Study in Healthy Volunteers to Prove That Two Rotigotine Patches From Different Manufacturing Sites 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 2 rotigotine transdermal patches from 2 different manufacturing sites.

Official Title
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Single-site, Open-label, Randomized, Cross-over Trial to Evaluate the Bioequivalence of Single Dose Rotigotine Transdermal Patch (4.5 mg/10 cm^2) From 2 Different Manufacturing Sites.

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: rotigotine transdermal patch (Neupro®)


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/m² (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 thickly hair-covered abdomen resulting in difficulties in finding appropriate patch application sites

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: Sequence A-B (Test: PR 2.1.1 WCL - Reference: PR 2.1.1 AND)<br>Two single applications of rotigotine patches from two different manufacturing sites in the order A-B separated by a washout phase of at least 5 days | Drug: rotigotine transdermal patch (Neupro®)<br>* Rotigotine 4.5 mg/10 cm^2 patch applied for 24 hours<br>* Other names: Neupro®;|
| Experimental: Sequence B-A (Reference: PR 2.1.1 AND - Test: PR 2.1.1 WCL)<br>Two single applications of rotigotine patches from two different manufacturing sites in the order B-A separated by a washout phase of at least 5 days | Drug: rotigotine transdermal patch (Neupro®)<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 plasma concentration- time curve from zero up to the last analytically quantifiable concentration. | Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application. | 
| Cmax of Unconjugated Rotigotine | The Cmax is the maximum plasma concentration. | Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application. | 
| AUC(0-∞) of Unconjugated Rotigotine | The AUC(0-∞) is the area under the plasma concentration- time curve from zero up to infinity | Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application. | 

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). | Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application. | 
| AUC(0-tz) Norm (BW) 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). | Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application. | 
| AUC(0-∞) Norm (Apparent Dose) | The AUC(0-∞) norm (apparent dose) is the area under the plasma concentration- time curve from zero up to infinity normalized by apparent dose (mg). | Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application. | 
| AUC(0-∞) Norm (BW) | The AUC(0-∞) norm (BW) is the area under the plasma concentration- time curve from zero up to infinity normalized by body weight (kg). | Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application. | 
| Cmax,Norm (Apparent Dose) of Unconjugated Rotigotine | The Cmax,norm (apparent dose) is the maximum plasma concentration normalized by apparent dose(mg). | Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application. | 
| Cmax,Norm (BW) of Unconjugated Rotigotine | The Cmax,norm (BW) is the maximum plasma concentration normalized by body weight(kg). | Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application. | 
| Tmax of Unconjugated Rotigotine | The tmax is the time to reach a maximum plasma concentration after patch application. | Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application. | 
| MRT of Unconjugated Rotigotine | The MRT is the mean residence time. | Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application. | 
| λz of Unconjugated Rotigotine | The λz is the rate constant of elimination. | Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application. | 
| t1/2 of Unconjugated Rotigotine | The t1/2 is the terminal half- life. | Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application. | 
| CL/f of Unconjugated Rotigotine | The CL/f is the apparent total body clearance. | Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application. | 
| Apparent Dose | Apparent dose of unconjugated rotigotine in mg. The apparent dose of unconjugated rotigotine was determined from the patches removed on Day 2. | 48 hours | 

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