Dataset Information

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.

ABSTRACT:

Introduction

In a pivotal study, apomorphine sublingual film (APL; KYNMOBI^®) 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^®] and SC-APO-GO [APO-go^® 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_∞) was similar across apomorphine formulations within most dose groups. Relative bioavailability of APL was ~ 17% of SC apomorphine by AUC_∞; SC-APO and SC-APO-GO had similar bioavailability (98% and 83% by AUC_∞ and C_max, respectively). Apomorphine sulfate exposure was ~ three-fold higher for APL versus SC-APO and SC-APO-GO by AUC_∞ 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.

Trial registration

ClinicalTrials.gov, NCT03292016.

SUBMITTER: Agbo F

PROVIDER: S-EPMC8571442 | biostudies-literature |

REPOSITORIES: biostudies-literature

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