Safinamide in Levodopa Induced Dyskinesia in Parkinson's Disease Subjects

NCT01113320 | Completed Phase 2

• 1 other identifier: EMR701165_023
• Study Type: interventional
• Target: 26
• Locations: 5 countries
• Sites: 11

Brief Summary

Approximately twenty four (24) subjects will participate in this research trial. The research trial will be conducted in approximately twelve (12) medical centers in the following countries: Germany, France, South Africa, Austria and Canada. The research trial will last until December 2011.

Conditions

Parkinson's Disease

Keywords

Safinamide - Parkinson's disease - Levodopa induced dyskinesia; Advanced idiopathic PD patients treated with L-dopa and suffering from temporally predictable L-dopa induced peak-dose dyskinesia.

Outcome Measures

Primary Outcomes (1)

• The maximum reduction in Unified Dyskinesia Rating Score (UDysRS) compared to baseline across all post-baseline dose visits.

  Day 66

Secondary Outcomes (36)

• Complete new Movement Disorder Society - Unified Parkinson Disease Rating Scale (MDS-UPDRS) and subscales

  At each individual post-dose visit: Baseline

• Complete new Movement Disorder Society - Unified Parkinson Disease Rating Scale (MDS-UPDRS) and subscales

  At each individual post-dose visit: Day 8

• Complete new Movement Disorder Society - Unified Parkinson Disease Rating Scale (MDS-UPDRS) and subscales

  At each individual post-dose visit: Day 22

• Complete new Movement Disorder Society - Unified Parkinson Disease Rating Scale (MDS-UPDRS) and subscales

  At each individual post-dose visit: Day 36

• Complete new Movement Disorder Society - Unified Parkinson Disease Rating Scale (MDS-UPDRS) and subscales

  At each individual post-dose visit: Day 66

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Safinamide

ACTIVE COMPARATOR

Drug: Safinamide

Interventions

Placebo DRUG

Evaluable dose levels are 100 mg (8 days), 200 mg (10 days), and 300 mg (42 days). Intermediate dose levels are 150 mg (Study days 9-11) and 250 mg (Study days 23-25) and have a duration of three days. Safinamide and identical Placebo will be provided in tablets equivalent of 50 mg in blisters. Dosing will be achieved using appropriate multiples of these tablet strengths

Placebo

Safinamide DRUG

Evaluable dose levels are 100 mg (8 days), 200 mg (10 days), and 300 mg (42 days). Intermediate dose levels are 150 mg (Study days 9-11) and 250 mg (Study days 23-25) and have a duration of three days. Safinamide will be provided in tablets of 50 mg in blisters. Dosing will be achieved using appropriate multiples of these tablet strengths

Safinamide

Eligibility Criteria

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

You may qualify if:

• The subject has given his/her written informed consent to participate in the trial.
• The subject presents with a diagnosis of idiopathic Parkinson's disease according to the United Kingdom (UK) Parkinson's Disease Society Brain Bank Clinical Diagnosis Criteria
• The subject is an out-patient aged 30 years or above.
• PD subjects with a Hoehn and Yahr disease staging of II-IV (in the ON state).
• PD subjects experiencing levodopa induced dyskinesias, specifically predictable peak-dose dyskinesia.
• Peak-dose dyskinesia must be considered by the subject to be problematic and/or disabling.
• Peak-dose dyskinesia must warrant medical treatment in the Investigator's opinion.
• The subject has participated successfully in a diary-card training session.
• In the judgment of the Investigator based on the subject's history, previous treatments, and the clinical presentation, the subject is considered as being optimally treated at screening (i.e., further adjustments of current medication will not further improve the subject's symptoms of Parkinson's disease).
• Stable dose of PD drugs for at least 4 weeks before Screening Visit. This may include: levodopa dopamine agonists, c-ortho methyl transferase (COMT) inhibitors, and anticholinergics.
• The dose of levodopa and all PD drugs used during the trial must remain unchanged throughout the trial.
• Female subjects must be neither pregnant or breast-feeding and must lack child-bearing potential, as defined either by:
• be either post menopausal for at least 2 years , surgically sterilised or have undergone hysterectomy, or
• if of child bearing potential, be willing to avoid pregnancy by using an adequate method of contraception for four weeks prior to, during and four weeks after the last dose of trial medication. For the purposes of this trial, women of childbearing potential are defined as all female subjects after puberty unless they are post-menopausal for at least two years, are surgically sterile or are sexually inactive.
• The subject shows adequate compliance with the schedule for intake of trial medication and the completion of the diaries.

