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

Primary Purpose

Dyskinesias, Parkinson Disease, Movement Disorders

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
AFQ056
Placebo
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dyskinesias focused on measuring Parkinson Disease, L-dopa, Levodopa, Dyskinesia, Amantadine

Eligibility Criteria

30 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

AFQ056 150 mg

AFQ056 200 mg

Placebo

Arm Description

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.

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.)

Patients randomized to the Placebo arm will receive oral AFQ056 Placebo twice daily

Outcomes

Primary Outcome Measures

Change in modified AIMS (Abnormal Involuntary Movement Scale) total score from baseline to Week 12
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.
The incidence rate of adverse events
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.
Time to onset of adverse events
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.
The percentage of patients reaching and maintaining the target dose during the fixed dose treatment period
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.
The percentage of patients discontinued during the up titration period due to AE
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.

Secondary Outcome Measures

The change in total score and sub-score of UDysRS Parts I, II, III, and IV from baseline to Week 12
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.
Change in Lang-Fahn Activities of Daily Living Dyskinesia Scale (LFADLDS) total score from baseline to Week 12
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.
Change in clinician-rated global impression of change (CGIC) score from baseline to Week 12
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.
Change from baseline Total ON- and OFF-times and ON-time with dyskinesia and with troublesome dyskinesias (patient diary) to Week 12
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.
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
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.
Changes in vital signs from baseline to each post-baseline visit
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.
Changes in hematology/blood chemistry and urinalysis laboratory evaluations from baseline to each post-baseline visit where hematology/blood chemistry and urinalysis are collected
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.
Changes in electrocardiogram (ECG) from baseline to each post-baseline visit where ECGs are performed
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.
Percentage of adverse events including treatment emergent adverse events and serious adverse events
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.
Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III (Motor Examination) scores from baseline to Week 12
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.
Change in Mini Mental State Exam (MMSE) total scores from baseline to Week 12
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.
Change in cognitive test battery (CogState) scores form baseline to Week 12
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
Total scores of the Scales for Outcomes in Parkinson's disease - Psychiatric Complications (SCOPA-PC)
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.
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)
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.
Plasma Pharmacokinetics of AFQ056 in patients with Parkinson's disease with moderate to severe dyskinesias
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.
Pharmacokinetics of AFQ056 in patients with Parkinson's disease with moderate to severe dyskinesias
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.
Investigate the safety of concomitant administration of AFQ056 with amantadine
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.

Full Information

First Posted
December 12, 2011
Last Updated
December 15, 2020
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01491529
Brief Title
Evaluation of the Efficacy and Safety of Modified Release AFQ056 in Parkinson's Patients With L-dopa Induced Dyskinesias
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
April 2012 (undefined)
Primary Completion Date
April 2013 (Actual)
Study Completion Date
April 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

