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Safety, pharmacokinetics, and efficacy of AN2728 ointment, 2% in a phase II study of adolescents with mild to moderate atopic dermatitis
P8355
P8629
Reducing ashiness in skin of color: The impact of mild cleansing Stacy Hawkins, PhD, Unilever R&D, Trumbull, CT, United States; K. P. Ananthapadmanabhan, PhD, Unilever R&D, Trumbull, CT, United States; Li Feng, PhD, Unilever R&D, Trumbull, CT, United States In skin of color subjects, maintenance of a healthy skin barrier and reduction of skin dryness is especially important as very dry skin can lead to a gray or ‘‘ashy’’ appearance. It was therefore of interest to investigate the effects of a mild, moisturizing syndet bar in skin of color subjects with dry, ashy skin, because the protection benefits may be particularly relevant for this group. Twenty-seven healthy female subjects, Fitzpatrick type IV-VI, age 20-50 years, with a moderate degree of visual skin ashiness, as assessed by a dermatologist, provided informed consent to participate in this IRB-approved home-use cleansing study, where subjects replaced their normal cleanser with the syndet bar provided and washed daily for 3 weeks of product application. During this time, subjects refrained from using moisturizers on their arms or legs. Expert clinical evaluation of dryness and ashiness and self-perception assessments on forearms and legs were obtained at baseline and after 3 weeks of product application. Transepidermal water loss (TEWL) and skin hydration measurements were obtained on forearms and legs at baseline and at week 3 as an objective measure of skin barrier. Clinical visual dryness significantly improved on outer forearms and elbows after 3 weeks of normal use washing. The severity of clinical skin ashiness was also significantly reduced on outer legs. TEWL and hydration measurements showed significant improvement. Subjects perceived significant improvement to moisturization, softness, and smoothness, as well as reduced itch, and dryness on elbows. These results demonstrate a mild, moisturizing syndet bar provides skin condition benefits in barrier-compromised, ashy skin.
Safety, pharmacokinetics, and efficacy of AN2728 ointment, 2% in a phase II study of adolescents with mild to moderate atopic dermatitis Wynnis Tom, Rady Children’s Hospital, San Diego, CA, United States; Lee Zane, MD, Anacor Pharmaceuticals, Inc, Palo Alto, CA, United States; Liang Liu, PhD, Anacor Pharmaceuticals, Inc, Palo Alto, CA, United States; Merrie Van Syoc, Anacor Pharmaceuticals, Inc, Palo Alto, CA, United States; Sanjay Chanda, PhD, Anacor Pharmaceuticals, Inc, Palo Alto, CA, United States Purpose: To evaluate the safety, tolerability, efficacy, and systemic exposure of AN2728 topical ointment, 2%, in subjects with atopic dermatitis (AD).
Sponsored 100% by Unilever R&D.
Methods: Multicenter, phase II, open-label study with a PK phase (Days 1-9) and a safety and tolerability phase (Days 10-28). Twenty-three adolescents, ages 12 to 17 years, with mild to moderate AD involving 10-35% body surface area (BSA) were treated twice daily (BID) with AN2728 ointment, 2% for 28 days, except on Days 1 and 8 when only an AM dose was applied. Plasma samples for PK analysis were collected on Days 1 and 8 predose and at 1, 2, 4, 6, 8, and 24 hours postdosing, as well as on Days 4 and 6 before the AM dose. Global assessment of disease severity was based on the Investigator Static Global Assessment (ISGA), a 5-point scale from 0 (clear) to 4 (severe). Erythema, excoriation, exudation, lichenification, and pruritus were graded on a 4-point scale from 0 (none) to 3 (severe). Results: AN2728 ointment, 2% was found to be generally safe and well-tolerated with the most common adverse events (AEs) being application site reactions. No serious AEs were observed. One subject discontinued because of an AE (contact dermatitis). Plasma levels of AN2728 were low and dependent on the BSA being treated. Disease severity improved over the 28-day treatment period as demonstrated in several outcomes: mean ISGA score decreased by 1.08 points from baseline; 73.9% of subjects achieved an ISGA score of 0 (clear) or 1 (almost clear); and treatment success, defined as an ISGA score of ¼ 1 with a minimum 2-grade improvement from baseline, was achieved in 34.8% of subjects. Mean values for the individual signs and symptoms of AD improved during treatment, most notably a 70% reduction in mean pruritus severity score. Conclusion: AN2728 is a boron-based phosphodiesterase-4 inhibitor that is wellsuited for the topical treatment of inflammatory skin disorders. Based on these phase II results in adolescents with AD, AN2728 ointment, 2% applied BID for 4 weeks was generally safe and well-tolerated, provided low systemic exposure, and produced substantial improvements in global disease severity as well as in individual signs and symptoms of AD. Sponsored 100% by Anacor Pharmaceuticals, Inc.
