurata come modificazione del punteggio totale della scala AISM (Abnormal Involuntary Movement Scale) alla settimana 12 rispetto al basale, di AFQ056 somministrato con dose incrementale ad intervalli di due settimane fino a raggiungere il dosaggio finale di 200 mg b.i.d. o 150 mg b.i.d 100 mg b.i.d rispetto a placebo in pazienti con PD-LID di grado da moderato a severo. |
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| E.2.2 | Secondary objectives of the trial |
| To assess the anti-dyskinetic efficacy as measured by the UDysRS (Unified Dyskinesia Rating Scale), parts I-IV To assess the anti-dyskinetic efficacy as measured by the Revised Lang- Fahn Activities of Daily Living Dyskinesia Scale (LFADLDS) patient and caregiver versions To evaluate change from baseline on patient's disability caused by the dyskinesia as assessed by a clinician-rated global impression of change (CGIC) To evaluate the Total ON- and OFF-times and ON-time with dyskinesia and with troublesome dyskinesias (patient diary) To evaluate anti-dyskinetic efficacy as measured by items 32, 33 and 34 of Part IV of the UPDRS (Unified Parkinson's Disease Rating Scale) To evaluate the safety of AFQ056 as measured by changes in vital signs, laboratory values and ECGs and percentages of treatment-emergent adverse events and serious adverse events Pls see protocol |
| • Valutare l’efficacia anti-discinetica sulla base della scala UDysRS (Unified Dyskinesia Rating Scale), parti I-IV • Valutare l’efficacia anti-discinetica sulla base della scala LFADLDS (Revised Lang-Fahn Activities of Daily Living Dyskinesia Scale) compilata dal paziente e dalla persona incaricata alla cura dello stesso • Valutare il cambiamento rispetto al basale della disabilità legata alla discinesia del paziente sulla base dell’impressione globale della variazione stimata dal clinico (CGIC) • Valutare i periodi ON e OFF totali e il periodo ON con discinesie o discinesie complicate (diario del paziente) • Valutare l’efficacia anti-discinetica sulla base dei parametri 32, 33 e 34 della sezione IV della scala UPDRS (Unified Parkinson’s Disease Rating Scale) • Per favore vedere sinossi |
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| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
PHARMACOGENETIC:
Vers:orig. prot
Date:2011/12/05
Title:Pharmacogenetics
Objectives:identify persons who will have fewer side effects in order to maximize their benefit from AFQ056.
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FARMACOGENETICA:
Vers:orig. prot
Data:2011/12/05
Titolo:Farmacogenetica
Obiettivi:identificare le persone che manifesteranno il minor numero di effetti collaterali al fine di massimizzare il beneficio che trarranno da AFQ056
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| E.3 | Principal inclusion criteria |
| - Males and Females 30-80 years old - Use of highly effective methods of contraception during study in women of childbearing potential - Outpatients - Clinical diagnosis of Parkinson's Disease according to UK Parkinson's Disease Society Brain Bank Clinical Diagnosis criteria - Score of >/= 2 on UPDRS items 32 and 33 -Dyskinesias for at least 3 months before baseline -On stable treatment regimen with L-dopa and other anti-parkinsonian treatment for 4 weeks prior to baseline - Demonstrate capacity to complete accurate diary ratings - Patients who have a primary caregiver willing to assess the condition of the patient throughout the study in accordance with protocol requirements |
| • Uomini e donne di età 30-80 anni (estremi inclusi) • Le donne in grado di avere figli dovranno utilizzare metodi contraccettivi altamente efficaci durante il periodo di somministrazione del trattamento e per 96 ore dopo l’interruzione del trattamento in studio • Pazienti ambulatoriali • Diagnosi clinica di malattia di Parkinson secondo i criteri diagnostici clinici della Parkinson’s Disease Society Brain Bank del Regno Unito • Punteggio ≥ 2 all’item 32 della UPDRS e punteggio ≥ 2 all’item 33 della UPDRS • Discinesie da almeno 3 mesi prima della BL1 • Pazienti in trattamento stabile con L-dopa e altro trattamento anti-Parkinson (da almeno 4 settimane prima della BL1) • Pazienti che mostrano la capacità di compilare le valutazioni del diario in modo accurato |
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| E.4 | Principal exclusion criteria |
| Atypical/secondary form of Parkinson's disease - History of surgical treatment of PD, including deep brain stimulation - A score of 5 in the ''ON''- state on the Modified Hoehn and Yahr scale - Advanced, severe, or unstable disease other than PD - Evidence of dementia - Treatment with certain prohibited medications Other protocol-defined inclusion/exclusion criteria may apply. E.5 |
