Pharmacokinetics of peginterferon BETA-1A delivered by single-use autoinjector and prefilled syringe

BACKGROUND: Peginterferon beta‐1a demonstrated efficacy to treat multiple sclerosis (MS) in a Phase III study (n=1512), in which pre‐filled syringe (PFS) was used as delivery device. Autoinjector (AI) can simplify administration process and reduce injection burden. This study was to characterize pharmacokinetics of peginterferon beta‐1a delivered subcutaneously by either device to support the development of AI. METHODS: This was an open‐label, two‐sequence, crossover study with a 3‐week washout period. Subjects were randomized into two groups (1:1). Group 1 was treated with PFS (Day 1) followed by AI (Day 22); Group 2 was treated with a reversed sequence. Thirty subjects were planned to have 24 evaluable subjects (not powered to establish bioequivalence). PK samples were collected at pre‐dose and up to 240 hours post‐dose following each dosing. Drug concentration was measured using enzyme‐linked immunosorbent assay. PK parameters were calculated using non‐compartmental analysis. RESULTS: Twenty‐four subjects received both PFS and AI treatments. One subject was excluded from the summary analysis because no drug was detectable after PFS injection on Day 22 and high‐ titer anti‐PEG antibody was detected at pre‐dose. The exposure was similar between the two devices. The geometric mean AUC inf , Cmax , and t 1/2 was 41.0 hng/mL, 427 pg/mL, and 39.9 h, respectively, following AI injection; the geometric mean AUCinf , Cmax , and t 1/2 was 38.3 hng/mL, 365 pg/mL, and 46.0 h, respectively, following PFS injection. The percent difference in geometric means were 7.14% for AUC inf , 17.1% for Cmax , and ‐13.3% for t 1/2 . The safety profiles of the two devices were similar. CONCLUSION: These data demonstrated PK similarity between AI and PFS, supporting the development of the AI to improve treatment convenience.