Inhaled dry powder apomorphine (VR040) for 'off ' periods in Parkinson's disease: an in-clinic double-blind dose ranging study

Grosset, K.A., Malek, N., Morgan, F. and Grosset, D.G. (2013) Inhaled dry powder apomorphine (VR040) for 'off ' periods in Parkinson's disease: an in-clinic double-blind dose ranging study. Acta Neurologica Scandinavica, 128(3), pp. 166-171. (doi: 10.1111/ane.12107) (PMID:23527823)

Abstract

Background: ‘Off’ periods increase as Parkinson's disease (PD) progresses and the benefits of standard therapy wane. Subcutaneous apomorphine rescues ‘off’ periods, but patient self‐injection and adverse cutaneous effects are sometimes problematic. Methods: We assessed safety, tolerability and efficacy of inhaled dry powder apomorphine (VR040) in a double‐blind clinic‐based Phase II study. Of 48 patients recruited at nine sites, 47 were randomized 2:1 inhaled apomorphine/placebo. Respirable doses (drug predicted to reach the lung), ascending through 1.5, 2.3, 3.0 and 4.0 mg until efficacy was achieved, were administered to patients in a practically defined ‘off’ state. The primary endpoint was the response in unified PD rating scale Part 3 (UPDRS 3), at the highest dose received by the patient. Secondary endpoints included time to ‘on’, the proportion of patients converting from ‘off’ to ‘on’, and duration of ‘on’. Results: In the 47 intent‐to‐treat patients with PD, mean age 60.6 years, the mean UPDRS 3 improvement was significantly greater for VR040 at 26.8 points (standard deviation 12.0), vs 14.9 (16.3) for placebo (treatment difference 11.6, 95% confidence interval 2.3–20.9, P = 0.016). Rapid apomorphine absorption (2–7 min) translated to rapid (mean 10 min) reversal from the ‘off’ state. Adverse effects did not differ between VR040 and placebo; no patient discontinued due to an adverse event; one serious adverse event (constipation) in the VR040 group was considered unrelated to trial medication. Conclusions: Inhaled apomorphine shows significant promise as a replacement for intermittent subcutaneous injections; further studies are appropriate to optimize efficacy and tolerability.

• Item Type: Articles
• Additional Information: This work was funded by Vectura plc.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Grosset, Dr Katherine and Grosset, Professor Donald
• Authors: Grosset, K.A., Malek, N., Morgan, F., and Grosset, D.G.
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Acta Neurologica Scandinavica
• Publisher: Wiley
• ISSN: 0001-6314
• ISSN (Online): 1600-0404
• Published Online: 26 March 2013