The safety and efficacy of clindamycin phosphate foam 1% versus clindamycin phosphate topical gel 1% for the treatment of acne vulgaris

Journal of Drugs in Dermatology, Jan-Feb, 2005 by Alan R. Shalita, Judith A. Myers, Lincoln Krochmal, Alex Yaroshinsky

Abstract

Clindamycin phosphate is the most widely used topical antibacterial agent for acne treatment. Treatment of patients with mild to moderate acne vulgaris with a new foam formulation (clindamycin foam, CF) for 12 weeks was at least as effective as clindamycin gel (CG) based on the Investigator's Static Global Assessment (ISGA) score. CF was superior to CG based on the reduction from baseline in total (P = .0014), inflammatory (P = .0478), and noninflammatory (P = .0037) acne lesion counts. Additionally, CF achieved efficacy that was superior to that of vehicle foam based on ISGA score (P = .0025) and all 3 lesion counts (all P < .05). Adverse experiences in the active treatment groups were mild or moderate and transient in nature. Thus the foam formulation of clindamycin is a safe and effective acne treatment; the unique foam delivery vehicle may offer cosmetic benefits to the patient and thus increase compliance.

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Introduction

Acne vulgaris is the most common dermatologic disorder, affecting approximately 85% of individuals between the ages of 12 and 24 years. (1) Acne can present at any age and affects 8% of adults aged 25 to 34 and 3% of those aged 35 to 44 years. (2) Because nearly 6 million people in the US experience and require treatment for acne vulgaris, they represent the largest patient group seen by dermatologists. (3)

The pathogenesis of acne is multifactorial, involving seborrhea, bacterial proliferation, inflammation, and abnormal desquamation of follicular epithelium. (4) Excessive sebum production and altered follicular epithelial cell growth and differentiation induce formation of the microcomedo, the precursor of all acne lesions. The microcomedo gives rise to either noninflammatory comedones or inflammatory acne lesions, and patients often have a mixture of both types of lesions. The combination of sebum and cells provides an environment in which Propionibacterium acnes (P. acnes), the predominant microorganism, can flourish. Proliferation of P. acnes generates proinflammatory signals, which cause microcomedones to become inflamed. (5)

Antibiotics are a mainstay of acne treatment, and clindamycin phosphate is the most widely used topical antibacterial agent. Although there are several effective therapies for acne vulgaris, lack of adherence to the treatment regimen is believed to contribute to treatment failure, (6) or to less-than-optimal results. Notably, the vehicle for topical drug delivery can play a role in patient compliance with acne treatment. Some vehicles commonly used in topical acne medications may have cosmetic disadvantages, as they can be greasy, leave residues, and are not convenient for large skin surfaces. With current vehicles, multiple prescriptions may be required if the acne is present on multiple body areas such as the face, chest, and back. A novel triphasic (organic, aqueous, and lipid) foam vehicle (VersaFoam[TM]) has been developed that facilitates the topical delivery of a variety of active ingredients to multiple body areas and is preferred by patients to the current topical vehicles. (7) Clindamycin phosphate 1% (clindamycin foam) formulated in this foam vehicle may provide clinical benefit to acne patients in a cosmetically elegant manner.

This study was undertaken to evaluate the efficacy of once-daily treatment with clindamycin foam relative to that of clindamycin phosphate gel 1% (clindamycin gel) and to establish that the efficacy of clindamycin foam is noninferior (similar or better) to that of clindamycin gel. Establishment of noninferiority allowed subsequent testing for superiority. Finally, the safety of clindamycin foam was also evaluated.

Methods

Study Design

This was a multicenter (18 sites), randomized, double-blind, double-dummy, vehicle- and active-controlled study. The efficacy and safety of once-daily treatment with clindamycin foam were evaluated relative to those of clindamycin gel in 1026 patients with mild to moderate acne vulgaris. All 18 sites received institutional review board approval prior to initiating the study, and all patients provided written informed consent.

Inclusion and Exclusion Criteria

Eligible patients were male or female, 12 years of age or older, with mild to moderate facial acne vulgaris and an Investigator's Static Global Assessment (ISGA) score of 2 or greater at baseline. Patients were required to have a minimum of 17, but not more than 40 facial inflammatory lesions (papules and pustules), including nasal lesions, and a minimum of 20, but not more than 150 facial noninflammatory lesions (open and closed comedones), excluding nasal lesions. Patients with any active nodulo-cystic lesions and those who had used topical or systemic treatments within 4 weeks prior to study entry were excluded. Other than the study medication, no treatment for acne vulgaris was permitted during the study.

Treatments

Patients were randomly assigned to receive clindamycin foam, vehicle foam, clindamycin gel, 1%, or vehicle gel in a 3:1:3:1 ratio. Treatment allocation was determined prior to enrollment in the study, and the study was stratified by center. Sealed copies of the randomization code were held at Connetics and at the study site. Breaking of the randomization code was forbidden except in the event of a medical emergency. The study medication was self-administered once a day (either in the morning or evening) for 12 weeks. Patients were instructed to apply a sufficient amount of study medication to cover the entire face (including forehead, nose, cheeks, and chin). The patients were also permitted to apply study medication to acne on the neck, upper chest, and/or upper back, but only facial acne was included in the efficacy evaluations.