cortodoxone and Acne-Vulgaris

Clascoterone is a novel topical antiandrogen medication approved for the treatment of acne. Conventional oral antiandrogen treatments targeting acne such as combined oral contraceptives and spironolactone exert systemic hormonal effects which commonly preclude their usage in male patients while hampering their application in certain female patients. In contrast, clascoterone is a first-in-class antiandrogen proven to be both safe and effective for female and male patients above the age of 12. Outside of occasional localized skin irritation, clascoterone is usually well tolerated, however, some adolescents in a phase II clinical trial experienced biochemical evidence of HPA suppression, which resolved after discontinuing treatment. In this review, we provide an overview of clascoterone including its preclinical pharmacology, pharmacokinetics and metabolism, safety, clinical studies and indications.

Topics: Acne Vulgaris; Adolescent; Androgen Antagonists; Cortodoxone; Female; Humans; Male; Propionates

Acne vulgaris is a ubiquitous condition in men and women starting in adolescence. It is often persistent and refractory to multiple treatment methods. Although multiple medications may be used on- or off-label for treatment, many adverse effects and risks exist with these treatments, and there has not been an agent with a novel mechanism of action introduced in 40 years. Clascoterone is a recently approved topical acne medication with the first novel mechanism of action since isotretinoin. The purpose of this article was to review the clinical data regarding the safety and efficacy of topical clascoterone for the treatment of acne vulgaris in male and female subjects aged >12 years.. A literature search of PubMed, EMBASE, and MEDLINE was conducted for clinical trials published between January 2014 and March 2021 in the English language using the key words Winlevi, clascoterone, and acne vulgaris. Articles were selected if they were related to the approval by the US Food and Drug Administration of clascoterone or provided novel data regarding this drug entity.. Two Phase III randomized controlled trials (NCT02608450 and NCT02608476) were ultimately selected, as these trials provided pivotal information to the US Food and Drug Administration for the approval of topical clascoterone.. The findings of this review show that topical clascoterone is likely an effective and safe option for the treatment of acne vulgaris. It offers efficacy rates similar to those of current medications through a novel mechanism of action. Its place in therapy remains unclear, but it might be placed ahead of other androgen receptor antagonists such as spironolactone due to its avoidance of systemic side effects.

Topics: Acne Vulgaris; Adolescent; Androgen Receptor Antagonists; Cortodoxone; Female; Humans; Male; Propionates; Treatment Outcome

Acne vulgaris, a common and chronic disorder of the pilosebaceous unit, affects up to 85% of adolescent and young adults. While a lot is already known about acne and its treatment, still the gaps in our understanding of acne remains. This article will review the emerging evidence in the complex pathogenesis of acne and provide an overview of the potential future therapy in management of acne vulgaris.Key points

Topics: Acne Vulgaris; Anti-Bacterial Agents; Antibodies, Monoclonal; Antioxidants; Biofilms; Cortodoxone; Diet; Enzyme Inhibitors; Humans; Propionibacterium acnes

To systematically and meta-analytically pool evidence from randomized placebo-controlled trials that examined the efficacy and safety of topical clascoterone cream in patients with acne vulgaris. Four databases were screened from inception to 10 October 2020. Included studies were assessed for risk of bias. Efficacy outcomes included investigator's global assessment (IGA) treatment success and absolute change in inflammatory lesion counts (ILCs) and noninflammatory lesion counts (NILCs). Safety outcomes included the proportion of patients with any treatment-emergent adverse event (TEAE) as well as incidence of any TEAE, serious adverse events (AEs), AEs related to study drug, AEs leading to study drug discontinuation, nasopharyngitis, headache, oropharyngeal pain, and vomiting. Dichotomous data were analyzed using the risk ratio (RR) and 95% confidence interval (95% CI) whereas continuous data were analyzed using the mean difference (MD) and 95% CI. Review Manager Software version 5.4.1 was used for statistical analysis. Five clinical trials, comprising 2457 patients (1357 and 1100 patients received clascoterone and placebo, respectively) were included. Studies revealed an overall low risk of bias. Clascoterone significantly increased IGA success rates (RR = 2.87, 95% CI [2.11, 3.89], P < .001) and decreased NILCs (MD = -5.64, 95% CI [-8.41, -2.87], P < .01) without substantially impacting the ILCs (MD = -1.82, 95% CI [-5.06, 1.43], P = .27). No significant differences were noted between both groups for all safety outcomes, except for nasopharyngitis which was significantly lower in the clascoterone group (RR = 0.47, 95% CI [0.27, 0.83], P = .01). Topical clascorterone cream is safe and effective in the treatment of acne vulgaris.

