Subcutaneous apomorphine in patients with advanced Parkinson's disease: a dose-escalation study with randomized, double-blind, placebo-controlled crossover evaluation of a single dose.

OBJECTIVE

To further explore the efficacy and safety of subcutaneous apomorphine (APO) in treating off episodes in APO-naïve patients with advanced Parkinson's disease (PD).

METHODS

56 patients receiving optimized oral anti-PD medication were evaluated on separate days for response to single increasing doses of APO. Acute response to oral anti-PD medication and APO dose escalation (2-10 mg) was evaluated under unblinded conditions. At the 4 mg APO dose, placebo was randomly introduced under double-blind crossover conditions.

RESULTS

Mean changes from pre-dose in Unified Parkinson's Disease Rating Scale motor scores indicated significant improvement following APO 4 mg versus placebo at 20 min (p=0.0002), 40 min (p<0.0001; maximum improvement) and 90 min (p=0.0229). Improvements showed significant dose-response at 20 min, 40 min (both p<0.0001) and 90 min (p=0.0049). Adverse events were more common with APO than placebo, and also showed significant dose-response (p<0.0001). Common adverse events associated with APO included yawning, dizziness, nausea, somnolence and dyskinesias, and were generally mild to moderate. There were no significant differences between APO and placebo in the incidence of hypotension associated with a postural change from a sitting to standing position.

CONCLUSIONS

Subcutaneous APO provided rapid, effective relief of off episodes associated with advanced PD.