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Open-label, Long-term Safety Extension Study of 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
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

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients who have completed a previous AFQ056A study or are eligible as defined in the core study protocol
  • Outpatients
  • Patients who have a primary caregiver willing and able to assess the condition of the patient throughout the study in accordance with protocol requirements

Exclusion Criteria:

  • Atypical or secondary form of Parkinson's disease
  • History of surgical treatment for PD including deep brain stimulation
  • Advanced, severe, or unstable disease (other than PD)
  • History of malignancy
  • Evidence of dementia
  • Untreated/ineffectively treated mental disorders
  • Treatment with certain prohibited medications
  • Abnormal lab values or heart abnormalities
  • Pregnant or nursing women

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AFQ056

Arm Description

Patients entering the study will be titrated to target dose of AFQ056 twice daily or the highest tolerated dose at weekly intervals.

Outcomes

Primary Outcome Measures

Incidence rate of adverse events including serious adverse events
The occurrence of adverse events would be sought by non-directive questioning of the patient at each visit. Adverse events may also be detected when they are volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessment.
Severity of adverse events including serious adverse events
The occurrence and severity of adverse events would be sought by non-directive questioning of the patient at each visit. Adverse events may also be detected when they are volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessment.
Change in vital signs from baseline to Weeks 1, 2, 4, 8, 12, Months 6, 9, 12, every 6 months thereafter.
Pulse and blood pressure at each visit as indicated above. If a patient discontinues in between these visits, this will be assessed at the time of discontinuation.
Changes in hematology/blood chemistry and urinalysis laboratory evaluations from baseline to Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter
Standard hematology with differential, aPTT, PT/INR;, clinical chemistry consists of albumin, alkaline phosphatase, amylase, total bilirubin, calcium, cholesterol, creatinine, CK, γ-GT, glucose, lipase, lactate dehydrogenase, inorganic phosphorus, magnesium, potassium, total protein, AST, ALT, sodium, triglycerides, urea and uric acid, FSH, LH, oxytocin, prolactin, TBG, TSH, and T4; urinalysis (specific gravity, protein, glucose and blood) If a patient discontinues in between these visits, these will be assessed at the time of discontinuation.
Change in ECGs from baseline to Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter
A standard 12-lead ECG will be performed. A central facility will be used for interpretation and analysis of the ECGs. If a patient discontinues in between these visits, this will be assessed at the time of discontinuation.
Change in Unified Parkinson's Disease Rating Scale (UPDRS) part III scores from baseline to Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter
Part III of the UPDRS (items 18-31; total score 0-56), has been proven to be a reliable instrument in assessing the anti-parkinsonian effect in PD patients. This scale measures 14 items such as 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 is indicative of worsening of symptoms. If a patient discontinues in between these visits, this will be assessed at the time of discontinuation.
Incidence of AEs related to an exacerbation of the underlying movement disorder Parkinson's disease
The occurrence of adverse events relating to the underlying movement disorder Parkinson's disease would be sought by non-directive questioning of the patient at each visit. Adverse events may also be detected when they are volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessment.

Secondary Outcome Measures

Change in mAIMS (modified Abnormal Involuntary Movement Scale) total score from baseline to Weeks 1, 2, 4, 8, 12, Months 6, 9, 12, every 6 months thereafter.
The AIMS is a scale for assessing dyskinesia. The modified version of this scale used in this study focuses on 6 different parts of the body and rates abnormal movements from 0 (absence of dyskinesia) to 4 (severe) (maximal score, 24). If a patient discontinues in between these visits, this will be assessed at the time of discontinuation.
Change in Revised Lang-Fahn Activities of Daily Living Dyskinesia Scale (LFADLDS) scores (patient and caregiver versions) from baseline to Weeks 4, 12, Months 6, 9, 12, every 6 months thereafter
The LFADLDS is a questionnaire asking the patient about the degree to which dyskinesia interferes with activities of daily living. The LFADLDS is modified from the ADL section of the UPRDS (part II). 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. Two versions of the revised LFADLDS will be used in this study: a patient version and a caregiver version. If a patient discontinues in between these visits, this will be assessed at the time of discontinuation.
Change in score for items 32, 33, and 34 of Part IV of the UPDRS from baseline to Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter
The UPDRS is a standardized instrument for measuring the disease state of PD patients. Question 32 assesses duration of dyskinesias expressed in percentage of the day . Question 33 makes a historical assessment of disability due to dyskinesia during the previous week (not disabling, mildly disabling, moderately disabling, severely disabling, completely disabling). Question 34 of part IV assesses how painful the dyskinesias are from 0 (no painful dyskinesias) to 4 (marked). If a patient discontinues in between these visits, this will be assessed at the time of discontinuation.
Change in Mini Mental State Exam (MMSE) score from baseline to Months 6, 12, every 6 months thereafter
The MMSE is a brief test of cognitive dysfunction consisting of five sections (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 indicating better function. If a patient discontinues in between these visits, this will be assessed at the time of discontinuation.
Change in the Scales for outcomes in Parkinson's disease - Psychiatric Complications (SCOPA-PC) score from baseline to Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter
The SCOPA-PC is an easily administered semi-structured, questionnaire developed for the assessment of psychiatric symptoms, including compulsive behavior, 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. If a patient discontinues in between these visits, this will be assessed at the time of discontinuation.
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.

