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

This study has been terminated.
(The Dopamine transporter brain imaging trial is terminated due to a company decision to return all rights for Safinamide back to Newron Pharmaceuticals)
Sponsor:
Information provided by (Responsible Party):
Newron Sweden AB
ClinicalTrials.gov Identifier:
NCT01264861
First received: December 20, 2010
Last updated: March 28, 2013
Last verified: February 2012
  Purpose

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.


Condition Intervention Phase
Parkinson Disease
Drug: Safinamide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Newron Sweden AB:

Primary Outcome Measures:
  • 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. [ Time Frame: Every two weeks for six weeks ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Every two weeks for six weeks ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Every two weeks for six weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. [ Time Frame: Every two weeks for six weeks ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Every two weeks for six weeks ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Every two weeks for six weeks ] [ Designated as safety issue: No ]

Enrollment: 5
Study Start Date: December 2010
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.


  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01264861

Locations
United States, Connecticut
Molecular Neuroimaging, LLC
New Haven, Connecticut, United States
Sponsors and Collaborators
Newron Sweden AB
Investigators
Study Director: Kenneth Marek, MD Molecular Neuroimaging / Institute for Neurodegenerative Disorders
  More Information

No publications provided

Responsible Party: Newron Sweden AB
ClinicalTrials.gov Identifier: NCT01264861     History of Changes
Other Study ID Numbers: 28849
Study First Received: December 20, 2010
Last Updated: March 28, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Newron Sweden AB:
Evaluate dopamine and serotonin activity in the brain at 3 doses of Safinamide

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Serotonin
Dopamine
Dopamine Agents
Serotonin Receptor Agonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Cardiotonic Agents
Cardiovascular Agents
Therapeutic Uses
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Protective Agents

ClinicalTrials.gov processed this record on September 30, 2014