Tolerability of High-Volume Subcutaneous Injections of a Viscous Placebo Buffer: A Randomized, Crossover Study in Healthy Subjects

• Published in: AAPS PharmSciTech Vol. 16; no. 5; pp. 1101 - 1107
• Main Authors: Dias, Clapton, Abosaleem, Bassam, Crispino, Caroline, Gao, Bing, Shaywitz, Adam
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2015
• Subjects: Adult; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - chemistry; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Buffers; California; Cross-Over Studies; Drug Compounding; Female; Healthy Volunteers; Humans; Infusions, Subcutaneous; Injections, Subcutaneous; Male; Middle Aged; Pain - etiology; Pain Measurement; Pharmaceutical Vehicles - administration & dosage; Pharmaceutical Vehicles - adverse effects; Pharmaceutical Vehicles - chemistry; Pharmacology/Toxicology; Pharmacy; Research Article; Time Factors; Viscosity; viscous; placebo buffer; subcutaneous injections; tolerability
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-015-0288-y

Monoclonal antibody biotherapeutics are often administered by subcutaneous (SC) injection. Due to dose requirements and formulation limitations, SC injections >1 mL are often required. We used a viscous placebo buffer (5 cP), characteristic of a high-concentration antibody formulation, to investigate the effect of dose volume and injection rate on the tolerability of higher-volume SC injections. In this randomized, crossover, single-center study, 48 healthy adults received one 1.2-mL bolus injection over 5 s and three 3.5-mL injections over 1, 4, and 10 min in different abdominal quadrants, with each injection separated by approximately 2 h. The primary objective was to compare pain scores associated with the injections, immediately after administration and 1 h later, using a 100-mm visual analog scale (VAS). Secondary objectives included assessment of adverse events, including injection site reactions and swelling. Mean age was 38.4 (11.6) years and 20 subjects (42%) were female. Lowest mean VAS score was for the 10-min (6.83 mm) and highest for the 1-min injection (19.13 mm). One hour after administration, mean VAS scores were <3.5 mm for all injections. Swelling was similar among the three 3.5-mL injections. After needle removal, leakage occurred following 14 (29%) 1.2-mL injections, eight (17%) 4-min injections, five (10%) 1-min injections, and four (8%) 10-min injections. Fifteen subjects (31%) experienced an adverse event, none of which was serious, fatal, or led to study discontinuation. All injection durations were well tolerated, suggesting a single large-volume SC injection of a biotherapeutic agent could be used instead of multiple injections.