Roflumilast foam 0.3% for adolescent and adult patients with seborrheic dermatitis: A randomized, double-blinded, vehicle-controlled, phase 3 trial.

BACKGROUND: The topical phosphodiesterase 4 inhibitor roflumilast has been studied in several dermatologic conditions. OBJECTIVE: Roflumilast foam 0.3% is being investigated as a topical treatment for seborrheic dermatitis (SD). METHODS: In this phase 3, double-blinded trial, patients with SD were randomly assigned (2:1 ratio) to once-daily roflumilast foam 0.3% or vehicle foam for 8 weeks. The primary efficacy outcome was Investigator Global Assessment (IGA) Success at week 8, defined as IGA of 0 (Clear) or 1 (Almost Clear) plus ≥2-point improvement from baseline. Safety was also assessed. RESULTS: 79.5% of roflumilast-treated and 58.0% of vehicle-treated patients met the primary endpoint (P < .001); statistically significant differences in IGA Success also favored roflumilast at week 2 (roflumilast: 43.0%; vehicle: 25.7%; P < .001) and week 4 (roflumilast: 73.1%; vehicle: 47.1%; P < .001). Roflumilast was well-tolerated with a low rate of treatment-emergent adverse events. LIMITATIONS: Study limitations include the 8-week treatment period for this chronic condition. CONCLUSIONS: Once-daily roflumilast foam was superior to vehicle in leading to IGA of Clear or Almost Clear plus ≥2-point improvement from baseline at 8 weeks in patients with SD. Longer trials are needed to determine durability and safety of roflumilast foam in SD.

Pharmacokinetics, Safety, and Tolerability of a Single 5-Day Treatment of Tirbanibulin Ointment 1% in 100 cm2 : A Phase 1 Maximal-Use Trial in Patients with Actinic Keratosis.

Tirbanibulin ointment 1% is approved in the United States and Europe for the treatment of actinic keratosis with demonstrated efficacy, safety, and tolerability when applied over a field up to 25 cm2 . This Phase 1 maximal-use trial determines the plasma pharmacokinetics, safety, and tolerability of tirbanibulin ointment 1% applied to 100 cm2 of the face or balding scalp in adults with actinic keratosis. Twenty-eight patients self-applied tirbanibulin once daily for a single 5-day treatment course. On Day 5, the mean maximum plasma concentration was 1.06 ng/mL and area under the plasma concentration-time curve during a dosing interval was 16.2 ng â€¢ h/mL. Systemic exposure was approximately 4-fold higher than in a previous pharmacokinetic study with a 25 cm2 field, consistent with the increase in the treated area. Tirbanibulin applied to a 100-cm2 treatment field showed favorable safety and tolerability. The most common treatment-emergent adverse events were application site reactions (in 35.7% of patients). All treatment-emergent adverse events and most of the tolerability signs were mild/moderate and resolved or returned to baseline by Day 29. In summary, under maximal-use conditions, tirbanibulin ointment 1% was safe and well tolerated supporting its potential use over a field up to 100 cm2 .

Clinical and molecular effects of oral CCR4 antagonist RPT193 in atopic dermatitis: A Phase 1 study.

BACKGROUND: RPT193 is an orally administered small molecule antagonist of the human C-C motif chemokine receptor 4 (CCR4) that inhibits the migration and downstream activation of T-helper Type 2 (Th2) cells. We investigated single- and multiple-ascending doses of RPT193 in healthy subjects, and multiple doses of RPT193 in subjects with moderate-to-severe atopic dermatitis (AD). METHODS: This was a first-in-human randomized, placebo-controlled Phase 1a/1b monotherapy study (NCT04271514) to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and CCR4 surface receptor occupancy in eligible healthy subjects and subjects with moderate-to-severe AD. Clinical efficacy and skin biomarker effects of RPT193 monotherapy were assessed as exploratory endpoints in AD subjects. RESULTS: In healthy (n = 72) and AD subjects (n = 31), once-daily RPT193 treatment was generally well tolerated, with no serious adverse events reported and all treatment-emergent adverse events reported as mild/moderate. In AD subjects, numerically greater improvements in clinical efficacy endpoints were observed with RPT193 monotherapy versus placebo up to the end of the treatment period (Day 29), with statistically significant improvement, compared to Day 29 and placebo, observed 2 weeks after the end of treatment (Day 43) on several endpoints (p < .05). Moreover, significant changes in the transcriptional profile were seen in skin biopsies of RPT193-treated versus placebo-treated subjects at Day 29, which were also significantly correlated with improvements in clinical efficacy measures. CONCLUSIONS: To our knowledge, this is the first clinical study with an oral CCR4 antagonist that showed clinical improvement coupled with modulation of the cutaneous transcriptomic profile in an inflammatory skin disease.

