Insights into retention and safety/tolerability of apomorphine sublingual film in patients with Parkinson's disease and OFF episodes: post hoc analyses of a phase III, open-label study

Abstract

Background: Managing OFF episodes in patients with Parkinson's disease becomes increasingly challenging over time, making it critical to tailor treatment to each patient's needs and characteristics for effective care.

Objectives: Study CTH-301 assessed the long-term safety/tolerability and efficacy of sublingual apomorphine (SL-APO) for the on-demand treatment of OFF episodes.

Design: The findings from four post hoc analyses of Study CTH-301, conducted to understand factors influencing SL-APO retention and safety/tolerability, with a particular focus on oropharyngeal treatment-emergent adverse events (TEAEs) are reported.

Methods: The first analysis evaluated baseline variables differing between patients who completed the study and those who discontinued due to either lack of efficacy or adverse events to help define patients more likely to benefit from SL-APO therapy: The second and third analyses compared safety/tolerability between the subgroups of patients who were or were not receiving dopamine agonist (DA) treatment, and in those aged <70 or ⩾70 years at baseline, respectively. The fourth analysis examined oropharyngeal TEAEs.

Results: Patients in a younger age group, those experiencing morning akinesia or delayed ON, and those taking lower dose/fewer intakes of levodopa and concomitant DAs were more likely to benefit from SL-APO therapy. Patients taking concomitant DAs reported lower rates of DA-related TEAEs and a higher mean SL-APO optimal dose. Specific analyses in patients aged ⩾70 years indicated that this age group reported similar rates of TEAEs and a similar profile of the most common TEAEs compared with the group aged <70 years. A lower total daily dose of SL-APO was associated with a reduced risk of developing oropharyngeal TEAEs. Such events were mostly mild or moderate, occurring within the first months after SL-APO initiation, and generally resolved, with worsening being rare.

Conclusion: These analyses provided insights into retention and safety/tolerability of SL-APO, helping clinicians and patients make informed treatment decisions.

Keywords: OFF episodes; Parkinson’s disease; adverse events; dopamine agonist; post hoc analysis; sublingual apomorphine.

Figure 1.

Baseline variables that differed significantly between the subgroups of patients who completed the study and those who discontinued due to lack of efficacy. (a) Number of daily levodopa intakes. (b) Total daily levodopa dose at baseline. (c) Presence of morning akinesia.

Figure 2.

Baseline variables that differed significantly between the subgroups of patients who completed the study and those who discontinued due to adverse events. (a) Dopamine agonists use. (b) Age. (c) Presence of delayed ON.

Figure 3.

Distribution of days to onset of the first oropharyngeal TEAEs during the dose-optimisation phase and long-term safety phase. Black lines indicate smoothed density estimate of the histograms; turquoise vertical lines on x-axes indicate days to onset of oropharyngeal TEAEs for each individual patient; dashed red line indicates the median; continuous red line indicates the mean. SD, standard deviation; TEAE, treatment-emergent adverse event.

Figure 4.

Frequency of oropharyngeal AEs by SL-APO total daily dose and number of intakes during the long-term safety phase. Patients were grouped based on their use of SL-APO. (a) Mean total daily dose above or below the median value (28.1 mg) or (b) mean number of daily intakes above or below the median value (1.5 intakes). Red colour indicates the percentage of patients reporting oropharyngeal AEs; blue indicates the percentage of patients without oropharyngeal AEs. AEs, adverse events; SL-APO, sublingual apomorphine.