Clinical Pharmacology and Safety of Trifarotene, a First‐in‐Class RARγ‐Selective Topical Retinoid
| Autor: | Khaled Benkali, Michael Graeber, Nathalie Wagner, Alessandra B Alió Saenz, Michel Poncet |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Drug
medicine.medical_specialty Erythema MUsT media_common.quotation_subject Retinoic acid receptor activity 030226 pharmacology & pharmacy trifarotene law.invention 03 medical and health sciences 0302 clinical medicine Pharmacokinetics drug‐drug interaction law Internal medicine medicine Pharmacology (medical) Levonorgestrel Adverse effect Acne media_common Pharmacology Clinical pharmacology business.industry Clinical Pharmacology TQC study medicine.disease 030220 oncology & carcinogenesis medicine.symptom business pharmacokinetics medicine.drug |
| Zdroj: | Journal of Clinical Pharmacology |
| ISSN: | 1552-4604 0091-2700 |
| Popis: | 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 QTC 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. QTC 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. |
| Databáze: | OpenAIRE |
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