Vehicle Cream Research Articles

325 Ruxolitinib cream rapidly decreases skin pain in atopic dermatitis

Atopic dermatitis (AD) is an inflammatory skin disease associated with skin pain. Efficacy outcomes, with a focus on skin pain, from a pooled analysis of two phase 3 studies (TRuE-AD1, TRuE-AD2) in 1249 patients (≥12 y) with AD for ≥2 y with Investigator’s Global Assessment (IGA) score 2 or 3 and 3%–20% affected body surface area are reported. Patients were randomized (2:2:1) to twice-daily 0.75% or 1.5% ruxolitinib (RUX; Janus kinase [JAK] 1/JAK2 inhibitor) or vehicle cream for 8 weeks. At Week 8, more patients who applied RUX (0.75%/1.5%) achieved IGA treatment success (IGA of 0/1 and ≥2-grade improvement from baseline) vs vehicle (44.7%/52.6% vs 11.5%; P<0.0001). Significantly greater reductions in itch numerical rate scale (NRS) score were observed within 12 h of first application (mean change from baseline, –0.4/–0.5 vs –0.1; P<0.02). Greater mean reductions from baseline in skin pain NRS scores were observed within 12 h with RUX vs vehicle (−0.3/−0.3 vs −0.04; P<0.03); further reductions were observed over time (Week 8, –2.5/–2.6 vs –1.3; P<0.0001). A substantial proportion of patients who applied RUX achieved ‘no pain/discomfort’ per EQ-5D-5L (fourth dimension) at Week 2 (57.8%/61.8% vs 36.3%), which was sustained through Week 8 (67.0%/69.4% vs 42.8%). In summary, RUX cream significantly decreased inflammation, itch, and skin pain in patients with AD.

313 Itch-free state in patients with atopic dermatitis treated with ruxolitinib cream

Atopic dermatitis (AD) is a highly pruritic, inflammatory skin disease. In two phase 3 studies (TRuE-AD1, TRuE-AD2), 1249 patients (≥12 y) with AD for ≥2 y, an Investigator’s Global Assessment (IGA) score of 2 or 3, and 3%–20% affected body surface area were randomized (2:2:1) to twice-daily 0.75% or 1.5% ruxolitinib (RUX) cream (Janus kinase [JAK] 1/JAK2 inhibitor) or vehicle cream for 8 weeks. In this pooled analysis, effects of RUX on itch were assessed by the proportion of patients achieving an itch Numerical Rating Scale score of 0 or 1 (NRS 0/1) and no days of itch per Item 1 (frequency of itch) of the Patient-Oriented Eczema Measure (POEM). At Week 8, more patients who applied RUX (0.75%/1.5%) vs vehicle achieved NRS 0/1 (45.5%/51.5% vs 23.1%; P<0.0001); median time to NRS 0/1 was significantly shorter with RUX vs vehicle (12/8 days vs 51 days; P<0.0001). More patients achieved no days of itch per POEM with RUX (28.3%/32.9%) vs vehicle (9.0%; both P<0.0001). As assessed by NRS 0/1 or POEM, more patients achieved itch-free status at Week 8 with RUX vs vehicle (47.7%/52.0% vs 23.4%; both P<0.0001) regardless of baseline itch score (NRS <6: 57.4%/58.1% vs 27.5%, P<0.0001; NRS ≥6: 34.2%/41.3% vs 17.7%, P<0.01). In summary, a significant number of patients with AD treated with RUX cream achieved and sustained an itch-free state.