Topics: Acne Vulgaris; Cortodoxone; Humans; Propionates; Randomized Controlled Trials as Topic; Skin Cream

To review the efficacy and safety of clascoterone 1% cream for the treatment of acne vulgaris in patients 12 years of age and older.. A literature search through PubMed, MEDLINE, and ClinicalTrials.gov was conducted using the following keywords:. Preclinical and clinical studies describing the efficacy and safety of topical clascoterone cream were included.. Early preclinical studies demonstrated that clascoterone exhibits local antiandrogenic effects without any systemic effects. Phase 2 and 3 trials demonstrated a statistically significant reduction in inflammatory and noninflammatory lesions and mild erythema with clascoterone use. Long-term studies confirmed the favorable safety profile of the drug in subjects for up to 9 months of use, with erythema being the most common treatment-emergent local skin reaction.. Pharmacological treatment options for acne vulgaris include topical and systemic agents. Systemic antiandrogen medications are associated with adverse effects and should be avoided in pregnancy and male patients. Clascoterone is a novel topical antiandrogen drug with no systemic adverse effects. This drug provides prescribers with an appealing treatment option for male and female patients 12 years of age and older, who are not candidates for systemic drugs because of contraindications or adverse effects or who have failed other topical therapies.. Clascoterone, a novel topical androgen receptor inhibitor, is a safe and effective treatment option for patients with acne vulgaris.

Topics: Acne Vulgaris; Cortodoxone; Female; Humans; Male; Propionates; Receptors, Androgen; Treatment Outcome

Topics: Acne Vulgaris; Androgen Receptor Antagonists; Androgens; Cortodoxone; Female; Humans; Male; Propionates

Topics: Acne Vulgaris; Cortodoxone; Humans; Propionates; Treatment Outcome

Clascoterone (Winlevi

Topics: Acne Vulgaris; Administration, Topical; Alopecia; Androgen Receptor Antagonists; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Cortodoxone; Dose-Response Relationship, Drug; Drug Approval; Germany; Humans; Multicenter Studies as Topic; Propionates; Randomized Controlled Trials as Topic; Receptors, Androgen; Skin; Skin Cream; Solutions; United States; United States Food and Drug Administration

Hormones and androgens play an important role in the pathogenesis of acne. Multiple hormonal modulators are now available for the treatment of acne. The efficacies and side effects of currently available hormonal agents are reviewed here including the use of oral contraceptives, spironolactone, flutamide, cyproterone acetate, finasteride, and cortexolone 17α-propionate. Hormonal therapies are an efficacious treatment option for acne among females. With the growing need to reduce antibiotic exposures, hormonal therapies should be more widely studied and incorporated into acne treatment strategies.

Topics: Acne Vulgaris; Administration, Oral; Contraceptive Agents; Cortodoxone; Cyproterone Acetate; Dermatologic Agents; Female; Finasteride; Flutamide; Hormones; Humans; Male; Meta-Analysis as Topic; Mineralocorticoid Receptor Antagonists; Propionates; Spironolactone; Treatment Outcome

The pathogenesis of acne is multifactorial and involves inflammation, bacterial dysbiosis, and androgen stimulation. Existing systemic therapies target hormonal pathways to mitigate acne lesions; however, their use is limited to the female population and associated with systemic adverse effects. Clascoterone is the first topical therapy to target the hormonal pathogenesis of acne approved to treat acne vulgaris. In two identical phase 3 trials, clascoterone showed favorable efficacy over placebo in treating acne, with higher treatment success and a greater reduction in acne lesions. Large scale trials are required to assess the efficacy of clascoterone against its comparators and in combination with existing acne therapies; however, results from the current phase 3 trials support the therapeutic value of clascoterone, suggesting that this novel topical androgen inhibitor represents a valuable addition to the catalogue of acne therapy.

Topics: Acne Vulgaris; Administration, Topical; Cortodoxone; Female; Humans; Propionates; Treatment Outcome

Acne is a common, multifactorial skin condition, and treatments with novel mechanisms have been elusive.. To assess the safety and efficacy of clascoterone cream, 1%, a novel topical androgen receptor inhibitor, in 2 phase 3 randomized clinical trials (CB-03-01/25 and CB-03-01/26).. Two identical, multicenter, randomized, vehicle-controlled, double-blind, phase 3 studies conducted from November 2015 to April 2018 evaluated the efficacy and safety of use of clascoterone cream, 1%, in males and nonpregnant females 9 years and older with moderate or severe facial acne as scored on the Investigator's Global Assessment scale. Participants were enrolled if they had 30 to 75 inflammatory lesions and 30 to 100 noninflammatory lesions.. Patients were randomized to treatment with clascoterone cream, 1%, or vehicle cream and applied approximately 1 g to the whole face twice daily for 12 weeks.. Treatment success was defined as an Investigator's Global Assessment score of 0 (clear) or 1 (almost clear), and a 2-grade or greater improvement from baseline and absolute change from baseline in noninflammatory and inflammatory lesion counts at week 12. Safety measures included adverse event frequency and severity.. A total of 1440 patients were randomzied in 2 studies. In CB-03-01/25, 353 participants were randomized to treatment with clascoterone cream, 1% (median [range] age, 18.0 [10-58] years; 221 [62.6%] female), and 355 participants were randomized to treatment with vehicle cream (median [range] age, 18.0 [9-50] years; 215 (60.6%) female); in CB-03-01/26, 369 participants were randomized to treatment with clascoterone cream, 1% (median [range] age, 18.0 [10-50] years; 243 [65.9%] female), and 363 participants were randomized to treatment with vehicle cream (median [range] age, 18.0 [range, 11-42] years; 221 [60.9%] female). At week 12, treatment success rates in CB-03-01/25 and CB-03-01/26 with clascoterone cream, 1%, were 18.4% (point estimate, 2.3; 95% CI, 1.4-3.8; P < .001) and 20.3% (point estimate, 3.7; 95% CI, 2.2-6.3; P < .001) vs 9.0% and 6.5% with vehicle, respectively. At week 12, in both CB-03-01/25 and CB-03-01/26, treatment with clascoterone cream, 1%, resulted in a significant reduction in absolute noninflammatory lesions from baseline to -19.4 (point estimate difference, -6.4; 95% CI, -10.3 to -2.6; P < .001) and -19.4 (point estimate difference, -8.6; 95% CI, -12.3 to -4.9; P < .001) vs -13.0 and -10.8 with vehicle, respectively, as well as a reduction in inflammatory lesions from baseline to -19.3 (point estimate difference, -3.8; 95% CI, -6.4 to -1.3; P < .001) and -20.0 (point estimate difference, -7.4; 95% CI, -9.8 to -5.1; P < .001) vs -15.5 and -12.6 with vehicle, respectively. Adverse events rates were low and mostly mild; the predominant local skin reaction was trace or mild erythema.. Use of clascoterone cream, 1%, for acne treatment appears to demonstrate favorable efficacy and safety with low adverse event rates.. ClinicalTrials.gov Identifiers: NCT02608450 and NCT02608476.

