Objective: We evaluated a subset of patients who were enrolled in the AMIMPAKT trial of sc apomorphine injection to treat morning akinesia (see reference) who experienced dose failure of at least one morning first levodopa dose during a one week period of diary completion.

Background: OFF episodes are common and persist despite polypharmacy with adjunctive therapy. Daily OFF time includes wearing off at end-of-dose, delayed onset of next levodopa dose, and dose failures. OFF time reflects pharmacokinetic (ie, short levodopa half-life), central (ie, striatal denervation), and peripheral (ie, delayed gastric emptying, protein competition) factors. While greater recognition of delayed time-to-ON and end-of-dose wearing OFF has led to improved treatment strategies, dose failures (no-ON) may be more common than presently recognized.

Methods: In the AMIMPAKT trial, 88 subjects with morning akinesia were enrolled. These patients had a mean time-to-ON of the first levodopa morning dose of approximately 60 minutes. Half of enrolled patients had PD duration of less than 10 years. Patients completed a 7 day diary assessment every 5 minutes after taking their morning levodopa (in the first week) or apomorphine sc injection (second week) of whether they had turned ON. Patients not turning ON within 60 minutes were deemed to have a dose failure.

Results: In this trial, 40% of enrolled subjects had at least one dose failure during the 7 day diary period. Over 50% of completed diary days during the 7 day levodopa period were dose failures after taking levodopa, but only 7% of days after using apokyn. Patients who had dose failures after levodopa invariably had rapid ON with apomorphine.

Conclusions: Dose failure may be more common than presently recognized. Incidence of dose failures may be higher in patients experiencing morning akinesia. SC injection of apomorphine successfully reduced time-to-ON in patients experiencing dose failure, as well as morning akinesia. This highlights the value of non-oral delivery of dopaminergic medications to treat OFF episodes when the gastric delivery and / or intestinal absorption of levodopa is compromised leading to delayed ON and dose failures.

References: Apomorphine subcutaneous injection for the management of morning akinesia in Parkinosn’s disease,Mov Dis Colin Practice, 2017, 4:78-83.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/treatment-of-levodopa-dose-failure-with-subcutaneous-apomorphine-injection/