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

NCT01491529 | Completed Phase 2

• 2 other identifiers: CAFQ056A22232011-002074-23
• Study Type: interventional
• Target: 154
• Locations: 10 countries
• Sites: 39

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)

Conditions

Dyskinesias; Parkinson Disease; Movement Disorders; Parkinsonian Disorders; Anti-Dyskinesia Agents

Keywords

Parkinson Disease; L-dopa; Levodopa; Dyskinesia; Amantadine

Outcome Measures

Primary Outcomes (5)

• 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.

  12 weeks

• 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.

  Monitored for the duration of the study which is 13 weeks

• 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.

  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

  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

  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

Secondary Outcomes (17)

• The change in total score and sub-score of UDysRS Parts I, II, III, and IV from baseline to Week 12

  12 weeks

• Change in Lang-Fahn Activities of Daily Living Dyskinesia Scale (LFADLDS) total score from baseline to Week 12

  12 weeks

• Change in clinician-rated global impression of change (CGIC) score from baseline to Week 12

  12 weeks

• Change from baseline Total ON- and OFF-times and ON-time with dyskinesia and with troublesome dyskinesias (patient diary) to Week 12

  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

  12 weeks

Study Arms (3)

AFQ056 150 mg

EXPERIMENTAL

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.

Drug: AFQ056

AFQ056 200 mg

EXPERIMENTAL

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.)

Drug: AFQ056

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

AFQ056 DRUG

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.)

AFQ056 150 mg; AFQ056 200 mg

Placebo DRUG

Placebo for AFQ056 will be supplied as oral tablets.

Placebo

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (39)

Novartis Investigative Site

Sunnyvale, California, 94089, United States

Location

Novartis Investigative Site

Englewood, Colorado, 80113, United States

Location

Novartis Investigative Site

Tampa, Florida, 33612, United States

Location

Novartis Investigative Site

Kansas City, Kansas, 66160, United States

Location

Novartis Investigative Site

Milwaukee, Wisconsin, 53233, United States

Location

Novartis Investigative Site

Innsbruck, A-6020, Austria

Location

Novartis Investigative Site

Linz, A-4020, Austria

Location

Novartis Investigative Site

Vienna, A-1220, Austria

Location

Novartis Investigative Site

London, Ontario, N6A 5A5, Canada

Location

Novartis Investigative Site

Clermont-Ferrand, 63003, France

Location

Novartis Investigative Site

Lille, 59037, France

Location

Novartis Investigative Site

Pessac, 33604, France

Location

Novartis Investigative Site

Poitiers, 86021, France

Location

Novartis Investigative Site

Beelitz-Heilstätten, 14547, Germany

Location

Novartis Investigative Site

Berlin, 12163, Germany

Location

Novartis Investigative Site

Bochum, 44791, Germany

Location

Novartis Investigative Site

Düsseldorf, 40225, Germany

Location

Novartis Investigative Site

Kassel, 34128, Germany

Location

Novartis Investigative Site

Leipzig, 04103, Germany

Location

Novartis Investigative Site

München, 80804, Germany

Location

Novartis Investigative Site

München, 81675, Germany

Location

Novartis Investigative Site

Stadtroda, 07646, Germany

Location

Novartis Investigative Site

Budapest, 1085, Hungary

Location

Novartis Investigative Site

Kaposvár, 7400, Hungary

Location

Novartis Investigative Site

Szeged, H-6725, Hungary

Location

Novartis Investigative Site

Brescia, BS, 25123, Italy

Location

Novartis Investigative Site

Bolzano, BZ, 39100, Italy

Location

Novartis Investigative Site

Pisa, PI, 56126, Italy

Location

Novartis Investigative Site

Roma, RM, 00163, Italy

Location

Novartis Investigative Site

Roma, RM, 00179, Italy

Location

Novartis Investigative Site

Bratislava, 82606, Slovakia

Location

Novartis Investigative Site

Bratislava, 83305, Slovakia

Location

Novartis Investigative Site

Donostia / San Sebastian, Basque Country, 20014, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08025, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

Location

Novartis Investigative Site

Sant Cugat del Vallès, Catalonia, 08190, Spain

Location

Novartis Investigative Site

Madrid, 28006, Spain

Location

Novartis Investigative Site

Bern, 3010, Switzerland

Location

Novartis Investigative Site

Lausanne, 1011, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 27214258 DERIVED

Related Links

• Results for CAFQ056A2223 from the Novartis Clinical Trials Website

MeSH Terms

Conditions

Dyskinesias; Parkinson Disease; Movement Disorders; Parkinsonian Disorders

Interventions

mavoglurant

Condition Hierarchy (Ancestors)

Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Basal Ganglia Diseases; Brain Diseases; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2011
• First Posted: December 14, 2011
• Study Start: April 1, 2012
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: December 23, 2020

Record last verified: 2016-03

Locations

US (5); CA (1); HU (3); IT (5); ES (5); FR (4); CH (2); SL (2); DE (9); AU (3)