Full Information

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

Unique Protocol Identification Number
NCT01491932
Brief Title
Open-label, Long-term Safety Extension Study of AFQ056 in Parkinson's Patients With L-dopa Induced Dyskinesias
Official Title
An Open-label Treatment Study to Evaluate the Safety, Tolerability and Efficacy of AFQ056 in Parkinson's Patients With L-dopa Induced Dyskinesias
Study Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
March 2012 (undefined)
Primary Completion Date
October 2013 (Actual)
Study Completion Date
October 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 is to evaluate long-term safety, tolerability and efficacy for AFQ056 in patients who have completed an AFQ056A study in 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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
129 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AFQ056
Arm Type
Experimental
Arm Description
Patients entering the study will be titrated to target dose of AFQ056 twice daily or the highest tolerated dose at weekly intervals.
Intervention Type
Drug
Intervention Name(s)
AFQ056
Intervention Description
AFQ056 will be supplied as oral capsules.
Primary Outcome Measure Information:
Title
Incidence rate of adverse events including serious adverse events
Description
The occurrence of adverse events would be sought by non-directive questioning of the patient at each visit. Adverse events may also be detected when they are volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessment.
Time Frame
Monitored for the duration of the study (anticipated to be an average of 3 years)
Title
Severity of adverse events including serious adverse events
Description
The occurrence and severity of adverse events would be sought by non-directive questioning of the patient at each visit. Adverse events may also be detected when they are volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessment.
Time Frame
Monitored for the duration of the study (anticipated to be an average of 3 years)
Title
Change in vital signs from baseline to Weeks 1, 2, 4, 8, 12, Months 6, 9, 12, every 6 months thereafter.
Description
Pulse and blood pressure at each visit as indicated above. If a patient discontinues in between these visits, this will be assessed at the time of discontinuation.
Time Frame
Assessed at Day -14 to -3, Day 1, Weeks 1, 2, 4, 8, 12, Months 6, 9, 12, every 6 months thereafter
Title
Changes in hematology/blood chemistry and urinalysis laboratory evaluations from baseline to Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter
Description
Standard hematology with differential, aPTT, PT/INR;, clinical chemistry consists of albumin, alkaline phosphatase, amylase, total bilirubin, calcium, cholesterol, creatinine, CK, γ-GT, glucose, lipase, lactate dehydrogenase, inorganic phosphorus, magnesium, potassium, total protein, AST, ALT, sodium, triglycerides, urea and uric acid, FSH, LH, oxytocin, prolactin, TBG, TSH, and T4; urinalysis (specific gravity, protein, glucose and blood) If a patient discontinues in between these visits, these will be assessed at the time of discontinuation.
Time Frame
Assessed at Day -14 to -3, Day 1(only urinalysis and only done if abnormalities), Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter
Title
Change in ECGs from baseline to Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter
Description
A standard 12-lead ECG will be performed. A central facility will be used for interpretation and analysis of the ECGs. If a patient discontinues in between these visits, this will be assessed at the time of discontinuation.
Time Frame
Assessed at Day -14 to -3, Day 1, (repeated if abnormalities seen), Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter
Title
Change in Unified Parkinson's Disease Rating Scale (UPDRS) part III scores from baseline to Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter
Description
Part III of the UPDRS (items 18-31; total score 0-56), has been proven to be a reliable instrument in assessing the anti-parkinsonian effect in PD patients. This scale measures 14 items such as 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 is indicative of worsening of symptoms. If a patient discontinues in between these visits, this will be assessed at the time of discontinuation.
Time Frame
Assessed at Day 1, Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter
Title
Incidence of AEs related to an exacerbation of the underlying movement disorder Parkinson's disease
Description
The occurrence of adverse events relating to the underlying movement disorder Parkinson's disease would be sought by non-directive questioning of the patient at each visit. Adverse events may also be detected when they are volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessment.
Time Frame
Monitored for the duration of the study (anticipated to be an average of 3 years)
Secondary Outcome Measure Information:
Title
Change in mAIMS (modified Abnormal Involuntary Movement Scale) total score from baseline to Weeks 1, 2, 4, 8, 12, Months 6, 9, 12, every 6 months thereafter.
Description