DMT310, a novel once-weekly topical treatment for patients with moderate-to-severe acne vulgaris: Results of a phase 2b randomized, double-blind, placebo-controlled trial.

BACKGROUND: Poor patient adherence with antiacne medications is a common clinical challenge. DMT310, a natural, topical product with a once-weekly application schedule, may alleviate this obstacle. OBJECTIVE: Evaluate the safety, tolerability, and efficacy of DMT310 in treating moderate-to-severe acne. METHODS: This 12-week, randomized, double-blind, placebo-controlled, multicenter clinical trial enrolled participants 12 years and older with moderate-to-severe acne. RESULTS: The intent-to-treat population included a total of 181 participants (DMT310, N = 91; placebo, N = 90). Participants who received DMT310 vs participants treated with placebo demonstrated a statistically significant greater reduction in the number of inflammatory and noninflammatory lesions at all time points: inflammatory lesion counts at week 12 (-15.64 vs -10.84, P < .001); noninflammatory lesion counts at week 12 (-18.26 vs -12.41, P < .001). DMT310-treated participants also had higher rates of Investigator's Global Assessment treatment success than participants in the placebo group at all time points: Investigator's Global Assessment at week 12 (44.40% vs 17.78%; P < .001). No serious treatment related adverse events occurred. CONCLUSIONS: DMT310 once-weekly topical treatment significantly reduced both inflammatory and noninflammatory lesions and yielded a greater proportion of Investigator's Global Assessment treatment success at all time points in participants with moderate-to-severe acne.

Once-daily roflumilast foam 0.3% for scalp and body psoriasis: a randomized, double-blind, vehicle-controlled phase IIb study.

BACKGROUND: Scalp psoriasis affects most patients with psoriasis, but it can be difficult to treat. OBJECTIVES: To evaluate the efficacy and safety of once-daily roflumilast foam 0.3% on scalp and body psoriasis. METHODS: In a phase IIb randomized controlled trial, adults and adolescents aged ≥ 12 years with scalp and body psoriasis were randomized (2 : 1) to roflumilast foam 0.3% or vehicle for 8 weeks. The primary efficacy endpoint was scalp Investigator Global Assessment (S-IGA) success (score of 'clear' or 'almost clear' plus ≥ 2-grade improvement from baseline) at week 8. Safety and tolerability were also evaluated. RESULTS: Significantly more roflumilast-treated patients (59.1%) than vehicle-treated patients (11.4%) achieved S-IGA success at week 8 (P < 0.001); differences favoured roflumilast as early as the first postbaseline visit at week 2 (P < 0.001). Significant improvements were also seen for secondary endpoints, including body IGA success, Scalp Itch Numeric Rating Scale and the Psoriasis Scalp Severity Index. The safety of roflumilast was generally similar to vehicle. Patients treated with roflumilast experienced low rates of treatment-emergent adverse events (AEs), with few discontinuations due to an AE. Few patients with skin of colour (11%) and few adolescents (0.7%) were included. CONCLUSIONS: The results support the further development of roflumilast foam for treating scalp and body psoriasis.

Efficacy of Roflumilast Foam, 0.3%, in Patients With Seborrheic Dermatitis: A Double-blind, Vehicle-Controlled Phase 2a Randomized Clinical Trial.

