title: Tolerability of High-Volume Subcutaneous Injections of a Viscous Placebo Buffer: A Randomized, Crossover Study in Healthy Subjects.
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.
authors.affiliation: Amgen Inc., 1 Amgen Center Drive, Thousand Oaks, California, 91320, USA. claptondias@gmail.com.
authors.forename: Clapton
authors.initials: C
authors.lastname: Dias
authors.affiliation: Amgen Inc., 1 Amgen Center Drive, Thousand Oaks, California, 91320, USA.
authors.forename: Bassam
authors.initials: B
authors.lastname: Abosaleem
authors.affiliation: Amgen Inc., 1 Amgen Center Drive, Thousand Oaks, California, 91320, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Crispino
authors.affiliation: Amgen Inc., 1 Amgen Center Drive, Thousand Oaks, California, 91320, USA.|Currently at BioMarin Pharmaceutical, Inc., San Rafael, California, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Gao
authors.affiliation: Amgen Inc., 1 Amgen Center Drive, Thousand Oaks, California, 91320, USA.|Currently at Gilead Sciences, Foster City, California, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Shaywitz
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000737:chemistry; D002021:Buffers; D002140:California; D018592:Cross-Over Studies; D004339:Drug Compounding; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D055104:Infusions, Subcutaneous; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000209:etiology; D010147:Pain Measurement; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D013997:Time Factors; D014783:Viscosity
chemical_list: D000911:Antibodies, Monoclonal; D002021:Buffers; D014677:Pharmaceutical Vehicles
keywords: placebo buffer; subcutaneous injections; tolerability; viscous