Ropinirole 24-hour prolonged release and ropinirole immediate release in early Parkinson's disease: a randomized, double-blind, non-inferiority crossover study

ABSTRACT

Objective: This study compares once-daily ropinirole 24-h prolonged release and three-times-daily ropinirole immediate release in patients with early Parkinson's disease.

Methods: This multicentre, double-blind, non-inferiority crossover study involved 161 patients randomized to one of four formulation sequences: (1) immediate release–immediate release–prolonged release; (2) immediate release–prolonged release–prolonged release; (3) prolonged release–prolonged release–immediate release; (4) prolonged release–immediate release–immediate release. During a 12-week dose-titration period, ropinirole immediate release was titrated according to the approved labelling; titration of ropinirole 24-h prolonged release started at a higher dose and was more rapid. Patients then entered three consecutive, flexible-dose, 8-week maintenance periods. At the end of the first maintenance period, half of the patients in each formulation group switched to the same or closest dose of the alternative formulation; remaining patients switched at the end of the second maintenance period.

Results: At the end of titration, before the first dose switch, there were substantial reductions in mean Unified Parkinson's Disease Rating Scale (UPDRS) motor scores. During maintenance periods, both groups showed similar efficacy on the UPDRS motor score. Overall mean (standard error) change from period baseline was −0.1 (0.28) for ropinirole 24-h prolonged release, and 0.6 (0.30) for ropinirole immediate release (adjusted mean treatment difference −0.7; 95% confidence interval [CI]: −1.51, 0.10; p = 0.0842). The upper limit of the 95% CI was less than the predefined threshold of 3 points for non-inferiority. Ropinirole 24-h prolonged release was well-tolerated when titrated more rapidly than ropinirole immediate release; overnight switching between formulations was also well-tolerated. Study limitations included complexity of the non-inferiority study design and the forced dose-titration schedule.

Conclusion: Ropinirole 24-h prolonged release was effective and well-tolerated in patients with early Parkinson's disease.

Key words: :

• Once-daily treatment
• Parkinson's disease
• Ropinirole

Acknowledgements

Declaration of Interest: This study was supported by GlaxoSmithKline Research and Development, Greenford, UK, and SkyePharma, London, UK. L.G. is an employee of GlaxoSmithKline. F.S. has received honoraria and consulting fees from GlaxoSmithKline, Teva, Lundbeck, Boehringer-Ingelheim, Novartis, Vernalis, Valeant Pharmaceuticals and Chiesi Farmaceutici. B.H. has received research grant support or participated in clinical trials for GlaxoSmithKline, Skye Pharma, Novartis, Valeant, Eisai and Solvay pharmaceuticals, and is a consultant and speaker for GlaxoSmithKline, Teva, Novartis, Boehringer-Ingelheim, and Valeant Pharmaceuticals. B.S. is on the speaker's bureau for, and has received research funding from GlaxoSmithKline. P.N. has no conflicts of interest to report.

The authors take full responsibility for the content of the paper, and thank Jackie van Bueren and Sarah Brown (Caudex Medical, Oxford, UK) for assistance with preparing the manuscript and collating author comments, financial support for which was provided by the study sponsors.

The EASE-PD Monotherapy Study Investigators are:

Belgium: Bourgeois P, De Deyn PP, Dom R, Jeanjean A.

Czech Republic: Roubcova D, Ruzicka E, Valis M.

France: Destée A, Gil R, Viallet F.

Hungary: Csanyi A, Csiba L, Harcos P, Czopf J, Takács A.

Italy: Barone P, Nordera G, Onofri M, Stocchi F.

Poland: Drozdowski W, Kwiecinski H, Nyka W, Opala G, Szczudlik A.

UK: Boothman B, Burn D, Castleton B, Grosset D, Weiser R.

USA: Bernick C, Cohen S, Colcher A, Hersh B, Leopold N, Nausieda P, Seeberger L, Scott B, Stover N.

Previous presentations: Material from this article has been presented as posters at the following meetings: European Federation of Neurological Societies, Glasgow, UK, 2–6 September 2006; International Congress of Parkinson's Disease and Movement Disorders, Kyoto, Japan, 28 October–2 November 2006; European Federation of Neurological Societies, Brussels, Belgium, 25–28 August 2007; World Federation of Neurology World Congress on Parkinson's Disease and Related Disorders, Amsterdam, The Netherlands, 9–13 December 2007.

Notes

* Geomatrix is a registered trade name of SkyePharma, London, UK

†Tiltab is a registered trade name of GlaxoSmithKline, Brentford, UK