Tretinoin gel microsphere pump 0.04% plus 5% benzoyl peroxide wash for treatment of acne vulgaris: morning/morning regimen is as effective and safe as morning/evening regimen.

Topical tretinoin and benzoyl peroxide (BPO) are often prescribed in combination for the treatment of acne vulgaris; however, these products have not traditionally been administered simultaneously because of the potential for tretinoin degradation by BPO as well as the instability of tretinoin in daylight. The primary objective of this randomized, investigator-blinded, 12-week, phase 4 trial was to determine non-inferiority of a once-daily morning combination regimen of 5% BPO wash + tretinoin gel microsphere (TGM) 0.04% pump versus a sequential regimen (BPO in the morning/TGM in the evening) in patients > or = 12 years old with moderate facial acne vulgaris. The primary efficacy endpoint was the change from baseline in total acne lesions; the primary safety endpoint was the change in cutaneous irritation scores. The 247 participants (mean age: 18.5 years) were randomized to either the morning/morning regimen (n = 123) or the morning/evening regimen (n = 124). The morning/morning regimen was determined to be non-inferior to the morning/evening regimen in reduction of total acne lesions. The tolerability of both regimens was comparable. The morning/morning regimen is a safe and effective treatment option for patients with moderate acne vulgaris.

Irritation potential of tretinoin gel microsphere pump versus adapalene plus benzoyl peroxide gel.

This single-center, investigator-blinded, randomized, split-face, phase 4 study compared the irritation potential of tretinoin gel microsphere (TGM) 0.04% in a pump dispenser with adapalene 0.1% plus benzoyl peroxide 2.5% gel (ADA-BPO 0.1%/2.5%) in a panel of 170 subjects. Participants were treated with TGM 0.04% pump on a randomly assigned side of the face and ADA-BPO 0.1%/2.5% gel on the other side of the face daily for three consecutive weeks. Expert grader assessments of erythema and dryness and subject self-assessments of burning/stinging and itching were conducted daily, except on weekends. TGM 0.04% pump was associated with better facial tolerance as demonstrated by significantly less cumulative erythema (P < 0.0001), dryness (P < 0.0001), burning/stinging (P < 0.0001) and itching (P < 0.0001) compared with ADA-BPO 0.1%/2.5% gel. While both agents were well tolerated by most patients, TGM 0.04% pump demonstrated significantly better tolerance than ADA-BPO 0.1%/2.5% gel in both neurosensory parameters and signs of contact irritation.

Applications of extensions of bivariate rank sum statistics to the crossover design to compare two treatments through four sequence groups.

This article describes applications of extensions of bivariate rank sum statistics to the crossover design with four sequence groups for two treatments. A randomized clinical trial in ophthalmology provides motivating background for the discussion. The bilateral design for this study has four sequence groups T:T, T:P, P:T, and P:P, respectively, for T as test treatment or P as placebo in the corresponding order for the left and right eyes. This article describes how to use the average of the separate Wilcoxon rank sum statistics for the left and right eyes for the overall comparison between T and P with the correlation between the two eyes taken into account. An extension of this criterion with better sensitivity to potential differences between T and P through reduction of the applicable variance has discussion in terms of a conceptual model with constraints for within-side homogeneity of groups with the same treatment and between-side homogeneity of the differences between T and P. Goodness of fit for this model can have assessment with test statistics for its corresponding constraints. Simulation studies for the conceptual model confirm better power for the extended test statistic with its full invocation than other criteria without this property. The methods summarized here are illustrated for the motivating clinical trial in ophthalmology, but they are applicable to other situations with the crossover design with four sequence groups for either two locations for two treatments at the same time for a patient or two successive periods for the assigned treatments for a recurrent disorder. This article also notes that the methods based on its conceptual model can have unsatisfactory power for departures from that model where the difference between T and P via the T:T and P:P groups is not similar to that via the T:P and P:T groups, as might occur when T has a systemic effect in a bilateral trial. For this situation, more robust test statistics have identification, but there is recognition that the parallel groups design with only the T:T and P:P groups may be more useful than the bilateral design with four sequence groups.