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

• Rotigotine (Test product PR 2.3.1) (Drug): * Pharmaceutical form: Transdermal patch * Concentration: 8 mg/24 hours * Route of administration: Transdermal
• Rotigotine (Reference product PR 2.1.1) (Drug), also known as Neupro: * Pharmaceutical form: Transdermal patch * Concentration: 8 mg/24 hours * Route of administration: Transdermal

Primary outcomes

• 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 [Patch adhesiveness was measured after 24 hours (±1 hour) after previous patch application on Day 2, 3, 4 and 5]: 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.

Secondary outcomes

• 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 [Patch adhesiveness was measured 24 hours (±1 hour) after previous patch application on Day 2 and 4]: 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 Per Day as Rated by the Investigator 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 2 [Patch adhesiveness was measured 24 hours (±1 hour) after previous patch application on Day 3 and 5]: 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 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 [Patch adhesiveness was measured 24 hours (±1 hour) after previous patch application on Day 2 and 4]: 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 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 [Patch adhesiveness was measured 24 hours (±1 hour) after previous patch application on Day 3 and 5]: 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 Per Day as Rated by the Subject 24 Hours After Patch Application for Patch 1 [Patch adhesiveness was measured 24 hours (±1 hour) after previous patch application on Day 2 and 4]: 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 Per Day as Rated by the Subject 24 Hours After Patch Application for Patch 2 [Patch adhesiveness was measured 24 hours (±1 hour) after previous patch application on Day 3 and 5]: 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
• 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 [Patch adhesiveness was measured 24 hours (±1 hour) after previous patch application on Day 2, 3, 4 and 5]: 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.

Sex: All, ages: 18 Years to any

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)

Participant flow

Outcome results

• 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 (Primary), Mean, units on a scale: Treatment A 1.04 +/- 1.33; Treatment B 2.15 +/- 1.96
• 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 (Secondary), Number, percentage of patches: Treatment A 65.4; Treatment B 46.2
• Patch Adhesiveness Per Day as Rated by the Investigator 24 Hours After Patch Application According to the EMA Draft Guideline for Patch 2 (Secondary), Number, percentage of patches: Treatment A 71.2; Treatment B 36.5
• 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 (Secondary), Number, percentage of patches: Treatment A 76.9; Treatment B 63.5
• 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 2 (Secondary), Number, percentage of patches: Treatment A 76.9; Treatment B 44.2
• Patch Adhesiveness Per Day as Rated by the Subject 24 Hours After Patch Application for Patch 1 (Secondary), Number, percentage of patches: Treatment A 75.0; Treatment B 65.4
• Patch Adhesiveness Per Day as Rated by the Subject 24 Hours After Patch Application for Patch 2 (Secondary), Number, percentage of patches: Treatment A 73.1; Treatment B 59.6
• 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 (Secondary), Mean, units on a scale: Treatment A 0.40 +/- 0.60; Treatment B 0.85 +/- 1.03

Adverse events

Time frame: Treatment-emergent Adverse Events were collected from Visit 2 (Day 1) up to the Safety Follow-up Visit (Day 12).

Other adverse events by term

• Results publication: Elshoff JP, Bauer L, Goldammer N, Oortgiesen M, Pesch H, Timmermann L. Randomized, double-blind, crossover study of the adhesiveness of two formulations of rotigotine transdermal patch in patients with Parkinson's disease. Curr Med Res Opin. 2018 Jul;34(7):1293-1299. doi: 10.1080/03007995.2018.1430559. Epub 2018 Feb 20. PMID 29461870

• UCB Clinical Trial Call Center, Study director, UCB Pharma

NIH grants: 2014