Investigation into the Acceptability of Moderate-to-Large Volume Subcutaneous Injections in Healthy Volunteers: Results from a Single-Center Randomized Controlled Study.

Abstract

Therapeutic proteins are often delivered by subcutaneous (SC) autoinjector to enable self-administration. Autoinjectors typically deliver up to 1 mL injected volumes per dose. Delivery of larger volumes may be limited by injection site discomfort, including pain, swelling, and redness. Delivery at a slower rate may mitigate this discomfort. This single-center, randomized, crossover study evaluated the acceptability and tolerability of varying volumes and delivery rates of SC saline in healthy volunteers. Eligible participants were adults (18-65 years) with a body mass index of 18.5-32.0 kg/m2. Participants (N = 24) were randomized to multiple sequences of infusions over five visits, with infusions ranging from 1 to 5 mL at rates of 1.50-6.00 mL/minute (min) and including a 1 mL SC infusion in 10seconds (s) at a rate of 6.00 mL/min. The primary objective was to identify acceptable volume and delivery rates of SC saline, as assessed by visual analogue scale (VAS) pain scores, a tolerability and acceptability questionnaire, and infusion leakage. Infusions that met the acceptability criteria were 1 mL in 10s, 4 mL in 58s, and 3 mL in 2mins. Higher delivery volumes and rates were associated with higher VAS pain scores but remained within the VAS acceptability criteria. These findings may support the development of larger-volume injectors for self-administration of future medicines.