Session Information
Date: Tuesday, September 24, 2019
Session Title: Parkinsonisms and Parkinson-Plus
Session Time: 1:45pm-3:15pm
Location: Agora 3 West, Level 3
Objective: Exposure-response models were developed to characterize the relationship between apomorphine exposure and (1) efficacy using Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III score in patients with Parkinson’s disease (PD) and “OFF” episodes, (2) systolic/diastolic blood pressure (sBP/dBP) in healthy subjects/patients, and (3) nausea/oral adverse events (AEs) in patients following apomorphine sublingual film (APL-130277; APL) administration.
Background: APL was found to be effective and generally well tolerated as an acute, intermittent treatment for “OFF” episodes in patients with PD in a controlled Phase 3 trial.
Method: Data were analyzed using nonlinear mixed effects modeling methodology as implemented in NONMEM® software. Final model simulations estimated apomorphine concentration and its association with MDS-UPDRS Part III score. For BP, nominal time-matched data were evaluated by linear and maximum effect models. Time-to-event and extended Cox proportional hazard models described nausea and oral AEs.
Results: For efficacy, a 23-point decrease from baseline in MDS-UPDRS score was estimated as the inhibitory maximum effect; a cutoff of ≤ –12.5 points was associated with a FULL “ON” response; response duration increased from 1.6-3.1 hours for a 10-mg and 35-mg dose of APL, respectively; and average apomorphine concentrations of 2.66-2.94 ng/mL corresponded with these outcomes. For BP, single doses of 10 and 35 mg APL were predicted to decrease sBP by 3 and 7 mmHg, respectively, and dBP by 1 and 3 mmHg, respectively; decreases were more prevalent in patients than in healthy subjects. For AEs, predicted risk of nausea (hazard ratio, 2.01) and oral events (hazard ratio, 1.34) were higher for single doses of APL 35 vs 10 mg, respectively.
Conclusion: Longitudinal and time-to-event exposure-response models demonstrated a correlation between apomorphine exposure and efficacy using MDS-UPDRS Part III score. Increases in apomorphine plasma concentration were associated with a modest decrease in sBP/dBP, and an increase in risk for nausea and less so for oral AEs following administration of sublingual apomorphine in patients with PD and “OFF” episodes.
To cite this abstract in AMA style:
F. Agbo, Y. Chiu, S. Chapel, G. Galluppi, D. Blum, B. Navia. Population Exposure-Response Models of Apomorphine Sublingual Film in Healthy Subjects and Patients With Parkinson’s Disease and “OFF” Episodes [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/population-exposure-response-models-of-apomorphine-sublingual-film-in-healthy-subjects-and-patients-with-parkinsons-disease-and-off-episodes/. Accessed May 16, 2025.« Back to 2019 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/population-exposure-response-models-of-apomorphine-sublingual-film-in-healthy-subjects-and-patients-with-parkinsons-disease-and-off-episodes/