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

An Open-label Treatment Study to Evaluate the Safety, Tolerability and Efficacy of AFQ056 in Parkinson's Patients With L-dopa Induced Dyskinesias

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).

Study Overview

• Status: Completed
• Conditions: Parkinson Disease; Parkinsonian Disorders; Movement Disorders; Dyskinesias; Anti-Dyskinesia Agents
• Intervention / Treatment: Drug: AFQ056

• Study Type: Interventional
• Enrollment (Actual): 129
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, A-6020
    • Novartis Investigative Site
  • Linz, Austria, A-4020
    • Novartis Investigative Site
  • Vienna, Austria, A-1220
    • Novartis Investigative Site
• Canada
  • Ontario
    • London, Ontario, Canada, N6A 4G5
      • Novartis Investigative Site
• France
  • Clermont-Ferrand Cedex 1, France, 63003
    • Novartis Investigative Site
  • Lille Cedex, France, 59037
    • Novartis Investigative Site
  • Pessac, France, 33604
    • Novartis Investigative Site
• Germany
  • Beelitz-Heilstaetten, Germany, 14547
    • Novartis Investigative Site
  • Berlin, Germany, 12163
    • Novartis Investigative Site
  • Bochum, Germany, 44791
    • Novartis Investigative Site
  • Kassel, Germany, 34128
    • Novartis Investigative Site
  • Leipzig, Germany, 04103
    • Novartis Investigative Site
  • München, Germany, 81675
    • Novartis Investigative Site
  • Stadtroda, Germany, 07646
    • Novartis Investigative Site
  • Westerstede/Oldenburg, Germany, 26655
    • Novartis Investigative Site
• Hungary
  • Kaposvár, Hungary, 7400
    • Novartis Investigative Site
  • Szeged, Hungary, H-6725
    • Novartis Investigative Site
• Italy
  • BS
    • Brescia, BS, Italy, 25123
      • Novartis Investigative Site
  • PI
    • Pisa, PI, Italy, 56126
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00163
      • Novartis Investigative Site
    • Roma, RM, Italy, 00179
      • Novartis Investigative Site
• Slovakia
  • Bratislava, Slovakia, 82606
    • Novartis Investigative Site
  • Bratislava, Slovakia, 83305
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08025
    • Novartis Investigative Site
  • Madrid, Spain, 28006
    • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08036
      • Novartis Investigative Site
    • Sant Cugat, Catalunya, Spain, 08190
      • Novartis Investigative Site
  • Pais Vasco
    • San Sebastian, Pais Vasco, Spain, 20014
      • Novartis Investigative Site
• Switzerland
  • Bern, Switzerland, 3010
    • Novartis Investigative Site
• United States
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Novartis Investigative Site
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Novartis Investigative Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53233
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AFQ056; Patients entering the study will be titrated to target dose of AFQ056 twice daily or the highest tolerated dose at weekly intervals.	Drug: AFQ056; AFQ056 will be supplied as oral capsules.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Monitored for the duration of the study (anticipated to be an average of 3 years)
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.	Monitored for the duration of the study (anticipated to be an average of 3 years)
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.	Assessed at Day -14 to -3, Day 1, Weeks 1, 2, 4, 8, 12, Months 6, 9, 12, every 6 months thereafter
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.	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
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.	Assessed at Day -14 to -3, Day 1, (repeated if abnormalities seen), Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter
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.	Assessed at Day 1, Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter
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.	Monitored for the duration of the study (anticipated to be an average of 3 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Assessed at Day 1, Weeks 1, 2, 4, 8, 12, Months 6, 9, 12, every 6 months thereafter
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.	Assessed at Day 1, Weeks 4, 12, Months 6, 9, 12, every 6 months thereafter
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.	Assessed at Day 1, Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter
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.	Assessed at Day -14 to -3, Day 1 (only if not done in the respective core study), Months 6, 12, every 6 months thereafter
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.	Assessed at Day 1, Weeks 4, 8, 12, Months 6, 9, 12, every 6 months thereafter
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.	Monitored for the duration of the study (anticipated to be an average of 3 years)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results from CAFQ056A2299 from the Novartis Clinical Trial Results website

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: December 1, 2011
• First Submitted That Met QC Criteria: December 12, 2011
• First Posted (Estimate): December 14, 2011

Study Record Updates

• Last Update Posted (Actual): December 23, 2020
• Last Update Submitted That Met QC Criteria: December 15, 2020
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Parkinson Disease; Levodopa; L-dopa; Dyskinesia
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Basal Ganglia Diseases; Synucleinopathies; Neurodegenerative Diseases; Disease; Parkinson Disease; Dyskinesias; Movement Disorders; Parkinsonian Disorders
• Other Study ID Numbers: CAFQ056A2299; 2011-004378-27 (EudraCT Number)