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Evaluation of the Efficacy and Safety of Modified Release AFQ056 in Parkinson's Patients With L-dopa Induced Dyskinesias

15. prosince 2020 aktualizováno: Novartis Pharmaceuticals

13-week, Double-blind, Placebo-controlled, Fixed-dose, Multicenter Study to Evaluate the Efficacy and Safety of Modified Release AFQ056 in Reducing Moderate to Severe L-dopa Induced Dyskinesias in Patients With Parkinson's Disease

This study will assess the efficacy and safety of modified release AFQ056 in patients that have Parkinson's Disease L-dopa Induced Dyskinesias (PD-LID)

Přehled studie

Postavení

Dokončeno

Podmínky

Intervence / Léčba

Typ studie

Intervenční

Zápis (Aktuální)

154

Fáze

  • Fáze 2

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní místa

  • Francie
      • Clermont-Ferrand Cedex 1, Francie, 63003
        • Novartis Investigative Site
      • Lille Cedex, Francie, 59037
        • Novartis Investigative Site
      • Pessac, Francie, 33604
        • Novartis Investigative Site
      • Poitiers, Francie, 86021
        • Novartis Investigative Site
  • Itálie
    • BS
      • Brescia, BS, Itálie, 25123
        • Novartis Investigative Site
    • BZ
      • Bolzano, BZ, Itálie, 39100
        • Novartis Investigative Site
    • PI
      • Pisa, PI, Itálie, 56126
        • Novartis Investigative Site
    • RM
      • Roma, RM, Itálie, 00163
        • Novartis Investigative Site
      • Roma, RM, Itálie, 00179
        • Novartis Investigative Site
  • Kanada
    • Ontario
      • London, Ontario, Kanada, N6A 5A5
        • Novartis Investigative Site
  • Maďarsko
      • Budapest, Maďarsko, 1085
        • Novartis Investigative Site
      • Kaposvár, Maďarsko, 7400
        • Novartis Investigative Site
      • Szeged, Maďarsko, H-6725
        • Novartis Investigative Site
  • Německo
      • Beelitz-Heilstaetten, Německo, 14547
        • Novartis Investigative Site
      • Berlin, Německo, 12163
        • Novartis Investigative Site
      • Bochum, Německo, 44791
        • Novartis Investigative Site
      • Duesseldorf, Německo, 40225
        • Novartis Investigative Site
      • Kassel, Německo, 34128
        • Novartis Investigative Site
      • Leipzig, Německo, 04103
        • Novartis Investigative Site
      • Muenchen, Německo, 80804
        • Novartis Investigative Site
      • München, Německo, 81675
        • Novartis Investigative Site
      • Stadtroda, Německo, 07646
        • Novartis Investigative Site
  • Rakousko
      • Innsbruck, Rakousko, A-6020
        • Novartis Investigative Site
      • Linz, Rakousko, A-4020
        • Novartis Investigative Site
      • Vienna, Rakousko, A-1220
        • Novartis Investigative Site
  • Slovensko
      • Bratislava, Slovensko, 82606
        • Novartis Investigative Site
      • Bratislava, Slovensko, 83305
        • Novartis Investigative Site
  • Spojené státy
    • California
      • Sunnyvale, California, Spojené státy, 94089
        • Novartis Investigative Site
    • Colorado
      • Englewood, Colorado, Spojené státy, 80113
        • Novartis Investigative Site
    • Florida
      • Tampa, Florida, Spojené státy, 33612
        • Novartis Investigative Site
    • Kansas
      • Kansas City, Kansas, Spojené státy, 66160
        • Novartis Investigative Site
    • Wisconsin
      • Milwaukee, Wisconsin, Spojené státy, 53233
        • Novartis Investigative Site
  • Španělsko
      • Madrid, Španělsko, 28006
        • Novartis Investigative Site
    • Cataluña
      • Barcelona, Cataluña, Španělsko, 08025
        • Novartis Investigative Site
      • Barcelona, Cataluña, Španělsko, 08036
        • Novartis Investigative Site
      • Sant Cugat, Cataluña, Španělsko, 08190
        • Novartis Investigative Site
    • Pais Vasco
      • San Sebastian, Pais Vasco, Španělsko, 20014
        • Novartis Investigative Site
  • Švýcarsko
      • Bern, Švýcarsko, 3010
        • Novartis Investigative Site
      • Lausanne, Švýcarsko, 1011
        • Novartis Investigative Site