You may not qualify if:

• The subject has participated in any safinamide clinical trial before.
• The subject is experiencing exclusively diphasic, off state, myoclonic, dystonic, or akathetic dyskinesias without peak dose dyskinesia.
• (For female subjects) The subject is pregnant or lactating.
• Treatment with a MAO-B inhibitor within the eight weeks prior to the screening visit.
• Treatment with amantadine in the four weeks prior to the screening visit or budipine in the eight weeks prior to the screening visit.
• Treatment with opioids (e.g., tramadol, meperidine derivatives), serotonin norepinephrine reuptake inhibitors (SNRIs) (e.g. venlafaxine, duloxetine), tri- or tetra-cyclic antidepressants, in the past 8 weeks prior to the screening visit. Dextromethorphan will be permitted if used for treating cough.
• The subject has received neurosurgical intervention related to PD (e.g. deep brain stimulation, thalamotomy etc.) or is scheduled to do so during the trial period.
• Neoplastic disorder, which is either currently active or has been in remission for less than one year.
• Diagnosis of HIV, or positive test for Hepatitis C antibodies, or Hepatitis B surface antigen.
• Concomitant disease likely to interfere with trial medication (e.g. capable of altering absorption, metabolism, or elimination of the trial drug).
• The subject has any clinically significant illness that, in the Investigator's opinion, might interfere with the subject's ability to participate in the trial.
• Second- or third-degree atrio-ventricular block or sick sinus syndrome, uncontrolled atrial fibrillation, severe or unstable angina, congestive heart failure, myocardial infarction within 3 months of the screening visit, or a significant ECG abnormality, including corrected QT interval (QTc) - 450 msec (males) or - 470 msec (females), where QTc is based on Bazett's correction method.
• Ophthalmologic history including any of the following conditions: albino subjects, family history of hereditary retinal disease, progressive and/or severe diminution of visual acuity (i.e., 20/70), retinitis pigmentosa, retinal pigmentation due to any cause, any active retinopathy or ocular inflammation (uveitis), or diabetic retinopathy
• The subject is suffering from any dementia or other psychiatric illness that prevents him/her from giving informed consent, i.e. Montreal Cognitive Assessment (MoCA) \<23 points.
• Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such.

Sponsors & Collaborators

• Newron Pharmaceuticals SPA: lead

Study Sites (11)

Medical University Graz, Klinische Abteilung für Spezielle Neurologie

Graz, Austria

Location

Medical University Innsbruck, Dept. of Neurology

Innsbruck, Austria

Location

Quebec Memory and Motor Skills Disorders

Québec, Canada

Location

Hôpital Roger Sallengro

Lille, France

Location

CIC-Hospital Purpan

Toulouse, France

Location

Neurologie Berlin Praxen

Berlin, Germany

Location

St. Josef Hospital, Klinik für Neurologie

Bochum, Germany

Location

Facharzt für Neurologie und Psychiatrie

Düsseldorf, Germany

Location

Medical and Dental center (ZAF)

Johannesburg, South Africa

Location

Sunninghill Hospital

Johannesburg, South Africa

Location

Willows Medical Centre

Pretoria, South Africa

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

safinamide

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Jonathan Willmer, MD

  Merck Serono S.A., Geneva

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: April 8, 2010
• First Posted: April 29, 2010
• Study Start: April 1, 2010
• Primary Completion: November 1, 2011
• Study Completion: January 1, 2012
• Last Updated: March 29, 2013

Record last verified: 2012-01

Locations

ZA (3); CA (1); AU (2); FR (2); DE (3)