P8672 Safety and efficacy of AN2728 topical ointment, 2% and 0.5%, in a phase II dose-ranging study of adolescents with mild to moderate atopic dermatitis Linda Stein-Gold, MD, Henry Ford Hospital, Detroit, MI, United States; Lee Zane, MD, Anacor Pharmaceuticals, Inc, Palo Alto, CA, United States; Lynda Spelman, MBBS, Queensland Institute of Dermatology, Holland Park, Australia; Mary Spellman, MD, Spellman Consulting, San Francisco, CA, United States; Matilda Hughes, Anacor Pharmaceuticals, Inc, Palo Alto, CA, United States Purpose: AN2728 is a novel oxaborole compound and phosphodiesterase-4 inhibitor with antiinflammatory activity. A clinical dose-ranging study was conducted to determine the safety and efficacy of AN2728 topical ointment, 2% and 0.5%, administered once a day (QD) or twice a day (BID), in the treatment of mild to moderate atopic dermatitis (AD) in adolescents.
P8580
Results: AN2728 topical ointment, 2% and 0.5%, were found to be generally safe and well-tolerated. No serious adverse events (AEs) were reported, and no treatment discontinuation occurred due to AEs. Application site symptoms were uncommon. Based on improved ADSI scores relative to baseline, a clear dose-response was seen across the 4 dosing regimens. The greatest improvement in ADSI score was noted with treatment with AN2728 topical ointment, 2% BID, which yielded a 71% improvement in ADSI score from baseline after 28 days, with 62% of lesions in this treatment group achieving total or partial clearance. This treatment group also demonstrated the greatest improvement across all 5 signs and symptoms of AD after 28 days, including a notable 79% reduction in pruritus severity. Conclusions: Of the 4 dosing regimens examined in this phase II study of adolescents with AD, AN2728 topical ointment, 2% BID produced the greatest improvements in disease severity and was generally safe and well tolerated.
The benefits of ultramild cleansing under normal use conditions for reduction of winter dry skin itch Stacy Hawkins, PhD, Unilever R&D, Trumbull, CT, United States; Diana Marrero, Unilever R&D, Trumbull, CT, United States; K. P. Ananthapadmanabhan, PhD, Unilever R&D, Trumbull, CT, United States; Li Feng, Unilever R&D, Trumbull, CT, United States Damage to stratum corneum proteins and lipids induced by harsh cleansers and/or severe environmental conditions may also lead to the perception of itch. Previously, a novel lipid-rich moisturizing body wash (LBW) demonstrated significant clinical benefits for reducing dryness and improvement of self-perceived skin moisturization. The goal of this research was to understand the impact of ultramild cleansing on subjective perception of winter dry skin itch. Thirty-four white females, ages 18 to 65 years, provided informed consent to participate in this randomized, doubleblind, IRB-approved 3-week controlled application leg wash study. Subjects were enrolled into 2 skin condition groups: cell 1—subjects with moderate to severe clinical visual dryness on their lower legs and self-reported itch (at least 2 itch episodes 48 hours before the study; N ¼ 18), and cell 2—subjects with none to low clinical visual dryness and no self-reported itch on their lower legs (N ¼ 16). Each leg was washed with either the LBW or NMW once daily for 3 weeks during severe winter conditions (in Connecticut). Clinical evaluation of skin dryness, skin hydration, and subjective surveys were obtained at baseline, and after 1 and 3 weeks of application. The LBW wash led to a significant reduction in visual dryness, improved skin hydration, and reduction in perception of itch compared to the NMW in both low and dry itchy skin subject groups. In addition, the LBW wash showed a time-dependent reduction in perception of the number of itch episodes and the intensity of itch. These results demonstrate that the LBW technology is not only effective for reducing signs of clinical dryness, but also for reducing the symptoms of itch typically associated with dry winter skin.