311 Effects of ruxolitinib cream in patients with atopic dermatitis with head and/or neck involvement

Atopic dermatitis (AD) often involves the head and/or neck (HN). In two phase 3 studies (TRuE-AD1, TRuE-AD2), 1249 patients (≥12 y) with AD for ≥2 y, an Investigator’s Global Assessment (IGA) score of 2/3, and 3%–20% affected body surface area were randomized (2:2:1) to twice-daily 0.75% or 1.5% ruxolitinib (RUX) cream (Janus kinase [JAK] 1/JAK2 inhibitor) or vehicle cream for 8 weeks of double-blind treatment. In this analysis, pooled efficacy at Week 8 was assessed by the proportion of patients achieving IGA treatment success (IGA of 0/1 and ≥2-grade improvement from baseline), ≥75% improvement in Eczema Area and Severity Index (EASI-75) vs baseline, and ≥4-point improvement in itch Numerical Rating Scale score (NRS4) in patients who had HN involvement at baseline (n=696 [55.7% of randomized patients]); data in the overall population (OP) were also included.

Phase 3 Trials of Tirbanibulin Ointment for Actinic Keratosis

BackgroundThe tubulin polymerization and Src kinase signaling inhibitor tirbanibulin is being investigated as a topical treatment for actinic keratosis, a precursor of squamous-cell carcinoma.MethodsIn two identically designed double-blind trials, we randomly assigned, in a 1:1 ratio, adults with actinic keratoses on the face or scalp to receive either topical tirbanibulin or vehicle (placebo) ointment. The ointment was applied by the patients to a 25-cm2 contiguous area containing four to eight lesions once daily for 5 consecutive days. The primary outcome was the percentage of patients with a complete (100%) reduction in the number of lesions in the application area at day 57. The secondary outcome was the percentage of patients with a partial (≥75%) reduction in the number of lesions within the application area at day 57. The incidence of recurrence was evaluated at 1 year. Local reactions were scored with the use of 4-point scale (ranging from 0 [absent] to 3 [severe]).ResultsA total of 702 patients were enrolled in the two trials (351 patients per trial). Complete clearance in trial 1 occurred in 44% of the patients (77 of 175) in the tirbanibulin group and in 5% of those (8 of 176) in the vehicle group (difference, 40 percentage points; 95% confidence interval [CI], 32 to 47; P<0.001); in trial 2, the percentages were 54% (97 of 178 patients) and 13% (22 of 173), respectively (difference, 42 percentage points; 95% CI, 33 to 51; P<0.001). The percentages of patients with partial clearance were significantly higher in the tirbanibulin groups than in the vehicle groups. At 1 year, the estimated percentage of patients with recurrent lesions was 47% among patients who had had a complete response to tirbanibulin. The most common local reactions to tirbanibulin were erythema in 91% of the patients and flaking or scaling in 82%. Adverse events with tirbanibulin were application-site pain in 10% of the patients and pruritus in 9%, all of which resolved.ConclusionsIn two identically designed trials, tirbanibulin 1% ointment applied once daily for 5 days was superior to vehicle for the treatment of actinic keratosis at 2 months but was associated with transient local reactions and recurrence of lesions at 1 year. Trials comparing tirbanibulin with conventional treatments and that have longer follow-up are needed to determine the effects of tirbanibulin therapy on actinic keratosis. (Funded by Athenex; ClinicalTrials.gov numbers, NCT03285477 and NCT03285490.)

Effect of Gentamicin Ointment in Patients with Nagashima-type Palmoplantar Keratosis: A Double-blind Vehicle-controlled Study.

Gentamicin ointment has potential in the treatment of Nagashima-type palmoplantar keratosis. However, there is a lack of reliable study data. The aim of this study was to perform a prospective, randomized, double-blinded, contralateral, vehicle-controlled clinical trial. A total of 20 subjects diagnosed with Nagashima-type palmoplantar keratosis by genetic test, who carried nonsense mutations, enrolled in the 30-day study. Gentamicin ointment was applied to the hand and foot on one side of the body, and vehicle ointment was applied to the hand and foot on the other side. The choice of hand and foot in each subject was randomly allocated. The severity of the patient’s skin lesions and quality of life were assessed by a blinded evaluator, using the Dermatology Life Quality Index, visual analogue scale scores and digital photography. Gentamicin ointment treatment resulted in a significant improvement in symptoms of hyperkeratosis and foul smell compared with vehicle. No difference was found in the effect on erythema between gentamicin and vehicle. In conclusion, gentamicin ointment demonstrated positive responses and good tolerance in treating Nagashima-type palmoplantar keratosis caused by nonsense mutations.

