Apomorphine: North American clinical experience

Abstract

This manuscript reviews North American clinical trials examining subcutaneous injection of apomorphine in Parkinson's disease (PD) patients, and the available, cumulative apomorphine safety data for the US. These data provide strong documentation concerning dosing range (2-6 mg/injection), dosing frequency (1-10 injections/day), therapeutic response, and duration and onset of benefit. The US pivotal trial for subcutaneously injected apomorphine demonstrated robust and statistically significant benefit from drug administration when compared to subjects receiving placebo. Interestingly, these changes closely mirrored the response to levodopa in the same population, as measured by Unified Parkinson's Disease Rating Scale and Webster Step Seconds, and suggests that apomorphine may have greater potency than other agonists. A study of subjects ranging from early to advanced disease, conducted at the NIH, demonstrated a decline in duration of response and increased time to response in the advanced group when compared to levodopa naïve subjects, despite the observation that threshold and optimal response dosages did not differ. Pharmacodynamic responses from a single average-dosage administration of 4.2 mg apomorphine in several studies demonstrated a benefit as early as 7.5 minutes with a duration of benefit as long as 90 minutes. Serious adverse events occurred in 16% of the subjects in these studies with the most common adverse events including dyskinesias (21%), hallucinations (11%), and orthostatic hypotension (9%).