Clinical trial NCT01491529: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dyskinesias
Parkinson Disease
Movement Disorders
Parkinsonian Disorders
Anti-Dyskinesia Agents
Keywords: Parkinson Disease
L-dopa
Levodopa
Dyskinesia
Amantadine
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-12-14
Enrollment: 154
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


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.

Primary outcomes:
measure: Change in modified AIMS (Abnormal Involuntary Movement Scale) total score from baseline to Week 12
timeFrame: 12 weeks
measure: The incidence rate of adverse events
timeFrame: Monitored for the duration of the study which is 13 weeks
measure: Time to onset of adverse events
timeFrame: Monitored for the duration of the study which is 13 weeks
measure: The percentage of patients reaching and maintaining the target dose during the fixed dose treatment period
timeFrame: Assessed during the fixed dose treatment period of 6 weeks
measure: The percentage of patients discontinued during the up titration period due to AE
timeFrame: Assessed during the up titration period of 6 weeks
Secondary outcomes:
measure: The change in total score and sub-score of UDysRS Parts I, II, III, and IV from baseline to Week 12
timeFrame: 12 weeks
measure: Change in Lang-Fahn Activities of Daily Living Dyskinesia Scale (LFADLDS) total score from baseline to Week 12
timeFrame: 12 weeks
measure: Change in clinician-rated global impression of change (CGIC) score from baseline to Week 12
timeFrame: 12 weeks
measure: Change from baseline Total ON- and OFF-times and ON-time with dyskinesia and with troublesome dyskinesias (patient diary) to Week 12
timeFrame: 12 weeks
measure: 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
timeFrame: 12 weeks
measure: Changes in vital signs from baseline to each post-baseline visit
timeFrame: Monitored at regular visits throughout duration of the study which is 13 weeks
measure: Changes in hematology/blood chemistry and urinalysis laboratory evaluations from baseline to each post-baseline visit where hematology/blood chemistry and urinalysis are collected
timeFrame: Monitored at regular visits throughout duration of the study which is 13 weeks
measure: Changes in electrocardiogram (ECG) from baseline to each post-baseline visit where ECGs are performed
timeFrame: Monitored at regular visits throughout duration of the study which is 13 weeks
measure: Percentage of adverse events including treatment emergent adverse events and serious adverse events
timeFrame: Monitored for the duration of the study which is 13 weeks
measure: Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III (Motor Examination) scores from baseline to Week 12
timeFrame: 12 weeks
measure: Change in Mini Mental State Exam (MMSE) total scores from baseline to Week 12
timeFrame: 12 weeks
measure: Change in cognitive test battery (CogState) scores form baseline to Week 12
timeFrame: 12 weeks
measure: Total scores of the Scales for Outcomes in Parkinson's disease - Psychiatric Complications (SCOPA-PC)
timeFrame: Assessed for 12 weeks
measure: 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)
timeFrame: This will be assessed for the duration of the study which is 13 weeks
measure: Plasma Pharmacokinetics of AFQ056 in patients with Parkinson's disease with moderate to severe dyskinesias
timeFrame: At Week 12 or earlier if the patient discontinues the study before Week 12
measure: Pharmacokinetics of AFQ056 in patients with Parkinson's disease with moderate to severe dyskinesias
timeFrame: Monitored at regular visits throughout duration of the study which is 13 weeks
measure: Investigate the safety of concomitant administration of AFQ056 with amantadine
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Sunnyvale
country: United States
facility: Novartis Investigative Site
state: California
city: Englewood
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Tampa
country: United States
facility: Novartis Investigative Site
state: Florida
city: Kansas City
country: United States
facility: Novartis Investigative Site
state: Kansas
city: Milwaukee
country: United States
facility: Novartis Investigative Site
state: Wisconsin
city: Innsbruck
country: Austria
facility: Novartis Investigative Site
city: Linz
country: Austria
facility: Novartis Investigative Site
city: Vienna
country: Austria
facility: Novartis Investigative Site
city: London
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Clermont-Ferrand Cedex 1
country: France
facility: Novartis Investigative Site
city: Lille Cedex
country: France
facility: Novartis Investigative Site
city: Pessac
country: France
facility: Novartis Investigative Site
city: Poitiers
country: France
facility: Novartis Investigative Site
city: Beelitz-Heilstaetten
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Bochum
country: Germany
facility: Novartis Investigative Site
city: Duesseldorf
country: Germany
facility: Novartis Investigative Site
city: Kassel
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: München
country: Germany
facility: Novartis Investigative Site
city: Stadtroda
country: Germany
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Kaposvár
country: Hungary
facility: Novartis Investigative Site
city: Szeged
country: Hungary
facility: Novartis Investigative Site
city: Brescia
country: Italy
facility: Novartis Investigative Site
state: BS
city: Bolzano
country: Italy
facility: Novartis Investigative Site
state: BZ
city: Pisa
country: Italy
facility: Novartis Investigative Site
state: PI
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Cataluña
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Cataluña
city: Sant Cugat
country: Spain
facility: Novartis Investigative Site
state: Cataluña
city: San Sebastian
country: Spain
facility: Novartis Investigative Site
state: Pais Vasco
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Bern
country: Switzerland
facility: Novartis Investigative Site
city: Lausanne
country: Switzerland
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
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.