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

Abstract

Chika Akinseye,1 Andrew Fiorini,2 Emily Louise Jarvis,3 Michelle Fry,4 Abid Raza,5 Sara Soleman,6 Stephanie Igwe,6 Mark Palmer2 1GSK R&D, Discovery Medicine, Stevenage, UK; 2GSK R&D, Device Engineering, Ware, UK; 3GSK R&D, Biostatistics, Stevenage, UK; 4GSK Rx Global Clinical Delivery, Stockley Park, UK; 5GSK R&D, Stockley Park, UK; 6GSK Clinical Unit, Addenbrooke’s Centre for Clinical Investigation, Cambridge, UKCorrespondence: Mark Palmer, GSK R&D, Harris’s Lane Ware, Hertfordshire, SG12 0DP, United Kingdom, Email [email protected]: 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.Patients and Methods: 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 10 seconds (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.Results: Infusions that met the acceptability criteria were 1 mL in 10s, 4 mL in 58s, and 3 mL in 2 mins. Higher delivery volumes and rates were associated with higher VAS pain scores but remained within the VAS acceptability criteria.Conclusion: These findings may support the development of larger-volume injectors for self-administration of future medicines.Keywords: drug delivery system, skin, formulation, pain scores, tolerability and acceptability questionnaire

Keywords

• drug delivery system
• skin
• formulation
• pain scores
• tolerability and acceptability questionnaire