Central Laboratory, Shanghai Xuhui Central Hospital/Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
Shanghai Engineering Research Center of Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai, China.
Clin Transl Sci. 2022 Oct;15(10):2458-2467. doi: 10.1111/cts.13374. Epub 2022 Jul 31.
This study aimed to evaluate the pharmacokinetics (PKs), safety, and immunogenicity of the biosimilar (RD12014) compared to reference liraglutide (Victoza) in healthy Chinese male subjects, so as to provide the basis for the similarity evaluation of the two drugs. Eligible subjects were randomized 1:1 to two sequences (RD12014-Victoza or Victoza-RD12014). Subjects received a single 0.6 mg dose of Victoza or RD12014 by abdominal subcutaneous injection during the first period. After a 7-day washout period, subjects received the alternative drug during the second period. Blood samples were collected at predefined timepoints for PKs and immunogenicity assessment. The primary PK end points were maximum plasma concentration (C ) and area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC ). PK bioequivalence was achieved, if the 90% confidence intervals (CIs) of the geometric mean ratio (GMR) of C and AUC were within the range of 80.00-125.00%. Safety was assessed throughout the study. The 90% CIs of the GMR of RD12014 to Victoza for C and AUC were completely within the range of 80.00-125.00%. Thirteen treatment-related adverse events (TRAEs) were reported in 11 subjects (22.4%) in the RD12014 group, compared to 12 TRAEs reported in 12 subjects (24.5%) in the Victoza group. The blood samples of 49 subjects were negative for anti-drug antibody and the neutralizing antibody was not further detected. This study demonstrated PK similarity of RD12014 to Victoza in healthy Chinese male subjects. Safety and immunogenicity profiles were comparable between the two groups.
本研究旨在评估生物类似药 RD12014 与参照利拉鲁肽（诺和力）在中国健康男性受试者中的药代动力学（PK）、安全性和免疫原性，为两种药物的相似性评价提供依据。符合条件的受试者按 1:1 随机分为两组（RD12014-诺和力或诺和力-RD12014）。第 1 个周期中，受试者接受单次 0.6 mg 剂量的诺和力或 RD12014 腹部皮下注射；洗脱期 7 天后，第 2 个周期中接受替代药物。根据预先设定的时间点采集血样，用于 PK 和免疫原性评估。主要 PK 终点为最大血浆浓度（C ）和从零时到最后可定量浓度的浓度-时间曲线下面积（AUC ）。如果 C 和 AUC 的几何均数比值（GMR）的 90%置信区间（CI）在 80.00-125.00%范围内，则达到 PK 生物等效性。整个研究过程中评估安全性。RD12014 与诺和力的 C 和 AUC 的 GMR 的 90%CI 完全在 80.00-125.00%范围内。RD12014 组 11 名受试者（22.4%）报告了 13 例与治疗相关的不良事件（TRAEs），诺和力组 12 名受试者（24.5%）报告了 12 例 TRAEs。49 份血样抗药物抗体检测均为阴性，未进一步检测中和抗体。本研究表明 RD12014 在中国健康男性受试者中与诺和力具有 PK 相似性。两组安全性和免疫原性特征相当。
