Bioequivalence of Foslevodopa/Foscarbidopa continuous subcutaneous infusion to arm, thigh, or flank versus abdomen in healthy and advanced Parkinson’s disease individuals

Abstract

Background

Foslevodopa/foscarbidopa (LDp/CDp) are soluble prodrugs of levodopa/carbidopa delivered as a continuous subcutaneous infusion (CSCI) via a portable pump to provide continuous levodopa exposures.

Objective

To assess the safety of LDp/CDp and the relative bioavailability of levodopa/carbidopa following LDp/CDp 24-hour CSCI administration to the arm, thigh, and flank versus the abdomen.

Methods

Two open-label, randomized crossover studies (healthy adult volunteers [HV]; adults with advanced Parkinson’s disease [aPD]; NCT05094050) evaluated 24-hr CSCI of LDp/CDp to different infusion sites (abdomen, arm, thigh, flank), each designated as a study regimen. Participants in the aPD study had levodopa-responsive idiopathic Parkinson’s disease with ≥2.5 h of “Off” time/day. In the HV study, each LDp/CDp regimen was administered over 24 h, with 72-hour washout periods between regimens. In the aPD study, LDp/CDp was administered for 2 consecutive days at each infusion site, with no washout between regimens.

Results

For both levodopa and carbidopa, the 90% confidence intervals for both exposure measures (AUC and C_max) were within the 80–125% range for the comparison between the abdomen and each alternate infusion site, meeting the criteria for bioequivalence. The most commonly reported treatment-emergent adverse events (TEAEs) were mild infusion site reactions, which occurred in 3/12 participants (HV study) and 9/16 participants (aPD study). There were no serious TEAEs and no event led to early discontinuation in either study.

Conclusions

The pharmacokinetics of levodopa and carbidopa demonstrated that the abdomen, arm, thigh, and flank are interchangeable sites for CSCI of LDp/CDp. There were no concerning patterns of adverse events.