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

30 let až 80 let (Dospělý, Starší dospělý)

Přijímá zdravé dobrovolníky

Ne

Pohlaví způsobilá ke studiu

Všechno

Popis

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
  • Group 2 only: Patients must be on a stable and well tolerated dose of amantadine for at least 4 weeks prior to BL1 and must maintain the stable dose of amantadine during the remainder of the study

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
  • Amantadine within 2 weeks prior to BL1 visit (applies to Group 1 only)

Other protocol-defined inclusion/exclusion criteria may apply.

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Přidělení: Randomizované
  • Intervenční model: Paralelní přiřazení
  • Maskování: Čtyřnásobek

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: AFQ056 150 mg
Patients randomized to the AFQ056 150 mg arm will receive AFQ056 oral tablets to be titrated until reaching the target dose of 150 mg twice daily.
Lék: AFQ056

AFQ056 will be supplied as oral modified release tablets in 25 mg, 50 mg, 100 mg, 150 mg, and 200 mg.

Patients will be randomized in two groups by amantadine status.

  • Group 1: Patients are not permitted to take amantadine within 2 weeks prior to the BL1 visit.
  • Group 2: Patients must be on a stable and well tolerated dose of amantadine for at least 4 weeks prior to BL1 and must maintain the stable dose of amantadine during the remainder of the study.)
Experimentální: AFQ056 200 mg

Patients randomized to the AFQ056 200 mg arm will receive AFQ056 oral tablets to be titrated until reaching the target dose of 200 mg twice daily.

Patients will be randomized in two groups by amantadine status.

  • Group 1: Patients are not permitted to take amantadine within 2 weeks prior to the BL1 visit.
  • Group 2: Patients must be on a stable and well tolerated dose of amantadine for at least 4 weeks prior to BL1 and must maintain the stable dose of amantadine during the remainder of the study.)
Lék: AFQ056

AFQ056 will be supplied as oral modified release tablets in 25 mg, 50 mg, 100 mg, 150 mg, and 200 mg.

Patients will be randomized in two groups by amantadine status.

  • Group 1: Patients are not permitted to take amantadine within 2 weeks prior to the BL1 visit.
  • Group 2: Patients must be on a stable and well tolerated dose of amantadine for at least 4 weeks prior to BL1 and must maintain the stable dose of amantadine during the remainder of the study.)
Komparátor placeba: Placebo
Patients randomized to the Placebo arm will receive oral AFQ056 Placebo twice daily
Lék: Placebo
Placebo for AFQ056 will be supplied as oral tablets.

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Change in modified AIMS (Abnormal Involuntary Movement Scale) total score from baseline to Week 12
Časové okno: 12 weeks

The modified AIMS is a scale used to assess dyskinesia. It focuses on six different parts of the body and rates abnormal movements from 0 (absence of dyskinesia to 4 (severe) (maximal score, 24).

Change from baseline to Week 12 will be analyzed using the mixed effect repeated measures model (MMRM) including treatment, pooled center, week, treatment by week interaction as fixed effects and baseline total score as covariate with an unstructured covariance structure.
12 weeks
The incidence rate of adverse events
Časové okno: Monitored for the duration of the study which is 13 weeks

The occurrence of adverse events would be sought by non-directive questioning of the patient. Adverse events may also be detected when they are volunteered by the patient or through physical examination, laboratory test, or other assessments.