The AIMS is a scale for assessing dyskinesia. The modified version of this scale used in this study focuses on 6 different parts of the body and rates abnormal movements from 0 (absence of dyskinesia) to 4 (severe) (maximal score, 24). If a patient discontinues in between these visits, this will be assessed at the time of discontinuation.
Time Frame
Assessed at Day 1, Weeks 1, 2, 4, 8, 12, Months 6, 9, 12, every 6 months thereafter
Title
Change in Revised Lang-Fahn Activities of Daily Living Dyskinesia Scale (LFADLDS) scores (patient and caregiver versions) from baseline to Weeks 4, 12, Months 6, 9, 12, every 6 months thereafter
Description
The LFADLDS is a questionnaire asking the patient about the degree to which dyskinesia interferes with activities of daily living. The LFADLDS is modified from the ADL section of the UPRDS (part II). 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. Two versions of the revised LFADLDS will be used in this study: a patient version and a caregiver version. If a patient discontinues in between these visits, this will be assessed at the time of discontinuation.
Time Frame
Assessed at Day 1, Weeks 4, 12, Months 6, 9, 12, every 6 months thereafter
Title
Change in score for items 32, 33, and 34 of Part IV of the UPDRS from baseline to Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter
Description
The UPDRS is a standardized instrument for measuring the disease state of PD patients. Question 32 assesses duration of dyskinesias expressed in percentage of the day . Question 33 makes a historical assessment of disability due to dyskinesia during the previous week (not disabling, mildly disabling, moderately disabling, severely disabling, completely disabling). Question 34 of part IV assesses how painful the dyskinesias are from 0 (no painful dyskinesias) to 4 (marked). If a patient discontinues in between these visits, this will be assessed at the time of discontinuation.
Time Frame
Assessed at Day 1, Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter
Title
Change in Mini Mental State Exam (MMSE) score from baseline to Months 6, 12, every 6 months thereafter
Description
The MMSE is a brief test of cognitive dysfunction consisting of five sections (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 indicating better function. If a patient discontinues in between these visits, this will be assessed at the time of discontinuation.
Time Frame
Assessed at Day -14 to -3, Day 1 (only if not done in the respective core study), Months 6, 12, every 6 months thereafter
Title
Change in the Scales for outcomes in Parkinson's disease - Psychiatric Complications (SCOPA-PC) score from baseline to Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter
Description
The SCOPA-PC is an easily administered semi-structured, questionnaire developed for the assessment of psychiatric symptoms, including compulsive behavior, 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. If a patient discontinues in between these visits, this will be assessed at the time of discontinuation.
Time Frame
Assessed at Day 1, Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter
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
Monitored for the duration of the study (anticipated to be an average of 3 years)

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients who have completed a previous AFQ056A study or are eligible as defined in the core study protocol Outpatients Patients who have a primary caregiver willing and able to assess the condition of the patient throughout the study in accordance with protocol requirements Exclusion Criteria: Atypical or secondary form of Parkinson's disease History of surgical treatment for PD including deep brain stimulation Advanced, severe, or unstable disease (other than PD) History of malignancy Evidence of dementia Untreated/ineffectively treated mental disorders Treatment with certain prohibited medications Abnormal lab values or heart abnormalities Pregnant or nursing women
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
Englewood
State/Province
Colorado
ZIP/Postal Code
80113
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 4G5
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
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
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
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
Westerstede/Oldenburg
ZIP/Postal Code
26655
Country
Germany
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
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
Catalunya
ZIP/Postal Code
08036
Country
Spain
Facility Name
Novartis Investigative Site
City
Sant Cugat
State/Province
Catalunya
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
Barcelona
ZIP/Postal Code
08025
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

12. IPD Sharing Statement

Links:
URL
https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=12843
Description
Results from CAFQ056A2299 from the Novartis Clinical Trial Results website

Learn more about this trial

Open-label, Long-term Safety Extension Study of AFQ056 in Parkinson's Patients With L-dopa Induced Dyskinesias

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