Evaluation of the Effect of Topical Artemisia dracunculus Administration on Serum Levels of Selected Interleukins and Spleen Index in Imiquimod-Induced Psoriasis in Male Mice Compared to Clobetasol Propionate (Dermovate (R)) Ointment

Psoriasis is a long-lasting autoimmune disease that is characterized by swollen skin patches. Normally, these skin patches are dark, swollen, itchy and scaly. The single application of the innate TLR7/8 ligand Imiquimod (IMQ) in mice easily induces a dermatitis that closely resembles human psoriasis, critically dependent on the axis of IL-23/IL-17. Artemisia dracunculus prepared as an ointment and has been used topically to mice before imiquimod application. The results of the current study showed that A. dracunculus ointment can significantly reduce psoriasis area and severity index in (A. dracunculus ointment + imiquimod group as compared with both control group and (vehicle ointment + imiquimod) group.

Randomized controlled study for the anti-aging effect of human adipocyte-derived mesenchymal stem cell media combined with niacinamide after laser therapy.

Recent advancements in laser-assisted drug delivery have emphasized the importance of post-laser use of active ingredients. We evaluated the effect of topical post-laser treatment with adipocyte-derived stem cell-containing medium (ADSC-CM) in combination with niacinamide through a double-blind, randomized, vehicle-controlled study. Twenty-five patients with aging skin underwent ablative fractional laser (AFL) treatment on both sides of the face for skin rejuvenation. Moisturizers with or without ADSC-CM plus 2% niacinamide was applied to the designated sides of faces for 3weeks. The wrinkle and the melanin indices were assessed using a specialized digital photography analyzer. Additional in vitro assays were performed. The wrinkle index, melanin index, patient satisfaction score, and the investigator's global esthetic improvement scale (GAIS) after use of ADSC-CM plus niacinamide were significantly higher than after use of the vehicle cream. The in vitro UVB irradiation assays with human keratinocytes showed decreased levels of pro-inflammatory cytokines upon incubation with ADSC-CM plus niacinamide, and the cell scratch assay displayed decreased MMP-1 and MMP-2 expression as well as increased Type 1 collagen expression. We demonstrated that post-laser topical application of ADSC-CM in combination with niacinamide has anti-aging effect on skin.

Red Deer Umbilical Cord-Derived Stem Cell Conditioned Media Combined With Ablative Resurfacing of the Face.

Laser resurfacing is the gold standard procedure for photodamage, but is not without downtime and risk. Use of periprocedural products containing stem cell conditioned media may improve results and optimize healing. This was a prospective, randomized controlled, double-blind study, evaluating the efficacy and tolerability of red deer umbilical cord-derived stem cell conditioned media (USCCM) cream and serum pre- and post- ablative facial resurfacing. Twenty patients with moderate to severe photodamage were randomized to receive vehicle or USCCM cream and serum pre- and post- ablative resurfacing of the face. Blinded investigators rated healing, tolerability, and efficacy, while subjects rated post-procedure symptoms, tolerability, and satisfaction. Both the active and vehicle pre-procedure cream were soothing, calming and easy to use by all patients. There was a trend towards decreased facial erythema and crusting in the active versus vehicle group. A greater improvement in wrinkling occurred in the active group. The majority of subjects were very satisfied with the active products. There were no serious adverse events. Red deer umbilical cord-derived stem cell conditioned media (USCCM) is well tolerated, safe and efficacious for use pre- and post- facial laser resurfacing.J Drugs Dermatol. 2020;19(11): 1044-1048 doi:10.36849/JDD.2020.5246.

Thermo-Mechanical Fractional Injury Enhances Skin Surface- and Epidermis- Protoporphyrin IX Fluorescence: Comparison of 5-Aminolevulinic Acid in Cream and Gel Vehicles.

