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

2020年12月15日 更新者：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)

調査の概要

状態

完了

条件

介入・治療

研究の種類

介入

入学 (実際)

154

段階

  • フェーズ2

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究場所

  • アメリカ
    • California
      • Sunnyvale、California、アメリカ、94089
        • Novartis Investigative Site
    • Colorado
      • Englewood、Colorado、アメリカ、80113
        • Novartis Investigative Site
    • Florida
      • Tampa、Florida、アメリカ、33612
        • Novartis Investigative Site
    • Kansas
      • Kansas City、Kansas、アメリカ、66160
        • Novartis Investigative Site
    • Wisconsin
      • Milwaukee、Wisconsin、アメリカ、53233
        • Novartis Investigative Site
  • イタリア
    • BS
      • Brescia、BS、イタリア、25123
        • Novartis Investigative Site
    • BZ
      • Bolzano、BZ、イタリア、39100
        • Novartis Investigative Site
    • PI
      • Pisa、PI、イタリア、56126
        • Novartis Investigative Site
    • RM
      • Roma、RM、イタリア、00163
        • Novartis Investigative Site
      • Roma、RM、イタリア、00179
        • Novartis Investigative Site
  • オーストリア
      • Innsbruck、オーストリア、A-6020
        • Novartis Investigative Site
      • Linz、オーストリア、A-4020
        • Novartis Investigative Site
      • Vienna、オーストリア、A-1220
        • Novartis Investigative Site
  • カナダ
    • Ontario
      • London、Ontario、カナダ、N6A 5A5
        • Novartis Investigative Site
  • スイス
      • Bern、スイス、3010
        • Novartis Investigative Site
      • Lausanne、スイス、1011
        • Novartis Investigative Site
  • スペイン
      • Madrid、スペイン、28006
        • Novartis Investigative Site
    • Cataluña
      • Barcelona、Cataluña、スペイン、08025
        • Novartis Investigative Site
      • Barcelona、Cataluña、スペイン、08036
        • Novartis Investigative Site
      • Sant Cugat、Cataluña、スペイン、08190
        • Novartis Investigative Site
    • Pais Vasco
      • San Sebastian、Pais Vasco、スペイン、20014
        • Novartis Investigative Site
  • スロバキア
      • Bratislava、スロバキア、82606
        • Novartis Investigative Site
      • Bratislava、スロバキア、83305
        • Novartis Investigative Site
  • ドイツ
      • Beelitz-Heilstaetten、ドイツ、14547
        • Novartis Investigative Site
      • Berlin、ドイツ、12163
        • Novartis Investigative Site
      • Bochum、ドイツ、44791
        • Novartis Investigative Site
      • Duesseldorf、ドイツ、40225
        • Novartis Investigative Site
      • Kassel、ドイツ、34128
        • Novartis Investigative Site
      • Leipzig、ドイツ、04103
        • Novartis Investigative Site
      • Muenchen、ドイツ、80804
        • Novartis Investigative Site
      • München、ドイツ、81675
        • Novartis Investigative Site
      • Stadtroda、ドイツ、07646
        • Novartis Investigative Site
  • ハンガリー
      • Budapest、ハンガリー、1085
        • Novartis Investigative Site
      • Kaposvár、ハンガリー、7400
        • Novartis Investigative Site
      • Szeged、ハンガリー、H-6725
        • Novartis Investigative Site
  • フランス
      • Clermont-Ferrand Cedex 1、フランス、63003
        • Novartis Investigative Site
      • Lille Cedex、フランス、59037
        • Novartis Investigative Site
      • Pessac、フランス、33604
        • Novartis Investigative Site
      • Poitiers、フランス、86021
        • Novartis Investigative Site

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

30年～80年 (大人、高齢者)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

説明

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.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：処理
  • 割り当て：ランダム化
  • 介入モデル：並列代入
  • マスキング：4倍

武器と介入

参加者グループ / アーム
介入・治療
実験的：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.
薬：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.)
実験的：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.)
薬：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.)
プラセボコンパレーター：Placebo
Patients randomized to the Placebo arm will receive oral AFQ056 Placebo twice daily
薬：Placebo
Placebo for AFQ056 will be supplied as oral tablets.

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Change in modified AIMS (Abnormal Involuntary Movement Scale) total score from baseline to Week 12
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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

二次結果の測定

結果測定
メジャーの説明
時間枠
The change in total score and sub-score of UDysRS Parts I, II, III, and IV from baseline to Week 12
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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)
時間枠：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)
時間枠：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
時間枠：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
時間枠：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
時間枠：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

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

Novartis Pharmaceuticals

出版物と役立つリンク

研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。

一般刊行物

便利なリンク

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始

2012年4月1日

一次修了 (実際)

2013年4月1日

研究の完了 (実際)

2013年4月1日

試験登録日

最初に提出

2011年12月12日

QC基準を満たした最初の提出物

2011年12月12日

最初の投稿 (見積もり)

2011年12月14日

学習記録の更新

投稿された最後の更新 (実際)

2020年12月23日

QC基準を満たした最後の更新が送信されました

2020年12月15日

最終確認日

2016年3月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

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

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

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