Clinical Pharmacology and Safety of Trifarotene, a First‐in‐Class RARγ‐Selective Topical Retinoid
Open accessAbstract
Trifarotene is a new drug with retinoic acid receptor activity and selectivity for retinoic acid receptor‐γ. The reported studies aimed at assessing the clinical pharmacology and safety of trifarotene. The clinical pharmacology of topical trifarotene up to 100 µg/g was extensively investigated through 2 maximal usage pharmacokinetic trials (MUsT) conducted in adult (≥18 years) and pediatric patients (9‐17 years) with moderate to severe acne and two studies conducted in healthy volunteers: 1 thorough QT C study and 1 drug‐drug interaction study with concomitantly administered oral levonorgestrel (0.15 mg)/ethinyl estradiol (0.03 mg). Safety assessments included adverse event reporting and assessment of erythema, scaling, dryness, and stinging/burning using a scale from 0 = none to 4 = severe, as well as the evaluation of the systemic safety of trifarotene through routine laboratory testing. Systemic absorption of trifarotene was generally unquantifiable in the target population, especially when applied at 50 µg/g. QT C investigations did not show any risk of cardiovascular health issues; trifarotene did not reduce the systemic exposure to oral contraceptives such as levonorgestrel/ethinyl estradiol. Safety analyses did not show local or systemic safety concerns with trifarotene up 100 µg/g, a dose twice as high as the intended market dose. Results showed that trifarotene 50 µg/g cream is well tolerated and safe, even when applied under maximized conditions in adults and pediatric acne patients presenting with severe acne. Daily use of trifarotene 50 µg/g cream was not associated with cardiovascular effects and did not result in drug‐drug interaction in women of childbearing potential using oral contraception.
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At least four molecules have reached phase 4 clinical trials: bexarotene, tazarotene, adapalene, and trifarotene.
“At least four molecules have reached phase 4 clinical trials: bexarotene, tazarotene, adapalene, and trifarotene29–31.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [31]
Trifarotene is a selective RAR-γ agonist, approved in late 2019 in the USA, for the topical treatment of acne in patients as young as 9 years old.
“Trifarotene is a selective RAR-γ agonist, approved in late 2019 in the USA, for the topical treatment of acne in patients as young as 9 years old31.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [31]
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- Authors
- Wagner, N., Benkali, K., Alió Sáenz, A., Poncet, M., & Graeber, M.
- Affiliations
- Galderma (United States) (US)
- Galderma (France) (FR)
- Galderma Research and Development LLC Fort Worth Texas USA
- Corresponding author
- Wagner, Nathalie
- Venue
- The Journal of Clinical Pharmacology
- Publisher
- Wiley
- Published
- 2020-02-03
- Volume
- 60
- Issue
- 5
- Pages
- 660-668
- ISSN
- 0021-9754 (ISSN-L)
- 0091-2700
- 1552-4604
- PMC
- PMC7187247
- OpenAlex
- W3004977969
- Cited by
- 33
- References
- 11
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 7 · 2023: 2 · 2022: 4 · 2021: 6 · 2020: 3
- FWCI
- 2.74
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Clinical Pharmacology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Galderma
- Topics
- Health Sciences › Medicine › Dermatology › Acne and Rosacea Treatments and Effects
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Keywords
- trifarotene, retinoic acid receptor gamma, topical retinoids, acne, pharmacokinetics, QTc interval, drug-drug interactions, oral contraceptives, skin irritation, systemic absorption, drug safety, pediatric acne
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