Thermo-mechanical fractional injury (TMFI) impacts the skin barrier and may increase cutaneous drug uptake. This study investigated the potential of TMFI in combination with 5-aminolevulinic acid (ALA) cream and gel formulations to enhance Protoporphyrin IX (PpIX) fluorescence at the skin surface and in the skin. In healthy volunteers (n = 12) a total of 144 test areas were demarcated on the upper back. Test areas were randomized to (i) TMFI (6 milliseconds, 400 µm at a single pass) or no pretreatment and (ii) 20% ALA in cream or gel formulations. Skin surface PpIX fluorescence was quantified by PpIX fluorescence photography and photometry in 30-minute intervals until 3 hours. PpIX fluorescence microscopy quantified separate PpIX fluorescence in the epidermis, and in superficial-, mid-, and deep- dermis from punch biopsies sampled after 3 hours of ALA incubation. Local skin reactions (LSR) and pain intensities (numerical rating scale 0-10) were evaluated immediately, at 3 hours and 14 days after the intervention. TMFI exposure before photosensitizer application significantly increased skin surface PpIX fluorescence, both for ALA cream (TMFI-ALA-cream 7848 arbitrary units [AU] vs. ALA-cream 5441 AU, 3 hours, P < 0.001) and ALA gel (TMFI + ALA-gel 4591 AU vs. ALA-gel 3723 AU, 3 hours, P < 0.001). The TMFI-mediated increase in PpIX fluorescence was similar for ALA-cream and -gel formulations (P = 0.470) at the skin surface. In the epidermis, PpIX fluorescence intensities increased from combination treatment with TMFI and ALA-cream (TMFI + ALA-cream 421 AU vs. ALA-cream 293 AU, P = 0.034) but not from combination with TMFI and ALA-gel (TMI + ALA-gel 264 AU vs. ALA-gel 261 AU, P = 0.791). Dermal fluorescence intensities (superficial-, mid-, or deep dermis) were unaffected by TMFI pretreatment in both ALA-cream and ALA-gel exposed skin (P = 0.339). ALA-cream generally induced higher PpIX fluorescence intensities than ALA-gel (skin surface P < 0.001 and epidermis P < 0.03). TMFI induced low pain intensities (median 3) and mild LSR that were resolved at 14 days follow-up. Given the present study design, TMFI, in combination with the standardized application of 20% ALA cream and gel formulations, significantly enhanced skin surface PpIX fluorescence compared to no pretreatment. Additionally, TMFI increased epidermal PpIX fluorescence combined with 20% ALA cream vehicle. Thus, TMFI pretreatment and formulation characteristics exert influence on PpIX fluorescence intensities in normal skin. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Trial of Roflumilast Cream for Chronic Plaque Psoriasis

BackgroundSystemic oral phosphodiesterase type 4 (PDE-4) inhibitors have been effective in the treatment of psoriasis. Roflumilast cream contains a PDE-4 inhibitor that is being investigated for the topical treatment of psoriasis.MethodsIn this phase 2b, double-blind trial, we randomly assigned adults with plaque psoriasis in a 1:1:1 ratio to use roflumilast 0.3% cream, roflumilast 0.15% cream, or vehicle (placebo) cream once daily for 12 weeks. The primary efficacy outcome was the investigator’s global assessment (IGA) of a status of clear or almost clear at week 6 (assessed on a 5-point scale of plaque thickening, scaling, and erythema; a score of 0 indicates clear, 1 almost clear, and 4 severe). Secondary outcomes included an IGA score indicating clear or almost clear plus a 2-grade improvement in the IGA score for the intertriginous area and the change in the Psoriasis Area and Severity Index (PASI) score (range, 0 to 72, with higher scores indicating worse disease). Safety was also assessed.ResultsAmong 331 patients who underwent randomization, 109 were assigned to roflumilast 0.3% cream, 113 to roflumilast 0.15% cream, and 109 to vehicle cream. An IGA score indicating clear or almost clear at week 6 was observed in 28% of the patients in the roflumilast 0.3% group, in 23% in the roflumilast 0.15% group, and in 8% in the vehicle group (P<0.001 and P=0.004 vs. vehicle for roflumilast 0.3% and 0.15%, respectively). Among the approximately 15% of patients overall who had baseline intertriginous psoriasis of at least mild severity, an IGA score at week 6 indicating clear or almost clear plus a 2-grade improvement in the intertriginous-area IGA score occurred in 73% of the patients in the roflumilast 0.3% group, 44% of those in the roflumilast 0.15% group, and 29% of those in the vehicle group. The mean baseline PASI scores were 7.7 in the roflumilast 0.3% group, 8.0 in the roflumilast 0.15% group, and 7.6 in the vehicle group; the mean change from baseline at week 6 was −50.0%, −49.0%, and −17.8%, respectively. Application-site reactions occurred with similar frequency in the roflumilast groups and the vehicle group.ConclusionsRoflumilast cream administered once daily to affected areas of psoriasis was superior to vehicle cream in leading to a state of clear or almost clear at 6 weeks. Longer and larger trials are needed to determine the durability and safety of roflumilast in psoriasis. (Funded by Arcutis Biotherapeutics; ARQ-151 201 ClinicalTrials.gov number, NCT03638258.)