5. Study Description

Brief Summary
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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dyskinesias, Parkinson Disease, Movement Disorders, Parkinsonian Disorders, Anti-Dyskinesia Agents
Keywords
Parkinson Disease, L-dopa, Levodopa, Dyskinesia, Amantadine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
154 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AFQ056 150 mg
Arm Type
Experimental
Arm Description
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.
Arm Title
AFQ056 200 mg
Arm Type
Experimental
Arm Description
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.)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Patients randomized to the Placebo arm will receive oral AFQ056 Placebo twice daily
Intervention Type
Drug
Intervention Name(s)
AFQ056
Intervention Description
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.)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo for AFQ056 will be supplied as oral tablets.
Primary Outcome Measure Information:
Title
Change in modified AIMS (Abnormal Involuntary Movement Scale) total score from baseline to Week 12
Description
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.
Time Frame
12 weeks
Title
The incidence rate of adverse events
Description
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.
Time Frame
Monitored for the duration of the study which is 13 weeks
Title
Time to onset of adverse events
Description
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.
Time Frame
Monitored for the duration of the study which is 13 weeks
Title
The percentage of patients reaching and maintaining the target dose during the fixed dose treatment period
Description
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.
Time Frame
Assessed during the fixed dose treatment period of 6 weeks
Title
The percentage of patients discontinued during the up titration period due to AE
Description
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.
Time Frame
Assessed during the up titration period of 6 weeks
Secondary Outcome Measure Information:
Title
The change in total score and sub-score of UDysRS Parts I, II, III, and IV from baseline to Week 12
Description
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.
Time Frame
12 weeks
Title
Change in Lang-Fahn Activities of Daily Living Dyskinesia Scale (LFADLDS) total score from baseline to Week 12
Description
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.
Time Frame
12 weeks
Title
Change in clinician-rated global impression of change (CGIC) score from baseline to Week 12
Description
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.
Time Frame
12 weeks
Title
Change from baseline Total ON- and OFF-times and ON-time with dyskinesia and with troublesome dyskinesias (patient diary) to Week 12
Description
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.
Time Frame
12 weeks
Title
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
Description
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.
Time Frame
12 weeks
Title
Changes in vital signs from baseline to each post-baseline visit
Description
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.
Time Frame
Monitored at regular visits throughout duration of the study which is 13 weeks
Title
Changes in hematology/blood chemistry and urinalysis laboratory evaluations from baseline to each post-baseline visit where hematology/blood chemistry and urinalysis are collected
Description
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.
Time Frame
Monitored at regular visits throughout duration of the study which is 13 weeks
Title
Changes in electrocardiogram (ECG) from baseline to each post-baseline visit where ECGs are performed
Description
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.
Time Frame
Monitored at regular visits throughout duration of the study which is 13 weeks
Title
Percentage of adverse events including treatment emergent adverse events and serious adverse events
Description
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.
Time Frame
Monitored for the duration of the study which is 13 weeks
Title
Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III (Motor Examination) scores from baseline to Week 12
Description
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.
Time Frame
12 weeks
Title
Change in Mini Mental State Exam (MMSE) total scores from baseline to Week 12
Description
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.
Time Frame
12 weeks
Title
Change in cognitive test battery (CogState) scores form baseline to Week 12
Description
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
Time Frame
12 weeks
Title
Total scores of the Scales for Outcomes in Parkinson's disease - Psychiatric Complications (SCOPA-PC)
Description
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.
Time Frame
Assessed for 12 weeks
Title
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)
Description
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.
Time Frame
This will be assessed for the duration of the study which is 13 weeks
Title
Plasma Pharmacokinetics of AFQ056 in patients with Parkinson's disease with moderate to severe dyskinesias
Description
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.
Time Frame
At Week 12 or earlier if the patient discontinues the study before Week 12
Title
Pharmacokinetics of AFQ056 in patients with Parkinson's disease with moderate to severe dyskinesias
Description
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.
Time Frame
Monitored at regular visits throughout duration of the study which is 13 weeks
Title
Investigate the safety of concomitant administration of AFQ056 with amantadine
Description
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.
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Sunnyvale
State/Province
California
ZIP/Postal Code
94089
Country
United States
Facility Name
Novartis Investigative Site
City
Englewood
State/Province
Colorado
ZIP/Postal Code
80113
Country
United States
Facility Name
Novartis Investigative Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Novartis Investigative Site
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Novartis Investigative Site
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53233
Country
United States
Facility Name
Novartis Investigative Site
City
Innsbruck
ZIP/Postal Code
A-6020
Country
Austria
Facility Name
Novartis Investigative Site
City
Linz
ZIP/Postal Code
A-4020
Country
Austria
Facility Name
Novartis Investigative Site
City
Vienna
ZIP/Postal Code
A-1220
Country
Austria
Facility Name
Novartis Investigative Site
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5A5
Country
Canada
Facility Name
Novartis Investigative Site
City
Clermont-Ferrand Cedex 1
ZIP/Postal Code
63003
Country
France
Facility Name
Novartis Investigative Site
City
Lille Cedex
ZIP/Postal Code
59037
Country
France
Facility Name
Novartis Investigative Site
City
Pessac
ZIP/Postal Code
33604
Country
France
Facility Name
Novartis Investigative Site
City
Poitiers
ZIP/Postal Code
86021
Country
France
Facility Name
Novartis Investigative Site
City
Beelitz-Heilstaetten
ZIP/Postal Code
14547
Country
Germany
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
12163
Country
Germany
Facility Name
Novartis Investigative Site
City
Bochum
ZIP/Postal Code
44791
Country
Germany
Facility Name
Novartis Investigative Site
City
Duesseldorf
ZIP/Postal Code
40225
Country
Germany
Facility Name
Novartis Investigative Site
City
Kassel
ZIP/Postal Code
34128
Country
Germany
Facility Name
Novartis Investigative Site
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Novartis Investigative Site
City
Muenchen
ZIP/Postal Code
80804
Country
Germany
Facility Name
Novartis Investigative Site
City
München
ZIP/Postal Code
81675
Country
Germany
Facility Name
Novartis Investigative Site
City
Stadtroda
ZIP/Postal Code
07646
Country
Germany
Facility Name
Novartis Investigative Site
City
Budapest
ZIP/Postal Code
1085
Country
Hungary
Facility Name
Novartis Investigative Site
City
Kaposvár
ZIP/Postal Code
7400
Country
Hungary
Facility Name
Novartis Investigative Site
City
Szeged
ZIP/Postal Code
H-6725
Country
Hungary
Facility Name
Novartis Investigative Site
City
Brescia
State/Province
BS
ZIP/Postal Code
25123
Country
Italy
Facility Name
Novartis Investigative Site
City
Bolzano
State/Province
BZ
ZIP/Postal Code
39100
Country
Italy
Facility Name
Novartis Investigative Site
City
Pisa
State/Province
PI
ZIP/Postal Code
56126
Country
Italy
Facility Name
Novartis Investigative Site
City
Roma
State/Province
RM
ZIP/Postal Code
00163
Country
Italy
Facility Name
Novartis Investigative Site
City
Roma
State/Province
RM
ZIP/Postal Code
00179
Country
Italy
Facility Name
Novartis Investigative Site
City
Bratislava
ZIP/Postal Code
82606
Country
Slovakia
Facility Name
Novartis Investigative Site
City
Bratislava
ZIP/Postal Code
83305
Country
Slovakia
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Cataluña
ZIP/Postal Code
08025
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Cataluña
ZIP/Postal Code
08036
Country
Spain
Facility Name
Novartis Investigative Site
City
Sant Cugat
State/Province
Cataluña
ZIP/Postal Code
08190
Country
Spain
Facility Name
Novartis Investigative Site
City
San Sebastian
State/Province
Pais Vasco
ZIP/Postal Code
20014
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28006
Country
Spain
Facility Name
Novartis Investigative Site
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
Facility Name
Novartis Investigative Site
City
Lausanne
ZIP/Postal Code
1011
Country
Switzerland

12. IPD Sharing Statement

Citations:
PubMed Identifier
27214258
Citation
Trenkwalder C, Stocchi F, Poewe W, Dronamraju N, Kenney C, Shah A, von Raison F, Graf A. Mavoglurant in Parkinson's patients with l-Dopa-induced dyskinesias: Two randomized phase 2 studies. Mov Disord. 2016 Jul;31(7):1054-8. doi: 10.1002/mds.26585. Epub 2016 May 23.
Results Reference
derived
Links:
URL
https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=11843
Description
Results for CAFQ056A2223 from the Novartis Clinical Trials Website

Learn more about this trial

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

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