AEs will be summarized by presenting, for each treatment group the number and percentage of patients having any adverse event, having an adverse event in each system organ class and having each individual adverse event by system organ class and preferred term.
Monitored for the duration of the study which is 13 weeks
Time to onset of adverse events
Časové okno: Monitored for the duration of the study which is 13 weeks

The occurrence of adverse events (AEs) would be sought by non-directive questioning of the patient. Adverse events may also be detected when they are volunteered by the patient or through physical examination, laboratory test, or other assessments.

AEs will be summarized by presenting, for each treatment group the number and percentage of patients having any adverse event, having an adverse event in each system organ class and having each individual adverse event by system organ class and preferred term.
Monitored for the duration of the study which is 13 weeks
The percentage of patients reaching and maintaining the target dose during the fixed dose treatment period
Časové okno: Assessed during the fixed dose treatment period of 6 weeks

Randomized patients will be up titrated to the target dose and remain on the target dose for the duration of the fixed dose treatment period.

AEs will be summarized by presenting, for each treatment group the number and percentage of patients having any adverse event, having an adverse event in each system organ class and having each individual adverse event by system organ class and preferred term.
Assessed during the fixed dose treatment period of 6 weeks
The percentage of patients discontinued during the up titration period due to AE
Časové okno: Assessed during the up titration period of 6 weeks

Patients randomized will be up titrated to the target doses at regular intervals during the up titration period.

AEs will be summarized by presenting, for each treatment group the number and percentage of patients having any adverse event, having an adverse event in each system organ class and having each individual adverse event by system organ class and preferred term.
Assessed during the up titration period of 6 weeks

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
The change in total score and sub-score of UDysRS Parts I, II, III, and IV from baseline to Week 12
Časové okno: 12 weeks

The UDysRS captures dyskinesia and has 4 parts: I: Historical Disability of On-Dyskinesia impact (max 44 pts); II: Historical Disability of Off-Dystonia impact (max 16 pts); III: Objective Impairment dyskinesia (max 28 pts); IV: Objective Disability based on Part III activities (max 16 pts). Higher scores mean greater severity.

Change from baseline to Week 12 will be analyzed using mixed-effect repeated measure model (MMRM) including treatment, pooled center, week, treatment by week interaction as fixed effects and baseline total score as covariate with an unstructured covariance structure.
12 weeks
Change in Lang-Fahn Activities of Daily Living Dyskinesia Scale (LFADLDS) total score from baseline to Week 12
Časové okno: 12 weeks

The LFADLDS assesses the degree of dyskinesia interfering with activities of daily living. Specific definitions for severity rating codes (range, 0-4 for each task) will be provided for reproducibility of results. A higher score indicates more severe impairment. A patient and caregiver version of the revised LFADLDS will be used in this study.

Change from baseline to Week 12 will be analyzed using MMRM including treatment, pooled center, week, treatment by week interaction as fixed effects and baseline total score as covariate with an unstructured covariance structure.
12 weeks
Change in clinician-rated global impression of change (CGIC) score from baseline to Week 12
Časové okno: 12 weeks

The CGIC provides investigator-rated assessment of change from baseline to assess disability due to dyskinesia. Change from baseline will be rated on a 7-point, Likert-type scale where 1 = markedly improved, 2 = moderately improved, 3 = minimally improved, 4 = unchanged, 5 = minimally worse, 6 = moderately worse, and 7 = markedly worse.

The CGIC score at week 12 last observation carried forward (LOCF) will be analyzed using analysis of covariance (ANCOVA) model with treatment group, pooled center, and baseline CGIS (Clinical Global Impression of Severity) score as factors.
12 weeks
Change from baseline Total ON- and OFF-times and ON-time with dyskinesia and with troublesome dyskinesias (patient diary) to Week 12
Časové okno: 12 weeks

A patient home diary developed and validated for use in PD patients will be used to record whether the patient is asleep, OFF, ON without dyskinesia, ON with troublesome dyskinesias, and ON with non-troublesome dyskinesia.