Ruxolitinib cream for treatment of vitiligo: a randomised, controlled, phase 2 trial

Vitiligo is a chronic autoimmune disease resulting in skin depigmentation and reduced quality of life. There is no approved treatment for vitiligo repigmentation and current off-label therapies have limited efficacy, emphasising the need for improved treatment options. We investigated the therapeutic potential of ruxolitinib cream in patients with vitiligo and report the efficacy and safety results up to 52 weeks of double-blind treatment. We did a multicentre, randomised, double-blind, phase 2 study for adult patients with vitiligo in 26 US hospitals and medical centres in 18 states. Patients with depigmentation of 0·5% or more of their facial body surface area (BSA) and 3% or more of their non-facial BSA were randomly assigned (1:1:1:1:1) by use of an interactive response technology system to receive ruxolitinib cream (1·5% twice daily, 1·5% once daily, 0·5% once daily, or 0·15% once daily) or vehicle (control group) twice daily on lesions constituting 20% or less of their total BSA for 24 weeks. Patients in the control group in addition to patients in the 0·15% once daily group who did not show a 25% or higher improvement from baseline in facial Vitiligo Area Scoring Index (F-VASI) at week 24 were re-randomised to one of three higher ruxolitinib cream doses (0·5% once daily, 1·5% once daily, 1·5% twice daily). Patients in the 0·5% once daily, 1·5% once daily, or 1·5% twice daily groups remained at their original dose up to week 52. Patients, investigators, and the study sponsor (except members of the interim analysis and primary endpoint analysis data monitoring teams) remained masked to treatment assignment throughout the study. The primary endpoint was the proportion of patients achieving a 50% or higher improvement from baseline in F-VASI (F-VASI50) at week 24, assessed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT03099304. Between June 7, 2017, and March 21, 2018, 205 patients were screened for eligibility, 48 were excluded and 157 patients (mean age, 48·3 years [SD 12·9]; 73 [46%] male and 84 [54%] female) were randomly assigned to either an intervention group or the control group. 32 (20%) of 157 were assigned to the control group, 31 (20%) to the 0·15% once daily group, 31 (20%) to the 0·5% once daily group, 30 (19%) to the 1·5% once daily group, and 33 (21%) to the 1·5% twice daily group. F-VASI50 at week 24 was reached by significantly more patients given ruxolitinib cream at 1·5% twice daily (15 [45%] of 33) and 1·5% once daily (15 [50%] of 30) than were treated with vehicle (one [3%] of 32). Four patients had serious treatment-emergent adverse events (one patient in the 1·5% twice daily group developed subdural haematoma; one patient in the 1·5% once daily group had a seizure; one patient in the 0·5% once daily group had coronary artery occlusion; and one patient in the 0·5% once daily group had oesophageal achalasia), all of which were unrelated to study treatment. Application site pruritus was the most common treatment-related adverse event among patients given ruxolitinib cream (one [3%] of 33 in the 1·5% twice daily group; three [10%] of 30 in the 1·5% once daily group; three [10%] of 31 in the 0·5% once daily group; and six [19%] of 31 in the 0·15% once daily group)with three [9%] of 32 patients showing application site pruritis in the control group. Acne was noted as a treatment-related adverse event in 13 (10%) of 125 patients who received ruxolitinib cream and one (3%) of 32 patients who received vehicle cream. All treatment-related adverse events were mild or moderate in severity and similar across treatment groups. Treatment with ruxolitinib cream was associated with substantial repigmentation of vitiligo lesions up to 52 weeks of treatment, and all doses were well tolerated. These data suggest that ruxolitinib cream might be an effective treatment option for patients with vitiligo. Incyte.

