A Study to Assess the Effect of Safinamide on Levodopa Pharmacokinetics

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT01026428
• Date of registration: 01/12/2009
• Prospective Registration: No
• Primary sponsor: Newron
• Public title: A Study to Assess the Effect of Safinamide on Levodopa Pharmacokinetics
• Scientific 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
• Date of first enrolment: September 2009
• Target sample size: 24
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT01026428
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
• Phase: Phase 1/Phase 2

Countries of recruitment

Italy

Contacts

• Name: Sonja Krösser, PhD
• Affiliation: Merck KGaA

Key inclusion & exclusion 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.



Age minimum: 30 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Idiopathic Parkinson's Disease

Intervention(s)

Drug: Safinamide + Levodopa

Other: Placebo + Levodopa

Primary Outcome(s)

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

Secondary Outcome(s)

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

Secondary ID(s)

28780

Source(s) of Monetary Support

Please refer to primary and secondary sponsors