Levodopa Concentration Profile With Stalevo 75/125 mg

Study Overview
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Brief Summary
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The purpose of this study is to confirm that the dose levels and dosing frequency utilising the new Stalevo strengths would result into more stable levodopa plasma levels. Therefore, it is anticipated that when lower dose of Stalevo is administered after the first higher dose of Stalevo, this would result in equally high levodopa maximum concentration values (Cmax) after each dose throughout the day compared to Cmax after the first dose.

Official Title
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Levodopa Concentration Profile After Repeated Doses of Different Stalevo® Strengths With 3.5 Hours Dosing Frequency; an Open, Randomised, Crossover, Levodopa/Carbidopa Controlled Single Centre Study in Healthy Subjects, Two Parallel Groups

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: Stalevo (levodopa/ carbidopa/ entacapone)
* Drug: Sinemet (levodopa/carbidopa)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent (IC) obtained. Good general health ascertained by detailed medical history, and laboratory and physical examinations. Finnish speaking males or females, 18-70 years of age inclusive. Normal weight defined as body mass index (BMI) 18.5-30.0 kg/m2 (inclusive) (BMI = weight/height2). Weight at least 50.0 kg. Regular intestinal transit (no recent history of recurrent constipation, diarrhoea, or other intestinal problems). Exclusion Criteria: Evidence of a clinically significant cardiovascular, renal, hepatic, haematological, gastrointestinal, pulmonary, metabolic-endocrine, neurological, urogenital or psychiatric disease as judged by the investigator. Any condition requiring regular concomitant treatment (including vitamins and herbal products) or likely to need any concomitant treatment during the study. As an exception, contraceptives or hormone replacement therapy are allowed. Intake of any medication that could affect the outcome of the study. Any clinically significant abnormal laboratory value or physical finding (including electrocardiogram [ECG]) and vital signs) that may interfere with the interpretation of test results or cause a health risk for the subject if he/she participates in the study, as judged by the investigator. Orthostatic hypotension; systolic and diastolic BP and heart rate HR after 3 minutes in supine position and after 3 minutes of standing: decrease of ≥ 20 mmHg for systolic BP decrease of ≥ 10 mmHg for diastolic BP. Strong tendency to motion sickness. Known hypersensitivity to the active substance(s) or to any of the excipients of the drug. Pregnant or lactating females. Females of childbearing potential if they are not using proper contraception (hormonal contraception, intrauterine device (IUD) or surgical sterilization, spermicidal foam/Vagitorie, condom on male partner). Double methods (mentioned above) of contraception is needed during the study. (Note: women of childbearing potential with no current sexual relationship can be included without contraception according to the judgement of the investigator). Recent or current (suspected) drug abuse or positive result in the drug abuse test. Recent or current alcohol abuse (regular drinking more than 21 units per week for males and more than 16 units per week for females [1 unit = 4 cl spirits or equivalent]). Current use of nicotine containing products more than 5 cigarettes (or equivalent)/day and/or inability to refrain from the use of nicotine containing products during the stay at the study centre. Use of caffeine containing beverages more than 600 mg of caffeine/day and/or inability to refrain from the use of caffeine containing beverages while at the study centre. Blood donation or loss of significant amount of blood within 90 days prior to the first study treatment administration. Administration of another investigational treatment within 90 days prior to the first study treatment administration. Unsuitable veins for repeated venipuncture or for cannulation. Predictable poor compliance or inability to communicate well with the study centre personnel. Inability to participate in all treatment periods.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stalevo (levodopa/carbidopa/entacapone)<br>125mg or 75mg of levodopa during treatment period 1 in groups 1 and 2 respectively. 150mg or 100mg of levodopa during treatment period 2 in groups 1 and 2 respectively. | Drug: Stalevo (levodopa/ carbidopa/ entacapone)<br>* 150mg, 125 mg, 100mg, 75mg of levodopa q.i.d. in 3.5 h interval<br>* Other names: Stalevo;|
| Active Comparator: Sinemet (levodopa/carbidopa)<br>150mg or 100mg of levodopa during treatment period 3 in study groups 1 and 2 respectively | Drug: Sinemet (levodopa/carbidopa)<br>* 150 or 100 mg levodopa q.i.d. in 3.5 hr interval<br>* Other names: Sinemet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To demonstrate that reduced Stalevo strengths 75 mg and 125 mg following initial 100 mg and 150 mg strengths, will not increase Cmax of levodopa compared to Stalevo or levodopa/carbidopa dosing using equal strengths during the day. |  | 2-11 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmin, AUCo-tau |  | each subject 3 PK days between 1-6 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetic