E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
L-dopa induced dyskinesias in Parkinson's patients |
pazienti con malattia di Parkinson con discinesie indotte dalla L-dopa |
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E.1.1.1 | Medical condition in easily understood language |
dyskinesias (Abnormal Involuntary Movement) in Parkinson's patients |
pazienti con malattia di Parkinson con discinesie (Movimento involontario anormale) |
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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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10013113 |
E.1.2 | Term | Disease Parkinson's |
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 the anti-dyskinetic efficacy of multiple doses of AQW051 in Parkinson's patients with moderate to severe L-dopa induced dyskinesias using the modified Abnormal Involuntary Movement Scale (mAIMS). • To assess the anti-parkinsonian effect of multiple doses of AQW051 in combination with L-dopa in Parkinson's patients with moderate to severe L-dopa induced dyskinesias using the Unified Parkinson's Disease Rating Scale (UPDRS) – part III. • To assess the safety and tolerability of multiple doses of AQW051 in combination with Ldopa in Parkinson's patients with moderate to severe L-dopa induced dyskinesias. |
Valutare l’efficacia anti-discinetica di dosi multiple di AQW051 in pazienti affetti da malattia di Parkinson con discinesie indotte da L-dopa da moderate a severe utilizzando la scala modified Abnormal Involuntary Movement Scale (mAIMS). Valutare l’effetto anti-parkinsoniano di dosi multiple di AQW051 in combinazione con L-dopa in pazienti affetti da malattia di Parkinson con discinesie indotte da L-dopa da moderate a severe utilizzando la scala Unified Parkinson’s Disease Rating Scale (UPDRS) – parte III. Valutare la sicurezza e tollerabilita' di dosi multiple di AWQ051 in combinazione con L-dopa in pazienti affetti da malattia di Parkinson con discinesie indotte da L-dopa da moderate a severe |
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E.2.2 | Secondary objectives of the trial |
• To assess the anti-dyskinetic efficacy of multiple doses of AQW051 in Parkinson's patients with moderate to severe L-dopa induced dyskinesias using the Lang-Fahn Activities of Daily Living Dyskinesia Scale (LFADLDS) and UPDRS(32-33). • To assess the anti-dyskinetic efficacy of multiple doses of AQW051 on Track-PD assessments in Parkinson's patients with moderate to severe L-dopa induced dyskinesias. • To assess the cognitive effects of multiple doses of AQW051 in Parkinson's patients with moderate to severe L-dopa induced dyskinesias. • To measure the pharmacokinetics of multiple doses of AQW051 in Parkinson's patients. |
Valutare l’efficacia anti-discinetica di dosi multiple di AQW051 in pazienti affetti da malattia di Parkinson con discinesie indotte da L-dopa da moderate a severe utilizzando le scale Lang-Fahn Activities of Daily Living Dyskinesia Scale (LFADLDS) e UPDRS. Valutare l’efficacia anti-discinetica di dosi multiple di AQW051 sulle valutazioni Track-PD in pazienti affetti da malattia di Parkinson con discinesie indotte da L-dopa da moderate a severe.Valutare gli effetti sulle funzioni cognitive di dosi multiple di AQW051 in pazienti affetti da Parkinson con discinesie indotte da L-dopa da moderate a severe. Misurare la farmacocinetica di dosi multiple di AQW051 in pazienti affetti da malattia di Parkinson. |
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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:02
Date:2011/11/21
Title:N.A.
Objectives:Pharmacogenetics Exploratory pharmacogenetics research studies are planned as a part of this study
PHARMACOGENOMIC:
Vers:02
Date:2011/11/21
Title:N.A.
Objectives:Exploratory pharmacogenomics research studies are planned as a part of this study
PHARMACOKINETIC/PHARMACODYNAMIC:
Vers:02
Date:2011/11/21
Title:N.A.
Objectives:Pharmacokinetics Plasma samples will be obtained to determine AQW051 pharmacokinetics. Leftover samples may be used for analyses relating to metabolites of AQW051. See Sample log tables (Appendix 1-Section 13).
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FARMACOGENETICA:
Vers:02
Data:2011/11/21
Titolo:(N.A.) Anche se il protocollo non prevede sottostudi formalmente definiti (ovvero strutturati con un protocollo specifico) ma indagini complementari opzionali, le stesse vengono classificate come sottostudi. Di seguito il dettaglio: • Indagine sui marcatori biologici (farmacogenetica, farmacogenomica e indicatori biologici neurodegenerativi e infiammatori nel fluido cerebrospinale), a cui possono partecipare tutti i centri italiani coinvolti nello studio. L’eventuale non accettazione di tale sottostudio o di parte di esso da parte del Comitato Etico e/o da parte del paziente non compromettera' in alcun modo la partecipazione allo studio principale.
Obiettivi:Farmacogenetica Gli studi esplorativi di ricerca in farmacogenetica sono progettati come una parte di questo studio
FARMACOGENOMICA:
Vers:02
Data:2011/11/21
Titolo:N.A.
Obiettivi:Gli studi esplorativi di ricerca in farmacogenenomica sono progettati come una parte di questo studio
FARMACOCINETICA/FARMACODINAMICA:
Vers:02
Data:2011/11/21
Titolo:N.A.
Obiettivi:Farmacocinetica I campioni del plasma saranno ottenuti per determinare la farmacocinetica di AQW051. I campioni rimanenti possono essere utilizzati per le analisi per quanto riguarda i metaboliti di AQW051. Per favore, vedere(Appendice 1-Section 13).
