Therapeutic effect of an inhaled levodopa dry powder formulation on off episodes in patients with Parkinson’s disease
Lara de Jong1,2, Floris Grasmeijer2,3, Marianne Luinstra1, A.F. Aalbers1, L. Wijma-Vos1, E. D’Angremont4, A.A.E. van der Meulen5, A.W.F. Rutgers5, L. Steenhuis6, P. Hagendoorn2, T. van Laar7 and Erik Frijlink2
1 Department of Clinical Pharmacy, Martini Hospital Groningen, Van Swietenplein 1, Groningen, 9700 RM, the Netherlands.
2Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, Groningen, 9713 AV, the Netherlands.
3PureIMS B.V., Ceintuurbaan Noord 152, Roden, 9301 NZ, the Netherlands
4Department of Psychiatry, University Medical Centre Groningen, Hanzeplein 1, Groningen, 9713 GZ, The Netherlands.
5 Department of Neurology and Clinical Neurophysiology, Martini Hospital Groningen, Van Swietenplein 1, Groningen, 9700 RM, the Netherlands.
6 Department of Pulmonary Diseases, Martini Hospital Groningen, Van Swietenplein 1, Groningen, 9700 RM, the Netherlands.
7 Department of Neurology, University Medical Centre Groningen, Hanzeplein 1, Groningen, 9713 GZ, the Netherlands.
Summary
Limited treatment options are available with a rapid onset of action to counter off episodes in Parkinson’s disease (PD) patients. Therefore, an inhalable formulation of levodopa administered with the single-use inhaler Cyclops™ is investigated. The pharmacodynamics (efficacy), pharmacokinetics and safety of the levodopa dry powder inhalation formulation was determined in an open-label crossover trial. Nine participants in an off episode received one dose of inhaled levodopa (90 mg) or one dose (100/25 mg) of levodopa/benserazide orodispersible tablet on two consecutive days in randomised order. A timed finger-tapping test, Timed Up & Go test and Movement Disorders Society Unified Parkinson’s Disease Rating Scale III score were performed predose and on set time points up to 90 minutes postdose as a measure for motor function. In addition, blood samples were taken for a pharmacokinetic evaluation. Lung function was measured as a safety check upon admission and again upon discharge from the clinic. Inhaled levodopa from Cyclops™ had a clinically meaningful effect on improvement of off episodes in PD patients within 20 minutes. The motor function examinations showed a similar clinical improvement after pulmonary and oral administration despite the lower levodopa plasma concentrations after pulmonary administration. Inhaled levodopa was absorbed faster, reaching its peak plasma-concentration 6 minutes after dosing, as opposed to 28 minutes for oral doses. The levodopa inhalation powder was well tolerated. The overall results of this study suggest that the tested levodopa inhalation powder may be particularly beneficial as an alternative rescue therapy for PD patients with motor fluctuations.