W0261-101: A Phase 1, Single Center, Randomized, Open-Label Study to Evaluate the Bioavailability of Clindamycin From Clindamycin 1%-Benzoyl Peroxide 3% Gel, Topical Gel (Clindamycin 1%- Benzoyl Peroxide 5%), and Once Daily Gel (Clindamycin 1%-Benzoyl Peroxide 5%) in Subjects With Acne

Acne Vulgaris Clinical Trial

Official title: A Phase 1, Single Center, Randomized, Open-Label Study to Evaluate the Bioavailability of Clindamycin From Clindamycin 1%-Benzoyl Peroxide 3% Gel, Topical Gel (Clindamycin 1%- Benzoyl Peroxide 5%), and Once Daily Gel (Clindamycin 1%-Benzoyl Peroxide 5%) in Subjects With Acne Vulgaris

Status Completed

Clinical Trial Summary

This study was conducted to determine if the bioavailability of clindamycin and its metabolite clindamycin sulfoxide are altered by the concentration of BPO or the absence of methylparaben. This study compared the investigational study product and 2 marketed products:

• CLN 1%-BPO 3% Gel (clindamycin 1%-BPO 3%), methylparaben-free

• Topical Gel (clindamycin 1%-BPO 5%), methylparaben-preserved (Topical Gel-MP)

• Once Daily Gel ((clindamycin 1%-BPO 5%), methylparaben-free (Topical Gel-MPF)

Clinical Trial Description

Clindamycin and benzoyl peroxide (BPO) are both well-known treatments for acne vulgaris (acne) and are available as single-entity and fixed-dose combination products. The same excipients are used in the gel vehicle formulations, except inclusion of the preservative methylparaben in the vehicle is dependent on geographic region. While these products have been shown to be well tolerated, effective combination therapies for acne, concentration-dependent cutaneous irritation has been associated with the use of BPO.

Clindamycin 1%-benzoyl peroxide 3% gel (CLN 1%-BPO 3%) for the topical treatment of acne was developed. CLN 1%-BPO 3% contains the same concentration of clindamycin and a lower concentration of BPO than currently-marketed products, and CLN 1%-BPO 3% is formulated without methylparaben.

A study to evaluate the plasma concentrations of clindamycin and its metabolites after topical gel was applied once daily for 4 weeks in subjects with moderate-to-severe acne showed that the absorption of clindamycin and its metabolite clindamycin sulfoxide were comparable between Topical Gel and a representative single entity product with the same clindamycin concentration. An in vitro skin penetration study demonstrated that there were no significant differences in the delivery of clindamycin in and through the skin following application of either CLN 1%-BPO 3% or topical gel; therefore, the presence of BPO in the formulation at either 3% or 5% did not have an effect on the percutaneous absorption of clindamycin.

Benzoyl peroxide has been shown to be absorbed by the skin where it is converted to benzoic acid. Following topical application, less than 2% of the dose enters systemic circulation as benzoic acid. The transepidermal delivery of BPO is dependent on concentration and no systemic toxicity is expected due to rapid renal clearance of benzoic acid. Benzoic acid is frequently utilized as a preservative or to adjust the pH in food, cosmetics, and medicinal products; therefore, the limited systemic absorption from CLN 1%-BPO 3% is not expected to notably increase exposure to benzoic acid. Due to the low potential for systemic toxicity and the limited utility of assessing plasma concentrations of benzoic acid, the systemic exposure was not evaluated in this study.

Systemic exposure to clindamycin has been associated with severe cases of diarrhea, bloody diarrhea and colitis (including pseudomembranous colitis), which could be fatal. Several studies conducted with single-entity and fixed-combination topical clindamycin-containing products have determined that systemic absorption of clindamycin is low; however, there have been documented cases of colitis after topical administration of clindamycin phosphate. Clindamycin phosphate is rapidly hydrolyzed in vivo to clindamycin, the active parent compound. Topical application of Clindagel (clindamycin phosphate 1% gel) equivalent to 3 to 12 grams once daily for 5 days resulted in peak plasma clindamycin concentrations that were less than 5.5ng/mL. Multiple topical applications of Cleocin T (clindamycin phosphate at a concentration equivalent to 10mg/mL) resulted in clindamycin serum levels ranging from 0 to 3 ng/mL. The mean systemic bioavailability of clindamycin is less than 1%.

As there exists a potential for different topical formulations to have greater systemic exposure to the active ingredients than currently marketed products, this study was conducted to determine if the bioavailability of clindamycin and its metabolite clindamycin sulfoxide are altered by the concentration of BPO or the absence of methylparaben. This study compared the investigational study product and 2 marketed products:

• CLN 1%-BPO 3% Gel (clindamycin 1%-BPO 3%), methylparaben-free

• Topical Gel (clindamycin 1%-BPO 5%), methylparaben-preserved (Topical Gel-MP)

• Once Daily Gel ((clindamycin 1%-BPO 5%), methylparaben-free (Topical Gel-MPF) ;

Related Conditions & MeSH terms

• Acne Vulgaris

• NCT number: NCT01132443
• Study type: Interventional
• Source: GlaxoSmithKline
• Status: Completed
• Phase: Phase 1
• Start date: May 6, 2010
• Completion date: June 12, 2010