Sponsored 100% by Anacor Pharmaceuticals, Inc.
Sponsored 100% by Unilever R&D.
Methods: This multicenter, randomized, double-blind, bilateral, dose-ranging, phase II study enrolled 86 patients (40% male) aged 12-17 years with AD involving up to 35% of body surface area. Enrolled patients had 2 target lesions of similar severity based on AD severity index (ADSI) score of 6-12, a maximum 1 point difference in ADSI score between the 2 lesions, and an erythema subscore of at least 2 (moderate). The index comprises the sum of scores ranging from 0 (none) to 3 (severe) for erythema, pruritus, exudation, excoriation, and lichenification. Patients were randomized to QD or BID treatment frequency. In addition, patients treated 1 target lesion with AN2728 topical ointment, 2% and the other with AN2728 topical ointment, 0.5%, and the selection was randomly assigned. Patients were evaluated on days 1, 8, 15, 22, and 29. Disease severity was determined based on the ADSI score on days 8, 15, 22, and 29. The primary endpoint was the change from baseline in ADSI score.
MAY 2014
J AM ACAD DERMATOL
AB65
P8629
Reducing ashiness in skin of color: The impact of mild cleansing Stacy Hawkins, PhD, Unilever R&D, Trumbull, CT, United States; K. P. Ananthapadmanabhan, PhD, Unilever R&D, Trumbull, CT, United States; Li Feng, PhD, Unilever R&D, Trumbull, CT, United States In skin of color subjects, maintenance of a healthy skin barrier and reduction of skin dryness is especially important as very dry skin can lead to a gray or ‘‘ashy’’ appearance. It was therefore of interest to investigate the effects of a mild, moisturizing syndet bar in skin of color subjects with dry, ashy skin, because the protection benefits may be particularly relevant for this group. Twenty-seven healthy female subjects, Fitzpatrick type IV-VI, age 20-50 years, with a moderate degree of visual skin ashiness, as assessed by a dermatologist, provided informed consent to participate in this IRB-approved home-use cleansing study, where subjects replaced their normal cleanser with the syndet bar provided and washed daily for 3 weeks of product application. During this time, subjects refrained from using moisturizers on their arms or legs. Expert clinical evaluation of dryness and ashiness and self-perception assessments on forearms and legs were obtained at baseline and after 3 weeks of product application. Transepidermal water loss (TEWL) and skin hydration measurements were obtained on forearms and legs at baseline and at week 3 as an objective measure of skin barrier. Clinical visual dryness significantly improved on outer forearms and elbows after 3 weeks of normal use washing. The severity of clinical skin ashiness was also significantly reduced on outer legs. TEWL and hydration measurements showed significant improvement. Subjects perceived significant improvement to moisturization, softness, and smoothness, as well as reduced itch, and dryness on elbows. These results demonstrate a mild, moisturizing syndet bar provides skin condition benefits in barrier-compromised, ashy skin.
