A Study to Assess the Effect of Safinamide on Levodopa Pharmacokinetics

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01026428
Recruitment Status : Completed
First Posted : December 4, 2009
Last Update Posted : March 29, 2013
Information provided by (Responsible Party):
Newron Pharmaceuticals SPA

Brief Summary:

The objective of this study is to investigate the effect of safinamide on levodopa blood levels, both after single and multiple dosing of safinamide . A further objective of the study is to assess the safety and tolerability of safinamide when given together with levodopa in the applied regimen.

For that purpose, all study participants will undergo intensive blood sampling for investigation of levodopa levels and various tolerability examinations, such as the measurement of vital signs (blood pressure, pulse, body temperature), recording of ECGs and questioning to find out how the study participants are feeling. Furthermore, blood samples will be drawn and urine tests will be performed repeatedly for safety purpose during the course of the study.

The results of this clinical trial may be used for the drug registration of safinamide in the future.

Condition or disease Intervention/treatment Phase
Idiopathic Parkinson's Disease Drug: Safinamide + Levodopa Other: Placebo + Levodopa Phase 1 Phase 2

Detailed Description:
Treatments are given in a crossover design.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Official Title: A Randomised, Double-blind, Placebo-controlled, Two-period, Two-sequence-crossover Interaction Study to Assess the Effect of Safinamide on Levodopa Pharmacokinetics in Subjects With Parkinson's Disease
Study Start Date : September 2009
Actual Primary Completion Date : July 2010

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Safinamide + Levodopa Drug: Safinamide + Levodopa
Treatment A: 100mg safinamide once daily administration for 6 days + immediate release levodopa formulation (100 mg levodopa + 25 mg carbidopa = Nacom®).
Placebo Comparator: Placebo + Levodopa Other: Placebo + Levodopa
Treatment B: Placebo matching 100mg safinamide once daily administration for 6 days + immediate release levodopa formulation (100 mg levodopa + 25 mg carbidopa = Nacom®).

Primary Outcome Measures :
  1. AUC and Cmax of Levodopa [ Time Frame: Main pharmacocinetics measurements will be taken at Day 1 and 6 of each period. ]

Secondary Outcome Measures :
  1. tmax, CL, t1/2 of Levodopa [ Time Frame: Main pharmacocinetics measurements will be taken at Day 1 and 6 of each period. ]

Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Gender: male or female
  2. Age: 30 years
  3. Body Mass Index (BMI): 18 - 32 kg/m2
  4. Diagnosed with idiopathic Parkinson's disease, with Hoehn and Yahr (H&Y) of I-III
  5. Levodopa-responsive patients treated with a stable dose of levodopa/carbidopa
  6. Electrocardiogram recording (12 leads) normal or with abnormalities which are not hazardous to the patient according to the opinion of the investigator.
  7. Negative beta-HCG test and not lactating (females). Women who are of childbearing potential must be using acceptable methods of contraception and should be informed of the potential risks associated with becoming pregnant while enrolled within a clinical research study. Accepted forms of contraception are: i.e. intrauterine device and a barrier method, combined oral contraceptives and a barrier method, or double-barrier method throughout the study. Female volunteers who are post -menopausal or surgically sterile may be enrolled
  8. Ability to maintain an accurate and complete dosing diary, with the help of a caregiver, recording doses of levodopa and study medication taken at home All parameters will be determined within three weeks prior to first dosing. Subjects must have given written informed consent before any study-related activities are carried out

Exclusion Criteria:

To be eligible for inclusion in this study the subjects must not meet any of the following criteria:

  1. Co-administration of other drugs causing dopamine release (e.g. reserpine) or affecting levodopa metabolism (e.g COMT inhibitors except AADC inhibitors) or any other medication clinically contraindicated with MAO B inhibitors or with levodopa/carbidopa Note: Use of Selective serotonin reuptake inhibitors [SSRI] and selective noradrenalin reuptake inhibitors [SNRI] will be permitted, provided the dose is kept as low as possible and remains stable throughout the trial.
  2. Co-administration of other MAO inhibitors (e.g. selegiline, rasagiline)
  3. The patient is in a late stage of Parkinson's disease, and is experiencing severe, disabling peak-dose or biphasic dyskinesia and/or unpredictable or widely swinging fluctuations in their symptoms
  4. Any indication of forms of Parkinsonism, other than idiopathic Parkinson's disease.
  5. Treatment with any agent known to inhibit or induce drug-metabolizing enzymes (e.g., barbiturates, St John's Wort etc.) within 4 weeks prior study treatment
  6. Concomitant oral iron treatment
  7. History of hypersensitivity or contraindications to MAO-B inhibitors or levodopa
  8. Clinically relevant allergies (especially hypersensitivity toward any medicinal drugs)
  9. Significant hepatic impairment
  10. Significant renal impairment
  11. Diseases or surgeries of the gastrointestinal tract which could influence the gastrointestinal absorption and/or motility
  12. Diagnosis of Human Immunodeficiency Virus (HIV), or acute Hepatitis B or C
  13. Clinically relevant disease which in the investigator's opinion would exclude the subject from the study, such as significant cardiovascular and lung diseases, narrow-angle glaucoma or endocrinological diseases such as hyperthyroidism or pheochromocytoma
  14. A neoplastic disorder, which is either currently active or has been in remission for less than one year.
  15. Active psychiatric disease (e.g, schizophrenia, psychotic depression)
  16. History of melanoma or current cancer disease and undiagnosed, but melanoma suspicious skin lesion
  17. Signs for dementia which could interfere with the compliance to the study as judged by the investigator
  18. 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.
  19. Consumption of important quantities of coffee or tea corresponding to more than 600 mg caffeine/day, or tobacco smoking (more than 10 cigarettes per day)
  20. Diet considerably deviating from normal nutritional patterns (e.g. vegan; diets with very high protein content [Atkins])
  21. Participation in another clinical study within 30 days prior to the planned first drug administration
  22. Alcohol and drug abuse (during the past three years)
  23. Transfusion of blood or plasma derivatives within 3 month prior to the planned first drug administration
  24. Blood donation within 90 days before the start of the clinical study
  25. Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01026428

Research Site
Casino, Italy
Research Site
Roma, Italy
Sponsors and Collaborators
Newron Pharmaceuticals SPA
Study Director: Sonja Krösser, PhD Merck KGaA

Responsible Party: Newron Pharmaceuticals SPA Identifier: NCT01026428     History of Changes
Other Study ID Numbers: 28780
First Posted: December 4, 2009    Key Record Dates
Last Update Posted: March 29, 2013
Last Verified: January 2012

Keywords provided by Newron Pharmaceuticals SPA:
drug -drug interaction
Patients diagnosed with idiopathic Parkinson's disease, levodopa-responsive, treated with a stable dose of levodopa/carbidopa

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Antiparkinson Agents
Anti-Dyskinesia Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Aromatic Amino Acid Decarboxylase Inhibitors
Enzyme Inhibitors