J Drugs Dermatol. 2020 Sep 1;19(9):852-856. doi: 10.36849/JDD.2020.10.36849/JDD.2020.5048.
Clostridium collagenase histolyticum (CCH) is being evaluated in women as a cellulite treatment.
To report preclinical safety and human pharmacokinetics (PK) and safety data for CCH.
Across 3 PK studies, 41 women received 12 subcutaneous injections per thigh/buttock in 1 session (up to 3.36 mg/dose). Blood samples were taken at baseline; at 5, 10, 20, and 30 minutes postdose; and at 1, 2, 4, 8, 12, 24, 48, 168, and 504 hours postdose. In a preclinical study, rats received 0, 0.029, 0.13, or 0.29 mg/dose of CCH intravenously (IV) every other day (QOD) for 16 days (total, 8 doses) and were evaluated for histopathologic changes.
In human PK studies, no quantifiable plasma concentrations of AUX-I or AUX-II were observed postdose (n= 39 evaluable). Adverse events were injection site–related (bruising [97.6%], pain [87.8%], and edema/swelling [46.3%]). Antidrug antibodies were seen in most women at 504 hours postdose. In rats, plasma concentrations of AUX-I and AUX-II (CCH components) were measurable for 30 minutes and 1-2 hours, respectively, after IV administration. At ≥43× proposed human therapeutic dose on a mg/kg basis, rats experienced elevated liver enzyme levels, increased liver weights, and histologic changes that were mostly reversed during a 14-day recovery period.
In human studies, no quantifiable circulating CCH levels were observed after a single subcutaneous dose of CCH up to 3.36 mg. Preclinical data indicated that repeat IV dosing (QOD; 8 doses) at ≥43× proposed human dose on a mg/kg basis for CCH was generally well tolerated.J Drugs Dermatol. 2020;19(9):852-856. doi:10.36849/JDD.2020.5048THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.
胶原酶组织溶菌素（CCH）正在被评估用于治疗女性的脂肪团。
报告 CCH 的临床前安全性和人体药代动力学（PK）及安全性数据。
在 3 项 PK 研究中，41 名女性在 1 次治疗中于每侧大腿/臀部接受 12 次皮下注射（最高剂量为 3.36mg/次）。在基线时、给药后 5、10、20 和 30 分钟以及给药后 1、2、4、8、12、24、48、168 和 504 小时采血。在一项临床前研究中，大鼠每 2 天（每 2 天 1 次，共 16 天，共 8 个剂量）静脉内（IV）给予 0、0.029、0.13 或 0.29mg/d 的 CCH，评估组织病理学变化。
在人体 PK 研究中，在给药后未观察到可定量的 AUX-I 或 AUX-II 的血浆浓度（39 名可评估患者）。不良事件与注射部位相关（瘀伤[97.6%]、疼痛[87.8%]和水肿/肿胀[46.3%]）。大多数女性在 504 小时时出现抗药物抗体。在大鼠中，AUX-I 和 AUX-II（CCH 成分）的血浆浓度在 IV 给药后 30 分钟和 1-2 小时可测量。在基于 mg/kg 的提议人类治疗剂量的 ≥43×时，大鼠的肝酶水平升高，肝重增加，组织学变化在 14 天恢复期内大部分得到逆转。
在人体研究中，单次皮下给予高达 3.36mg 的 CCH 后，未观察到可定量的循环 CCH 水平。临床前数据表明，在基于 mg/kg 的提议人类剂量的 ≥43×时，重复 IV 给药（每 2 天 1 次，共 8 个剂量）通常可耐受。J 皮肤病学杂志。2020;19(9):852-856. doi:10.36849/JDD.2020.5048 本文已免费提供。请向下滚动访问本文的全文，而无需登录。无需购买。如有任何问题，请与出版商联系。