Efficacy and Safety of Topical Clascoterone Cream, 1%, for Treatment in Patients With Facial Acne

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.

Sphingolipid identification and skin barrier recovery capacity of a milk sphingolipid-enriched fraction (MSEF) from buttermilk powder.

In this study, we isolated the milk sphingolipid-enriched fraction (MSEF) of sweet buttermilk powder and conducted a clinical trial for evaluating its efficacy in skin barrier recovery. Milk sphingolipid-enriched fraction was isolated via solvent extraction of buttermilk powder, and further concentrated by removing the phospholipids and neutral lipids. A cream containing 1% MSEF was used during clinical trials to assess for water holding and skin barrier recovery capacities. The main components of the MSEF were sphingomyelin, glucosylceramide and lactosylceramide, confirmed by TLC, HPLC, MS and NMR. The MSEF cream-treated group had a significantly higher (P<0.05) water holding capacity, compared with the base cream (vehicle) group. Compared with that in the base cream group, transepidermal water loss (TEWL) recovery increased in the presence of the sphingolipid-containing MSEF cream (MSEF group), with a significant difference (P<0.05) recorded on day 14. The MSEF cream contributed to improving the water holding capacity and skin barrier recovery of damaged skin. Therefore, sphingolipid-containing MSEF can be useful for strengthening or repairing skin barrier function.

Efficacy of lidocaine 7 %, tetracaine 7 % self-occlusive cream in reducing MAL-cPDT-associated pain in subjects with actinic keratosis: A randomized, single-blind, vehicle-controlled trial (The "3P-Trial").

Conventional photodynamic therapy (cPDT) is considered a very effective treatment of actinic keratosis (AK) lesions. However, its use is limited by the fact that this procedure could be very painful. The use of topical anesthetics such as tetracaine or lignocaine/prilocaine has shown disappointing results in term of pain reduction. A self-occlusive topical 7% lidocaine/7% tetracaine anesthetic cream (LT-C) approved by the FDA to provide local topical anesthesia in adults undergoing superficial dermatological procedures is available. There are no data regarding its pain reducing effect during cPDT. We perform a prospective, randomized, single-blind, two-center trial (The 3P-Trial) to assess the pain reduction effect of LT-C versus vehicle in subjects with AK undergoing cPDT. Fifty AK subjects (74 ± 10 years, 32 men, 18 women) with on average 17 lesions were enrolled after their written informed consent. Eight subjects presented also a total of 16 basal cell carcinoma lesions. Twenty-five were randomized to LT-cream, applied 1 h before the Methyl amino levulinate (MAL)-cPDT session and 25 to cream vehicle. The main outcome was the patient-assessed evaluation of pain score during and just after the conclusion of cPDT session (mean of the two values) using a 10-point visual analog scale (VAS). The cPDT session (LED Red light 630 nm) was performed with a duration of 6 ± 2 min with a standard fluence of 37 J/cm2. All treated lesions were prepared by gentle superficial curettage. All the randomized subjects concluded the trial. The mean ± SD of VAS score in vehicle group was 6.2 ± 2.7 (95 % CI of the mean: 5.0-7.5). In the group treated with LT-cream the VAS score was 3.3 ± 1.9 (95 % CI of the mean: 2.5-4.1). The active cream reduced the VAS score by 47 %. Median values of pain VAS score in the active group was reduced by 60 % in comparison with vehicle group (3.0 vs 7.5). The difference between the two groups was statistically significant (p = 0.0009; Mann-Whitney test). The 3P-trial has demonstrated that the preventive application of the self-occlusive lidocaine 7%-tetracaine 7% cream is very effective in reducing the procedure-associated pain during MAL-cPDT for the treatment of AK lesions.

