Evaluate and characterize infusion site reactions (ISR) reported as a treatment-emergent adverse event (TEAE) with 24h ND0612 treatment in clinical studies.

ND0612 is an investigational, continuous 24h subcutaneous infusion of levodopa/carbidopa (max daily dose 720/90 mg, to be supplemented as needed with oral therapies), delivered via two cannulas (max 6mL per cannula per day) to reduce skin burden. Clinical trial experience indicates that, as expected with the subcutaneous route of administration, local ISRs are common.

An integrated safety analysis of ISRs reported as TEAEs in people with PD treated with a 24h regimen of ND0612 from two phase 2 (NCT02577523 and NCT02726386) and one phase 3 (NCT04006210) studies was conducted. Grouped terms were defined for infusion site nodules, hematoma, swelling, eschar, erythema, infection (including abscess and cellulitis), and pain.

A total of 419 patients were included in this analysis with a mean±SD [range] exposure of 395±471 days [2 days to 6.2 years]. Overall, 369 (88%) of patients reported ≥1 ISR as a TEAE, including 15 (4%) patients who reported serious TEAEs. Forty-nine (12%) patients discontinued due to an ISR. Of 2461 reported ISR events, the most reported were: nodules (1065 events, 43%), hematoma (815 events, 33%), pain (141 events, 6%), and infection (134 events, 5%). Most reported ISR TEAEs were mild (2079 events, 85%). Moderate ISR TEAEs accounted for 347 events (14%). Of the 34 (1%) severe ISR events reported, almost half were ISR-infection events (16 events reported in 13 patients). Presumed ISR-infections were mainly managed with oral antibiotics and abscess drainage; median time to resolution was 15 days.

While ISRs were commonly reported as TEAEs, 99% of ISR adverse events were mild or moderate in severity and resolved with or without treatment. Despite the incidence of ISR events, most patients continued in the trials.