Safety, pharmacokinetics, and efficacy of AN2728 ointment, 2% in a phase II study of adolescents with mild to moderate atopic dermatitis Wynnis Tom, Rady Children’s Hospital, San Diego, CA, United States; Lee Zane, MD, Anacor Pharmaceuticals, Inc, Palo Alto, CA, United States; Liang Liu, PhD, Anacor Pharmaceuticals, Inc, Palo Alto, CA, United States; Merrie Van Syoc, Anacor Pharmaceuticals, Inc, Palo Alto, CA, United States; Sanjay Chanda, PhD, Anacor Pharmaceuticals, Inc, Palo Alto, CA, United States Purpose: To evaluate the safety, tolerability, efficacy, and systemic exposure of AN2728 topical ointment, 2%, in subjects with atopic dermatitis (AD).
Sponsored 100% by Unilever R&D.
Methods: Multicenter, phase II, open-label study with a PK phase (Days 1-9) and a safety and tolerability phase (Days 10-28). Twenty-three adolescents, ages 12 to 17 years, with mild to moderate AD involving 10-35% body surface area (BSA) were treated twice daily (BID) with AN2728 ointment, 2% for 28 days, except on Days 1 and 8 when only an AM dose was applied. Plasma samples for PK analysis were collected on Days 1 and 8 predose and at 1, 2, 4, 6, 8, and 24 hours postdosing, as well as on Days 4 and 6 before the AM dose. Global assessment of disease severity was based on the Investigator Static Global Assessment (ISGA), a 5-point scale from 0 (clear) to 4 (severe). Erythema, excoriation, exudation, lichenification, and pruritus were graded on a 4-point scale from 0 (none) to 3 (severe). Results: AN2728 ointment, 2% was found to be generally safe and well-tolerated with the most common adverse events (AEs) being application site reactions. No serious AEs were observed. One subject discontinued because of an AE (contact dermatitis). Plasma levels of AN2728 were low and dependent on the BSA being treated. Disease severity improved over the 28-day treatment period as demonstrated in several outcomes: mean ISGA score decreased by 1.08 points from baseline; 73.9% of subjects achieved an ISGA score of 0 (clear) or 1 (almost clear); and treatment success, defined as an ISGA score of ¼ 1 with a minimum 2-grade improvement from baseline, was achieved in 34.8% of subjects. Mean values for the individual signs and symptoms of AD improved during treatment, most notably a 70% reduction in mean pruritus severity score. Conclusion: AN2728 is a boron-based phosphodiesterase-4 inhibitor that is wellsuited for the topical treatment of inflammatory skin disorders. Based on these phase II results in adolescents with AD, AN2728 ointment, 2% applied BID for 4 weeks was generally safe and well-tolerated, provided low systemic exposure, and produced substantial improvements in global disease severity as well as in individual signs and symptoms of AD. Sponsored 100% by Anacor Pharmaceuticals, Inc.
P8672 Safety and efficacy of AN2728 topical ointment, 2% and 0.5%, in a phase II dose-ranging study of adolescents with mild to moderate atopic dermatitis Linda Stein-Gold, MD, Henry Ford Hospital, Detroit, MI, United States; Lee Zane, MD, Anacor Pharmaceuticals, Inc, Palo Alto, CA, United States; Lynda Spelman, MBBS, Queensland Institute of Dermatology, Holland Park, Australia; Mary Spellman, MD, Spellman Consulting, San Francisco, CA, United States; Matilda Hughes, Anacor Pharmaceuticals, Inc, Palo Alto, CA, United States Purpose: AN2728 is a novel oxaborole compound and phosphodiesterase-4 inhibitor with antiinflammatory activity. A clinical dose-ranging study was conducted to determine the safety and efficacy of AN2728 topical ointment, 2% and 0.5%, administered once a day (QD) or twice a day (BID), in the treatment of mild to moderate atopic dermatitis (AD) in adolescents.
