Comparison of clindamycin/benzoyl peroxide, tretinoin plus clindamycin, and the combination of clindamycin/benzoyl peroxide and tretinoin plus clindamycin in the treatment of acne vulgaris: a randomized, blinded study

Journal of Drugs in Dermatology, Sept-Oct, 2005 by Steven Bowman, Michael Gold, Adnan Nasir, George Vamvakias

Sites were instructed to have the same investigator assess the patient's facial acne at each study visit. Lesion count was assessed by counting the number of facial open and closed comedones, pustules, papules, and nodulo-cystic lesions above the jaw line to the hairline, excluding lesions involving the eyes, nose, and scalp. The Investigator's Global Evaluation is the investigator's comprehensive evaluation of the patient's overall acne condition. In addition to number of lesions, the overall condition of acne included (but was not limited to) size of lesions, overall degree of inflammation, general erythema of the face (both lesions and background), and skin condition.

Clinical assessments were conducted at baseline at Days 14 (Week 2), 28 (Week 4), 49 (Week 7), and 70 (Week 10) [ or -] 4 days. All study visits included evaluation of lesion count, acne severity, and local irritation (Signs/Symptoms of Irritation assessment, with scores ranging from 0 [none] to 3 [severe, marked/intense]). The baseline visit also included a medical history, pregnancy test for females, and instruction on medication application and completion of patient diaries. Adverse events and treatment compliance were evaluated at all study visits (excluding baseline). The clinical course of each adverse event was followed until resolution.

Analysis of Data

The intent-to-treat (ITT) population was defined as all patients who received at least 1 dose of study drug. Baseline treatment group differences for continuous variables were analyzed by a 2-way analysis of variance (ANOVA) when normality and homogeneity assumptions could be supported, or by the Friedman's test when they could not. Baseline treatment group differences for categorical variables were evaluated by Cochran-Mantel-Haenszel procedures for pooling results across multiple clinical sites. Analyses of clinical efficacy parameters were performed on the efficacy analysis population, defined as those patients who completed the study with a dosing compliance rate of 80% to 120%, did not have significant protocol violations, and returned for the final study visit (Week 10) within the specified 4-day window. Treatment group differences in mean percent reduction in lesion counts were evaluated using ANOVA (with factors of treatment and center) when normality and homogeneity assumptions could be supported or by the Friedman's test when they could not. Treatment group differences in proportion of patients who were treatment successes (ie, Investigator's Global Acne Severity score of 0-0.5) were analyzed using a 2-sided z-test adjusted for center using Yates' continuity correction. Significance was determined at the 0.05 level using 2-sided tests. Safety analyses were performed on the ITT population with summary statistics generated for all adverse events.

Results

Patient Characteristics

Of 132 enrolled patients who received at least 1 dose of study drug (ITT population), 109 patients completed the study. Reasons for discontinuation included lost to follow-up (n = 14), consent withdrawn (n = 3), noncompliance or protocol violation (n = 2), adverse event (n = 2), use of prohibited concomitant medication (n = 1), and other (n = 1). A total of 26 patients who completed the study were excluded from the efficacy population due to a failure to appear for the final assessment within the 4-day assessment window (n = 16), use of prohibited medication (n = 6 [with 1 patient also outside of the 4-day assessment window]), and incomplete compliance (n = 5).