Topics: Acne Vulgaris; Adolescent; Adult; Androgen Antagonists; Child; Cortodoxone; Double-Blind Method; Drug Administration Schedule; Erythema; Face; Female; Humans; Male; Middle Aged; Propionates; Severity of Illness Index; Skin Cream; Treatment Outcome; Young Adult

Androgens foster acnegenic pathways.. To assess the long-term safety of an androgen receptor inhibitor, clascoterone cream, 1%, in patients who participated in phase 3 studies.. Clascoterone cream was applied twice daily for up to 9 months to the face or trunk, or both. Treatment-emergent adverse events (TEAEs) and local skin reactions were evaluated at months 1, 3, 6, and 9, and at any unscheduled visit(s). The statistical analysis was performed using SAS Windows 9.3 software (SAS Institute Inc, Cary, NC).. The study screened and enrolled 609 individuals (n = 317 clascoterone, n = 292 vehicle from original studies), and 347 completed the study (n = 179 clascoterone, n = 168 vehicle). Overall, 110 patients (18.1%) experienced 191 TEAEs. The most frequently reported TEAE was nasopharyngitis (n = 20). A total of 19 test article-related TEAEs occurred in 14 patients; of these, 9 experienced 9 TEAEs leading to discontinuation. There were 7 serious TEAEs in 6 individuals, but none were treatment related. One serious TEAE led to study discontinuation. Overall, treatment-emergent local skin reactions occurred in 18.1% (110 of 607). The most frequent local skin reactions on the face and trunk were erythema, scaling/dryness, and pruritus, and most were trace/minimal or mild in severity.. Long-term efficacy was not a primary end point.. A low frequency of TEAEs over 9 months of clascoterone treatment was observed.

Topics: Acne Vulgaris; Adolescent; Adult; Androgen Receptor Antagonists; Child; Cortodoxone; Drug Administration Schedule; Erythema; Face; Female; Follow-Up Studies; Humans; Male; Middle Aged; Propionates; Pruritus; Severity of Illness Index; Skin; Skin Cream; Torso; Young Adult

Clascoterone (cortexolone 17α-propionate, CB-03-01) 1% cream, a topical, androgen receptor (AR) inhibitor under investigation for the treatment of acne vulgaris, is rapidly metabolized to cortexolone in human plasma. The primary objectives of this study were to determine the pharmacokinetic (PK) properties and adrenal suppression potential of clascoterone topical cream, 1% in subjects with acne vulgaris.\ \ Study Design: This study was an open-label, multicenter study in 42 subjects ≥12 years of age with moderate-to-severe acne (Grade 3-4 on the Investigator’s Global Assessment [IGA]), on the face, chest and/or back. Cohort 1(>18 years of age) and Cohort 2 (12-18 years of age) applied clascoterone topical cream, 1% twice daily (BID) for 14 days. Primary safety endpoints included hypothalamic-pituitary-adrenal (HPA) axis response to cosyntropin via a Cosyntropin Stimulation Test (CST) upon screening (day 1) and at day 14 (HPA axis suppression was defined as a post-stimulation serum cortisol level <18 μg/dL at day 14); and PK evaluation including concentration-time profiles of clascoterone and cortexolone in plasma—PK parameters were determined using “non-compartmental” analysis. Secondary safety endpoints included clinical laboratory testing, local and systemic adverse events (AEs), physical examination/vital signs, and electrocardiogram (ECG).\ \ Results: 42 subjects (Cohort 1=20, Cohort 2= 22) enrolled. Cohort 1 was comprised of 15 females (15/20, 75%) and 5 males (5/20, 25%), non-Hispanic/Latino (20/20, 100%), mean age is 24.4 years. Cohort 2 was comprised of 12 females (12/22, 54.5%) and 10 males (10/22, 45.5%), non-Hispanic/Latino (21/22, 95.5%), and mean age is 15.6 years. Three subjects (3/42,7%), 1 adult and 2 adolescents, demonstrated an abnormal HPA axis response with post-stimulation serum cortisol levels ranging from 14.9 to 17.7 μg/dL at day 14. All returned to normal HPA axis function, four weeks after day 14. None showed clinical evidence of adrenal suppression. Clascoterone plasma concentrations achieved PK steady-state by day 5. Clascoterone systemic exposure was similar between both cohorts. At steady-state, plasma concentrations increased ~1.8 to 2.1 fold versus first dose with mean (coefficient of variation [CV] %) maximum plasma concentrations of 4.4 ng/mL (67%) and 4.6 ng/mL (103%) in Cohort 1 and Cohort 2, respectively. Cortexolone plasma concentrations trended below the lower limit of quantitation (0.5 ng/mL) in both cohorts. Local skin