Deep skin wound healing potential of lavender essential oil and licorice extract in a nanoemulsion form: Biochemical, histopathological and gene expression evidences

Cutaneous wound healing is one of the public health interests. This study aimed to investigate the effects of nanoemulsion cream containing lavender essential oil and licorice extract on the healing of deep skin wound in a rat model. Eighty-five male Wistar rats were randomly divided into five groups including untreated defects as negative control and defects treated with vehicle ointment, lavender essential oil and licorice extract in emulsion and nanoemulsion forms, and phenytoin 1% as the positive control with an excisional wound on the dorsal neck of each rat. On days 2, 7 and 14 oxidative stress factors were evaluated in wound tissue homogenates. The expression of transforming growth factor-β (TGF-β), and type I and type III collagen genes were evaluated. Also, wound tissue samples were processed for Hematoxylin & Eosin and Masson-Trichrome staining. Nanoemulsion reduced the wound area more than other groups significantly. Real-time PCR data demonstrated that nanoemulsion and phenytoin groups have shown the best result in increasing TGF-β1, Type I and type III collagen genes expression compared to the other groups. Reduction in lipid peroxidation level and increasing in SOD and GPx activity was also significant in the nanoemulsion and phenytoin groups. The formation of granular tissue likewise the appearance of collagen in nanoemulsion and phenytoin groups were faster than the other groups. Nanoemulsion cream containing lavender essential oil and licorice extract exhibited a promising wound healing potential towards the excisional wound model in rats.

Topical capsaicin cream with moderate exercise protects against hepatic steatosis, dyslipidemia and increased blood pressure in hypoestrogenic obese rats

The aim of this study was to evaluate the effects of capsaicin (Cap), moderate exercise (Ex), and their combination on arterial blood pressure (BP) and metabolic complications in hypoestrogenic (HE) obese (HEOb) rats. Female Wistar rats were ovariectomized and given 300 g L-1 sucrose solution (HEOb), or purified water (HE) ad libitum, for 28 weeks. After shaving the abdominal skin, cold cream vehicle was applied to sedentary (Sed) and exercise (Ex) groups, and 0.75 g kg-1 Cap cream was applied to Ex groups. Ex groups ran on a treadmill every day for 20 min at speeds from 0.15 to 0.3 m s-1 . For combination groups (Cap + Ex), topical Cap was applied 90 min before Ex. The treatments were performed for 6 weeks, and BP was recorded before and at the end of the experimental protocol. The animals were killed by decapitation, and blood and tissues were obtained to perform oxidative profile, as well as to undertake biochemical and histologic studies. Compared with individual treatments, the combined therapy (Cap + Ex) in HEOb rats caused a higher reduction in the caloric intake, body weight, abdominal fat percentage, oxidative stress, and hepatic steatosis. In HEOb groups, Cap was the only treatment that reduced BP and prevented dyslipidemia and oxidative stress. The present data show that Cap improves the metabolic alterations induced by obesity and hypoestrogenism, suggesting that Cap can be considered as an excellent candidate for therapy of these clinical conditions. © 2020 Society of Chemical Industry.

