A trial to determine if safinamide can attenuate levodopa induced dyskinesia in Parkinson’s disease.

• Conditions: Idiopathic Parkinson's disease; MedDRA version: 14.0Level: PTClassification code 10061536Term: Parkinson's diseaseSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2009-017174-20-DE
• Lead Sponsor: Merck Serono S.A. - Geneva

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-01-07
• Last Update Posted: 4 March 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

The desired population to trial is advanced idiopathic PD patients treated with L-dopa and suffering from temporally predictable L-dopa induced peak-dose dyskinesia.
For inclusion in the trial, all of the following inclusion criteria must be fulfilled:
1. The subject has given his/her written informed consent to participate in the trial.
2. The subject presents with a diagnosis of idiopathic Parkinson's disease according to the UK Parkinson's Disease Society Brain Bank Clinical Diagnosis Criteria.
3. The subject is an out-patient aged 30 years or above.
4. PD subjects with a Hoehn and Yahr disease staging of II-IV (in the ON state).
5. PD subjects experiencing levodopa induced dyskinesias, specifically predictable peak-dose dyskinesia.
6. Peak-dose dyskinesia must be considered by the subject to be problematic and/or disabling.
7. Peak-dose dyskinesia must warrant medical treatment in the Investigator’s opinion.
8. The subject has participated successfully in a diary-card training session.
9. 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 the present time (i.e., further adjustments of current medication are not expected to further improve the subject's symptoms of Parkinson's disease).
10. Stable dose of all PD drugs for at least 4 weeks before Screening Visit. This may include: levodopa dopamine agonists, COMT inhibitors, and anticholinergics.
11. The dose of levodopa and all PD drugs used during the trial must remain unchanged throughout the trial.
12. 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.
13. The subject shows adequate compliance with the schedule for intake of trial medication and the completion of the diaries.
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

Subjects are not eligible for this trial if they fulfil any of the following exclusion criteria:
1. The subject has participated in any safinamide clinical trial before.
2. The subject is experiencing exclusively diphasic, off state, myoclonic, dystonic, or akathetic dyskinesias without peak dose dyskinesia.
3. (For female subjects) The subject is pregnant or lactating.
4. Treatment with a MAO-B inhibitor within the eight weeks prior to the screening visit.
5. Treatment with amantadine in the four weeks prior to the screening visit or budipine in the eight weeks prior to the screening visit.
6. Treatment with opioids (e.g., tramadol, meperidine derivatives), SNRIs (e.g. venlafaxine, duloxetine), tri- or tetra-cyclic antidepressants, in the 8 weeks prior to the screening visit. Dextromethorphan will be permitted if used for treating cough.
7. 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.
8. Current clinically significant gastro-intestinal, renal, hepatic, endocrine, pulmonary or cardiovascular disease, including acute gastric ulcer, hypertension that is not well controlled, asthma, chronic obstructive pulmonary disease (COPD), and unstable Type I diabetes. Subjects with a history of gastric ulcer who have not had a recent episode of acute gastritis and are not currently experiencing gastric pain will be eligible for inclusion.
9. Neoplastic disorder, which is either currently active or has been in remission for less than one year.
10. Diagnosis of HIV, or positive test for Hepatitis C antibodies, or Hepatitis B surface antigen.
11. Concomitant disease likely to interfere with trial medication (e.g. capable of altering absorption, metabolism, or elimination of the trial drug).
12. 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.
13. 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 QTc – 450 msec (males) or – 470 msec (females), where QTc is based on Bazett’s correction method.
14. 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
15. The subject is suffering from dementia or other severe neuropsychiatric illness that prevents him/her from giving informed consent, or has a total score on the MoCA <23 points.
16. Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such.
17. Known hypersensitivity to the trial treatment(s), including placebo or other comparator drug(s).
18. The subject has legal incapacity or limited legal capacity.
19. The subject is participating in another clinical trial or has done so within the past 30 days.
20. Treatment with a drug that has hepatotoxic potential e.g., tamoxifen, within 4 weeks, or received radiation therapy or a drug with cytotoxic potential, e.g, chemotherapy, within 1 year prior to the screening v

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this trial is to determine the maximum reduction in Unified Dyskinesia Rating Score (UDysRS) compared to baseline across all post-baseline dose visits.;Secondary Objective: To explore the impact of safinamide dose for anti-dyskinetic activity of safinamide in late-stage Parkinson's Disease (PD) patients with l-dopa induced dyskinesias, and to evaluate changes from baseline in motor fluctuations, motor function, activities of daily living, and change in global clinical status.<br>To further characterize the safety and tolerability of safinamide in late-stage Parkinson’s disease patients with l-dopa induced dyskinesias. ;Primary end point(s): Unified Dyskinesia Rating Scale (UDysRS) - maximum reduction in UDysRS total score from baseline to all post-baseline dose visits.<br>;Timepoint(s) of evaluation of this end point: week 13

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Efficacy variables: <br>- Complete new MDS-UPDRS and subscales<br>- Patients diary <br>- Parkinson Disease Dyskinesia Scale – 26 items (PDYS-26) <br>- Clinician Global Impression (CGI) (dyskinesia specific)<br>- Patient Global Impression (PGI) (dyskinesia specific)<br><br>Safety variables including physical, neurological, ophthalmological, and dermatological examinations, medical history, adverse event assessments, hematologic, urine, and clinical chemistry results, and ECGs from baseline to end of trial.;Timepoint(s) of evaluation of this end point: week 13