Randomized, double-blind, crossover study of the adhesiveness of two formulations of rotigotine transdermal patch in patients with Parkinson’s disease

Abstract

Objective: In patch-based transdermal drug delivery, adhesiveness is critical for safe and effective treatment, especially in Parkinson’s disease (PD) where excessive sweating is common. This study compared the adhesiveness of two transdermal patch formulations of rotigotine (improved room temperature-stable [PR2.3.1/Treatment A] and intermediate cold storage product [PR2.1.1/Treatment B]), using the largest patch size (40 cm²).

Methods: PD0018 (NCT02230904) was a multicenter, randomized, double-blind, crossover study. PD patients received Treatments A and B in randomized order for 2 days each. Patch adhesiveness was measured immediately after patch application and 24 hours thereafter (before removal). Primary variable: change in average investigator-rated adhesiveness score between treatments, per modified European Medicines Agency scale (EMA/CHMP/QWP/911254/2011, 2012).

Results: Fifty-seven patients were randomized; 56 patients completed the study. Five patients were excluded from analysis for accidental unblinding. Treatment A had better average adhesiveness score (mean ± SD Treatment A – Treatment B: 1.115 ± 1.635). A higher percentage of patients on both days had patch adhesiveness ≥95% at 24 hours for Treatment A (first day: 65.4%, second day: 71.2%) vs. Treatment B (46.2%, 36.5%), and were satisfied with patch adhesiveness of Treatment A (first day: 75.0%, second day: 73.1%) vs. Treatment B (65.4%, 59.6%). Average patch-wear duration was similar between formulations (23.761 hours vs. 23.495 hours per patch). Both formulations were well tolerated with no new safety observations.

Conclusion: Results indicated greater adhesiveness for the improved room temperature-stable formulation (PR2.3.1) vs. intermediate cold storage product (PR2.1.1) using the largest patch-size, with comparable safety and skin tolerability.

Keywords:

• Adhesiveness
• bioequivalence
• formulation
• patch
• Parkinson’s disease
• rotigotine
• transdermal

Transparency

Declaration of funding

This study was supported by UCB Pharma, Monheim am Rhein, Germany.

Author contributions: J.-P.E., L.B., N.G., M.O. and L.T. were involved in the conception or design of the study. All authors were involved in the analysis and interpretation of the data, drafting of the manuscript or revising it critically for intellectual content, and approved the final version to be published and agree to be accountable for all aspects of the work.

Declaration of financial/other relationships

L.T. has disclosed that he has received payments for consulting services from Medtronic Inc., Boston Scientific, GE Medical and UCB Pharma; and received honoraria for speakers’ activities sponsored by Bial, Zambon Pharma, UCB Pharma, Desitin Pharma, Medtronic, Boston Scientific, Abbott and Bayer. The institution of Lars Timmermann, not L.T. personally, has received funding from the German Research Foundation, German Federal Ministry of Education and Research, Manfred and Ursula Müller Foundation, Klüh Foundation, Hoffnungsbaum eV, NBIA Disorders Association USA, Cologne Fortune, Medtronic, German Parkinson Association, Archimedes Pharma, Abbott, Bayer, UCB Pharma, zur Rose Pharma and Teva. L.B., N.G., J.-P.E., M.O. and H.P. have disclosed that they are salaried employees of UCB Pharma. L.B., J.-P.E. and M.O. have disclosed that they receive stock options from their employment.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors thank the patients and their caregivers in addition to the investigators and their teams who contributed to the study. The authors also acknowledge Karolina Rzeniewicz PhD CMPP and Nicole Meinel PhD CMPP (Evidence Scientific Solutions, London, UK) for writing assistance which was funded by UCB Pharma, Brussels, Belgium, and Cédric Laloyaux PhD (Strategic Publication Lead Neurology, UCB Pharma, Brussels, Belgium) for publication coordination. The authors also acknowledge Elisabeth Dohin MD (UCB Pharma, Brussels, Belgium) for scientific and medical input into the data analyses and interpretation. Data in this paper has not been presented previously.