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

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• 作者：Clapton Dias ; Bassam Abosaleem ; Caroline Crispino ; Bing Gao…
• 关键词：placebo buffer ; subcutaneous injections ; tolerability ; viscous
• 刊名：AAPS PharmSciTech
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：16
• 期：5
• 页码：1101-1107
• 全文大小：226 KB
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• 作者单位：Clapton Dias (1)
  Bassam Abosaleem (1)
  Caroline Crispino (1)
  Bing Gao (1) (2)
  Adam Shaywitz (1) (3)
  
  1. Amgen Inc., 1 Amgen Center Drive, Thousand Oaks, California, 91320, USA
  2. Currently at BioMarin Pharmaceutical, Inc., San Rafael, California, USA
  3. Currently at Gilead Sciences, Foster City, California, USA
  
• 刊物主题：Pharmacology/Toxicology; Biotechnology; Biochemistry, general; Pharmacy;
• 出版者：Springer US
• ISSN：1530-9932

文摘

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. KEY WORDS placebo buffer subcutaneous injections tolerability viscous