Once-Daily Oral Sarecycline 1.5 mg/kg/day Is Effective for Moderate to Severe Acne Vulgaris: Results from Two Identically Designed, Phase 3, Randomized, Double-Blind Clinical Trials

September 2018 | Volume 17 | Issue 9 | Original Article | 987 | Copyright © 2018

Angela Moore MD,a Lawrence J. Green MD,b Suzanne Bruce MD,c Neil Sadick MD,d Eduardo Tschen MD MBA,e Philip Werschler MD FAAD FAACS,f Fran E. Cook-Bolden, MD,g Sunil S. Dhawan MD,h Douglass Forsha MD,i Michael H. Gold MD FAAD,j Scott Guenthner MD,k Steven E. Kempers MD,l Leon H. Kircik MD,m Jennifer L. Parish MD,n Marta I. Rendon MD,o Phoebe Rich MD,p Linda Stein-Gold MD,q Stephen K. Tyring MD PhD,r Robert A. Weiss MD FAAD,s Adnan Nasir MD,t Carsten Schmitz MD PhD,u* Terry I. Boodhoo MS,u Alexandre Kaoukhov MD,u,* and David R. Berk MDu

aArlington Research Center, Inc., Arlington, TX bLawrence J. Green, MD, LLC, George Washington University School of Medicine, Washington, DC cSuzanne Bruce and Associates, PA, Houston, TX dSadick Research Group, New York, NY eAcademic Dermatology Associates, Albuquerque, NM fPremier Clinical Research, Spokane, WA gSkin Specialty Dermatology, New York, NY hCenter for Dermatology Clinical Research, Inc, Fremont, CA iJordan Valley Dermatology Center, Jordan, UT jTennessee Clinical Research Center, Nashville, TN kThe Dermatology Center of Indiana, PC, Plainfield, IN lAssociated Skin Care Specialists, Fridley, MN mDermResearch, PLLC, Louisville, KY nParish Dermatology, Philadelphia, PA oRendon Center, Boca Raton, FL pOregon Dermatology and Research Center, Portland, OR qHenry Ford Health System, West Bloomfield, MI rUniversity of Texas Health Science Center, Department of Dermatology, Houston, TX sLaser Skin & Vein Institute, Hunt Valley, MD tWake Research Associates, Raleigh, NC uAllergan plc, Irvine, CA *Former employee

Abstract

Background: Side effects may limit the use of current tetracycline-class antibiotics for acne. Objective: Evaluate the efficacy and safety of once-daily sarecycline, a novel, narrow-spectrum tetracycline-class antibiotic, in moderate to severe acne. Methods: Patients 9–45 years with moderate to severe facial acne (Investigator’s Global Assessment [IGA] score ≥ 3, 20–50 inflammatory and ≤ 100 noninflammatory lesions, and ≤ 2 nodules) were randomized 1:1 to sarecycline 1.5 mg/kg/day or placebo for 12 weeks in identically designed phase 3 studies (SC1401 and SC1402). Results: In SC1401 (sarecycline n=483, placebo n=485) and SC1402 (sarecycline n=519, placebo n=515), at week 12, IGA success (≥ 2-grade improvement and score 0 [clear] or 1 [almost clear]) rates were 21.9% and 22.6% (sarecycline), respectively, versus 10.5% and 15.3% (placebo; P less than 0.0001 and P equals 0.0038). Onset of efficacy in inflammatory lesions occurred by the first visit (week 3), with mean percentage reduction in inflammatory lesions at week 12 in SC1401 and SC1402 of −51.8% and −49.9% (sarecycline), respectively, versus −35.1% and −35.4% (placebo; P less than 0.0001). Onset of efficacy for absolute reduction of noninflammatory lesion count occurred at week 6 in SC1401 (P less than 0.05) and week 9 in SC1402 (P less than 0.01). In SC1401, the most common TEAEs (in ≥ 2% of either sarecycline or placebo group) were nausea (4.6% [sarecycline]; 2.5% [placebo]), nasopharyngitis (3.1%; 1.7%), headache (2.7%; 2.7%), and vomiting (2.1%; 1.4%) and, in SC1402, nasopharyngitis (2.5%; 2.9%) and headache (2.9%; 4.9%). Most were not considered treatment-related. Vestibular (dizziness, tinnitus, vertigo) and phototoxic (sunburn, photosensitivity) TEAEs both occurred in ≤ 1% of sarecycline patients. Gastrointestinal TEAE rates for sarecycline were low. Among females, vulvovaginal candidiasis (SC1401: 1.1% [sarecycline] and 0 [placebo]; SC1402: 0.3% and 0) and mycotic infection (0.7% and 0; 1.0% and 0) rates were low. Conclusion: The narrow-spectrum antibiotic sarecycline was safe, well tolerated, and effective for moderate to severe acne, with low rates of side effects common with tetracycline antibiotics. J Drugs Dermatol. 2018;17(9):987-996.