Change from baseline to Week 12 will be analyzed using MMRM including treatment, pooled center, week, treatment by week interaction as fixed effects and baseline total score as covariate with an unstructured covariance structure.
12 weeks
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
Časové okno: 12 weeks

UPDRS assesses the disease state of PD. Question 32 assesses length of dyskinesias in percentage of the day. Question 33 assesses disability during the previous week (not disabling, mildly disabling, moderately disabling, severely disabling, completely disabling). Question 34 assesses painfulness of dyskinesias from 0 (no painful dyskinesias) to 4 (marked).

The change will be analyzed using MMRM including treatment, pooled center, week, treatment by week interaction as fixed effects and baseline total score as covariate with an unstructured covariance structure.
12 weeks
Changes in vital signs from baseline to each post-baseline visit
Časové okno: Monitored at regular visits throughout duration of the study which is 13 weeks
Pulse and blood pressures are taken at each visit. Vital sign data will be summarized by presenting summary statistics for change from baseline values. The incidence rates of clinically notable vital sign abnormalities will be summarized.
Monitored at regular visits throughout duration of the study which is 13 weeks
Changes in hematology/blood chemistry and urinalysis laboratory evaluations from baseline to each post-baseline visit where hematology/blood chemistry and urinalysis are collected
Časové okno: Monitored at regular visits throughout duration of the study which is 13 weeks
Standard hematology with differential; measures of coagulability: aPTT, PT/INR; standard clinical chemistry; FSH, LH, oxytocin, prolactin, TBG, TSH, and T4; urinalysis (specific gravity, protein, glucose and blood) Laboratory data will be summarized by presenting shift tables, by presenting summary statistics, change from baseline values, and incidence rates of clinically notable abnormalities summarized.
Monitored at regular visits throughout duration of the study which is 13 weeks
Changes in electrocardiogram (ECG) from baseline to each post-baseline visit where ECGs are performed
Časové okno: Monitored at regular visits throughout duration of the study which is 13 weeks

A standard 12-lead ECG will be performed. A central facility will be used for interpretation and analysis of the ECGs.

ECG intervals will be summarized by summary statistics for change from baseline values and incidence rates of clinically notable abnormalities summarized.
Monitored at regular visits throughout duration of the study which is 13 weeks
Percentage of adverse events including treatment emergent adverse events and serious adverse events
Časové okno: Monitored for the duration of the study which is 13 weeks

The occurrence of adverse events would be sought by non-directive questioning of the patient. Adverse events may be detected when they are volunteered by the patient or through physical examination, laboratory test, or other assessments.

Treatment-emergent adverse events (TEAEs) will be summarized by presenting, for each treatment group, the number and percentage of patients having an AE, having an AE in each system organ class and having each AE by system organ class and preferred term.
Monitored for the duration of the study which is 13 weeks
Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III (Motor Examination) scores from baseline to Week 12
Časové okno: 12 weeks

Part III of the UPDRS (items 18-31; score 0-56), measures speech, facial expression, tremor, action or postural tremor, rigidity, finger taps, hand movement, alternating movement, leg agility, arising from a chair, posture, gait, postural stability, and bradykinesia. A higher score means worsening of symptoms.

Changes from baseline to Week 12 will be analyzed using MMRM including treatment, pooled center, week, treatment by week interaction as fixed effects and baseline total score as covariate with an unstructured covariance structure.
12 weeks
Change in Mini Mental State Exam (MMSE) total scores from baseline to Week 12
Časové okno: 12 weeks

The MMSE is a test of cognitive dysfunction consisting of orientation, registration, attention-calculation, recall, and language administered by a health care professional. The MMSE results in total possible score of 30, with higher scores meaning better function.

The change from baseline to endpoint at Week 12 in MMSE total score will be analyzed using LOCF ANCOVA with treatment group and pooled center as factors and the baseline score as a covariate. Treatment differences in the change from baseline for scores with 90% CI will be reported as descriptive statistics.
12 weeks
Change in cognitive test battery (CogState) scores form baseline to Week 12
Časové okno: 12 weeks

This test consists of: Detection Task, Identification Task, One Card Learning Task, One Back Task, and International Shopping List Task. Speed times and working memory will be measured by the number of correct responses.

