Skip to main content
SpringerLink
Log in

The safety and tolerability of rotigotine transdermal system over a 6-year period in patients with early-stage Parkinson’s disease

  • Neurology and Preclinical Neurological Studies - Original Article
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Abstract

This open-label extension (SP716; NCT00599196) of a 6-month, double-blind, randomized study (SP513) investigated the safety and tolerability of rotigotine transdermal system over up to ~6 years in patients with Parkinson’s disease (PD; early-stage PD at double-blind enrollment). Eligible patients completing the 6-month study received optimal dose open-label rotigotine (≤16 mg/24 h) for up to ~6 years. Adjunctive levodopa was permitted. Primary outcomes included adverse events (AEs) and extent of rotigotine exposure. Analysis of adjunctive levodopa use, dyskinesias [unified Parkinson’s disease rating scale (UPDRS) IV], and efficacy (UPDRS II + III total score) were also assessed. Of 381 patients enrolled in the open-label extension, 52 % were still in the study at time of closure; 24 % withdrew because of AEs and 6 % because of lack of efficacy. Patients received rotigotine for a median duration of 1,564.5 days (~4 years, 3 months; range 5–2, 145 days). 69 % of patients started supplemental levodopa; median time to levodopa was 485 days (~1 year, 4 months). Most common AEs (% per patient-year) were somnolence (18 %), application site reactions (12 %), nausea (9 %), peripheral edema (7 %), and fall (7 %). AEs indicative of impulsive–compulsive behavior were recorded in 25 (7 %) patients. Dyskinesias were experienced by 65 (17 %) patients; the majority [47 of 65 (72 %)] reported first dyskinesia after starting levodopa. Mean UPDRS II + III total scores remained below double-blind baseline for 4 years (assessment of all patients). In conclusion, rotigotine was generally well tolerated for up to ~6 years in patients with early-stage PD. The AEs reported were in line with previous studies of rotigotine transdermal system, with typical dopaminergic side effects and application site reactions seen.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Elmer LW, Surmann E, Boroojerdi B, Jankovic J (2012) Long-term safety and tolerability of rotigotine transdermal system in patients with early-stage idiopathic Parkinson’s disease: a prospective, open-label extension study. Parkinsonism Relat Disord 18:488–493. doi:10.1016/j.parkreldis.2012.01.008

    Article  PubMed  Google Scholar 

  • Elshoff JP, Braun M, Andreas JO, Middle M, Cawello W (2012) Steady-state plasma concentration profile of transdermal rotigotine: an integrated analysis of three, open-label, randomized, phase I multiple dose studies. Clin Ther 34:966–978. doi:10.1016/j.clinthera.2012.02.008

    Article  PubMed  CAS  Google Scholar 

  • Factor SA (2008) Current status of symptomatic medical therapy in Parkinson’s disease. Neurotherapeutics 5:164–180

    Article  PubMed  CAS  Google Scholar 

  • Giladi N, Boroojerdi B, Korczyn AD, Burn DJ, Clarke CE, Schapira AH (2007) Rotigotine transdermal patch in early Parkinson’s disease: a randomized, double-blind, controlled study versus placebo and ropinirole. Mov Disord 22:2398–2404

    Article  PubMed  Google Scholar 

  • Giladi N, Fichtner A, Poewe W, Boroojerdi B (2010) Rotigotine transdermal system for control of early morning motor impairment and sleep disturbances in patients with Parkinson’s disease. J Neural Transm 117:1395–1399

    Article  PubMed  CAS  Google Scholar 

  • Hauser RA, Rascol O, Korczyn AD, Jon Stoessl A, Watts RL, Poewe W, De Deyn PP, Lang AE (2007) Ten-year follow-up of Parkinson’s disease patients randomized to initial therapy with ropinirole or levodopa. Mov Disord 22:2409–2417

    Article  PubMed  Google Scholar 

  • Holloway RG, Shoulson I, Fahn S et al (2004) Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial. Arch Neurol 61:1044–1053

    Article  PubMed  Google Scholar 

  • Jankovic J (2005) Motor fluctuations and dyskinesias in Parkinson’s disease: clinical manifestations. Mov Disord 20(Suppl 11):S11–S16

    Article  PubMed  Google Scholar 

  • Jankovic J, Aguilar LG (2008) Current approaches to the treatment of Parkinson’s disease. Neuropsychiatr Dis Treat 4:743–757

    Article  PubMed  CAS  Google Scholar 

  • Jankovic J, Watts RL, Martin W, Boroojerdi B (2007) Transdermal rotigotine: double-blind, placebo-controlled trial in Parkinson disease. Arch Neurol 64:676–682

    Article  PubMed  Google Scholar 

  • LeWitt PA, Lyons KE, Pahwa R (2007) Advanced Parkinson disease treated with rotigotine transdermal system: PREFER Study. Neurology 68:1262–1267

    Article  PubMed  CAS  Google Scholar 

  • Parkinson Study Group (2009) Long-term effect of initiating pramipexole vs levodopa in early Parkinson disease. Arch Neurol 66:563–570

    Article  Google Scholar 

  • Poewe W (2006) The natural history of Parkinson’s disease. J Neurol 253(Suppl 7):VII2–VII6

    Article  PubMed  Google Scholar 

  • Poewe WH, Rascol O, Quinn N, Tolosa E, Oertel WH, Martignoni E, Rupp M, Boroojerdi B (2007) Efficacy of pramipexole and transdermal rotigotine in advanced Parkinson’s disease: a double-blind, double-dummy, randomised controlled trial. Lancet Neurol 6:513–520

