In preclinical rat studies, repeat-dose IV administration at ≥43× the proposed therapeutic human dose (on a mg/kg basis) was reasonably well tolerated. The repeated systemic administration (QOD; 8 IV injections) in this animal study supports the presumption that inadvertent IV administration of CCH as a treatment for cellulite on the thighs or buttocks in women would likely not have a substantial negative impact on patient safety and tolerability. Additionally, the dosing technique for CCH administration involves 12 separate SC injections in a treatment area, thus effectively eliminating the risk of inadvertently administering the full CCH dose of 0.84 mg intravenously in any one particular treatment area.
The data described in the current manuscript support the clinical safety and benign immunogenicity profile of CCH, when administered into the thigh or buttock in women with cellulite. Limitations of the studies are the small sample size of the human PK studies in which to gain additional safety information, evaluation of only single-dose (1 session) SC administration, and use of animal data alone to evaluate inadvertent IV dosing. In conclusion, no quantifiable circulating CCH levels were observed in humans after a single SC dose of CCH up to 3.36 mg, and CCH was generally well tolerated, supporting a lack of systemic exposure after injection of CCH. These data add to the overall favorable safety and tolerability profile of CCH injection.
SV and MPM are employees of Endo Pharmaceuticals Inc.
TP is a former employee of Endo Pharmaceuticals Inc.
MKG reports serving in the speakers’ bureau for Endo Pharmaceuticals Inc., and serving as a consultant for BioSpecifics Technologies Corporation.
Funding: Supported by Endo Pharmaceuticals Inc., Malvern, PA.
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