Importance: Current topical treatment options for seborrheic dermatitis are limited by efficacy and/or safety. Objective: To assess safety and efficacy of roflumilast foam, 0.3%, in adult patients with seborrheic dermatitis affecting the scalp, face, and/or trunk. Design, Setting, and Participants: This multicenter (24 sites in the US and Canada) phase 2a, parallel group, double-blind, vehicle-controlled clinical trial was conducted between November 12, 2019, and August 21, 2020. Participants were adult (aged ≥18 years) patients with a clinical diagnosis of seborrheic dermatitis for a 3-month or longer duration and Investigator Global Assessment (IGA) score of 3 or greater (at least moderate), affecting 20% or less body surface area, including scalp, face, trunk, and/or intertriginous areas. Data analysis was performed from September to October 2020. Interventions: Once-daily roflumilast foam, 0.3% (n = 154), or vehicle foam (n = 72) for 8 weeks. Main Outcomes and Measures: The main outcome was IGA success, defined as achievement of IGA score of clear or almost clear plus 2-grade improvement from baseline, at week 8. Secondary outcomes included IGA success at weeks 2 and 4; achievement of erythema score of 0 or 1 plus 2-grade improvement from baseline at weeks 2, 4, and 8; achievement of scaling score of 0 or 1 plus 2-grade improvement from baseline at weeks 2, 4, and 8; change in Worst Itch Numeric Rating Scale (WI-NRS) score from baseline; and WI-NRS success, defined as achievement of 4-point or greater WI-NRS score improvement in patients with baseline WI-NRS score of 4 or greater. Safety and tolerability were also assessed. Results: A total of 226 patients (mean [SD] age, 44.9 [16.8] years; 116 men, 110 women) were randomized to roflumilast foam (n = 154) or vehicle foam (n = 72). At week 8, 104 (73.8%) roflumilast-treated patients achieved IGA success compared with 27 (40.9%) in the vehicle group (P < .001). Roflumilast-treated patients had statistically significantly higher rates of IGA success vs vehicle at week 2, the first time point assessed. Mean (SD) reductions (improvements) on the WI-NRS at week 8 were 59.3% (52.5%) vs 36.6% (42.2%) in the roflumilast and vehicle groups, respectively (P < .001). Roflumilast was well tolerated, with the rate of adverse events similar to that of the vehicle foam. Conclusions and Relevance: The results from this phase 2a randomized clinical trial of once-daily roflumilast foam, 0.3%, demonstrated favorable efficacy, safety, and local tolerability in the treatment of erythema, scaling, and itch caused by seborrheic dermatitis, supporting further investigation as a nonsteroidal topical treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT04091646.

Tapinarof Cream 1% for Extensive Plaque Psoriasis: A Maximal Use Trial on Safety, Tolerability, and Pharmacokinetics.

BACKGROUND: Tapinarof is a novel topical therapeutic aryl hydrocarbon receptor modulating agent in development for the treatment of psoriasis and atopic dermatitis. OBJECTIVE: This multicenter, open-label trial assessed the safety, tolerability, pharmacokinetics (PK), and efficacy of tapinarof cream 1% once daily (QD) under maximal use conditions in extensive plaque psoriasis. METHODS: Adults with a baseline Physician Global Assessment (PGA) score of ≥ 3 and body surface area (BSA) involvement ≥ 20% received tapinarof cream 1% QD for 29 days. Safety and tolerability assessments included adverse events (AEs) and local tolerability scales. PK parameters were calculated using non-compartmental analysis. Efficacy assessments included change in PGA, Psoriasis Area and Severity Index score, and %BSA affected. RESULTS: Twenty-one patients were enrolled. Common AEs were folliculitis, headache, back pain, and pruritus (none led to discontinuation). Tapinarof plasma exposure was low, with the majority of concentrations being below detectable limits. At day 29, 14 patients (73.7%) had a ≥ 1-grade improvement in PGA score and six patients (31.6%) had a ≥ 2-grade improvement; four patients (21.1%) achieved treatment success (PGA 0 or 1 and ≥ 2-grade improvement). CONCLUSION: Tapinarof cream 1% QD was well tolerated, with limited systemic exposure and significant efficacy at 4 weeks in patients with extensive plaque psoriasis. ClinicalTrials.gov Identifier NCT04042103.

Clinical Pharmacokinetics and Safety of a 10% Aminolevulinic Acid Hydrochloride Nanoemulsion Gel (BF-200 ALA) in Photodynamic Therapy of Patients Extensively Affected With Actinic Keratosis: Results of 2 Maximal Usage Pharmacokinetic Trials.