A Study to Assess Recurrence of Actinic Keratosis in Participants Treated With Methyl Aminolevulinate Hydrochloride Cream or Vehicle Cream Who Achieved Complete Response to Treated Lesions in Earlier Study

A Study to Assess Recurrence of Actinic Keratosis in Participants Treated With Methyl Aminolevulinate Hydrochloride Cream or Vehicle Cream Who Achieved Complete Response to Treated Lesions in Earlier Study

Delgocitinib ointment, a topical Janus kinase inhibitor, in adult patients with moderate to severe atopic dermatitis: A phase 3, randomized, double-blind, vehicle-controlled study and an open-label, long-term extension study

Previousstudies showed the potential effectiveness of delgocitinib ointment, a novel topical Janus kinase inhibitor, in atopic dermatitis (AD). This study aimed to evaluate the efficacy and safety of delgocitinib 0.5% ointment. In part 1, a 4-week double-blind period, Japanese patients aged 16years or older with moderate or severe AD were randomly assigned in a 2:1 ratio to delgocitinib 0.5% ointment or vehicle ointment. Eligible patients entered part 2, a 24-week extension period, to receive delgocitinib 0.5% ointment. At the end of treatment in part 1, the least-squares mean percent changes from baseline in the modified Eczema Area and Severity Index score, the primary efficacy endpoint, were significantly greater in the delgocitinib group than in the vehicle group (-44.3% vs 1.7%, P<.001). The improvement in modified Eczema Area and Severity Index score was maintained in part 2. Most adverse events were mild and unrelated to delgocitinib across the study periods. Only Japanese patients were included. The vehicle-controlled period lasted only 4weeks. In part 2, topical corticosteroids were allowed for the treatment of worsening of AD. Delgocitinib ointment was effective and well tolerated in Japanese adult patients with moderate to severe AD for up to 28weeks.

The palliative effect of topical Artemisia dracunculus administration in imiquimod-induced psoriasis in mice

Psoriasis is a serious inflammatory skin disease with an etiology which is not fully understood. The disease is characterized by dark, scaly, and well-demarcated skin lesions formed by epidermal keratinocyte hyper proliferation. Inflammation of the skin caused by Imiquimod (IMQ) is the most widely accepted animal model of psoriasis. The objective of the study is to test Artemisia dracunculus (steroidal fraction of it in a concentration of 5%) possible protective effects on imiquimod-induced psoriasis in mice in its topical dosage form and to compare this effect with Clobetasol Propionate (Dermovate (R)) ointment. An ointment was prepared from the aerial parts of A. dracunculus and was applied topically to mice skin before imiquimod application. The results of the current study showed that A. dracunculus ointment could significantly reduce skin cytokines and psoriasis area and severity index in (A. dracunculus ointment + imiquimod) (Group IV) treatments compared with both control group (Group I) and (vehicle ointment + imiquimod) (Group III).

Efficacy and safety of indigo naturalis ointment in Treating Atopic Dermatitis: A randomized clinical trial.

Indigo naturalis, a herbal medicine with a history of use dating back to ancient times, may be a good alternative topical treatment for atopic dermatitis (AD). To provide empirical evidence of the efficacy and safety of Indigo naturalis ointment in treating AD. In this randomized double-blind clinical trial, participants aged 6 to 65 years with AD affecting less than 40% of their body surface area (BSA) and an Investigator's Global Assessment (IGA) score of 2 to 4 were randomized (2:1) to receive either Lindioil ointment or a vehicle ointment twice daily for 6 weeks. The primary endpoint was the percentage change in the Eczema Area Severity Index (EASI) from baseline to week 6. Secondary endpoints were as follows: EASI improvement ≥50%, 75%, and 90%; IGA score; BSA affected by AD; pruritus severity; and Dermatology Life Quality Index. The safety assessment included adverse events (AEs), laboratory tests, and physical examinations. The Lindioil group (32 participants) and vehicle group (16 participants) achieved mean percentage EASI reductions of 49.9%±36.5% (95% CI 36.8%-63.1%) and 19.6%±52.2% (95% CI -8.2%-47.4%), respectively (P=0.0235). The Lindioil group also showed greater improvement in every secondary assessment category. No significant AEs occurred. Indigo naturalis ointment is effective for treating mild to severe AD topically, and appears to be safe. This is the first clinical trial to provide evidence supporting topical indigo-based AD treatment. ClinicalTrials.gov identifier: NCT02669888.