Session Information
Date: Tuesday, June 21, 2016
Session Title: Parkinson's disease: Pathophysiology
Session Time: 12:30pm-2:00pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: Determine the pharmacokinetic/pharmacodynamic effects of APL-130277 on OFF episodes in patients with Parkinson’s disease (PD).
Background: APL-130277 is a sublingual film being studied in Phase 3 trials to rapidly turn patients ON from OFF episodes by delivering apomorphine via the oral mucosa.
Methods: PD patients with at least one OFF episode/day and = or > 2 hours of daily OFF were included. Patients were dosed in the morning OFF state, starting with APL-130277 10 mg and increased in 5 mg increments until a full ON was achieved, to a maximum of 30 mg. Eight patients had pharmacokinetic analyses, 6 of whom turned fully ON.
Results: Of these 6 responders, mean plasma apomorphine concentration upon turning ON was 2.64 ng/ml 
. Concentrations reached this level within 20 minutes and were maintained over this level through 90 minutes. This corresponded with mean decreases in MDS-UPDRS Part III scores of 9.7, 20, 19.7, 17.3 and 8.7 at 15, 30, 45, 60 and 90 minutes post-dosing, respectively and confirmed ON for over 40 minutes. The average plasma apomorphine concentration for the two non-responders for all doses at each time point never reached 2.64 ng/ml.
Conclusions: On average, a minimum apomorphine concentration of 2.64 ng/ml was needed to turn a patient fully ON, lower than that which was previously reported. Plasma levels above the minimum efficacious concentration resulted in sustained improvements in motor function and ON time.
Presented, in part, at the American Neurology Association (September 27-29, 2015; Chicago, IL). Dubow J, Dzyngel B, Bilbault T, Giovinazzo A, Agro A. Pharmacokinetic-pharmacodynamic effects of sublingual apomorphine (APL-130277) for the acute management of OFF episodes in Parkinson’s disease patients (S416). Annals of Neurology. 2015;78(Suppl 19):S48.
To cite this abstract in AMA style:
E.J. Pappert, B. Dzyngel, T. Bilbault, A. Agro. Pharmacokinetic-pharmacodynamic effects of apomorphine sublingual film (APL-130277) for the rapid management of OFF episodes in patients with Parkinson’s disease [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/pharmacokinetic-pharmacodynamic-effects-of-apomorphine-sublingual-film-apl-130277-for-the-rapid-management-of-off-episodes-in-patients-with-parkinsons-disease/. Accessed November 22, 2024.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/pharmacokinetic-pharmacodynamic-effects-of-apomorphine-sublingual-film-apl-130277-for-the-rapid-management-of-off-episodes-in-patients-with-parkinsons-disease/