P8580
Results: AN2728 topical ointment, 2% and 0.5%, were found to be generally safe and well-tolerated. No serious adverse events (AEs) were reported, and no treatment discontinuation occurred due to AEs. Application site symptoms were uncommon. Based on improved ADSI scores relative to baseline, a clear dose-response was seen across the 4 dosing regimens. The greatest improvement in ADSI score was noted with treatment with AN2728 topical ointment, 2% BID, which yielded a 71% improvement in ADSI score from baseline after 28 days, with 62% of lesions in this treatment group achieving total or partial clearance. This treatment group also demonstrated the greatest improvement across all 5 signs and symptoms of AD after 28 days, including a notable 79% reduction in pruritus severity. Conclusions: Of the 4 dosing regimens examined in this phase II study of adolescents with AD, AN2728 topical ointment, 2% BID produced the greatest improvements in disease severity and was generally safe and well tolerated.
The benefits of ultramild cleansing under normal use conditions for reduction of winter dry skin itch Stacy Hawkins, PhD, Unilever R&D, Trumbull, CT, United States; Diana Marrero, Unilever R&D, Trumbull, CT, United States; K. P. Ananthapadmanabhan, PhD, Unilever R&D, Trumbull, CT, United States; Li Feng, Unilever R&D, Trumbull, CT, United States Damage to stratum corneum proteins and lipids induced by harsh cleansers and/or severe environmental conditions may also lead to the perception of itch. Previously, a novel lipid-rich moisturizing body wash (LBW) demonstrated significant clinical benefits for reducing dryness and improvement of self-perceived skin moisturization. The goal of this research was to understand the impact of ultramild cleansing on subjective perception of winter dry skin itch. Thirty-four white females, ages 18 to 65 years, provided informed consent to participate in this randomized, doubleblind, IRB-approved 3-week controlled application leg wash study. Subjects were enrolled into 2 skin condition groups: cell 1—subjects with moderate to severe clinical visual dryness on their lower legs and self-reported itch (at least 2 itch episodes 48 hours before the study; N ¼ 18), and cell 2—subjects with none to low clinical visual dryness and no self-reported itch on their lower legs (N ¼ 16). Each leg was washed with either the LBW or NMW once daily for 3 weeks during severe winter conditions (in Connecticut). Clinical evaluation of skin dryness, skin hydration, and subjective surveys were obtained at baseline, and after 1 and 3 weeks of application. The LBW wash led to a significant reduction in visual dryness, improved skin hydration, and reduction in perception of itch compared to the NMW in both low and dry itchy skin subject groups. In addition, the LBW wash showed a time-dependent reduction in perception of the number of itch episodes and the intensity of itch. These results demonstrate that the LBW technology is not only effective for reducing signs of clinical dryness, but also for reducing the symptoms of itch typically associated with dry winter skin.
Sponsored 100% by Anacor Pharmaceuticals, Inc.
Sponsored 100% by Unilever R&D.
Methods: This multicenter, randomized, double-blind, bilateral, dose-ranging, phase II study enrolled 86 patients (40% male) aged 12-17 years with AD involving up to 35% of body surface area. Enrolled patients had 2 target lesions of similar severity based on AD severity index (ADSI) score of 6-12, a maximum 1 point difference in ADSI score between the 2 lesions, and an erythema subscore of at least 2 (moderate). The index comprises the sum of scores ranging from 0 (none) to 3 (severe) for erythema, pruritus, exudation, excoriation, and lichenification. Patients were randomized to QD or BID treatment frequency. In addition, patients treated 1 target lesion with AN2728 topical ointment, 2% and the other with AN2728 topical ointment, 0.5%, and the selection was randomly assigned. Patients were evaluated on days 1, 8, 15, 22, and 29. Disease severity was determined based on the ADSI score on days 8, 15, 22, and 29. The primary endpoint was the change from baseline in ADSI score.
MAY 2014
J AM ACAD DERMATOL
AB65