The nanoemulsion-based 10% aminolevulinic acid (ALA) hydrochloride gel BF-200 ALA optimizes epidermal penetration of its active ingredient and is approved for topical photodynamic therapy (PDT) for the treatment of actinic keratosis in the United States and Europe. To characterize systemic absorption from dermal application during PDT, ALA and its key active metabolite protoporphyrin IX (PpIX) were analyzed in 2 maximal usage pharmacokinetic trials (MUsT) in patients severely affected with actinic keratosis. The primary objective of both MUsTs was to assess baseline-adjusted plasma concentration-time curves for ALA and PpIX after a single PDT treatment applying either 2 g (1 tube) of BF-200 ALA on the face (MUsT-1) or applying 6 g (3 tubes) of BF-200 ALA on the face/scalp or body periphery (MUsT-2), to 20 or 60 cm2 , respectively. All PDTs were performed using red light at around 635 nm wavelength. Safety and tolerability were documented along with pharmacokinetics. In both MUsTs, ALA plasma concentrations were transiently increased to a maximum concentration at about 2.5 to 3.3 times above endogenous baseline with time to maximum concentration at ≈3 hours after dosing. Plasma levels subsequently returned to baseline within 10 hours after dosing. Overall baseline-adjusted mean area under the baseline-adjusted plasma concentration-time curve from time zero to the last sampling time point at which the concentration was at or above the lower limit of quantification ranged from 142.8 to 146.2, indicating that a similar, minor fraction of topical ALA is systemically absorbed under both dosing regimens. Systemic PpIX exposure after administration of either dose of BF-200 ALA was equally minimal. Application site skin reactions were treatment area size-related, albeit transient and consistent with the known safety profile of BF-200 ALA.

Setipiprant for Androgenetic Alopecia in Males: Results from a Randomized, Double-Blind, Placebo-Controlled Phase 2a Trial.

PURPOSE: To evaluate oral setipiprant versus placebo for scalp hair growth in men with androgenetic alopecia (AGA). PATIENTS AND METHODS: Males aged 18 to 49 years with AGA were enrolled in a double-blind, multicenter, 32-week, phase 2a trial; randomized to twice-daily (BID) 1000-mg (2×500 mg for a total daily dose of 2000 mg) setipiprant tablets or placebo for 24 weeks; and assessed at weeks 4, 8, 16, and 24, with a week 32 follow-up. The study initially included a finasteride 1-mg once-daily group, removed by protocol amendment. Changes from baseline to week 24 in target area hair count (TAHC) and blinded Subject Self-Assessment (SSA) of target area photographs were coprimary efficacy endpoints. Hair growth was also evaluated using blinded Investigator Global Assessment (IGA). Safety assessments included adverse events (AEs) and clinical laboratory tests. Analysis of covariance models were used to test statistical significance for TAHC, SSA, and IGA. Data were summarized without statistical analysis for finasteride. RESULTS: Randomized subjects (N=169) included 74 placebo, 83 setipiprant, and 12 finasteride subjects; 117 (69.2%) and 113 (66.9%) subjects completed week 24 and 32 visits, respectively. Treatment groups had similar baseline characteristics. Neither coprimary efficacy endpoint was met. At week 24, TAHC and SSA findings indicated no hair growth improvements with setipiprant versus placebo. Setipiprant also did not improve hair growth versus placebo per the IGA. Treatment-related AEs, all mild or moderate in severity, occurred in 12.3%, 25.9%, and 25.0% of the placebo, setipiprant, and finasteride groups, respectively. Two treatment-emergent serious AEs (TESAEs), cellulitis and multiple sclerosis, were reported in the placebo group, both unrelated to treatment. No TESAEs were reported with setipiprant or finasteride. CONCLUSION: Setipiprant 1000 mg BID was safe and well tolerated but did not demonstrate efficacy versus placebo for scalp hair growth in men with AGA.

Assessing Patients' Satisfaction With Hydrogen Peroxide Topical Solution, 40% for Treatment of Raised Seborrheic Keratoses.