Topics: Acne Vulgaris; Adolescent; Adult; Androgen Receptor Antagonists; Child; Cortodoxone; Female; Humans; Hypothalamo-Hypophyseal System; Male; Pituitary-Adrenal System; Propionates; Severity of Illness Index; Skin Cream; Treatment Outcome; Young Adult

Androgens play a key role in acne pathogenesis in both males and females. Clascoterone (CB-03-01, Cortexolone 17α propionate) cream is a topical anti-androgen under investigation for the treatment of acne. The results from a phase 2b dose escalating study are discussed.\ \ Methods: Primary objective: to compare the safety and efficacy of topical creams containing clascoterone 0.1% (twice daily [BID]), 0.5% (BID), or 1% (daily [QD] or BID) versus vehicle (QD or BID) in male and female subjects ≥12 years with facial acne vulgaris. Efficacy was assessed by: Investigator’s Global Assessment (IGA)--the overall severity of acne using a five-point scale (from 0=clear to 4=severe); inflammatory and non-inflammatory acne lesion counts (ALC); and subject satisfaction with treatment--subjects assessed overall treatment satisfaction using a 4-point scale. Safety assessments: local and systemic adverse events (AEs), physical examination/vital signs, laboratory tests, local skin reactions (LSRs), and electrocardiograms (ECGs). Treatment success required a score of “clear” or “almost clear” (IGA score of 0 or 1) and a two or more-grade improvement from baseline.\ \ Results: 363 subjects (N=72, 0.1% BID; N=76, 0.5% BID; N=70, 1% QD; N=70, 1% BID; and N=75, vehicle QD or BID) enrolled. 304 subjects (83.7%) completed the study. Intention to Treat (ITT) population: 196/363 (54.0%) females; 167/363 46.0%) males; (257/363 (70.2%) were white; average age=19.7 years. Demographic and baseline characteristics were similar across all groups. Treatment success at week 12 were highest for the 1% BID (6/70, 8.6%) and 0.1% BID (6/72, 8.3%) groups versus vehicle (2/75, 2.7%). Absolute change in inflammatory (P=0.0431) and non-inflammatory (P=0.0303) lesions was statistically significant among the treatment groups. The median change from baseline at week 12 in inflammatory and non-inflammatory lesions was greatest in the 1% BID group -13.5 and -17.5, respectively. Similar results were observed for the secondary efficacy endpoints whereby the highest success rate and greatest reduction in lesion counts from baseline to week 12 occurred with 1% BID.\ 93/363 subjects (25.6%) reported ≥1 AEs; total number of AEs=123 with 2 probably/possibly related to treatment (N=1, 1% QD group). Subjects with ≥1AEs: 0.1% BID=25.0%, 0.5% BID=38.2%, 1% QD=22.9%, 1% BID=18.6%, and vehicle=22.7%. AEs were mostly mild in severity and similar across all groups. Most AEs (93/121 76.8%) resolved by the end of the stud

Topics: Acne Vulgaris; Adolescent; Adult; Cortodoxone; Dose-Response Relationship, Drug; Double-Blind Method; Face; Female; Humans; Male; Pharmaceutical Vehicles; Propionates; Severity of Illness Index; Skin Cream; Treatment Outcome; Young Adult

Acne vulgaris is a disorder of the pilosebaceous unit in which the androgens contribute to its onset and persistence. The use of antiandrogens is therefore potentially effective; however, antiandrogens for topical use are not available on the market. Cortexolone 17α-propionate (CB-03-01; Cosmo S.p.A, Lainate, Italy) is a new potent topical antiandrogen potentially useful in acne vulgaris.. To evaluate the safety and the topical efficacy of CB-03-01 1% cream in acne vulgaris as compared with placebo and with tretinoin 0·05% cream (Retin-A® ; Janssen-Cilag).. Seventy-seven men with facial acne scored 2-3 according to Investigator's Global Assessment (IGA) were randomized to receive placebo cream (n = 15), or CB-03-01 1% cream (n = 30), or tretinoin 0·05% cream (n = 32) once a day at bedtime for 8 weeks. Clinical efficacy was evaluated every 2 weeks including total lesion count (TLC), inflammatory lesion count (ILC), acne severity index (ASI) and IGA. Safety assessment included local irritancy score, laboratory tests, physical examination, vital signs and recording of adverse events.. CB-03-01 1% cream was very well tolerated, and was significantly better than placebo regarding TLC (P = 0·0017), ILC (P = 0·0134) and ASI (P = 0·0090), and also clinically more effective than comparator. The product also induced a faster attainment of 50% improvement in all the above parameters.. This pilot study supports the rationale for the use of topical antiandrogens in the treatment of acne vulgaris. CB-03-01 1% cream seems to fit with the profile of an ideal antiandrogen for topical use.

