Triple Combination Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% for Acne: Efficacy and Safety from a Pooled Phase 3 Analysis

Leon H Kircik; Linda Stein Gold; Michael Gold; Jonathan S Weiss; Julie C Harper; James Q Del Rosso; Christopher G Bunick; Neal Bhatia; Emil A Tanghetti; Lawrence F Eichenfield; Hilary Baldwin; Zoe D Draelos; Valerie D Callender; George Han; Melinda J Gooderham; Neil Sadick; Mary P Lupo; Edward Ted Lain; William Philip Werschler

doi:10.1007/s13555-024-01155-7

Triple Combination Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% for Acne: Efficacy and Safety from a Pooled Phase 3 Analysis

Dermatol Ther (Heidelb). 2024 May;14(5):1211-1227. doi: 10.1007/s13555-024-01155-7. Epub 2024 May 9.

Authors

Leon H Kircik^{1

2

3

4

5}, Linda Stein Gold⁶, Michael Gold⁷, Jonathan S Weiss^{8

9}, Julie C Harper¹⁰, James Q Del Rosso^{11

12

13}, Christopher G Bunick¹⁴, Neal Bhatia¹⁵, Emil A Tanghetti¹⁶, Lawrence F Eichenfield^{17

18}, Hilary Baldwin^{19

20}, Zoe D Draelos²¹, Valerie D Callender^{22

23}, George Han²⁴, Melinda J Gooderham^{25

26}, Neil Sadick^{27

28}, Mary P Lupo²⁹, Edward Ted Lain³⁰, William Philip Werschler³¹

Affiliations

¹ Icahn School of Medicine at Mount Sinai, New York, NY, USA. [email protected].
² Indiana University School of Medicine, Indianapolis, IN, USA. [email protected].
³ Physicians Skin Care, PLLC, 1169 Eastern Pkwy #2310, Louisville, KY, 40217, USA. [email protected].
⁴ DermResearch, PLLC, Louisville, KY, USA. [email protected].
⁵ Skin Sciences, PLLC, Louisville, KY, USA. [email protected].
⁶ Henry Ford Hospital, Detroit, MI, USA.
⁷ Tennessee Clinical Research Center, Nashville, TN, USA.
⁸ Georgia Dermatology Partners, Snellville, GA, USA.
⁹ Gwinnett Clinical Research Center, Inc., Snellville, GA, USA.
¹⁰ Dermatology & Skin Care Center of Birmingham, Birmingham, AL, USA.
¹¹ JDR Dermatology Research/Thomas Dermatology, Las Vegas, NV, USA.
¹² Advanced Dermatology and Cosmetic Surgery, Maitland, FL, USA.
¹³ Touro University Nevada, Henderson, NV, USA.
¹⁴ Department of Dermatology and Program in Translational Biomedicine, Yale University, New Haven, CT, USA.
¹⁵ Therapeutics Clinical Research, San Diego, CA, USA.
¹⁶ Center for Dermatology and Laser Surgery, Sacramento, CA, USA.
¹⁷ School of Medicine, University of California, San Diego, CA, USA.
¹⁸ Rady Children's Hospital, San Diego, CA, USA.
¹⁹ The Acne Treatment and Research Center, Brooklyn, NY, USA.
²⁰ Robert Wood Johnson University Hospital, New Brunswick, NJ, USA.
²¹ Dermatology Consulting Services, PLLC, High Point, NC, USA.
²² Callender Dermatology and Cosmetic Center, Glenn Dale, MD, USA.
²³ Howard University College of Medicine, Washington, DC, USA.
²⁴ Department of Dermatology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, New York, NY, USA.
²⁵ Queens University, Peterborough, ON, Canada.
²⁶ SKiN Centre for Dermatology and Probity Medical Research, Peterborough, ON, Canada.
²⁷ Weill Cornell Medical College, New York, NY, USA.
²⁸ Sadick Dermatology, New York, NY, USA.
²⁹ Lupo Center for Aesthetic and General Dermatology, New Orleans, LA, USA.
³⁰ Austin Institute for Clinical Research, Austin, TX, USA.
³¹ Elson S. Floyd College of Medicine, Washington State University, Spokane, WA, USA.

Abstract

Introduction: A three-pronged approach to acne treatment combining an antibiotic, antimicrobial, and retinoid may be more efficacious than single/double treatments while potentially reducing antibiotic resistance. This study evaluated the efficacy and safety of the first fixed-dose, triple-combination topical acne product, clindamycin 1.2%/adapalene 0.15%/benzoyl peroxide (BPO) 3.1% gel (CAB) using pooled phase 3 data.

Methods: In two identical phase 3 (N = 183; N = 180), double-blind, 12-week studies, participants aged ≥ 9 years with moderate-to-severe acne were randomized 2:1 to receive once-daily CAB or vehicle gel. Endpoints included ≥ 2-grade reduction from baseline in Evaluator's Global Severity Score and clear/almost clear skin (treatment success) and least-squares mean percent change from baseline in acne lesion counts. Treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability were evaluated.

Results: At week 12, 50.0% of participants achieved treatment success with CAB versus 22.6% with vehicle gel (P < 0.001). CAB resulted in > 70% reductions in inflammatory and noninflammatory lesions at week 12 (77.9% and 73.0%, respectively), which were significantly greater than vehicle (57.9% and 48.2%; P < 0.001, both). Most TEAEs were of mild-moderate severity, and < 3% of CAB-treated participants discontinued study/treatment because of AEs. Transient increases from baseline in scaling, erythema, itching, burning, and stinging were observed with CAB, but resolved back to or near baseline values by week 12.

Conclusions: The innovative fixed-dose, triple-combination clindamycin phosphate 1.2%/adapalene 0.15%/BPO 3.1% gel was efficacious and well tolerated in children, adolescents, and adults with moderate-to-severe acne. Half of participants achieved clear/almost clear skin by 12 weeks, rates not previously seen in clinical studies of other topical acne products.

Trial registration: ClinicalTrials.gov identifier NCT04214639 and NCT04214652.

Keywords: Acne; Antibiotic; Antimicrobial; Clinical trial; Combination treatment; Retinoid; Topical.

Associated data

ClinicalTrials.gov/NCT04214639
ClinicalTrials.gov/NCT04214652