Phase IIa randomized double-blind, placebo-controlled study of inhaled apomorphine as acute challenge for rescuing 'off' periods in patients with established Parkinson's disease

Background and purposeIn this first study of inhaled apomorphine (VR040) in patients with Parkinson's disease, the primary objective was to find the minimum efficacious dose of apomorphine that was useful in rescuing patients during off' periods. Safety, tolerability and pharmacokinetics of inhaled apomorphine were assessed during the study. MethodsA double-blind, placebo-controlled, randomized trial of three escalating single doses of inhaled apomorphine (0.2, 0.5 and 0.8mg fine particle dose) versus placebo (3:1 active:placebo) was performed. Parkinson's motor severity assessments by a clinician, and disease state assessment by the patient, were performed at baseline during an off' state, and at specified times after test drug administration. Safety assessments (including vital signs, electrocardiogram and forced expiratory volume) were performed, and plasma apomorphine levels measured. ResultsAll 24 patients completed the study, and considering the three dose levels together, inhaled apomorphine did not significantly increase the proportion of patients switching from off' to on' (0/6 at 0.2mg, 3/6 at 0.5mg and 2/6 at 0.8mg vs. 1/6 for placebo), or decrease the time from off' to on' post-treatment (10min for 0.5mg, 40min for 0.8mg, vs. 20min for placebo). However, there was a suggestion of benefit at the higher doses (5/12 switched on' at the 0.5 or 0.8mg doses, vs. 1/6 for placebo). There were no serious adverse events and treatment was well tolerated. Peak plasma concentration was 1-3min post-dose, and plasma level dose proportionality was observed. ConclusionsInhaled apomorphine was safe and well tolerated at the doses tested for an acute challenge to rescue off' periods, but efficacy at these doses was limited. A follow-up study at higher doses is appropriate given these initial findings. Click here to view the accompanying paper in this issue.