Topics: Acne Vulgaris; Administration, Topical; Adolescent; Adult; Androgen Antagonists; Anti-Inflammatory Agents; Cortodoxone; Double-Blind Method; Emollients; Humans; Keratolytic Agents; Male; Middle Aged; Pilot Projects; Propionates; Severity of Illness Index; Tretinoin; Young Adult

Acne vulgaris is the most common skin condition in the US, affecting up to 50 million Americans. The American Academy of Dermatology (AAD) guidelines on acne treatment were developed to provide recommendations for the diagnosis, grading, and treatment of acne in adolescents and adults to support clinicians in their therapeutic decision-making process. The most recent acne guidelines were published in 2016, and the approach to care and the therapeutic landscape of acne have evolved since that time. The Acne Management Consensus Roundtable was convened in 2022 to discuss unmet needs in the management of acne. The main focus of the meeting was the role of androgens in acne pathology; the evaluation of clascoterone, the first topical anti-androgen that specifically addresses sebum production in acne; and the identification of the place of clascoterone in therapy. Clascoterone was approved by the US Food and Drug Administration for the treatment of acne in patients 12 years and older in 2020. This report aims to highlight important limitations of the 2016 AAD treatment guidelines and to familiarize practitioners with clascoterone and its indication, efficacy and safety profile, and potential use across diverse patient populations. With its new mechanism of action, clascoterone may be able to fulfill important unmet needs in acne treatment. Baldwin H, Farberg AS, Frey C, et al. Unmet needs in the management of acne vulgaris: a consensus statement. J Drugs Dermatol. 2023;22(6):582-587. doi:10.36849/JDD.7587.

Topics: Acne Vulgaris; Adolescent; Adult; Cortodoxone; Humans; Propionates; Sebum; Treatment Outcome

Acne is a prevalent chronic inflammatory disease that can cause severe psychiatric effects and physical scarring of the skin. Historically, although systemic antiandrogen acne medications have been effective in women, the utility of these systemic medications has been limited due to potential systemic side effects in men and pregnant women. Therefore, research has been focused on developing topical formulations of antiandrogen therapy for acne. Topical clascoterone cream 1% is the first topical anti-androgen medication approved for the treatment of acne vulgaris in patients 12 years and older and represents a breakthrough in acne treatment. Clascoterone, or cortexolone-17α propionate, is an androgen receptor inhibitor with highly localized activity. Thismedication is thought to compete with dihydrotestosterone (DHT) for androgen receptors located in pilosebaceous units, thus inhibiting the acnegenic downstream effects of DHT such as lipid synthesis and inflammatory cytokine production in a dose-dependent manner. Two phase III clinical trials have been conducted thus far; both trials have shown clascoterone 1% cream applied BID to be significantly more effective than placebo cream at treating acne vulgaris in patients ages 12 and older with moderate-to-severe acne. Clascoterone has also been shown to have a similar safety profile to that of placebo cream in clinical studies, without any systemic antiandrogenic effects observed in the clinical setting. Due to its novel mechanism of action and activity limited to the skin, clascoterone presents an exciting opportunity for dermatologists to further optimize care for eligible acne patients, either as a monotherapy or in combination with other anti-acne medications. J Drugs Dermatol. 2023;22:56(Suppl 1):s7-14.

Topics: Acne Vulgaris; Androgen Antagonists; Cortodoxone; Emollients; Female; Humans; Male; Pregnancy; Propionates; Skin Cream; Treatment Outcome

Topics: Acne Vulgaris; Androgen Receptor Antagonists; Cortodoxone; Humans; Propionates; Skin Cream

Many patients with acne remain unsatisfied with results from the various topical treatments available and often do not improve, because of poor adherence. Even if topical clascoterone, a safe and effective treatment, were more potent than existing topicals, it could face the same poor adherence hurdle as existing treatments. Real-life efficacy will likely not reflect trial results because, for several reasons, adherence is better in trials than in real-life practice. Although topical clascoterone may be exciting initially for its promise to improve acne outcomes, the long-term place in therapy may be another topical option that minimally enhances patients' treatment outcomes.

Topics: Acne Vulgaris; Cortodoxone; Humans; Propionates; Receptors, Androgen

The efficacy of clascoterone cream was demonstrated in two phase three vehicle-controlled clinical trials that enrolled over 1,400 subjects. Its safety profile allowed it to be approved for treating patients as young as 12 years old. During clinical trials, the occurrence of local skin reactions (edema, erythema, pruritus, dryness) was similar to treatment with vehicle alone.. All publications describing the clinical development of clascoterone cream (cortexolone 17α-propionate) are reviewed and discussed in relation to with existing topical and systemic therapies for acne vulgaris.. Clascoterone 1% cream is a novel first-in-class topical androgen receptor inhibitor for the treatment of acne vulgaris. Topical clascoterone 1% cream represents the first new type of therapy for acne treatment in almost 40 years and may become first-line therapy.