OBJECTIVES: Assess participants’ satisfaction following treatment with a proprietary hydrogen peroxide topical solution 40%, w/w (HP40) for raised seborrheic keratoses (SKs). METHODS: In this Phase 4, open-label study, eligible participants aged 30–75 years had clinically typical raised SKs including 2 target SKs (Physician’s Lesion Assessment™ [PLA] grade of ≥2 [0 = clear; 1 = near clear; 2 = thin (≤1 mm); 3 = thick (>1 mm)]; 5–15 mm diameter) on the face and 1 target SK on the neck or décolletage. SKs received HP40 treatment on day 1. All SKs with PLA grade ≥1 were retreated on days 15 and 29. Endpoints included patients’ satisfaction with their skin’s appearance at day 113, relationships between patients’ satisfaction and lesion PLA grade (evaluated by chi-square test), and patients’ satisfaction with their treatment experience. RESULTS: Forty-one patients (mean [range] age, 62.4 [46–73] years) completed the study. 95% of patients were at least moderately satisfied with their skin’s appearance and 90.2% of target lesions were clear. A statistically significant association was observed between the number of target lesions achieving clearance and patients’ satisfaction with skin appearance level (χ2=22.03; P=0.001). 93% of patients were at least moderately satisfied with their HP40 treatment experience. Eight patients experienced treatment-emergent adverse events (TEAEs), most of which were mild or moderate; 4 experienced TEAEs considered treatment-related. CONCLUSIONS: Most patients with SKs on the face, neck, and décolletage were satisfied or very satisfied with both their skin’s appearance and their treatment experience following HP40 treatment. These results support the use of HP40 for raised SKs. J Drugs Dermatol. 2020;19(12): doi:10.36849/JDD.2020.4974.

Tirbanibulin Ointment 1% as a Novel Treatment for Actinic Keratosis: Phase 1 and 2 Results.

BACKGROUND: Current field-directed treatments of actinic keratosis (AK), a pre-malignant condition, are often limited by severe local reactions and/or complex treatment. Tirbanibulin, a novel potent anti-proliferative synthetic agent that inhibits tubulin polymerization and Src kinase signalling, is being developed as a convenient, safe, and effective field treatment of actinic keratosis. HYPOTHESIS: A short course of tirbanibulin ointment 1% safely reduces AK lesions. METHODS: In the Phase 1 study, 4 treatment cohorts with forearm lesions received tirbanibulin ointment 1% over 25 or 100 cm2 once daily for 3 or 5 days and were evaluated through day 45. In the Phase 2 study, 2 treatment cohorts with face or scalp lesions received tirbanibulin ointment 1% once daily for 3 or 5 days over 25 cm2 and were evaluated through day 57. Lesion reductions, clearance rates, safety, and pharmacokinetics were assessed. RESULTS: Forearm AK lesions were reduced by day 45 in all Phase 1 cohorts (N=30). Complete AK clearance at day 57 for face/scalp AK lesions in Phase 2 cohorts (N=168) was demonstrated in 43% and 32% of participants of the 5-day and 3-day cohorts, respectively. Adverse reactions were mainly transient mild local erythema and flaking/scaling, pruritus, and pain. Tirbanibulin plasma concentrations were low or undetectable. CONCLUSION: Tirbanibulin ointment 1% was well tolerated and active in AK reduction. Based on activity, the 5-day regimen was selected for Phase 3 development. Clinicaltrials.gov: NCT02337205; NCT02838628 J Drugs Dermatol. 2020;19(11):1093-1100. doi:10.36849/JDD.2020.5576THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

Subject Satisfaction with Trifarotene 50 µg/g Cream in the Treatment of Facial and Truncal Acne Vulgaris: A Case Series.

There is a paucity of literature covering patient-reported outcomes of treatments for truncal acne. Trifarotene 50 µg/g cream is a novel retinoid molecule approved for once-daily topical treatment of facial and truncal acne vulgaris. As physicians are starting to gain real-world experience with this retinoid treatment, their access to reporting from the patient's perspective provides a valuable adjunct to the pivotal studies. We report a case series of three subjects with moderate facial and truncal acne treated with trifarotene 50 µg/g cream on the face, shoulders, upper back and upper anterior chest for 12 weeks and evaluated by satisfaction questionnaires. This case series illustrating the treatment of facial and truncal acne with trifarotene 50 µg/g cream, in the form of real-world data, describes high overall satisfaction and excellent tolerability to support the use of this new retinoid molecule in the treatment of acne vulgaris on both the face and trunk.

