Objective: Determine the tolerance of and potential for cheek pouch buccal mucosa irritation following the administration of apomorphine film (APL-130277).

Background: APL-130277 is a sublingual film being studied in Phase 3 trials to rapidly turn patients ON from OFF episodes in patients with Parkinson’s disease by delivering apomorphine via the oral mucosa.

Methods: This toxicology study, in Syrian Golden Hamsters using either a 2.08 mg strip of APL-130277 or placebo, was conducted utilizing a blinded methodology. APL-130277 (N=16) or placebo (N=16) was administered 3 times per day for 28 days. Clinical observations, body weight, food consumption and the appearance of the cheek pouch mucosa were recorded. Buccal mucosa irritation was evaluated using the Draize system of scoring whereby 0=no erythema, no edema; 1=very slight erythema (barely perceptible) and very slight edema (barely perceptible); 2=well-defined erythema; slight edema; 3=moderate to severe erythema and moderate edema; and, 4=severe erythema and severe edema. Necropsy and histopathological examinations were also performed.

Results: Mild to moderate motor hyperactivity was noted on Days 1 and 2 in the APL-130277 group. On Days 3 to 28, only mild motor hyperactivity was observed following each dosing which lasted ∼20-40 minutes. Hamsters in the active treatment group initially lost weight; however, by the end of the study, they began to regain weight (study days 25-28). There was a correlation between body weight loss and motor hyperactivity, observed following dosing with APL-130277. The administration of APL-130277 three times a day for 28 consecutive days did not result in any observable local irritation of the buccal mucosa as determined by clinical, macroscopic and histopathologic evaluations.

Conclusions: Dosing with APL-130277 (2.08 mg of apomorphine) in Golden Syrian Hamsters resulted in initially mild to moderate motor hyperactivity during the first 2 days, followed by mild motor hyperactivity for the remainder of the treatment periods. These findings are consistent with previously reported effects of apomorphine observed in hamsters. Initial small reductions of body weight with APL-130277 were later reversed. APL-130277 produced no irritation of the cheek pouch buccal mucosa.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/oral-apomorphine-film-apl-130277-produces-no-buccal-mucosal-irritation-results-of-a-toxicological-study/