Study in Healthy Volunteers to Prove That Two Different Formulations of Rotigotine Patches Deliver Equivalent Drug Amount to the Body

Study Overview
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Brief Summary
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The major aim of this study is to investigate and compare the drug amount delivered to the body after sequential application of two Rotigotine patches of two different formulations

Official Title
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Single-site, Open-label, Randomized, Cross-over Trial to Evaluate the Bioequivalence of Single Dose Rotigotine Transdermal Patch (4.5mg/10cm2) Comparing Two Different Formulations

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Rotigotine transdermal patch


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy White, male volunteers between 18 and 55 years of age (inclusive). BMI between 19 and 28 kg/m^2 (inclusive) Exclusion Criteria: Previous participation in a clinical study with Rotigotine History or current condition of epilepsy and/or seizures Known clinically relevant allergy or known/suspected clinically relevant drug hypersensitivity History of significant skin hypersensitivity to adhesives or other transdermal products or recently unresolved contact dermatitis History or present condition of an atopic or eczematous dermatitis, psoriasis, and/or an active skin disease Clinically relevant abnormality in physical examination, ECG, vital signs or safety laboratory examinations Positive HIV, hepatitis B or C test or positive alcohol or drug test Relevant hepatic or renal dysfunction Intake of medication that might interfere with the test drug within 2 weeks prior to dosing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rotigotine PR2.2.1 first<br>Rotigotine transdermal patch 4.5 mg/10 cm^2, test drug product PR2.2.1 followed by Rotigotine transdermal patch 4.5 mg/10 cm^2, reference drug product PR2.1.1 separated by a washout phase of at least 5 days | Drug: Rotigotine transdermal patch<br>* Rotigotine 4.5 mg/10 cm^2 patch applied for 24 hours<br>* Other names: Neupro®;|
| Experimental: Rotigotine PR2.1.1 first<br>Rotigotine transdermal patch 4.5 mg/10 cm^2, reference drug product PR2.1.1 followed by Rotigotine transdermal patch 4.5 mg/10 cm^2, test drug product PR2.2.1 separated by a washout phase of at least 5 days | Drug: Rotigotine transdermal patch<br>* Rotigotine 4.5 mg/10 cm^2 patch applied 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 |
| --- | --- | --- |
| AUC(0-tz) of Unconjugated Rotigotine | The AUC(0-tz) is the area under the concentration-time curve from zero up to the last analytically quantifiable concentration. | 0 h (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 | 
| Cmax of Unconjugated Rotigotine | The Cmax is the maximum plasma concentration. | 0 h (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 | 
| AUC(0- ∞) of Unconjugated Rotigotine | The AUC(0- ∞) is the area under the plasma concentration-time curve from zero up to infinity | 0 h (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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC(0-tz) Norm (Apparent Dose) of Unconjugated Rotigotine | The AUC(0-tz) norm (apparent dose) is the area under the plasma concentration-time curve from zero up to the last analytically quantifiable concentration normalized by apparent dose (mg). | 0 h (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 | 
| AUC(0-tz) Norm (Body Weight) of Unconjugated Rotigotine | The AUC(0-tz) norm (BW) is the area under the plasma concentration-time curve from zero up to the last analytically quantifiable concentration normalized by body weight (kg). | 0 h (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 | 
| AUC(0- ∞) Norm (Apparent Dose) | The AUC(0-inf) norm (apparent dose) is the area under the plasma concentration-time curve from zero up to infinity normalized by apparent dose (mg). | 0 h (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 | 
| AUC(0- ∞) Norm (Body Weight) | The AUC(0-inf) norm (BW) is the area under the plasma concentration-time curve from zero up to infinity normalized by body weight (kg). | 0 h (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 | 
| Cmax, Norm (Apparent Dose) of Unconjugated Rotigotine | The Cmax, norm (apparent dose) is the maximum plasma concentration normalized by apparent dose (mg). | 0 h (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 | 
| Cmax, Norm (Body Weight) of Unconjugated Rotigotine | The Cmax, norm (BW) is the maximum plasma concentration normalized by body weight (kg). | 0 h (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 | 
| Tmax of Unconjugated Rotigotine | The tmax is the time to reach maximum plasma concentration after patch application. | 0 h (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 | 
| Mean Residence Time (MRT) of Unconjugated Rotigotine | The MRT is the mean residence time. | 0 h (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 | 
| Rate Constant of Elimination (λz) of Unconjugated Rotigotine | The λz of unconjugated rotigotine is the rate constant of elimination. | 0 h (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 | 
| Terminal Half-Life (t1/2) of Unconjugated Rotigotine | the t1/2 of unconjugated rotigotine is the terminal half-life, calculated as t1/2=ln2/ λz. | 0 h (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 | 
| Apparent Total Body Clearance (CL/f) of Unconjugated Rotigotine | The CL/f of unconjugated rotigotine is the apparent total body clearance. | 0 h (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 | 
| Apparent Dose | Apparent dose of unconjugated rotigotine in mg. The apparent dose was calculated by subtraction of the determined residual content of each rotigotine patch from the nominal content of rotigotine in the patch. | 24 hours | 

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