Tolerability of Clindamycin/Tretinoin Gel vs. Tretinoin Microsphere Gel and Adapalene Gel

April 2009 | Volume 8 | Issue 4 | Original Article | 383 | Copyright © April 2009

James Leyden MDa, Mitchell Wortzman PhDb, Edward K. Baldwin PhDc

a. Skin Study Center, Broomall, PA b. Medicis, Scottsdale, AZ c. Julie and Edward Baldwin Partners, Westborough, MA

Abstract

Background: Newer agents and formulations seek to improve the tolerability of topical retinoid therapy. Recently, a gel containing crystalline clindamycin 1.2% and tretinoin 0.025% (CLIN/RA) was approved by the U.S. Food and Drug Administration (FDA) for the treatment of treating mild-to-moderate acne.
Objective: This single-center, randomized, evaluator-blind phase 1 study compared the tolerability of CLIN/RA to 0.1% tretinoin gel or 0.1% adapalene gel.
Results: Forty-five patients applied CLIN/RA once daily to one side of their face every day for 21 days. Patients were randomized to either tretinoin 0.1% (n=23) or adapalene 0.1% (n=22) on the contralateral side. A clinical evaluator assessed degree of erythema and scaling; patients provided subjective evaluations of burning, stinging, and itching.
Conclusion: CLIN/RA was significantly better tolerated than was 0.1% tretinoin gel, as evidenced by significantly reduced erythema (P<0.04), scaling (P<0.03), itching (P<0.02), burning (P<0.03) and stinging (P<0.04). A trend for greater erythema, scaling, and subjective discomfort for 0.1% adapalene gel compared to CLIN/RA was also evident.

INTRODUCTION

Cutaneous tolerability is a significant concern for any acne therapy and has played an important role in the development of topical retinoids. The hydroalcoholic formulation of tretinoin, the first topical retinoid to become available, caused considerable levels of cutaneous irritation including redness, scaling, burning, and itching, primarily in the first few weeks of therapy.1-7 Although tretinoin was effective in reducing both comedones and inflammatory lesions, tolerability issues affected the tretinoin risk/benefit balance so that it was generally regarded as a second-line therapy and reserved for patients with non-inflammatory acne and those for whom antibiotic monotherapy failed.8
Development of various formulations and concentrations of tretinoin ensued, and as tretinoin concentrations progressively decreased in gels from 0.05% to 0.025% to 0.01%, in creams from 0.1% to 0.05% to 0.025%, and most recently in microsphere formulations,9 tretinoin’s tolerability progressively increased. In addition to new tretinoin formulations, other topical retinoid formulations with improved tolerability were also developed, such as adapalene.10-15 However, most dermatologists still find the tolerability of topical retinoids to be problematic.8 Several variables have been found to affect retinoid tolerability, including retinoid concentration, skin sensitivity and the vehicle (cream or gel), with the latter’s effect on tolerability varying depending on the specific retinoid.16
A novel gel formulation that combines clindamycin and tretinoin was recently approved by the FDA for treating mild-to-moderate acne (CLIN/RA). CLIN/RA consists of a crystalline suspension of clindamycin 1.2% (CLIN) in combination with 0.025% tretinoin (RA) gel. Trials of CLIN/RA suggest that it may not provoke the degree of irritation associated with standard solubilized formulations of tretinoin.17 The current study provides a further evaluation of the irritancy and tolerability profile of CLIN/RA in comparison to 0.1% tretinoin gel or 0.1% adapalene gel.

METHODS

This was a safety/tolerability study. Due to the short length of therapy (21 days), efficacy evaluations were not conducted.
The study’s inclusion criteria are shown in Table 1. Forty-five patients with active acne volunteered to participate in this study and were randomized to enroll in a bilaterally paired comparison between products applied to the right and left sides of the face. Patients with a history of unusual skin reactions to tretinoin products or other topical retinoids, or any sensitivity to the test article components, were excluded.
Patients were randomly assigned to apply two of three products, with one side of the face treated with CLIN/RA and the contralateral side of the face treated with either tretinoin 0.1% (n=23) or adapalene 0.1% (n=22). The 0.1 % tretinoin was selected because of its extensive use in the microsponge. Tretinoin has been the mainstay of topical retinoid therapy for decades.3 Treatments were applied once daily (including weekends) for 21 days. Treatment application on Monday through Friday was supervised at the test facility, and Saturday and Sunday was applied, unsupervised, at the patient’s home. Patients applied