| • Malattia di Parkinson di forma atipica o secondaria • Storia di trattamento chirurgico per la PD, compresa la stimolazione cerebrale profonda • Punteggio 5 nello stato ON secondo la scala Modified Hoehn and Yahr • Qualsiasi patologia (diversa dalla PD) avanzata, severa o instabile • Evidenza di demenza (o MMSE [Mini-Mental State Exam] ≤ 26), disordine depressivo maggiore o pazienti che attualmente manifestano allucinazioni/psicosi che richiedono trattamento antipsicotico e/o stati confusionali (DSM-IVR, Diagnostic and Statistical Manual of Mental Disorders, 4° edizione, revisionata) PER FAVORE VEDERE SINOSSI |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| - Change in modified AIMS (Abnormal Involuntary Movement Scale) total score from baseline to Week 12 - incidence rate of adverse events - time to onset of adverse events - The percentage of patients reaching and maintaining the target dose during the fixed dose treatment period -The percentage of patients discontinued during the up titration period due to AE |
| • mAIMS - La variabile primaria di efficacia è la variazione rispetto al basale alla Settimana 12 dul punteggio totale della scala AIMS modificata. • incidenza degli eventi avversi • Percentuale di pazienti che raggiungono e mantengono il dosaggio finale stabilito durante il periodo di trattamento a dose fissa • Percentuale di pazienti che interrompono il trattamento per evento avverso |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| -Change of AIMS (timeframe 12 weeks): (week -6 to -3; -2; 0; 6; 12; 13) - Monitored for the duration of the study which is 13 weeks - Monitored for the duration of the study which is 13 weeks - Assessed during the fixed dose treatment period of 6 weeks - Assessed during the up titration period of 6 weeks |
| Modifica della AIMS (La variabile primaria di efficacia è la variazione rispetto al basale alla Settimana 12 dul punteggio totale della scala AIMS modificata): (sett -6 a -3; -2; 0; 6; 12; 13) - Controllo per la durata dello studio che è di 13 settimane - Controllo per la durata dello studio che è di 13 settimane - Valutato durante il periodo di trattamento della dose fissa di 6 settimane - Valutato durante il periodo di ''tritation''(incremento del dosaggio) di 6 settimane |
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| E.5.2 | Secondary end point(s) |
| The change in total score and sub-score of UDysRS Parts I, II, III, and IV from baseline to Week 12 Change in Lang-Fahn Activities of Daily Living Dyskinesia Scale (LFADLDS) total score from baseline to Week 12 Change in clinician-rated global impression of change (CGIC) score from baseline to Week 12 Change from baseline Total ON- and OFF-times and ON-time with dyskinesia and with troublesome dyskinesias (patient diary) to Week 12 Change in score for items 32, 33 and 34 of Part IV of the Unified Parkinson's Disease Rating Scale (UPDRS ) from baseline to Week 12 other secondary objectives may be defined in the protocol |
| • Cambiamenti nella scala UDysRS (Unified Dyskinesia Rating Scale), parti I – IV dal Baseline alla settimana 12 • Cambiamenti nella LFADLDS punteggio totale dal baseline alla settimana 12. • Cambiamenti nella Clinician Global Impression of Change (CGIC)....per favore vedere sinossi |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| The change in total score and sub-score of UDysRS Parts I, II, III, and IV from baseline to Week 12 (week 0; 8; 12) Change in Lang-Fahn Activities of Daily Living Dyskinesia Scale (LFADLDS) total score from baseline to Week 12 (week -2; 0;6; 8; 12) Change in clinician-rated global impression of change (CGIC) score from baseline to Week 12 (week 0; 6; 8; 12) Change from baseline Total ON- and OFF-times and ON-time with dyskinesia and with troublesome dyskinesias (patient diary) to Week 12 (week 0; 6; 8; 12) Change in score for items 32, 33 and 34 of Part IV of the Unified Parkinson's Disease Rating Scale (UPDRS ) from baseline to Week 12(week -6 to -3; -2; 0; 8; 12; 13) |
| Cambiamenti nel total score della UDysRS Parti I, II, III, e IV dal Baseline alla Settimana 12 (sett 0; 8; 12) Cambiamenti nella ''Lang-Fahn Activities of Daily Living Dyskinesia Scale'' (LFADLDS) total score dal baseline alla settimana 12 (sett -2; 0;6; 8; 12) Cambiamenti nella clinician-rated global impression of change (CGIC) score dal baseline alla Settimana 12 (sett 0; 6; 8; 12) Cambiamenti dal baseline Total ON- e OFF-times e ON-time con discinesie sett 0; 6; 8; 12) Cambiamenti nello score per gli items 32, 33 e 34 della Part IV del ''Unified Parkinson's Disease Rating Scale'' (UPDRS ) dal baseline alla Settimana 12(sett -6 a -3; -2; 0; 8; 12; 13 |
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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 | 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.8.2.4 | 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 31 |
| 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 |
| Canada |
| Switzerland |
| Turkey |
| United States |
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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 | 0 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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