Bioequivalence Study of Rotigotine Transdermal Patch With Two Different Formulations in Healthy Japanese Subjects

Study Overview
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Brief Summary
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To investigate and compare the drug amount delivered to the body after each single administration of Rotigotine patch with 2 different formulations in healthy Japanese subjects.

Official Title
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Single-site, Open-label, Randomized, Cross-over Study in Healthy Japanese Subjects to Evaluate the Bioequivalence of Single Dose Rotigotine Transdermal Patch (2 mg/24 h) Comparing 2 Different Formulations

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Rotigotine PR 2.1.4
* Drug: Rotigotine PR 2.2.1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Japanese male and female volunteers with the age between 20 and 55 years old Exclusion Criteria: Subject has participated or is participating in any other clinical studies of investigational drug or another Investigational Medical Product (IMP) within the last 3 months Subject is not healthy (eg, taking any drug treatments, excessive amount of alcohol, cigarettes, having any medical or emotional/psychological problems, a drug/alcohol abuse, having abnormal safety parameters) Subject has a QTcB (QT interval corrected for Heart Rate [HR] using Bazett´s formula) interval of ≥ 430 ms (≥ 450 ms for females) or any other clinically relevant finding in Electrocardiogram (ECG) at the Eligibility Assessment (EA) Subject is having clinically relevant allergy or clinically relevant drug hypersensitivity to any components of the Investigational Medical Product (IMP), or/and having an atopic or eczematous Dermatitis, Psoriasis and/or active skin disease Subject has a recent history (within 2 years) of chronic alcohol or drug abuse and has a history of significant skin hypersensitivity to transdermal products, and of an atopic or eczematous Dermatitis, Psoriasis, and/or active skin disease and have a history of suicide attempt, Epilepsy and/or seizures Subject has made a blood donation or a comparable blood loss within the last 3 months prior to the Eligibility Assessment (EA) Subject is pregnant or nursing

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 55 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: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A - Treatment B<br>Treatment A: Test; drug product PR 2.2.1 Treatment B: Reference; drug product PR 2.1.4 Sequence of two single applications of Rotigotine transdermal patches (PR 2.2.1 first) for 24 hours separated by a Washout Period of 5 days. | Drug: Rotigotine PR 2.1.4<br>* Treatment B: Rotigotine transdermal patch (2 mg/24 h [10 cm^2]). Reference; drug product PR 2.1.4. Single application of 1 patch for 24 hours.<br>* Other names: Neupro;Drug: Rotigotine PR 2.2.1<br>* Treatment A: Rotigotine transdermal patch (2 mg/24 h [10 cm^2]). Test; drug product PR 2.2.1. Single application of 1 patch for 24 hours.<br>* Other names: Neupro;|
| Experimental: Treatment B - Treatment A<br>Treatment B: Reference; drug product PR 2.1.4 Treatment A: Test; drug product PR 2.2.1 Sequence of two single applications of Rotigotine transdermal patches (PR 2.1.4 first) for 24 hours separated by a Washout Period of 5 days. | Drug: Rotigotine PR 2.1.4<br>* Treatment B: Rotigotine transdermal patch (2 mg/24 h [10 cm^2]). Reference; drug product PR 2.1.4. Single application of 1 patch for 24 hours.<br>* Other names: Neupro;Drug: Rotigotine PR 2.2.1<br>* Treatment A: Rotigotine transdermal patch (2 mg/24 h [10 cm^2]). Test; drug product PR 2.2.1. Single application of 1 patch for 24 hours.<br>* Other names: Neupro;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration of unconjugated Rotigotine (Cmax) | The value of the maximum plasma concentration is directly obtained from the observed plasma concentration versus time curves. | Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration | 
| Area under the plasma concentration-time curve from zero up to the last analytically quantifiable concentration of unconjugated Rotigotine (AUC 0-t) |  | Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve from zero up to infinity (AUC(0-∞)) | The area under the curve extrapolated to infinity is calculated as the sum of AUC(0-t) and a residual part extrapolated to infinite time. | Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration | 
| Area under the plasma concentration-time curve from zero up to the last analytically quantifiable concentration normalized by apparent dose (mg) (AUC(0-t) norm (apparent dose)) |  | Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration | 
| Area under the plasma concentration-time curve from zero up to the last analytically quantifiable concentration normalized by body weight (kg) (AUC(0-t) norm (BW)) |  | Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration | 
| Area under the plasma concentration-time curve from zero up to infinity normalized by apparent dose (mg) (AUC(0-∞) norm (apparent dose)) |  | Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration | 
| Area under the plasma concentration-time curve from zero up to infinity normalized by body weight (kg) (AUC(0-∞) norm (BW)) |  | Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration | 
| Maximum plasma concentration normalized by apparent dose (Cmax,norm (apparent dose)) |  | Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration | 
| Maximum plasma concentration normalized by body weight (Cmax,norm (BW)) |  | Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration | 
| Time to reach a maximum plasma concentration of unconjugated Rotigotine after patch application (tmax) |  | Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration | 
| Mean residence time (MRT) |  | Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration | 
| Rate constant of elimination (λz) |  | Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration | 
| Terminal half-life (t1/2) |  | Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration | 
| Relative bioavailability calculated based on maximum plasma concentration (fCmax) |  | Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration | 
| Relative bioavailability calculated based on the area under the plasma concentration-time curve (fAUC) |  | Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration | 
| Apparent total body clearance (CL/f) |  | Pharmacokinetic (PK) samples will be taken predose, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h and 48 h after Rotigotine administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rotigotine, Neupro®, Transdermal Patch, Bioequivalence