Topics: Acne Vulgaris; Administration, Topical; Androgen Receptor Antagonists; Child; Clinical Trials, Phase III as Topic; Cortodoxone; Humans; Propionates; Skin Cream; Treatment Outcome

Clascoterone is an androgen receptor inhibitor which has been approved by the United States Food and Drug Administration for the topical treatment of acne vulgaris in patients 12 years of age and older. It competes with androgens, especially dihydrotestosterone, for androgen-receptor binding and limits their binding, thus inhibiting downstream signaling of pathways involved in the pathogenesis of acne. It inhibits androgen receptor-regulated gene transcription, and antagonizes lipid and inflammatory cytokine production in a dose-dependent manner in human primary sebocytes. Clascoterone is commercially available as 1% (10 mg/g) cream. Adverse effects of topical clascoterone are mild and infrequent, and are mostly limited to local skin reactions. Long-term safety studies have shown an absence of systemic antiandrogenic effects like reduced libido or feminization in male participants. Clascoterone seems a promising topical drug with a novel mechanism of action that could be added to the armamentarium of therapies for acne.

Topics: Acne Vulgaris; Administration, Topical; Androgen Receptor Antagonists; Cortodoxone; Humans; Male; Propionates

Topics: Acne Vulgaris; Administration, Topical; Cortodoxone; Humans; Propionates; Randomized Controlled Trials as Topic

Of the four primary pathogenic factors that drive acne vulgaris—androgen excess, increased sebum production, faulty keratinization, and overgrowth of C. acnes—androgen excess has been the most elusive therapeutic target. Oral contraceptive pills (OCPs) have direct effect on circulating hormones, but their potential use is limited to a subset of women. As such, a sizable portion of the population affected by acne vulgaris cannot even consider treatment with OCPs. While these systemic agents are generally associated with a low risk profile and have a history of safe and effective use, they are not entirely risk-free. Indirect androgen modulation through the use of spironolactone has become increasingly popular.

Topics: Acne Vulgaris; Administration, Cutaneous; Cortodoxone; Dermatologic Agents; Humans; Propionates

Topics: Acne Vulgaris; Cortodoxone; Hidradenitis Suppurativa; Humans; Propionates; Randomized Controlled Trials as Topic

Topics: Acne Vulgaris; Androgen Antagonists; Cortodoxone; Humans; Propionates; Randomized Controlled Trials as Topic

Topics: Acne Vulgaris; Androgen Antagonists; Cortodoxone; Humans; Propionates; Randomized Controlled Trials as Topic

Cortexolone 17α-propionate (clascoterone) is a novel topical androgen antagonist that is being analyzed for its ability to treat acne. The pathogenesis of acne is attributed to multiple factors, including altered sebum production, inflammatory processes, dysregulation of the hormone microenvironment, and the proliferation of the skin commensal bacteria, Propionibacterium acnes (P. acnes). Androgens induce the proliferation and differentiation of sebocytes, (cells that comprise the sebaceous gland), help regulate the synthesis of the lipids that are incorporated into sebum and stimulate the production of cytokines that are found in inflammatory acne lesions. Several studies have established that clascoterone is a potent antiandrogen that is well tolerated and has selective topical activity. Its potency as an acne therapeutic is currently being analyzed in a large phase 3 clinical trial. The study described herein elucidates for the first time the mechanism of action of clascoterone. Clascoterone was found to bind the androgen receptor (AR) with high affinity in vitro, inhibit AR-regulated transcription in a reporter cell line, and antagonize androgen-regulated lipid and inflammatory cytokine production in a dose-dependent manner in human primary sebocytes. In particular, when compared to another AR antagonist, spironolactone, clascoterone was significantly better at inhibiting inflammatory cytokine synthesis from sebocytes. Therefore, clascoterone may be an excellent candidate to be the first topical antiandrogen to treat acne.\ \ J Drugs Dermatol. 2019;18(5):412-418.

Topics: Acne Vulgaris; Androgen Receptor Antagonists; Cell Line; Cortodoxone; Cytokines; Humans; Lipogenesis; Propionates; Propionibacterium acnes; Receptors, Androgen; Sebaceous Glands

Congenital adrenal hyperplasia is a group of autosomal recessive inherited disorders of steroidogenesis. The deficiency of steroid 11-hydroxylase (CYP11B1) resulting from mutations in the CYP11B1 gene is the second most frequent cause.. We studied the functional and structural consequences of two CYP11B1 missense mutations, which were detected in a 1.8-yr-old boy with acne and precocious pseudopuberty, to prove their clinical relevance and study their impact on CYP11B1 function.. The in vitro expression studies in COS-7 cells revealed an almost complete absence of CYP11B1 activity for the P94L mutant to 0.05% for the conversion of 11-deoxycortisol to cortisol. The A368D mutant severely reduced the CYP11B1 enzymatic activity to 1.17%. Intracellular localization studies by immunofluorescence revealed that the mutants were correctly localized. Introducing these mutations in a three-dimensional model structure of the CYP11B1 protein provides a possible explanation for the effects measured in vitro. We hypothesize that the A368D mutation interferes with structures important for substrate specificity and heme iron binding, thus explaining its major functional impact. However, according to structural analysis, we would expect only a minor effect of the P94L mutant on 11-hydroxylase activity, which contrasts with the observed major effect of this mutation both in vitro and in vivo.. Analyzing the in vitro enzyme function is a complementary procedure to genotyping and a valuable tool for understanding the clinical phenotype of 11-hydroxylase deficiency. This is the basis for accurate genetic counseling, prenatal diagnosis, and treatment. Moreover, the combination of in vitro enzyme function and molecular modeling provides valuable insights in cytochrome P450 structural-functional relationships, although one must be aware of the limitations of in silico-based methods.