Efficacy and safety of topical sofpironium bromide gel for the treatment of axillary hyperhidrosis: A phase II, randomized, controlled, double-blinded trial.

BACKGROUND: Primary axillary hyperhidrosis has limited noninvasive, effective, and well-tolerated treatment options. OBJECTIVE: To evaluate the topical treatment of axillary hyperhidrosis with the novel anticholinergic sofpironium bromide. METHODS: A phase II, multicenter, randomized, controlled, double-blinded study. Participants were randomized to 1 of 3 dosages or vehicle, with daily treatment for 42 days. Coprimary end points were the percentage of participants exhibiting ≥1-point improvement in the Hyperhidrosis Disease Severity Measure-Axillary (HDSM-Ax) score by logistic regression, and change in HDSM-Ax as a continuous measure by analysis of covariance. Pair-wise comparisons were 1-sided with α = 0.10. RESULTS: At the end of therapy, 70%, 79%, 76%, and 54% of participants in the 5%, 10%, 15%, and vehicle groups exhibited ≥1-point improvement in HDSM-Ax (P < .05). Least-square mean (SE) changes in HDSM-Ax were -2.02 (0.14), -2.09 (0.14), 2.10 (0.14), and -1.30 (0.14) (all P ≤ .0001). Most treatment-related adverse events were mild or moderate. LIMITATIONS: Not powered to detect changes in gravimetric sweat production. CONCLUSION: Sofpironium bromide gel produced meaningful reductions in hyperhidrosis severity and had an acceptable safety profile.

Patient-Reported Outcomes in Acne Patients With Skin of Color Using Adapalene 0.3%-Benzoyl Peroxide 2.5%: A Prospective Real-World Study

Background: Patients with skin of color (SOC) and Fitzpatrick skin types (FST) IV­VI frequently develop acne. Objective: Evaluate subject-reported outcomes after treatment with adapalene 0.3%/ benzoyl peroxide 2.5% gel (0.3% A/BPO) in subjects with SOC and moderate to severe acne vulgaris. Methods: This was an open-label interventional study conducted in 3 countries (Mauritius, Singapore, and USA) in subjects of Asian, Latin-American, or black/African-American ethnicity, with an Investigator's Global Assessment (IGA) of moderate or severe facial acne (enrollment 2:1), and FST IV to VI. For 16 weeks, subjects applied 0.3% A/BPO (once daily) and utilized a skin care regimen (oil control foam wash and oil control moisturizer SPF30). Assessments included quality of life (QoL) and subject questionnaires, IGA, Investigator's Global Assessment of Improvement (GAI), postinflammatory hyperpigmentation (PIH; if present at baseline), and safety. Results: Fifty subjects were enrolled: 20 Asians, 17 black/African-Americans, and 13 Latin-Americans. Most had FST IV (74%) or V (22%), with moderate (70%; IGA 3) or severe (30%; IGA 4) acne. At week 16, 77% of subjects were satisfied or very satisfied with treatment, 56% of subjects had an IGA of 0 or 1 (clear/almost clear), and 87% had a good to excellent improvement in GAI. QoL improved throughout the study for all subjects; subject selection of "no effect at all" of acne on QoL increased from 16% of subjects at baseline to 55% at week 16. Of those with baseline PIH (60%), all were rated very mild to moderate. By week 16, the majority (75%) had no or very mild PIH, and the mean decrease in PIH was 27%. There were no adverse events leading to study discontinuation. Conclusion: Patients with SOC and moderate or severe facial acne reported high satisfaction with 0.3% A/BPO treatment and experienced good tolerability, improved QoL, treatment efficacy, and improvement in PIH. Clinicaltrials.gov number: NCT02932267 J Drugs Dermatol. 2019;18(6):514-520.

