Safety and tolerability study of subcutaneous injections of larger volumes in abdominal and lower extremity sites suitable for autoinjectors

Objectives This study investigated pain and safety of subcutaneous injections, using larger volumes (>3 mL) and injection rates.Methods 32 subjects were recruited and had 4 injections: 2.5, 5.0, 10.0, and 15 mL administered in the abdomen and thigh using an infusion pump. Injection force was measured and pain assessments obtained using VAS (0–100 mm), and verbal pain ratings.Results All 125 infusions appropriately delivered the complete volume. VAS pain increased after start of injections: median VAS: 10.00 mm (IQR: 1.50–27.00) and peaked to 16 mm (IQR: 8.50–43.50) at 4 min for the 15 mL infusions. Median VAS after termination of infusions was 6.5 mm (IQR: 0–18). Verbal pain at start of injection was none to mild. VAS pain ratings were higher (p < 0.001) for 0.500 mL/sec and 0.333 mL/sec infusion rates compared to 0.023 mL/sec. Peak injection forces were significantly (p < 0.001) different from one another for the three infusion rates with a moderate correlation (R = 0.55, p < 0.001) between injection force and pain. Minimal saline leaked onto the skin surface for all volumes and delivery rates.Conclusion These results provide evidence that subcutaneous administration of >3 mL volumes into the subcutaneous tissue of the abdomen or thigh, was safe and well tolerated.Clinical trial registration NCT06194578.