Topics: Acne Vulgaris; Adrenal Hyperplasia, Congenital; Animals; Base Sequence; Chlorocebus aethiops; Cortodoxone; COS Cells; Fluorescent Antibody Technique; Gene Expression; Humans; Hydrocortisone; Infant; Male; Models, Molecular; Mutagenesis, Site-Directed; Mutation, Missense; Pedigree; Puberty, Precocious; Sequence Analysis, DNA; Steroid 11-beta-Hydroxylase; Structure-Activity Relationship; Transfection

Acne vulgaris is androgen related and in some cases is associated with excess androgen production, which in men would be mainly testicular or adrenal in origin. Ordinarily, testosterone synthesis in the testis is controlled by serum LH. In order to ascertain whether acne vulgaris in men might be consequent on abnormalities at the hypothalmic/pituitary level we have compared serum LH levels in men with and without acne.. 111 men with acne vulgaris were compared with 51 acne-free men.. Serum levels of LH, FSH and oestradiol were measured by automated ELISA. Dehydroepiandrosterone sulphate (DHEA-S), 17 alpha-hydroxyprogesterone, 11-deoxycortisol, androstenedione and testosterone were measured by radioimmunoassay, and SHBG by immunoradiometric assay.. The controls showed a fall in serum LH with age: the rate of fall was less in the acne patients (difference between the slopes 0.073 U/year (95% confidence interval (CI), 0.016 to 0.130)). The age distributions in the acne and control groups differed. In order to compare means, standardizations were used to assess the difference in the means in populations of men with age distributions similar to the cases and controls. After standardization to the age distribution of the controls, the acne patients had higher means of serum LH, difference between the means 0.80 U/I (95% CI, 0.31 to 1.30), androstenedione, 1.09 nmol/l (95% CI, 0.15 to 2.03) and testosterone levels, 2.74 nmol/l (95% CI, 0.53 to 4.95) and a lower mean BMI, -1.30 kg/m2 (95% CI, -2.40 to -0.19). After standardization to the age distribution of the acne patients the means of LH, androstenedione and testosterone were still higher in the acne patients but not necessarily significantly so.. LH fell more slowly with age in the men with acne as compared to the controls. In our heterogeneous group of patients with acne vulgaris the findings suggest that a sub-group of men with acne have raised serum LH levels.

Topics: 17-alpha-Hydroxyprogesterone; Acne Vulgaris; Adult; Aging; Androstenedione; Body Mass Index; Case-Control Studies; Cortodoxone; Dehydroepiandrosterone Sulfate; Estradiol; Follicle Stimulating Hormone; Humans; Linear Models; Luteinizing Hormone; Male; Middle Aged; Sex Hormone-Binding Globulin; Testosterone

We describe a patient with signs and symptoms of virilization caused by 21-hydroxylase deficiency. The patient, a Hispanic woman, first sought medical attention at age 24, when she presented to a medical clinic with an uncomplicated urinary tract infection. At that time several signs of virilization were noted and she was referred to the endocrinology clinic. Evaluation revealed temporal balding, hyperpigmentation, acne, absent breast development, a muscular habitus, and clitoromegaly. Radiological studies revealed bilaterally enlarged adrenal glands and ovaries. Laboratory evaluation revealed markedly increased concentrations of 17-hydroxyprogesterone, androstenedione, and testosterone. The patient was diagnosed with congenital adrenal hyperplasia (CAH) and received hormone therapy. In her sister, encouraged to undergo testing for this autosomal recessive disorder, HLA testing demonstrated that certain haplotypes in this family were associated with CAH. The case highlights key steps in the laboratory diagnosis and genetics of CAH.

