Английская Википедия:Clascoterone
Шаблон:Short description Шаблон:Use dmy dates Шаблон:Infobox drug
Clascoterone, sold under the brand name Winlevi, is an antiandrogen medication which is used topically in the treatment of acne.[1][2][3] It is also under development in a higher concentration for the treatment of androgen-dependent scalp hair loss, under the brand name Breezula.[2] The medication is used as a cream by application to the skin, for instance the face and scalp.[3]
Clascoterone is an antiandrogen, or antagonist of the androgen receptor (AR), the biological target of androgens such as testosterone and dihydrotestosterone.[4][5] It shows minimal systemic absorption when applied to skin.[3]
The medication, developed by Cassiopea and Intrepid Therapeutics,[2] was approved by the US Food and Drug Administration (FDA) for acne in August 2020.[6][7] The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[8]
Medical uses
Clascoterone is indicated for the topical treatment of acne vulgaris in people aged twelve years of age and older.[1][9]
Two large phase III randomized controlled trials evaluated the effectiveness of clascoterone for the treatment of acne over a period of 12 weeks.[1][9][10] Clascoterone decreased acne symptoms by about 8 to 18% more than placebo.[1][10] The defined treatment success endpoint was achieved in about 18 to 20% of individuals with clascoterone relative to about 7 to 9% of individuals with placebo.[1][9][10] The comparative effectiveness of clascoterone between males and females was not described.[1][10]
A small pilot randomized controlled trial in 2011 found that clascoterone cream decreased acne symptoms to a similar or significantly greater extent than tretinoin 0.05% cream.[9][11] No active comparator was used in the phase III clinical trials of clascoterone for acne.[9] Hence, it's unclear how clascoterone compares to other therapies used in the treatment of acne.[9]
Available forms
Clascoterone is available in the form of a 1% (10 mg/g) cream for topical use.[1]
Side effects
The effects of local skin reactions with clascoterone were similar to placebo in two large phase III randomized controlled trials.[1][10] Suppression of the hypothalamic–pituitary–adrenal axis (HPA axis) may occur during clascoterone therapy in some individuals due to its cortexolone metabolite.[1][9] HPA axis suppression as measured by the cosyntropin stimulation test was observed to occur in 3 of 42 (7%) of adolescents and adults using clascoterone for acne.[1][9] HPA axis function returned to normal within 4 weeks following discontinuation of clascoterone.[1][9] Hyperkalemia (elevated potassium levels) occurred in 5% of clascoterone-treated individuals and 4% of placebo-treated individuals.[1]
Pharmacology
Pharmacodynamics
Clascoterone is a steroidal antiandrogen, or antagonist of the androgen receptor (AR), the biological target of androgens such as testosterone and dihydrotestosterone (DHT).[1][4][5] In a bioassay, the topical potency of the medication was greater than that of progesterone, flutamide, and finasteride and was equivalent to that of cyproterone acetate.[12] Likewise, it is significantly more efficacious as an antiandrogen than other AR antagonists such as enzalutamide and spironolactone in scalp dermal papilla cells and sebocytes in vitro.[5]
Pharmacokinetics
Steady-state levels of clascoterone occur within 5 days of twice daily administration.[1] At a dosage of 6 g clascoterone cream applied twice daily, maximal circulating levels of clascoterone were 4.5 ± 2.9 ng/mL, area-under-the-curve levels over the dosing interval were 37.1 ± 22.3 h*ng/mL, and average circulating levels of clascoterone were 3.1 ± 1.9 ng/mL.[1] In rodents, clascoterone has been found to possess strong local antiandrogenic activity, but negligible systemic antiandrogenic activity when administered via subcutaneous injection.[12] Along these lines, the medication is not progonadotropic in animals.[12]
The plasma protein binding of clascoterone is 84 to 89% regardless of concentration.[1]
Clascoterone is rapidly hydrolyzed into cortexolone (11-deoxycortisol) and this compound is a possible primary metabolite of clascoterone based on in-vitro studies in human liver cells.[1][9] During treatment with clascoterone, cortexolone levels were detectable and generally below or near the low limit of quantification (0.5 ng/mL).[1] Clascoterone may also produce other metabolites, including conjugates.[1]
The elimination of clascoterone has not been fully characterized in humans.[1]
Chemistry
Clascoterone, also known as cortexolone 17α-propionate or 11-deoxycortisol 17α-propionate, as well as 17α,21-dihydroxyprogesterone 17α-propionate or 17α,21-dihydroxypregn-4-en-3,20-dione 17α-propionate, is a synthetic pregnane steroid and a derivative of progesterone and 11-deoxycortisol (cortexolone).[13] It is specifically the C17α propionate ester of 11-deoxycortisol.[12]
An analogue of clascoterone is 9,11-dehydrocortexolone 17α-butyrate (CB-03-04).[14]
Corticosteroids related to clascoterone, for instance cortisone acetate and prednisolone acetate, show antiandrogenic activity in animals similarly to clascoterone.[15]
History
C17α esters of 11-deoxycortisol were unexpectedly found to possess antiandrogenic activity.[12] Clascoterone, also known as cortexolone 17α-propionate, was selected for development based on its optimal drug profile.[12] The medication was approved by the US Food and Drug Administration (FDA) for the treatment of acne in August 2020.[6]
The FDA approved clascoterone based on evidence from two clinical trials (Trial 1/NCT02608450 and Trial 2/NCT02608476) of 1,440 participants 9 to 58 years of age with acne vulgaris.[16] The trials were conducted at 99 sites in the United States, Poland, Romania, Bulgaria, Ukraine, Georgia, and Serbia.[16] Participants applied clascoterone or vehicle (placebo) cream twice daily for 12 weeks.[16] Neither the participants nor the health care providers knew which treatment was being given until after the trial was completed.[16] The benefit of clascoterone in comparison to placebo was assessed after 12 weeks of treatment using the Investigator's Global Assessment (IGA) score that measures the severity of disease (on a scale from 0 to 4) and a decrease in the number of acne lesions.[16]
Society and culture
Names
Clascoterone is the international nonproprietary name and the United States Adopted Name.[13][17]
Research
Clascoterone has been suggested as a possible treatment for hidradenitis suppurativa (acne inversa), an androgen-dependent skin condition.[18]
References
External links
Шаблон:Androgen receptor modulators Шаблон:Portal bar
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- ↑ 9,0 9,1 9,2 9,3 9,4 9,5 9,6 9,7 9,8 9,9 Шаблон:Cite journal
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