Objective: To assess the effect of subcutaneous injection of apomorphine (APO) in patients with Parkinson’s disease (PD)and morning akinesia who experience dose failures after their first daily levodopa dose.

Background: Patients with PD and motor fluctuations often have delayed onset of levodopa in addition to end of dose wearing off. Dose failures also occur, and may be unpredictable probably reflecting imapired delivery and/or absorption of an oral dose of levodopa.

Methods: Subjects who reported morning akinesia at a clinic visit recorded their time-to-ON following each morning dose of levodopa for 7 days. Subjects who met inclusion criteria of >45 minute delay for at least 3>4 of 7 days were then titrated to a APO “optimal dose”, defined as providing >90% of motor UPDRS after levodopa within 15 min, without intolerable adverse effects. Subjects then recorded their TTO following each morning dose of APO for 7 days. Mean TTO represented the primary efficacy variable comparing APO treatment period vs baseline levodopa period. Dose failures were defined as lack of onset within 60 minutes. Safety and tolerability were also assessed.

Results: The full analysis set included 88 subjects. Mean dose onset reduced from 60.86 ±18.11 minutes after levodopa to 23.72 ±14.55 minutes after APO (p<0.0001). Dose failures (defined as >60 min) were reported for 144 of 310 (46%) completed diary entries during the levodopa baseline week, but only 20 of 307 (7%) diary entries following APO. Over 40% of subjects had a dose failure during the 7 day levodopa period. Overall, the most common adverse events were nausea, dizziness and orthostatic hypotension (most AEs were mild or moderate occurred during APO titration); no serious AEs occurred.

Conclusions: In patients with morning akinesia, dose failure of the first daily oral levodopa dose was surprisingly common. Subcutaneous injections of APO provided a robust motor improvement that was rapid, reliable, and safe. Dose failures were significantly reduced. APO was well tolerated by most subjects. Non-oral delivery may improve motor fluctuations by avoiding GI dysfunction that can delay levodopa absorption.

This analysis has not been previously preented. The primary results of the AM Impakt trial was presented at MDS in San Diego 2015.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/efficacy-of-apomorphine-subcutaneous-injections-in-patients-with-levodopa-dose-failures-and-morning-akinesia/