Topical Oxymetazoline Cream 1.0% for Persistent Facial Erythema Associated With Rosacea: Pooled Analysis of the Two Phase 3, 29-Day, Randomized, Controlled REVEAL Trials

Background: Rosacea is a chronic dermatologic condition with limited treatment options. Methods: Data were pooled from two identically designed phase 3 trials. Patients with moderate to severe persistent erythema of rosacea were randomized to receive oxymetazoline cream 1.0% or vehicle once daily for 29 days and were followed for 28 days posttreatment. The primary efficacy outcome was the proportion of patients with ≥2-grade improvement from baseline on both Clinician Erythema Assessment (CEA) and Subject Self-Assessment (SSA) at 3, 6, 9, and 12 hours postdose, day 29. Results: The pooled population included 885 patients (78.8% female); 85.8% and 91.2% had moderate erythema based on CEA and SSA, respectively. The primary outcome was achieved by significantly more patients in the oxymetazoline than vehicle group (P<0.001). Individual CEA and SSA scores and reduction in facial erythema (digital image analysis) favored oxymetazoline over vehicle (P<0.001). The incidence of treatment-emergent adverse events was low (oxymetazoline, 16.4%; vehicle, 11.8%). No clinically relevant erythema worsening (based on CEA and SSA) was observed during the 28-day posttreatment follow-up period (oxymetazoline, 1.7%; vehicle, 0.6%). Conclusion: Oxymetazoline effectively reduced moderate to severe persistent facial erythema of rosacea and was well tolerated. J Drugs Dermatol. 2018;17(11):1201-1208.

Phase 2 Randomized, Dose-Ranging Study of Oxymetazoline Cream for Treatment of Persistent Facial Erythema Associated With Rosacea.

BACKGROUND: Rosacea is a chronic dermatologic condition with limited treatment options. OBJECTIVE: This phase 2 study evaluated the optimal oxymetazoline dosing regimen in patients with moderate to severe persistent facial erythema of rosacea. METHODS: Patients were randomly assigned to oxymetazoline cream, 0.5%, 1.0%, or 1.5%, or vehicle, administered once daily (QD) or twice daily (BID) for 28 consecutive days. The primary efficacy endpoint was the proportion of patients with ≥2-grade improvement from baseline on the Clinician Erythema Assessment (CEA) and the Subject Self-Assessment of erythema (SSA-1) on day 28. Safety assessments included treatment-emergent adverse events and dermal tolerability. RESULTS: A total of 356 patients were treated (mean age, 50.0 years; 80.1% female). The proportions of patients achieving the primary endpoint were significantly higher with oxymetazoline 0.5% QD (P=0.049), 1.0% QD (P=0.006), 1.5% QD (P=0.012), 1.0% BID (P=0.021), and 1.5% BID (P=0.006) versus their respective vehicles. For both QD and BID dosing, the efficacy of oxymetazoline 1.0% was greater than the 0.5% dose and comparable to the 1.5% dose. Safety and application-site tolerability were similar across groups. LIMITATIONS: Short-term treatment period. CONCLUSION: Oxymetazoline 1.0% QD provided the optimal dosing regimen and was selected for evaluation in phase 3 clinical studies. J Drugs Dermatol. 2018;17(3):308-316.

Clinical Pharmacokinetics of Oxymetazoline Cream Following Topical Facial Administration for the Treatment of Erythema Associated With Rosacea.

BACKGROUND: Oxymetazoline cream 1.0% is FDA-approved for the topical treatment of persistent facial erythema associated with rosacea in adults. This phase 2, multicenter, randomized, double-blind, parallel-group study assessed the pharmacokinetics, safety, and tolerability of oxymetazoline in patients with moderate to severe erythema associated with rosacea. METHODS: Eligible patients were randomized to 1 of 8 treatment groups (oxymetazoline cream 0.5%, 1.0%, or 1.5% or vehicle applied topically either once or twice daily for 28 days). Pharmacokinetic analyses were conducted in patients receiving oxymetazoline. Plasma samples for pharmacokinetic assessments were collected prior to dosing and 6 times postdose on days 1 and 28. RESULTS: A total of 356 patients were included in the safety population (oxymetazoline, n=268; vehicle, n=88). Thirty patients (11.2%) in the oxymetazoline group reported treatment-related treatment-emergent adverse events, most of which were mild to moderate application-site reactions. Oxymetazoline, at all concentrations, was generally safe and well tolerated. Mean maximum observed plasma concentrations were ≤115 pg/mL across all groups; the highest mean values for area under the plasma concentration-time curve from time 0 to 24 hours following once- and twice-daily administration of oxymetazoline 1.5% were 1680 pg•h/mL and 2660 pg•h/mL, respectively. Systemic exposure to oxymetazoline increased dose proportionally with once- and twice-daily administration. CONCLUSION: These findings support the use of oxymetazoline for the treatment of persistent facial erythema associated with rosacea. J Drugs Dermatol. 2018;17(2):213-220.