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E.3 | Principal inclusion criteria |
1. Male and female, non-smoking patients between 30 and 85 years of age (both inclusive). 2. Written informed consent must be obtained before any assessment is XML File Identifier: VXYjImYpNkc8H5t03PaNfKGLF34= Page 14/27 performed. 3. Patients with idiopathic Parkinson's disease diagnosed by UK Parkinson's disease Society Brain Bank criteria. 4. Patients 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). 5. Patients with dyskinesias for at least 3 months before randomization. 6. Patients have to be on L-dopa treatment for at least 3 years prior to randomization and the 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 has to be the stable for individual patients). Other concomitant anti-parkinsonian medication (e.g. pramipexole, cabergoline, ropinirole) is allowed but the total daily dose and dosing regimen has to be stable for at least one month prior to randomization. 7. Patients treated with amantadine, antidepressants, and/or benzodiazepines are allowed to enter the study provided that they are on a stable regimen for at least 4 weeks prior to randomization. 8. Other than related to Parkinson's disease, patients must be in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and routine laboratory tests (hematology, biochemistry, urinalysis) at screening and baseline 9. Patients must weigh at least 45 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 - 32 kg/m2. See Appendix 3 of this protocol for BMI ranges. 10. Able to communicate well with the investigator, to understand and comply with the requirements of the study. |
Soggetti di sesso maschile e femminile, con diagnosi di malattia di Parkinson idiopatica, di eta' compresa tra i 30 e gli 85 anni (estremi inclusi) Pazienti con discinesie indotte da L-dopa superiori al 20% e di intensita' da moderata a severa Pazienti con discinesie da almeno 3 mesi prima della randomizzazione Pazienti in trattamento con L-dopa da almeno 3 anni prima della randomizzazione Soggetti con peso corporeo di almeno 45 kg, indice di massa corporea (Body Mass Index – BMI) compreso tra 18 e 32 kg/m2 |
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E.4 | Principal exclusion criteria |
Parkinson's disease related: 1. Patients with a prior surgery for Parkinson's disease (e.g. pallidotomy). 2. Patients with a Hoehn and Yahr score of 5 when 'off'. 3. Patients with atypical Parkinson's disease (Progressive Supranuclear Palsy (PSP), Multi Systemic Atrophy (MSA). 4. Patients who are under deep brain stimulation. 5. Patients with cognitive impairment (MMSE score of less than 24). 6. Patients with a presence of psychosis, confusional states and/or repeated hallucinations. 7. Patients who participated in an anti-dyskinetic clinical study in which drugs were administered within 3 months prior to randomization, or longer if required by local regulations, and any other limit on participation based on local regulations. 8. Patients who received neuroleptics or antipsychotics during 2 months before randomization. General: 9. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 halflives of enrollment, whichever is longer; or longer if required by local regulations, and for any other limitation of participation in an investigational trial based on local regulations. 10. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes. 11. History of seizures. 12. Patients using (or have used within 5 half-lives prior to first treatment with AQW051) concomitant medication that are strong inhibitors of CYP3A4 and CYP1A2 13. A history or presence of clinically significant ECG abnormalities at Screening or Baseline. 14. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. 15. Pregnant or nursing (lactating) women. 16. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use effective contraception during the study. Please see protocol for further details. 17. Smokers (use of tobacco products in the previous 3 months). Urine cotinine levels will be measured during screening and at baseline for all subjects. Smokers will be defined as any subject who reports tobacco use and/or who has a urine cotinine ≥ 500 ng/mL. 18. Donation or loss of 400 ml or more of blood within eight (8) weeks prior to initial dosing, or longer if required by local regulation. 19. Significant illness within two (2) weeks prior to initial dosing. 20. Recent (within the last three [3] years) and/or recurrent history of autonomic dysfunction (e.g., recurrent episodes of fainting, palpitations, etc). 21. Recent (within the last three [3] years) and/or recurrent history of acute or chronic bronchospastic disease (including asthma and chronic obstructive pulmonary disease, treated or not treated). 22. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study. The Investigator should make this determination in consideration of the subject's medical history and/or clinical or laboratory evidence. 23. History or presence of impaired renal function as indicated by clinically significantly abnormal creatinine or BUN and/or urea values, or abnormal urinary constituents (e.g., albuminuria). 24. Evidence of urinary obstruction or difficulty in voiding at screening. 25. History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result. 26. A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result. 27. History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during screening or baseline. |
Precedente intervento chirurgico per malattia di Parkinson o malattia di Parkinson atipica Pazienti con deterioramento cognitivo (MMSE inferiore a 24) Pazienti con presenza di psicosi, stati confusionali e/o allucinazioni ripetute Uso di qualsiasi trattamento anti-discinetico Anamnesi o presenza di anormalita' clinicamente significative dell’ECG allo screening o alla prima visita basale Anamnesi o presenza di patologia maligna di qualsiasi organo Qualsiasi condizione medica o chirurgica che potrebbe alterare in modo significativo l’assorbimento, la distribuzione, il metabolismo o l’escrezione dei farmaci Attuali fumatori Uso di droghe o abuso di alcol attuale o pregresso Per maggiori dettagli consultare i paragrafi 4.1 e 4.2 del protocollo originale. |
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E.5 End points |
E.5.1 | Primary end point(s) |
mAIMs and UPDRS score |
mAIMs e UPDRS punteggio |
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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) |
LFADLDS score |
LFADLDS punteggio |
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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 | No |
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 | Yes |
E.6.10 | Pharmacogenetic | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
- Stesso farmaco ad altro dosaggio |
- same IMP used at different dosage |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 |
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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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Last visit last subject : 15/OCT/2012 |
LVLS : 15/10/2012 |
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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 | 5 |
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 | 13 |
E.8.9.2 | In all countries concerned by the trial days | 0 |