A Study to Assess the Effect of Safinamide on Levodopa Pharmacokinetics

NCT01026428 | Completed Phase 1

• 1 other identifier: 28780
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

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.

Conditions

Idiopathic Parkinson's Disease

Keywords

safinamide; levodopa; drug -drug interaction; pharmacokinetics; Patients diagnosed with idiopathic Parkinson's disease, levodopa-responsive, treated with a stable dose of levodopa/carbidopa

Outcome Measures

Primary Outcomes (1)

• AUC and Cmax of Levodopa

  Main pharmacocinetics measurements will be taken at Day 1 and 6 of each period.

Secondary Outcomes (1)

• tmax, CL, t1/2 of Levodopa

  Main pharmacocinetics measurements will be taken at Day 1 and 6 of each period.

Study Arms (2)

Safinamide + Levodopa

EXPERIMENTAL

Drug: Safinamide + Levodopa

Placebo + Levodopa

PLACEBO COMPARATOR

Other: Placebo + Levodopa

Interventions

Safinamide + Levodopa DRUG

Treatment A: 100mg safinamide once daily administration for 6 days + immediate release levodopa formulation (100 mg levodopa + 25 mg carbidopa = Nacom®).

Safinamide + Levodopa

Placebo + Levodopa OTHER

Treatment B: Placebo matching 100mg safinamide once daily administration for 6 days + immediate release levodopa formulation (100 mg levodopa + 25 mg carbidopa = Nacom®).

Placebo + Levodopa

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Gender: male or female
• Age: 30 years
• Body Mass Index (BMI): 18 - 32 kg/m2
• Diagnosed with idiopathic Parkinson's disease, with Hoehn and Yahr (H\&Y) of I-III
• Levodopa-responsive patients treated with a stable dose of levodopa/carbidopa
• Electrocardiogram recording (12 leads) normal or with abnormalities which are not hazardous to the patient according to the opinion of the investigator.
• 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
• 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

You may not qualify if:

• 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.
• Co-administration of other MAO inhibitors (e.g. selegiline, rasagiline)
• 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
• Any indication of forms of Parkinsonism, other than idiopathic Parkinson's disease.
• 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
• Concomitant oral iron treatment
• History of hypersensitivity or contraindications to MAO-B inhibitors or levodopa
• Clinically relevant allergies (especially hypersensitivity toward any medicinal drugs)
• Significant hepatic impairment
• Significant renal impairment
• Diseases or surgeries of the gastrointestinal tract which could influence the gastrointestinal absorption and/or motility
• Diagnosis of Human Immunodeficiency Virus (HIV), or acute Hepatitis B or C
• 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
• A neoplastic disorder, which is either currently active or has been in remission for less than one year.
• Active psychiatric disease (e.g, schizophrenia, psychotic depression)

Sponsors & Collaborators

• Newron Pharmaceuticals SPA: lead

Study Sites (2)

Research Site

Casino, Italy

Location

Research Site

Roma, Italy

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

safinamide; Levodopa

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Tyrosine

Study Officials

• Sonja Krösser, PhD

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2009
• First Posted: December 4, 2009
• Study Start: September 1, 2009
• Primary Completion: July 1, 2010
• Last Updated: March 29, 2013

Record last verified: 2012-01

Locations

IT (2)