Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2015 Oct;16(5):1101-7.
doi: 10.1208/s12249-015-0288-y. Epub 2015 Feb 19.

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

Clapton Dias  1 , Bassam Abosaleem  2 , Caroline Crispino  2 , Bing Gao  2   3 , Adam Shaywitz  2   4
Affiliations
Randomized Controlled Trial

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

Clapton Dias et al. AAPS PharmSciTech. 2015 Oct.

Erratum in

Abstract

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.

Keywords: placebo buffer; subcutaneous injections; tolerability; viscous.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Visual-analog scale pain scores by treatment, immediately and 1 h after administration. Dots represent means, boxes represent Q1 to Q3 with lines showing medians, and whiskers indicate ranges
Fig. 2
Fig. 2
Pain rankings by treatment, after the fourth administration
See this image and copyright information in PMC

References

    1. Anderson G, Meyer D, Herrman CE, Sheppard C, Murray R, Fox EJ, et al. Tolerability and safety of novel half milliliter formulation of glatiramer acetate for subcutaneous injection: an open-label, multicenter, randomized comparative study. J Neurol. 2010;257(11):1917–23. doi: 10.1007/s00415-010-5779-x. - DOI - PMC - PubMed
    1. Braun J, Deodhar A, Inman RD, van der Heijde D, Mack M, Xu S, et al. Golimumab administered subcutaneously every 4 weeks in ankylosing spondylitis: 104-week results of the GO-RAISE study. Ann Rheum Dis. 2012;71(5):661–7. doi:10.1136/ard.2011.154799. - PMC - PubMed
    1. Davies M, Heller S, Sreenan S, Sapin H, Adetunji O, Tahbaz A, et al. Once-weekly exenatide versus once- or twice-daily insulin detemir: randomized, open-label, clinical trial of efficacy and safety in patients with type 2 diabetes treated with metformin alone or in combination with sulfonylureas. Diabetes Care. 2013;36(5):1368–76. doi: 10.2337/dc12-1333. - DOI - PMC - PubMed
    1. Giugliano RP, Desai NR, Kohli P, Rogers WJ, Somaratne R, Huang F, et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase 2 study. Lancet. 2012;380(9858):2007–17. doi: 10.1016/S0140-6736(12)61770-X. - DOI - PMC - PubMed
    1. Wang W, Wang EQ, Balthasar JP. Monoclonal antibody pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther. 2008;84(5):548–58. doi: 10.1038/clpt.2008.170. - DOI - PubMed

Publication types

MeSH terms