Bioequivalence of Foslevodopa/Foscarbidopa continuous subcutaneous infusion to arm, thigh, or flank versus abdomen in healthy and advanced Parkinson’s disease individuals
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/carbi...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-01-01
|
| Series: | Clinical Parkinsonism & Related Disorders |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590112525000635 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | 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 Cmax) 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. |
|---|---|
| ISSN: | 2590-1125 |