A Study to Evaluate Safinamide's Effect on Dopamine and Serotonin's Availability by Using Brain Imaging

Open-Label Escalating Dose Study Using [123|]ß-CIT SPECT Single Photon Emission Computerized Tomography (SPECT) to Evaluate Dopamine and Serotonin Transporter Occupancy by Safinamide in Parkinson Disease Patients

This is a study of safinamide, an investigational drug for Parkinson disease (PD). Safinamide is being developed as add-on therapy for the treatment of Parkinson disease. It is theorized that safinamide acts by increasing the available dopamine in those areas of the brain where dopamine is decreased as a result of Parkinson;s Disease. . Dopamine in the brain is involved in controlling body movements. Safinamide has been extensively studied in animals, and has been shown to increase the level of dopamine in these animals. Safinamide has also been tested in patients with Parkinson disease. The goal of this research trial is to see if safinamide is safe and well tolerated and to better understand how it affects the dopamine system in the brain in individuals with Parkinson disease. Data from this trial may provide essential information about the effectiveness and safety of these doses of safinamide in patients with early Parkinson disease, who are already receiving a stable dose of their normal Parkinson disease treatment.

Study Overview

• Status: Terminated
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: Safinamide

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Molecular NeuroImaging, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female, between 40-80 years of age.
2. Subject must have a diagnosis of idiopathic Parkinson's disease, and a Hoehn and Yahr stage of I-III.
3. Subjects must be concomitantly treated with a stable dose of a single dopamine agonist prior to the screening visit.
4. Subjects must be able to understand and willing to sign an approved Informed Consent form.
5. Female subjects must be neither pregnant or breast-feeding.

Exclusion Criteria:

1. Subjects with any form of Parkinsonism other than idiopathic Parkinson's disease.
2. Subjects currently experiencing motor fluctuations (end of dose wearing off), dyskinesias, or significant postural hypotension.
3. Subjects treated with l-dopa, anticholinergics, amantadine, MAO inhibitors, COMT inhibitors, tricyclic antidepressants, and / or SSRI and SNRI antidepressants.
4. Subjects with a history of psychosis, either previously or currently, or a score ≥ 3 on item 2 or 3 of the UPDRS Part I.
5. Subjects with evidence of dementia or cognitive dysfunction.
6. Subjects with current diagnosis of substance abuse or history of alcohol or drug abuse in the past three months.
7. Subjects with current clinically significant gastrointestinal, renal, hepatic, endocrine, pulmonary or cardiovascular disease, including hypertension that is not well controlled, asthma, chronic obstructive pulmonary disease, and Type I diabetes.
8. Subjects with a concomitant disease likely to alter absorption, metabolism or elimination of the study drug.
9. Female subjects must be neither pregnant nor lactating.
10. Subjects with hypersensitivity or contraindications to MAO-B inhibitors.
11. Subjects with a neoplastic disorder, which is either currently active or has been in remission for less than one year.
12. Subjects with second- or third-degree atrio-ventricular block or sick sinus syndrome, uncontrolled atrial fibrillation, severe or unstable angina, congestive heart failure, myocardial infarction within three months of the screening visit, or significant ECG abnormality, including QTc ≥ 450 msec (males) or ≥ 470 msec (females), where QTc is based on Bazett's correction method.
13. Subjects with a history or a current diagnosis of human immunodeficiency virus infection, or tests positive for Hepatitis B surface antigen, tests positive for Hepatitis B core antibody, but negative for Hepatitis B surface antibody, or tests positive for Hepatitis C antibodies.
14. Subjects who have participated in a previous clinical trial with safinamide, have participated in a previous clinical trial within 30 days of entry into the study, or have received treatment with any investigational compound within thirty days or five half-lives, whichever is longer, prior to screening.
15. Subjects with any abnormality that the investigator deems to be clinically relevant.
16. Legal incapacity or limited legal capacity
17. Other significant disease that in the Investigator's opinion would exclude the subject from the trial.
18. Treatment with a drug that has hepatotoxic potential within 4 weeks, or received radiation therapy or a drug with cytotoxic potential within one year prior to the screening visit.
19. Ophthalmologic history including any of the following conditions: albino subjects, family history of hereditary retinal disease, progressive and/or severe diminution of visual acuity, retinitis pigmentosa, retinal pigmentation due to any cause, any active retinopathy or ocular inflammation, or diabetic retinopathy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Arm 1: Arm 1: Eligible subjects will receive escalating doses of safinamide for the 6-week duration of treatment. Each dose level will be last 10-14 days. Doses 200mg and 300mg will have a 3 day intermediate step up dose, 150mg and 250mg dose.

Drug: Safinamide; Safinamide 100 mg/day = two 50 mg tablets administered orally, once a day, in the morning, with or without food. Safinamide 200 mg/day = four 50 mg tablets administered orally, once a day, in the morning, with or without food; this will be preceded by a three day titration of 150 mg = three 50 mg tablets administered orally, once a day, in the morning, with or without food. Safinamide 300 mg/day = six 50 mg tablets administered orally, once a day, in the morning, with or without food; this will be preceded by a three day titration of 250 mg = five 50 mg tablets administered orally, once a day, in the morning, with or without food.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The percent change from baseline to steady state (end of dosing period for 100 mg daily safinamide doses) on quantitative determinations of occupancy of the dopamine transporter in striatum as determined by [123|] ß-CIT SPECT scanning.	Every two weeks for six weeks
The percent change from baseline to steady state (end of dosing period for 200 mg daily safinamide doses) on quantitative determinations of occupancy of the dopamine transporter in striatum as determined by [123|] ß-CIT SPECT scanning.	Every two weeks for six weeks
The percent change from baseline to steady state (end of dosing period for 300 mg daily safinamide doses) on quantitative determinations of occupancy of the dopamine transporter in striatum as determined by [123|] ß-CIT SPECT scanning.	Every two weeks for six weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
The percent change from baseline to steady state (end of dosing period for 100 mg daily safinamide doses) on quantitative determinations of occupancy of the serotonin transporter in brainstem as determined by [123|] ß-CIT SPECT scanning.	Every two weeks for six weeks
The percent change from baseline to steady state (end of dosing period for 200 mg daily safinamide doses) on quantitative determinations of occupancy of the serotonin transporter in brainstem as determined by [123|] ß-CIT SPECT scanning.	Every two weeks for six weeks
The percent change from baseline to steady state (end of dosing period for 300 mg daily safinamide doses) on quantitative determinations of occupancy of the serotonin transporter in brainstem as determined by [123|] ß-CIT SPECT scanning.	Every two weeks for six weeks

Collaborators and Investigators

• Sponsor: Newron Pharmaceuticals SPA
• Investigators: Study Director: Kenneth Marek, MD, Molecular Neuroimaging / Institute for Neurodegenerative Disorders

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2011
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 24, 2012

Study Registration Dates

• First Submitted: December 20, 2010
• First Submitted That Met QC Criteria: December 20, 2010
• First Posted (Estimate): December 22, 2010

Study Record Updates

• Last Update Posted (Actual): September 18, 2017
• Last Update Submitted That Met QC Criteria: September 15, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Evaluate dopamine and serotonin activity in the brain at 3 doses of Safinamide
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: 28849