A multi-centre, randomized, double-blind, placebo-controlled, parallel-group, multiple oral dose titration study in patients with Parkinson’s disease to assess the efficacy of AFQ056 in reducing L-dopa induced dyskinesias, and the safety and tolerability of AFQ056 in combination with L-dopa

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-002900-16-DE
• Date of registration: 21/08/2007
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A multi-centre, randomized, double-blind, placebo-controlled, parallel-group, multiple oral dose titration study in patients with Parkinson’s disease to assess the efficacy of AFQ056 in reducing L-dopa induced dyskinesias, and the safety and tolerability of AFQ056 in combination with L-dopa
• Scientific title: A multi-centre, randomized, double-blind, placebo-controlled, parallel-group, multiple oral dose titration study in patients with Parkinson’s disease to assess the efficacy of AFQ056 in reducing L-dopa induced dyskinesias, and the safety and tolerability of AFQ056 in combination with L-dopa
• Date of first enrolment: 01/10/2007
• Target sample size: 34
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-002900-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Germany

Key inclusion & exclusion criteria

Inclusion criteria:
Patients who are eligible for enrollment in the study will be males and females, aged between 30 and 85 years of age (both inclusive), non-smokers, with idiopathic Parkinson’s disease (diagnosed by UK Parkinson’s disease Society Brain Bank criteria), with L-dopa induced dyskinesia greater than 20% (UPDRS item of 32, rating =1) of moderate to severe (complete disabling) intensity (UPDRS item 33 rating = 2), with dyskinesias for at least 3 months before randomization, and who are on L-dopa treatment for at least 3 years prior to randomization; L-dopa treatment has to be stable for at least 1 month prior to randomization (i.e. the total daily dose and dosing regimen can vary among patients but will be the same for individual patients). Other concomitant anti-parkinsonian medication is allowed but the total daily dose and dosing regimen has to be stable for at least one month prior to randomization. Female patients must be without childbearing potential (post-menopausal or surgically sterilized); for safety reasons they have to use a double-barrier local contraception (e.g., intra-uterine device plus condom) during the entire study from screening up to the study completion visit. Male patients must be using a double-barrier local contraception for the entire duration of the study (from screening up to the study completion visit), and refrain from fathering a child in the 3 months following last study drug administration. Patients must be able to provide written informed consent prior to study participation.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Following patients will be excluded from the study: smokers, with a prior surgery for Parkinson’s Disease, with a Hoehn and Yahr score of 5 when ‘off’, with cognitive impairment (MMSE less than 24), with atypical Parkinson’s disease (Progressive Supranuclear Palsy (PSP), Multi Systemic Atrophy (MSA)), with history or presence of psychosis and/or confusional states, with a history or presence of nephrolithiasis, renal impairment, and/or liver disease, who participated in an anti-dyskinetic clinical study within the 6 months before randomization, who are under deep brain stimulation, who received amantadine within 15 days, and/or other anti-dyskinetic medication (i.e. antipsychotics) within 4 weeks before randomization and/or neuroleptics during 2 months before randomization, who is unable to perform the cognitive assessments at screening as determined by the neurocognitive test guidelines which is part of the CANTAB test battery.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

The main objective of this study is to assess the efficacy of AFQ056 in reducing L-dopa induced dyskinesias.

Intervention(s)

Product Code: AFQ056
Pharmaceutical Form: Capsule, hard
CAS Number: 543906-09-8
Current Sponsor code: AFQ056
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Product Code: AFQ056
Pharmaceutical Form: Capsule, hard
CAS Number: 543906-09-8
Current Sponsor code: AFQ056
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Background, demographic and administrative assessments:
•Physical examination
•Hepatitis screen, HIV screen: Screening
•Hoehn and Yahr assessment (part of inclusion/exclusion criteria): screening
•Pregnancy test: Screening, Baseline (Day -4), Study Completion

Safety and tolerability assessments:
•Vital signs and body measurements
•ECG evaluation
•Hematology; Blood chemistry; Urinalysis
•Adverse events

Pharmacokinetic assessments:
•PK parameters and evaluations

Efficacy assessments
•Abnormal Involuntary Movement Scale (AIMS)
•Unified Parkinson Disease Rating Scale (UPDRS – part III)
•Unified Parkinson Disease Rating Scale (UPDRS – part IV)
•Lang-Fahn Activities of Daily Living Dyskinesia Scale (LFADLDS, sum score)
•Parkinson Disease Sleep Scale (PDSS)
•Beck depression scale
•Computerized CANTAB test battery including following cognitive functions tests

Exploratory biomarker assessments (optional)
•Pharmacogenomics

Secondary Objective: •To assess the anti-dyskinetic efficacy of multiple titrated doses of AFQ056 in combination with L-dopa in Parkinson’s patients with moderate to severe LIDs using the Abnormal Involuntary Movement Scale (AIMS) and UPDRS.

Exploratory objectives:
•To explore the potential relationship between the exposure of AFQ056 and the efficacy assessments after multiple dose treatment with AFQ056 in Parkinson’s patients with moderate to severe LIDs.
•To explore the potential effect of multiple doses of AFQ056 on the mGlu5 receptor pathway in Parkinson’s patients with moderate to severe LIDs.

Main Objective: •To assess the anti-dyskinetic efficacy of multiple titrated doses of AFQ056 on moderate to severe L-dopa induced dyskinesias (LIDs) in patients with Parkinson’s disease using the Lang-Fahn Activities of Daily Living Dyskinesia Scale (LFADLDS).
•To assess the potential anti-parkinsonian effect of multiple titrated doses of AFQ056 in combination with L-dopa in Parkinson’s patients with moderate to severe LIDs using the Unified Parkinson’s Disease Rating Scale (UPDRS) – part III.
•To assess the safety and tolerability of multiple titrated doses of AFQ056 in combination with L-dopa in Parkinson’s patients with moderate to severe LIDs.

Secondary ID(s)

Not applicable

CAFQ056A2203