A Study to Compare the Adhesiveness of 2 Different Rotigotine Patches Used for the Treatment of Parkinson's Disease

Study Overview
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Brief Summary
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The primary objective of the study is to compare the adhesiveness of 2 different patch formulations of Rotigotine using the largest patch size of 40 cm^2, under the assumption that both patch formulations show similar adhesiveness properties.

Official Title
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A Multicenter, Randomized, Double-blind, 2-way Cross-over Study to Compare the Adhesiveness of 2 Different Rotigotine Patch Formulations in Subjects With Parkinson's Disease

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: Rotigotine (Test product PR 2.3.1)
* Drug: Rotigotine (Reference product PR 2.1.1)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has a diagnosis of idiopathic Parkinson's Disease Subject has been on continuous treatment with commercially available Rotigotine transdermal patches (Neupro®) for at least 3 months prior to enrollment Subject has been taking a stable Rotigotine dose including an 8 mg/24 hours (40 cm^2) patch for at least 2 weeks prior to enrollment Exclusion Criteria: Subject has any medical or psychiatric condition which, in the opinion of the investigator, could jeopardize or would compromise the subject's well-being or ability to participate in this study Subject has a history of significant skin hypersensitivity to adhesives or other transdermal products or recently unsolved contact dermatitis Subject has a history or present condition of an atopic or eczematous Dermatitis, Psoriasis, or an active skin disease Subject has a lifetime history of suicide attempt (including an active attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response ('yes') to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening (Visit 1) or Baseline (Visit 2)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm A-B<br>4 day treatment (Treatment A: Rotigotine transdermal patch 8 mg/24 hours, test product PR 2.3.1 followed by Treatment B: Rotigotine transdermal patch 8 mg/24 hours reference product PR 2.1.1) | Drug: Rotigotine (Test product PR 2.3.1)<br>* Pharmaceutical form: Transdermal patch Concentration: 8 mg/24 hours Route of administration: Transdermal<br>Drug: Rotigotine (Reference product PR 2.1.1)<br>* Pharmaceutical form: Transdermal patch Concentration: 8 mg/24 hours Route of administration: Transdermal<br>* Other names: Neupro;|
| Experimental: Treatment Arm B-A<br>4 day treatment (Treatment B: Rotigotine transdermal patch 8 mg/24 hours reference product PR 2.1.1 followed by Treatment A: Rotigotine transdermal patch 8 mg/24 hours, test product PR 2.3.1) | Drug: Rotigotine (Test product PR 2.3.1)<br>* Pharmaceutical form: Transdermal patch Concentration: 8 mg/24 hours Route of administration: Transdermal<br>Drug: Rotigotine (Reference product PR 2.1.1)<br>* Pharmaceutical form: Transdermal patch Concentration: 8 mg/24 hours Route of administration: Transdermal<br>* Other names: Neupro;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Average Adhesiveness Score of 2 Days of 24 Hours Patch Application as Rated by the Investigator (or Designee) Assessed According to the EMA Draft Guideline | The assessment was performed according to the adhesion score adapted from the EMA draft guideline on quality of transdermal patches (EMA/CHMMP/QWP/911254/2011, 2012). 0 = > 95 - 100 % of the patch area adheres 1 = > 90 - 95 % of the patch adheres 2 = > 85 - 90 % of the patch adheres 3 = > 80 - 85 % of the patch adheres 4 = > 75 - 80 % of the patch adheres 5 = > 70 - 75 % of the patch adheres 6 = ≥ 50 - 70 % of the patch adheres 7 = < 50 % of the patch adheres 8 = Patch completely detached The recorded scores 6, 7, and 8 were combined in order to create a cumulative group less than or equal to 70 % adhered or patch detachment which was regarded as significant patch adhesion failure in the draft EMA guideline. The average of patches 1 and 2 is presented by Treatment Arm below. | Patch adhesiveness was measured after 24 hours (±1 hour) after previous patch application on Day 2, 3, 4 and 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patch Adhesiveness Per Day as Rated by the Investigator or Designee 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 1 | The assessment was performed according to the adhesion score adapted from the EMA draft guideline on quality of transdermal patches (EMA/CHMMP/QWP/911254/2011, 2012). 0 = >95 - 100 % of the patch area adheres 1 = >90 - 95 % of the patch adheres 2 = >85 - 90 % of the patch adheres 3 = >80 - 85 % of the patch adheres 4 = >75 - 80 % of the patch adheres 5 = >70 - 75 % of the patch adheres 6 = ≥50 - 70 % of the patch adheres 7 = <50 % of the patch adheres 8 = Patch completely detached The recorded scores 6, 7, and 8 were combined in order to create a cumulative group less than or equal to 70 % adhered or patch detachment which was regarded as significant patch adhesion failure in the draft EMA guideline. | Patch adhesiveness was measured 24 hours (±1 hour) after previous patch application on Day 2 and 4 | 
| Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 2 | The assessment was performed according to the adhesion score adapted from the EMA draft guideline on quality of transdermal patches (EMA/CHMMP/QWP/911254/2011, 2012). 0 = >95 - 100 % of the patch area adheres 1 = >90 - 95 % of the patch adheres 2 = >85 - 90 % of the patch adheres 3 = >80 - 85 % of the patch adheres 4 = >75 - 80 % of the patch adheres 5 = >70 - 75 % of the patch adheres 6 = ≥50 - 70 % of the patch adheres 7 = <50 % of the patch adheres 8 = Patch completely detached The recorded scores 6, 7, and 8 were combined in order to create a cumulative group less than or equal to 70 % adhered or patch detachment which was regarded as significant patch adhesion failure in the draft EMA guideline. | Patch adhesiveness was measured 24 hours (±1 hour) after previous patch application on Day 3 and 5 | 
| Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 1 | The assessment was performed according to the adhesion score adapted from the EMA draft guideline on quality of transdermal patches . Afterwards, EMA scores were translated into FDA/CDER scores: 0 (>95-100% of patch adheres) >> 0 (FDA/CDER) 1 (>90-95% of patch adheres) >> 0 (FDA/CDER) 2 (>85-90% of patch adheres) >> 1 (FDA/CDER) 3 (>80-85% of patch adheres) >> 1 (FDA/CDER) 4 ( >75-80% of patch adheres) >> 1 (FDA/CDER) 5 (>70-75% of patch adheres) >> 2 (FDA/CDER) 6 (≥50-70% of patch adheres) >> 2 (FDA/CDER) 7 (<50 % of patch adheres) >> 3 (FDA/CDER) 8 (Patch completely detached) >> 4 (FDA/CDER) Due to a slight mismatch of limits between FDA scores 0 and 1 as compared to EMA scores 1 and 2, the theoretical value of exactly 90 % of adh. fell into score 1 with the FDA scoring. A similar limit mismatch occured at exactly 75 %. These mismatches may have resulted in a slightly worse estimation of the adh. with the FDA score as compared to previous adh. studies. | Patch adhesiveness was measured 24 hours (±1 hour) after previous patch application on Day 2 and 4 | 
| Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the FDA/Center for Drug Evaluation and Research (CDER) Score for Patch 2 | The assessment was performed according to the adhesion score adapted from the EMA draft guideline on quality of transdermal patches . Afterwards, EMA scores were translated into FDA/CDER scores: 0 (>95-100% of patch adheres) >> 0 (FDA/CDER) 1 (>90-95% of patch adheres) >> 0 (FDA/CDER) 2 (>85-90% of patch adheres) >> 1 (FDA/CDER) 3 (>80-85% of patch adheres) >> 1 (FDA/CDER) 4 ( >75-80% of patch adheres) >> 1 (FDA/CDER) 5 (>70-75% of patch adheres) >> 2 (FDA/CDER) 6 (≥50-70% of patch adheres) >> 2 (FDA/CDER) 7 (<50 % of patch adheres) >> 3 (FDA/CDER) 8 (Patch completely detached) >> 4 (FDA/CDER) Due to a slight mismatch of limits between FDA scores 0 and 1 as compared to EMA scores 1 and 2, the theoretical value of exactly 90 % of adh. fell into score 1 with the FDA scoring. A similar limit mismatch occured at exactly 75 %. These mismatches may have resulted in a slightly worse estimation of the adh. with the FDA score as compared to previous adh. studies. | Patch adhesiveness was measured 24 hours (±1 hour) after previous patch application on Day 3 and 5 | 
| Patch Adhesiveness Per Day as Rated by the Subject 24 Hours After Patch Application for Patch 1 | The subject assessed the patch adhesiveness by using the following score: 0 = Satisfied with adhesiveness 1 = Moderately satisfied with adhesiveness 2 = Moderately unsatisfied with adhesiveness 3 = Unsatisfied with adhesiveness | Patch adhesiveness was measured 24 hours (±1 hour) after previous patch application on Day 2 and 4 | 
| Patch Adhesiveness Per Day as Rated by the Subject 24 Hours After Patch Application for Patch 2 | The subject assessed the patch adhesiveness by using the following score: 0 = Satisfied with adhesiveness 1 = Moderately satisfied with adhesiveness 2 = Moderately unsatisfied with adhesiveness 3 = Unsatisfied with adhesiveness | Patch adhesiveness was measured 24 hours (±1 hour) after previous patch application on Day 3 and 5 | 
| Change in Average Patch Adhesiveness Score of 2 Days of 24 Hour Patch Application as Rated by the Investigator (or Designee), Assessed According to the FDA/Center for Drug Evaluation and Research (CDER) Score | The assessment was performed according to the adhesion score adapted from the EMA draft guideline on quality of transdermal patches . Afterwards, EMA scores were translated into FDA/CDER scores: 0 (>95-100% of patch adheres) >> 0 (FDA/CDER) 1 (>90-95% of patch adheres) >> 0 (FDA/CDER) 2 (>85-90% of patch adheres) >> 1 (FDA/CDER) 3 (>80-85% of patch adheres) >> 1 (FDA/CDER) 4 ( >75-80% of patch adheres) >> 1 (FDA/CDER) 5 (>70-75% of patch adheres) >> 2 (FDA/CDER) 6 (≥50-70% of patch adheres) >> 2 (FDA/CDER) 7 (<50 % of patch adheres) >> 3 (FDA/CDER) 8 (Patch completely detached) >> 4 (FDA/CDER) Due to a slight mismatch of limits between FDA scores 0 and 1 as compared to EMA scores 1 and 2, the theoretical value of exactly 90 % of adh. fell into score 1 with the FDA scoring. A similar limit mismatch occured at exactly 75 %. These mismatches may have resulted in a slightly worse estimation of the adh. with the FDA score as compared to previous adh. studies. | Patch adhesiveness was measured 24 hours (±1 hour) after previous patch application on Day 2, 3, 4 and 5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rotigotine patch, Neupro, Parkinson's Disease