Pharmacokinetics and Comparative Bioavailability of Apomorphine Sublingual Film and Subcutaneous Apomorphine Formulations in Patients with Parkinson's Disease and OFF'' Episodes: Results of a Randomized, Three-Way Crossover, Open-Label Study

Introduction: In a pivotal study, apomorphine sublingual film (APL; KYNMOBI (R)) was an effective and generally well-tolerated on-demand treatment of OFF'' episodes in patients with Parkinson's disease (PD), approved across the dose range of 10-30 mg. Pharmacokinetics and comparative bioavailability of APL and two subcutaneous (SC) apomorphine formulations (SC-APO [APOKYN (R)] and SC-APO-GO [APO-go (R) PEN]) were evaluated in a randomized, three-way crossover, open-label study (NCT03292016). Methods: Patients with PD and OFF'' episodes received an open-label randomized sequence of single doses of SC-APO and SC-APO-GO at the currently prescribed dose (2/3/4/5 mg) and APL doses with similar plasma exposure (15/20/25/30 mg) with >= 1-day washout between formulations. Plasma pharmacokinetics of apomorphine and apomorphine sulfate (major inactive metabolite) were measured 0-6 h postdose. Results: Median time to maximum plasma concentration (t(max)) of apomorphine was 0.63-0.75 h for APL and 0.25-0.38 h for SC-APO and SC-APO-GO. Geometric mean maximum plasma concentration (C-max) of apomorphine was 4.31-11.2 ng/ml across APL doses and was generally lower compared with SC apomorphine formulations within dose groups. Area under the concentration-time curve from time 0 to infinity (AUC(infinity)) was similar across apomorphine formulations within most dose groups. Relative bioavailability of APL was similar to 17% of SC apomorphine by AUC(infinity); SC-APO and SC-APO-GO had similar bioavailability (98% and 83% by AUC(infinity) and C-max, respectively). Apomorphine sulfate exposure was similar to three-fold higher for APL versus SC-APO and SC-APO-GO by AUC(infinity) and C-max. Conclusion: In patients with PD and OFF'' episodes, APL demonstrated lower C-max and relative bioavailability but similar exposures (AUCs) versus SC apomorphine within the approved dose range.

Automated summary

In patients with PD experiencing OFF'' episodes, APL showed lower maximum plasma concentration and relative bioavailability compared to subcutaneous apomorphine, but similar exposures (AUCs) within the approved dose range.