Inhaled dry powder apomorphine (VR040) for 'off ' periods in Parkinson's disease: an in‐clinic double‐blind dose ranging study. (26th March 2013)

• Record Type: Journal Article
• Authors: Grosset, K. A.; Malek, N.; Morgan, F.; Grosset, D. G.
• Is Part Of: Acta neurologica Scandinavica. Volume 128:Number 3(2013:Sep.)
• Page Start: 166
• Page End: 171
• Publication Date: 2013-03-26
• Subjects: Neurology -- Periodicals; 616.8
• DOI: 10.1111/ane.12107
• Languages: English
• ISSNs: 0001-6314

Abstract

<abstract abstract-type="main" id="ane12107-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ane12107-sec-0001" sec-type="section"> <title>Background</title> <p>'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.</p> </sec> <sec id="ane12107-sec-0002" sec-type="section"> <title>Methods</title> <p>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'.</p> </sec> <sec id="ane12107-sec-0003" sec-type="section"> <title>Results</title> <p>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, <italic>P</italic> = 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.</p> </sec> <sec id="ane12107-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Inhaled apomorphine shows significant promise as a replacement for intermittent subcutaneous injections; further studies are appropriate to optimize efficacy and tolerability.</p> </sec> </abstract>