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

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

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.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: Rotigotine (Test product PR 2.3.1); Drug: Rotigotine (Reference product PR 2.1.1)

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Alzenau, Germany
    • 104
  • Aschaffenburg, Germany
    • 106
  • Berlin, Germany
    • 105
  • Böblingen, Germany
    • 107
  • Düsseldorf, Germany
    • 111
  • Erbach, Germany
    • 109
  • Essen, Germany
    • 110
  • Karlstadt, Germany
    • 102
  • Köln, Germany
    • 101
  • Stuttgart, Germany
    • 103
  • Würzburg, Germany
    • 108

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm A-B; 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); Pharmaceutical form: Transdermal patch; Concentration: 8 mg/24 hours; Route of administration: Transdermal; Drug: Rotigotine (Reference product PR 2.1.1); Pharmaceutical form: Transdermal patch; Concentration: 8 mg/24 hours; Route of administration: Transdermal; Other Names: Neupro
Experimental: Treatment Arm B-A; 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); Pharmaceutical form: Transdermal patch; Concentration: 8 mg/24 hours; Route of administration: Transdermal; Drug: Rotigotine (Reference product PR 2.1.1); Pharmaceutical form: Transdermal patch; Concentration: 8 mg/24 hours; Route of administration: Transdermal; Other Names: Neupro

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: UCB BIOSCIENCES GmbH
• Collaborators: Pharmaceutical Health Sciences; Bracket Global

Publications and helpful links

General Publications

• 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.

Helpful Links

• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: August 29, 2014
• First Submitted That Met QC Criteria: September 2, 2014
• First Posted (Estimate): September 3, 2014

Study Record Updates

• Last Update Posted (Estimate): November 1, 2015
• Last Update Submitted That Met QC Criteria: October 1, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Parkinson's Disease; Neupro; Rotigotine patch
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dopamine Agonists; Dopamine Agents; Rotigotine
• Other Study ID Numbers: PD0018; 2014-000932-41 (EudraCT Number)