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
Condition: Acne Vulgaris
MeSH terms: Acne Vulgaris
Study type: Interventional
Phase: Phase 1

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)
    

Detailed 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)
    

Intervention name(s): Clindamycin 1%-Benzoyl Peroxide (BPO) 3% Gel,
Intervention type(s): Drug
Intervention description(s): Apply topically once daily
Intervention MeSH terms: Clindamycin; Clindamycin palmitate; Clindamycin phosphate; Benzoyl Peroxide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment