A Study to Assess the Effect of Safinamide on Levodopa Pharmacokinetics

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Newron Sweden AB
ClinicalTrials.gov Identifier:
NCT01026428
First received: December 1, 2009
Last updated: March 27, 2013
Last verified: January 2012
  Purpose

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 Intervention Phase
Idiopathic Parkinson's Disease
Drug: Safinamide + Levodopa
Other: Placebo + Levodopa
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Newron Sweden AB:

Primary Outcome Measures:
  • AUC and Cmax of Levodopa [ Time Frame: Main pharmacocinetics measurements will be taken at Day 1 and 6 of each period. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • tmax, CL, t1/2 of Levodopa [ Time Frame: Main pharmacocinetics measurements will be taken at Day 1 and 6 of each period. ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: September 2009
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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®).

Detailed Description:

Treatments are given in a crossover design.

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT01026428

Locations
Italy
Research Site
Casino, Italy
Research Site
Roma, Italy
Sponsors and Collaborators
Newron Sweden AB
Investigators
Study Director: Sonja Krösser, PhD Merck KGaA
  More Information

No publications provided

Responsible Party: Newron Sweden AB
ClinicalTrials.gov Identifier: NCT01026428     History of Changes
Other Study ID Numbers: 28780
Study First Received: December 1, 2009
Last Updated: March 27, 2013
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by Newron Sweden AB:
safinamide
levodopa
drug -drug interaction
pharmacokinetics
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
Levodopa
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 19, 2014