A Randomized, Phase 2, Dose-Ranging Study in the Treatment of Moderate to Severe Inflammatory Facial Acne Vulgaris With Doxycycline Calcium
June 2013 | Volume 12 | Issue 6 | Original Article | 658 | Copyright © June 2013
James J. Leyden MD,a Suzanne Bruce MD,b Chai Sue Lee MD,c,* Mark Ling MD PhD,d Pranav B. Sheth MD,e Daniel M. Stewart DO,f William P. Werschler MD,g Richard D. Gilbert PhD,h and Leon Kircik MDi
aDepartment of Dermatology, University of Pennsylvania, Philadelphia, and the Skin Study Center, KGL, Inc., Broomall, PA
bThe Center for Skin Research, Houston, TX
cDepartment of Dermatology, UC Davis, Sacramento, CA
dMedaPhase, Inc., Atlanta, GA
eDermatology Research Center of Cincinnati, Group Health Associates, Trihealth Inc., Cincinnati, OH
fMichigan Center for Skin Care Research, Clinton Township, MI
gUniversity of Washington, Seattle, WA and Premier Clinical Research, Spokane, WA
hTKL Research, Inc., Rochelle Park, NJ
iIndiana University School of Medicine, Indianapolis, IN, Mount Sinai Medical Center, New York, NY, and DermResearch, PLLC, Louisville, KY
Abstract
BACKGROUND: Doxycycline calcium (WC2055) is a drug substance with a possible role in the treatment of acne. The objective of this
study was to evaluate the safety and efficacy of three doses of doxycycline calcium tablets compared with placebo in the treatment of
moderate to severe inflammatory facial acne vulgaris.
METHODS: This was a randomized, double-blind, phase 2 dose-ranging study in subjects with moderate to severe inflammatory acne
aged 12 years to 45 years. Subjects were randomized to receive doxycycline calcium tablets 0.6, 1.2, or 2.4 mg/kg/day or placebo, and
instructed to take their tablets once daily for 12 weeks, in the evening at least 1 hour before or 2 hours after mealtime. The primary efficacy variables were the dichotomized Investigator's Global Assessment score (success or failure) at week 12 (success defined as ≥2
score decrease from baseline) and the absolute change from baseline to week 12 in inflammatory lesion count.
RESULTS: A dose-response effect was seen with doxycycline calcium formulation in subjects with moderate to severe inflammatory
acne. The highest dose-group (corresponding to approximately 2.4 mg/kg/day) showed a statistically significant difference from placebo.
The dose-response effect was confirmed by logistic regression analysis for both treatment success and incidence of gastrointestinal
adverse events. A limitation of this study is that safety and efficacy were only studied on moderate to severe inflammatory acne.
Also, the study was not prospectively powered to show efficacy differences.
CONCLUSION: Doxycycline calcium shows a dose-response effect in reducing inflammatory lesions in subjects with moderate to severe
inflammatory acne.
J Drugs Dermatol. 2013;12(6):658-663.
INTRODUCTION
Treatment guidelines for moderate to severe acne recommend
early initiation of therapy with topical retinoids
and oral antibiotics (with or without the use of
benzoyl peroxide).1,2 Doxycycline and minocycline, both lipophilic
tetracyclines, are commonly prescribed for the treatment
of acne. Despite widespread use, however, no dose-response
data exist for doxycycline in subjects with acne.
A dose-ranging study with minocycline in subjects with acne reported
equivalent efficacy between the three oral doses studied (1,
2, or 3 mg/kg).3 However, it should be noted that although minocycline
1 mg/kg was significantly better tolerated, a dose-response
for efficacy was not seen; the robustness of these data are limited
by the lack of a logistic regression analysis.4 The present study is
the first dose-response study of doxycycline calcium (WC2055;
Warner Chilcott US LLC, Rockaway, NJ, USA), a substance formed
in situ from doxycycline hyclate and calcium chloride. The safety
and efficacy of three doses of doxycycline calcium tablets compared
with placebo were evaluated in the treatment of subjects
with moderate to severe, inflammatory, facial acne vulgaris.