WITHDRAWN: Efficacy and safety of topical oxymetazoline cream 1.0% for treatment of persistent facial erythema associated with rosacea: findings from the 2 phase 3, 29-day, randomized, controlled REVEAL trials.

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Pivotal Trial of the Efficacy and Safety of Oxymetazoline Cream 1.0% for the Treatment of Persistent Facial Erythema Associated With Rosacea: Findings from the First REVEAL Trial.

An unmet need exists for a safe, tolerable, effective treatment for moderate to severe persistent facial erythema in patients with rosacea. This pivotal phase 3, multicenter, double-blind study evaluated the efficacy and safety of topical oxymetazoline in patients with facial erythema associated with moderate to severe rosacea. Patients were randomly assigned to treatment with oxymetazoline hydrochloride cream 1.0% or vehicle applied once daily for 29 days, and were followed for 28 days posttreatment. The primary efficacy outcome was having at least a 2-grade decrease from baseline on both the Clinician Erythema Assessment (CEA) and the Subject Self-Assessment for rosacea facial redness (SSA) scales (composite success) at 3, 6, 9, and 12 hours postdose on day 29. Safety assessments included treatment-emergent adverse events (TEAEs) and posttreatment worsening of erythema (composite CEA/SSA increase of 1-grade severity from baseline; rebound effect). A total of 440 patients (mean age, 49.5 years; 78.9% females) were randomized (oxymetazoline, n=222; vehicle, n=218); most had moderate erythema. On day 29, significantly greater proportions of oxymetazoline recipients achieved the primary efficacy outcome at each time point (P less than 0.02) and overall (P less than 0.001) compared with vehicle recipients. The incidence of discontinuation due to TEAEs was low in both groups (oxymetazoline group, 1.8%; vehicle group, 0.5%). The most common TEAEs reported during the entire study period were application-site dermatitis, application-site erythema, and headache in the oxymetazoline group (1.4% each), and headache (0.9%) in the vehicle group. Following cessation of treatment, low proportions of patients experienced rebound effect (oxymetazoline group, 2.2%; vehicle group, 1.1%). Oxymetazoline applied to the face once daily for 29 days was effective, safe, and well tolerated in patients with moderate to severe persistent facial erythema of rosacea.

J Drugs Dermatol. 2018;17(1):97-105.

A-101, a Proprietary Topical Formulation of High-Concentration Hydrogen Peroxide Solution: A Randomized, Double-Blind, Vehicle-Controlled, Parallel Group Study of the Dose-Response Profile in Subjects With Seborrheic Keratosis of the Face.

BACKGROUND: Seborrheic keratosis (SK) is a common benign skin tumor, yet no topical treatments are approved in the United States. OBJECTIVE: To evaluate the proprietary, stabilized, high-concentration hydrogen peroxide-based topical solution A-101 (32.5% and 40% concentrations) for treatment of facial SK lesions. MATERIALS AND METHODS: In this multicenter, double-blind, vehicle-controlled study, eligible subjects were randomly assigned to receive up to 2 treatments of A-101 40%, A-101 32.5%, or vehicle solution applied to a single facial SK lesion. The primary efficacy assessment was the Physician's Lesion Assessment (PLA), a validated 4-ordinal scale. RESULTS: The primary end point, the mean reduction in PLA grade from baseline to Day 106 was 1.7 for A-101 40%, 1.4 for A-101 32.5%, and 0.1 for vehicle (p < .001, both concentrations vs vehicle). Lesions for 68%, 62%, and 5% of subjects, respectively, were judged to be clear or near clear (p < .001, both concentrations vs vehicle). Local skin reactions were predominantly mild and transient. No subjects discontinued because of treatment-related adverse events. CONCLUSION: A-101 solution demonstrated efficacy in treating SKs on the face. Greater magnitude of effect was seen with the 40% concentration than the 32.5% concentration. A-101 solution had a favorable safety and tolerability profile at both concentrations.