Journal
NEUROLOGY AND THERAPY
Volume 10, Issue 2, Pages 693-709Publisher
SPRINGER LONDON LTD
DOI: 10.1007/s40120-021-00251-6
Keywords
APL-130277; APL; Apomorphine sublingual film; Bioavailability; Exposure; OFF'' episodes; Parkinson's disease; Pharmacokinetics; Subcutaneous apomorphine
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Funding
- Sunovion Pharmaceuticals Inc. (Marlborough, Massachusetts)
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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.
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.
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