Human Pharmacokinetics and Safety of Subcutaneous Collagenase Clostridium Histolyticum in Women.

BACKGROUND: Clostridium collagenase histolyticum (CCH) is being evaluated in women as a cellulite treatment. OBJECTIVE: To report preclinical safety and human pharmacokinetics (PK) and safety data for CCH. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Rapid treatment of mild acne with a novel skin care system containing 1% salicylic acid, 10% buffered glycolic acid, and botanical ingredients.

The biggest hurdle in the treatment of acne vulgaris is patient non-compliance that is due in large part to poor tolerability to common acne medications. As such, new acne treatments must be developed that balance good anti-acne efficacy with excellent tolerability in order to ensure patient adherence and by extension ensure good clinical outcomes. The goal of the present study was to determine the tolerability and efficacy of a novel skin care system, composed of a cleanser, containing 1% salicylic acid and botanical ingredients, and a treatment gel, containing 1% salicylic acid, 10% buffered glycolic acid and botanical ingredients for the treatment of mild acne. In this single-center, open-label clinical study, 25 male and female volunteers used the test cleanser and test gel twice daily over six weeks. Tolerability assessments showed that the skin care regimen was very well tolerated by all study volunteers. Acne severity was significantly reduced by two acne grades at six weeks. Inflammatory lesion counts were significantly reduced, on average, by 59.06% (P ≤ 0.0001), 91.62% (P ≤ 0.0001), 90.85% (P ≤ 0.0001) and by 98.55% (P ≤ 0.0001) at weeks 1, 2, 4, and 6, respectively. Non-inflammatory lesion counts were reduced, on average, by 13.54% (ns), 38.95% (P ≤ 0.0001), 44.48% (P ≤ 0.0001), and by 56.10% (P ≤ 0.0001) at weeks 1, 2, 4, and 6, respectively. Standardized photography also demonstrated a progressive reduction in acne lesions over time. In conclusion, results of the present study suggest that the tested skin care regimen offers rapid acne clearance and excellent tolerability that together may help to improve patient adherence as well as treatment outcome.