Levodopa Concentration Profile With Stalevo 75/125 mg (NEWSTA)

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

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.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: Stalevo (levodopa/ carbidopa/ entacapone); Drug: Sinemet (levodopa/carbidopa)

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Finland
  • Espoo, Finland, 02101
    • Phase I Unit, Orion Pharma

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Orion Corporation, Orion Pharma
• Investigators: Principal Investigator: Kimmo Ingman, Orion Corporation, Orion Pharma

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): February 1, 2010

Study Registration Dates

• First Submitted: November 23, 2009
• First Submitted That Met QC Criteria: February 17, 2010
• First Posted (Estimate): February 18, 2010

Study Record Updates

• Last Update Posted (Estimate): August 13, 2010
• Last Update Submitted That Met QC Criteria: August 12, 2010
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Keywords: Pharmacokinetic
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunologic Factors; Dopamine Agonists; Dopamine Agents; Adjuvants, Immunologic; Antiparkinson Agents; Anti-Dyskinesia Agents; Catechol O-Methyltransferase Inhibitors; Aromatic Amino Acid Decarboxylase Inhibitors; Levodopa; Carbidopa; Carbidopa, levodopa drug combination; Entacapone
• Other Study ID Numbers: 2939131