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Introduction

Broad-spectrum tetracycline-class antibiotics, such as minocycline and doxycycline, are considered first-line therapy in the management of moderate to severe acne.1 In addition to their antimicrobial activity, tetracycline-class antibiotics have anti-inflammatory properties.2 However, currently available agents may be associated with gastrointestinal (GI) side effects, including nausea, diarrhea, and vomiting; other potential side effects include skin photosensitivity with doxycycline and vestibular events (eg, dizziness, vertigo) with minocycline.1,3 Additionally, given their broad spectrum of antibacterial activity, oral tetracycline therapies for acne may negatively impact the microbiome, potentially leading to antimicrobial resistance, which may limit the efficacy of tetracycline antibiotics for the treatment of infectious diseases and, more broadly, promote multidrug resistant bacteria.3-8 These limitations demonstrate a need for tetracycline-class antibiotics for acne with improved safety profiles and a targeted, narrow spectrum of antibacterial activity.1,3 Sarecycline is a once-daily, novel, tetracycline-class antibiotic for the treatment of moderate to severe acne. Sarecycline has a narrow antibacterial spectrum with limited activity against enteric gram-negative bacteria compared with minocycline, doxycycline, and tetracycline, which may confer less disruption of the GI microbiome at doses recommended for acne treatment. A 12-week, phase 2, dose-ranging trial demonstrated that sarecycline 1.5 mg/kg/day is well tolerated, safe, and effective in patients 12 to 45 years of age with moderate to severe facial acne.9 This report describes the results of 2 identically designed, phase 3 pivotal trials, SC1401 and SC1402, to evaluate the efficacy and safety of once-daily sarecycline 1.5 mg/kg for 12 weeks in patients aged 9 to 45 years with moderate to severe facial acne vulgaris.

METHODS

Study Design Two identically designed, randomized, double-blind, placebo-controlled, parallel-group, phase 3 studies (Figure 1) were conducted in the United States: study SC1401 (Clinicaltrials.gov identifier NCT02320149), conducted at 56 centers, and study SC1402 (NCT02322866), conducted at 54 centers. After screening and baseline assessments, study visits occurred at weeks 3, 6, 9, and 12 of treatment.The studies were conducted in compliance with Good Clinical Practice guidelines and approved by an Institutional Review Board. All patients provided written informed consent or assent.Patients Eligible patients were aged 9 to 45 years, weighed 33 to 136 kg, and had 20 to 50 inflammatory lesions, ≤100 noninflammatory lesions, ≤2 nodules, and a score of 3 (moderate) or 4 (severe) on the Investigator’s Global Assessment (IGA) scale for inflammatory lesions of acne.Individuals were excluded from the studies if they had a dermatologic condition or facial hair, any chronic illness interfering with study evaluations, allergy or resistance to tetracyclines, drug-induced acne, hormonal contraceptive initiation, systemic retinoids, systemic corticosteroids, androgens, or anti-androgens within 12 weeks prior to randomization.All randomized patients composed the intent-to-treat (ITT) populations.Figure1

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