The change from baseline to endpoint at Week 12 for cognitive function will be analyzed using LOCF ANCOVA with treatment group and pooled center as factors and the baseline score as a covariate. Treatment differences in the change from baseline for cognitive function with 90% CI will be reported as descriptive statistics
12 weeks
Total scores of the Scales for Outcomes in Parkinson's disease - Psychiatric Complications (SCOPA-PC)
Časové okno: Assessed for 12 weeks

The SCOPA-PC is an easily administered semi-structured, questionnaire developed for the assessment of psychiatric symptoms in Parkinson's disease patients administered by a clinician with input provided by patient and caregiver. The total SCOPA score ranges from 0-21, with higher scores reflecting more psychiatric complications.

The SCOPA-PC total score and each of the item scores will be summarized.
Assessed for 12 weeks
Proportion of patients who have suicidal ideation and behavior as mapped to Columbia Classification Algorithm for Suicide assessment (C-CASA) using data from Columbia-Suicide Severity Rating Scale (C-SSRS)
Časové okno: This will be assessed for the duration of the study which is 13 weeks

The C-SSRS assesses suicidal ideation/behavior using a patient interview. The data is mapped to Columbia Classification Algorithm for Suicide assessment. The code and categories are: completed suicide, suicide attempt, preparatory actions toward imminent suicide behavior, suicidal ideation, self-injurious behavior without suicidal intent.

The proportion of patients who are coded in the categories above, the proportion of patients with any suicidal behavior engaged in during the study, and the proportion of patients with suicidality will be summarized.
This will be assessed for the duration of the study which is 13 weeks
Plasma Pharmacokinetics of AFQ056 in patients with Parkinson's disease with moderate to severe dyskinesias
Časové okno: At Week 12 or earlier if the patient discontinues the study before Week 12

Blood samples will be taken by either direct venipuncture or an indwelling cannula inserted in a forearm vein. The first blood sample will be collected 1-3 hours after morning study medication dose. The second sample will be collected 3-5 hours after the morning study medication dose. The third blood sample will be collected 5-7 hours after the morning study medication dose.

Summary statistics for concentrations per sampling window will be provided and average plasma levels will be calculated.
At Week 12 or earlier if the patient discontinues the study before Week 12
Pharmacokinetics of AFQ056 in patients with Parkinson's disease with moderate to severe dyskinesias
Časové okno: Monitored at regular visits throughout duration of the study which is 13 weeks

Blood samples will be taken by either direct venipuncture or an indwelling cannula inserted in a forearm vein. An alternative sampling method will also be explored. At all visits, the sample will be collected 1-3 hours after morning study medication dose. At Week 12, the second sample will be collected 3-5 hours after the morning study medication dose and the third sample will be collected 5-7 hours after the morning study medication dose.

Summary statistics for concentrations per sampling window will be provided and average plasma levels will be calculated.
Monitored at regular visits throughout duration of the study which is 13 weeks
Investigate the safety of concomitant administration of AFQ056 with amantadine
Časové okno: 12 weeks
Investigation of the safety of AFQ056 with concomitant amantadine is being studied to gather drug-drug interaction data of amantadine and AFQ056 in this patient population.
12 weeks

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

Novartis Pharmaceuticals

Publikace a užitečné odkazy

Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.

Obecné publikace

Užitečné odkazy

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia

1. dubna 2012

Primární dokončení (Aktuální)

1. dubna 2013

Dokončení studie (Aktuální)

1. dubna 2013

Termíny zápisu do studia

První předloženo

12. prosince 2011

První předloženo, které splnilo kritéria kontroly kvality

12. prosince 2011

První zveřejněno (Odhad)

14. prosince 2011

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

23. prosince 2020

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

15. prosince 2020

Naposledy ověřeno

1. března 2016

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

Další identifikační čísla studie

  • CAFQ056A2223
  • 2011-002074-23 (Číslo EudraCT)

Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .

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