    Article  PubMed  CAS  Google Scholar 

  • Poewe W, Antonini A, Zijlmans JC, Burkhard PR, Vingerhoets F (2010) Levodopa in the treatment of Parkinson’s disease: an old drug still going strong. Clin Interv Aging 5:229–238

    PubMed  CAS  Google Scholar 

  • Rascol O, Brooks DJ, Korczyn AD, De Deyn PP, Clarke CE, Lang AE (2000) A five-year study of the incidence of dyskinesia in patients with early Parkinson’s disease who were treated with ropinirole or levodopa. 056 Study Group. N Engl J Med 342:1484–1491

    Article  PubMed  CAS  Google Scholar 

  • Scheller D, Ullmer C, Berkels R, Gwarek M, Lübbert H (2009) The in vitro receptor profile of rotigotine: a new agent for the treatment of Parkinson’s disease. Naunyn Schmiedebergs Arch Pharmacol 379:73–86

    Article  PubMed  CAS  Google Scholar 

  • Trenkwalder C, Kies B, Rudzinska M et al (2011) Rotigotine effects on early morning motor function and sleep in Parkinson’s disease: a double-blind, randomized, placebo-controlled study (RECOVER). Mov Disord 26:90–99

    Article  PubMed  Google Scholar 

  • Watts RL, Jankovic J, Waters C, Rajput A, Boroojerdi B, Rao J (2007) Randomized, blind, controlled trial of transdermal rotigotine in early Parkinson disease. Neurology 68:272–276

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by UCB Pharma, Raleigh, NC, USA. The authors acknowledge the study investigators for their contributions to data acquisition in the SP716 study (in alphabetical order): A. Albanese, T. Anderson, S. Asenbaum, F. Badenhorst, L. Battistin, M. Bomhof, B. Boothman, J. Breuer, B. Brew, V. Brinar, D. Burn, J. Carr, B. Chmielewska, C. E. Clarke, D. Crimmins, P. De Deyn, G.-L. Defer, V. Demarin, A. Destee, G. Deuschl, R. Djaldetti, D. Dolezil, P. Endre, V. Fung, J. Gardiner, W. Guldenpfennig, D. Grosset, Y. Hallstrom, M. Hayes, A. Jeanjean, T. Jolma, A. Kaelin, B. Kies, J. Kotowicz, M. Kronenbuerger, J. Kulisevsky, V. Lajos, J. Larsen, Ma R. Luquin Pindo, S. Mossman, V. Myllyla, G. Nappi, W. Nyka, S. Ochudlo, W. Oertel, R. Palm, M. Partinen, N. Puiu, W. Poewe, J. Polivka, D. Pruchnik-Wolinska, N. Quinn, I. Rektor, O. Rascol, C. Rozsa, S. Ruggieri, I. Sagi, J. Smuts, B. Snow, H. Soininen, M. Steiger, A. Szczudlik, A. Takacs, E. Tolosa Sarro, A. Tutaj, J. Valpas, F. Viallet, F. Vingerhoets, R. Weiser, A. Williams, P. Wood. The authors also acknowledge Ging-Ging Li CMPP (Global Publications Manager, movement and sleep disorders, UCB Pharma, Brussels, Belgium) for publication coordination, and Emily Thompson, PhD, Evidence Scientific Solutions, London, UK, for writing and editorial assistance, which was contracted by UCB Pharma, Brussels, Belgium. This manuscript was developed in accordance with International Committee of Medical Journal Editors (ICMJE) guidelines: ICMJE uniform requirements for manuscripts submitted to Biomedical Journals.

Conflict of interest

Nir Giladi has served as a paid consultant for Schwarz Pharma, Teva, Lundbeck, UCB Pharma, Eisai, Intec Pharma, GSK, Solvay, Merz, Biogen, and NeuroDerm; has received honoraria as a member of advisory boards for UCB Phama, Teva, Lundbeck, NeuroDerm, and Intec Pharma; has received honoraria for lectures from Schwarz Pharma, Teva, Lundbeck, GSK, Allergan, Novartis, and UCB; has received grant support from NIH, Michael J.Fox Foundation, National Parkinson Foundation USA, Israel Science Foundation, Parkinson’s Disease Foundation USA, and European Community; and has received other educational support from Schwarz Pharma, Teva, Lundbeck, Allergan, Novartis, Solvay and Medtronic’s. Babak Boroojerdi is an employee of UCB Pharma, Raleigh, NC, USA. Erwin Surmann is an employee of UCB Pharma, Monheim am Rhein, Germany.

Author information

Authors and Affiliations

  1. Movement Disorders Unit, Department of Neurology, Tel-Aviv Sourasky Medical Center, Sackler School of Medicine, Tel-Aviv University, 6 Weizmann Street, 64239, Tel-Aviv, Israel

    Nir Giladi

  2. UCB Pharma, Raleigh, NC, USA

    Babak Boroojerdi

  3. UCB Pharma, Monheim, Germany

    Erwin Surmann

Authors
  1. Nir Giladi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Babak Boroojerdi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Erwin Surmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nir Giladi.

Additional information

On behalf of the SP716 study investigators.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Giladi, N., Boroojerdi, B. & Surmann, E. The safety and tolerability of rotigotine transdermal system over a 6-year period in patients with early-stage Parkinson’s disease. J Neural Transm 120, 1321–1329 (2013). https://doi.org/10.1007/s00702-013-1001-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-013-1001-5

Keywords

Search

Navigation