Study to Evaluate the Pharmacokinetics, Safety, Tolerability of Repeated Dose Transdermal Rotigotine in Japanese and Caucasian Subjects

Study Overview
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Brief Summary
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To investigate the repeated dose Pharmacokinetics (PK) of transdermally delivered Rotigotine in Japanese and Caucasian female and male healthy subjects.

Official Title
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Parallel Group Trial to Evaluate the Pharmacokinetics and Safety/Tolerability of Repeated Dose Treatment With Rotigotine Continuous Delivery System (5 cm^2/2.25 mg, 10 cm^2/4.5 mg, 20 cm^2/9 mg) in Japanese and Caucasian Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Rotigotine transdermal patch 1mg / 24 hours
* Drug: Rotigotine transdermal patch 2 mg / 24 hours
* Drug: Rotigotine transdermal patch 4 mg / 24 hours


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is healthy according to assessments done at eligibility assessment (medical history, physical examination, blood pressure, heart rate, ECG, hematology, clinical chemistry, urinalysis) Subject is of normal body-weight as determined by a body mass index ranging between 18 to 28 kg/m² Subject is Japanese or Caucasian. Japanese subjects are born in Japan and left Japan not more than 10 years ago. Both parents of the Japanese subjects are 100 % Japanese Exclusion Criteria: Subjects (females) without medically adequate contraception or on lactation or pregnant women. Subjects with oral contraception or hormone replacement within 4 weeks prior to eligibility assessment Subject has a history of chronic alcohol or drug abuse Subject has a consumption of more than 20 g of alcohol/day (amount corresponds to 0.5 l of beer/day or 0.25 l of wine/day or 3 glasses (à 2 cl) of liquor/day) Subject has a clinically relevant allergy Subject has a known or suspected drug hypersensitivity in particular, to any component of the trial medication Subject has any clinically significant abnormality in physical examination Subject has a heart rate at rest less than 50 beats per minute (bpm) or more than 100 bpm Subject has systolic blood pressure lower than 100 mmHg or higher than 145 mmHg or diastolic blood pressure higher than 95 mmHg or lower than 60 mmHg Subject has an atopic or eczematous dermatitis and/or an active skin disease or skin tumors Subject has a history of significant skin hypersensitivity to adhesives or other transdermal products or recent unresolved contact dermatitis

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 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

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rotigotine in Japanese subjects<br>Repeated-Dose application of 1,2, and 4 mg / 24 hours Rotigotine in healthy Japanese subjects; Transdermal patch over 24 hours | Drug: Rotigotine transdermal patch 1mg / 24 hours<br>* Rotigotine transdermal patch, repeated dose application over 24 hours; 1 mg / 24 hours<br>* Other names: Neupro;Drug: Rotigotine transdermal patch 2 mg / 24 hours<br>* Rotigotine transdermal patch, repeated dose application over 24 hours; 2 mg / 24 hours<br>* Other names: Neupro;Drug: Rotigotine transdermal patch 4 mg / 24 hours<br>* Rotigotine transdermal patch, repeated dose application over 24 hours; 4 mg / 24 hours<br>* Other names: Neupro;|
| Experimental: Rotigotine in Caucasian subjects<br>Multiple-Dose application of 1, 2, and 4 mg / 24 hours Rotigotine in healthy Caucasian subjects; Transdermal patch over 24 hours | Drug: Rotigotine transdermal patch 1mg / 24 hours<br>* Rotigotine transdermal patch, repeated dose application over 24 hours; 1 mg / 24 hours<br>* Other names: Neupro;Drug: Rotigotine transdermal patch 2 mg / 24 hours<br>* Rotigotine transdermal patch, repeated dose application over 24 hours; 2 mg / 24 hours<br>* Other names: Neupro;Drug: Rotigotine transdermal patch 4 mg / 24 hours<br>* Rotigotine transdermal patch, repeated dose application over 24 hours; 4 mg / 24 hours<br>* Other names: Neupro;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve of unconjugated Rotigotine in steady-state within one dosing interval (AUCtau,ss) |  | Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours | 
| Area under the concentration-time curve of unconjugated Rotigotine in steady-state within one dosing interval normalized by Body Weight [AUCtau,ss,norm(BW)] |  | Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours | 
| Maximum concentration of unconjugated Rotigotine in plasma at steady-state (Cmax,ss) |  | Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours | 
| Maximum concentration of unconjugated Rotigotine in plasma at steady-state normalized by Body Weight [Cmax,ss,norm(BW)] |  | Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours | 
| Maximum concentration of unconjugated Rotigotine in plasma at steady-state normalized by apparent dose [Cmax,ss,norm(appd)] |  | Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours | 
| Maximum concentration of unconjugated Rotigotine in plasma at steady-state normalized by Body Weight and apparent dose [Cmax,ss,norm(BW,appd)] |  | Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours | 
| Area under the concentration-time curve of total Rotigotine in steady-state within one dosing interval (AUCtau,ss) |  | Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours | 
| Area under the concentration-time curve of total Rotigotine in steady-state within one dosing interval normalized by Body Weight [AUCtau,ss,norm(BW)] |  | Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours | 
| Maximum concentration of total Rotigotine in plasma at steady-state (Cmax,ss) |  | Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours | 
| Maximum concentration of total Rotigotine in plasma at steady-state normalized by Body Weight [Cmax,ss,norm(BW)] |  | Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours | 
| Maximum concentration of total Rotigotine in plasma at steady-state normalized by apparent dose [Cmax,ss,norm(appd)] |  | Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours | 
| Maximum concentration of total Rotigotine in plasma at steady-state normalized by Body Weight and apparent dose [Cmax,ss,norm(BW,appd)] |  | Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Terminal half-life (t1/2) of unconjugated Rotigotine in steady-state |  | Blood sampling at 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours | 
| Time of maximum concentration (tmax) of unconjugated Rotigotine in steady-state (tmax,ss) |  | Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours | 
| Apparent total body clearance of unconjugated Rotigotine normalized by Body Weight (CL/f/BW) |  | Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours | 
| Apparent volume of distribution of unconjugated Rotigotine normalized by Body Weight (Vz/f/BW) |  | Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours | 
| Terminal half-life (t1/2) of total Rotigotine in steady-state |  | Blood sampling at 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours | 
| Time of maximum concentration (tmax) of total Rotigotine in steady-state (tmax,ss) |  | Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours | 
| Apparent total body clearance of total Rotigotine normalized by Body Weight (CL/f/BW) |  | Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours | 
| Apparent volume of distribution of total Rotigotine normalized by Body Weight (Vz/f/BW) |  | Blood sampling at 0 hours (predose), 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 25 hours, 26 hours, 28 hours, 30 hours, 33 hours, 36 hours, 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rotigotine, Neupro, Japanese, Caucasian, Male, Female, Single dose, Pharmacokinetics