Topics: 17-alpha-Hydroxyprogesterone; Acne Vulgaris; Adrenal Hyperplasia, Congenital; Adult; Androstenedione; Clitoris; Cortodoxone; Dehydroepiandrosterone; Female; Gonadal Steroid Hormones; Hirsutism; Histocompatibility Testing; Humans; Hydroxyprogesterones; Hyperpigmentation; Testosterone; Urinary Tract Infections

Acne vulgaris is androgen dependent but the hormonal mechanisms are unclear. Although there have been many studies of serum hormones in women with acne there are few studies in men and the results are conflicting. We have therefore carried out a further study in men.. Fifty men with acne vulgaris were age-matched against 50 normal men.. Serum levels of dehydroepiandrosterone sulphate (DHEAS), 17 alpha-hydroxyprogesterone, 11-deoxycortisol, androstenedione and testosterone were measured by radioimmunoassay, sex hormone binding globulin (SHBG) by immunoradiometric assay and LH, FSH and oestradiol by automated ELISA.. The acne patients had higher levels of androstenedione, median 7.35 nmol/l, (interquartile range 2-7) vs 6.05 (2.3), P = 0.004; testosterone, 21.7 nmol/l (7.5) vs 17.55 (7.7), P = 0.04; and free androgen index (FAI) 78.26 (40) vs 65.06 (20), P = 0.007, but also had higher levels of 11-deoxycortisol, 13.65 nmol/l (4.3) vs 12.0 (4.3), P = 0.022. The LH, FSH, 17 alpha-hydroxyprogesterone, DHEAS, oestradiol and SHBG levels were not significantly different. Examination of the Spearman rank correlation coefficient matrices for the serum levels of 17 alpha-hydroxyprogesterone, androstenedione and 11-deoxycortisol showed that the strongest correlation was between androstenedione and 11-deoxycortisol.. Although there was overlap between the results of the acne patients and controls the acne patients tended to have higher levels of androstenedione, testosterone, free androgen index and 11-deoxycortisol. The higher levels of 11-deoxycortisol are suggestive of 11 beta-hydroyxlase dysfunction which could be due to a primary adrenal defect or a consequence of raised androgens. Also, a pathway between androstenedione and 11-deoxycortisol has been described in sheep and, although unsubstantiated in man, requires consideration.

Topics: 17-alpha-Hydroxyprogesterone; Acne Vulgaris; Adult; Androgens; Androstenedione; Cortodoxone; Humans; Hydroxyprogesterones; Male; Middle Aged; Testosterone

We developed and validated a coordinated set of RIAs for the following eight steroids in single small aliquots (< or = 1 mL) of plasma: androstenedione, dehydroepiandrosterone, 11-deoxycortisol, 21-deoxycortisol (21-DF), 11 beta-hydroxyandrostenedione, 17 alpha-hydroxypregnenolone (17-Hpreg), 17 alpha-hydroxyprogesterone, and testosterone. Samples were extracted and then chromatographed on celite microcolumns. Radioiodinated tracers were used for two of the assays (17-Hpreg and 21-DF). Tritiated tracers and scintillation proximity assay counting were used to give separation-free procedures for the other six assays, which considerably improved their practicability and reproducibility. The basal and postadrenocorticotropic hormone plasma values for these steroids in normal women sampled in the follicular phase are presented. Finally, the measurement of the eight steroids as a diagnostic method is evaluated with reference to data from 203 patients with hirsutism and (or) acne.

Topics: 17-alpha-Hydroxypregnenolone; 17-alpha-Hydroxyprogesterone; Acne Vulgaris; Adolescent; Adult; Androstenedione; Cortodoxone; Dehydroepiandrosterone; Female; Follicular Phase; Hirsutism; Humans; Hydroxyprogesterones; Radioimmunoassay; Reference Values; Sensitivity and Specificity; Steroids; Testosterone

The adrenal secretion of androgens were examined in 9 women (ages 19-39 yr) with postadolescent idiopathic acne and compared to age and sex-matched normal controls. Plasma dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), androstenedione (delta 4-delta), cortisol, 17-hydroxyprogesterone, 11-deoxycortisol, and testosterone were measured by radioimmunoassay in the basal state and during a 48 hr ACTH infusion. The mean plasma and time-integrated plasma levels of the 3 adrenal androgens in patients with acne were 15-25% higher than normal controls, but the groups were not significantly different (p greater than .05). The plasma testosterone values, on the other hand, were similar in both groups. In addition, cortisol, 11-deoxycortisol and 17-hydroxyprogesterone basal plasma values and responses to ACTH in patients with acne were similar to the normal control values. These findings suggest that adrenal androgen secretion is at most mildly elevated in patients with idiopathic acne and is unlikely to be the sole cause of acne since many patients without acne have similar hormone levels. Increased sensitivity of the sebaceous gland to androgens or increased local metabolism of androgen hormones in the skin to potent androgen metabolites may offer alternative mechanisms for the pathogenesis of this disorder.

Topics: Acne Vulgaris; Adrenal Glands; Adrenocorticotropic Hormone; Adult; Androgens; Androstenedione; Cortodoxone; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Humans; Hydrocortisone; Hydroxyprogesterones; Testosterone

To investigate the possible occurrence of partial 11- or 21-hydroxylase deficiences in acne, an androgen-dependent disorder, 11 women with chronic nodulocystic acne were subjected to a 24-hr infusion of ACTH and their urine analyzed for tetrahydro S and pregnanetrio. The results obtained were compared to those found in 8 control women. Seven of the patients exhibited elevated excretion of either tetrahydro S or pregnanetriol, probably indicative of partial 11- or 21-hydroxylase deficiencies, respectively.

Topics: Acne Vulgaris; Adolescent; Adrenocorticotropic Hormone; Adult; Cortodoxone; Female; Humans; Pregnanetriol; Steroid Hydroxylases; Testosterone; Tetrahydrocortisol