Clinical parkinsonism & related disorders · 2025
Bioequivalence of Foslevodopa/Foscarbidopa continuous subcutaneous infusion to arm, thigh, or flank versus abdomen in healthy and advanced Parkinson's disease individuals.
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Han Yi Rang, Jeong Anna, Ayub Kanwal, Gupta Shelly V, Bergmann Lars, Kern Drew S, Pagan Fernando, Rosebraugh Matthew
Аннотация
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.
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.