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The effect of laminaria saccharina extract on suppressing pigmentation in in-vitro system
Evaluation of a rinse cleansing gel specifically formulated for babies: An open medical-controlled multicenter study
(Poster reference number 4631)
Marjorie Biassette, Laboratoires Expanscience, Epernon, France; Bernard Chadoutaud, Clinreal Online, Toulouse, France; Franck Menu, Laboratoires Expanscience, Epernon, France; Nadege Lachmann, Laboratoires Expanscience, Epernon, France; Philippe Msika, Laboratoires Expanscience, Epernon, France Background: Early postnatal life is a period of active functional reorganization and cutaneous physiological adaptation to the extra uterine environment. Protection for baby’s skin must therefore be enhanced by the daily use of appropriate, welltolerated baby skin care products with a considered formulation rules as well as a specific evaluation of tolerance and nontoxicity. Following this process, a rinse cleansing gel for baby’s body and hair has been tested on babies. Protocol: An open multicenter study was conducted in Spain by 5 pediatricians and 2 dermatologists recruiting together 39 babies (mean age, 5.1 months; range, 10 days-2.5 years) with healthy skin. After clinical examination, the investigated product had to be daily use under normal conditions for 21 days. Evaluations were performed at D21 with a physical examination and evaluations questionnaires (mothers). Results: (1) Results were as follows for mothers: Efficacy 96%, gently cleanses the skin 100%, leaves the baby’s skin soft 100%, respects the body’s skin 95% and the scalp 92%, cosmetic qualities 96%, does not sting the eyes 92%, adapted for hygiene of baby’s skin/hair 100%/92%, global satisfaction 97%. (2) Results were as follows for clinicians: Gently cleanses the skin 100%, adapted for hygiene of baby’s skin/hair 100%/95%, global satisfaction 100%. Conclusion: The baby’s skin must be protected by using specific skin care products. This study proved that the product was perfectly tolerated and consequently validated our systemic process of raw material selection and tolerance evaluation as a predictive approach. Commercial support: None identified.
Results of a phase I/IIA maximal use pharmacokinetic study of luliconazole solution, 10% in subjects with moderate to severe distal subungual onychomycosis
(Poster reference number 5281)
Terry Jones, MD, J&S Studies, College Station, TX, United States; Jeremy Scott, J&S Studies, College Station, TX, United States; Mark W. Davis, MS, Topica Pharmaceuticals, Palo Alto, CA, United States Background: Onychomycosis affects 10% to 12% of adults worldwide. Luliconazole is a new imidazole with exceptional in-vitro activity against Trichophyton rubrum and Trichophyton mentagrophytes (MIC 90 of 0.001 g/mL). Luliconazole is being developed in a 10% solution formulation as a treatment for DSO based on its unique pharmacokinetic profile, excellent nail penetration, potent antifungal activity in in vitro human toenail models and excellent safety profile. Methods: This study assessed PK, tolerability, and preliminary safety. Subjects were 18 to 65 years and had[50% nail involvement with culture confirmed DSO. Subjects came to clinic each day for 29 days to receive 200 L applied to all ten toes and surrounding periungual tissue. Plasma samples were collected for 24 hours on days 1, 8, 15, and 29 and 2, 3 and 7 days after cessation of dosing. Application site tolerability was assessed throughout the study. A 24-hour Holter monitor recording was obtained on days 1, 8, and 29 and extractions were timed to align with plasma collections. Results: All 24 subjects enrolled completed the study with no alterations in dosing. Plasma levels were low and steady state was achieved by day 8; mean Cmax of 0.085 ng/mL, mean AUC of 1.288 ng*h/mL. The maximum observed plasma level was 0.307 ng/mL. These levels are [100 fold below levels at which toxicity occurred in toxicology studies and [100,000 fold less than levels that impact cardiac conduction based on IC50 determined in a hERG conduction study. Circulating plasma levels of luliconazole continued to be observed 7 days after cessation of dosing. There was no drug accumulation. Luliconazole solution, 10% was very well tolerated. Only one mild erythema was reported and resolved by the subsequent assessment. No serious adverse events occurred. ECG assessments showed no impact on cardiac safety. There was no prolongation of QTc intervals and no correlation of QTc with drug plasma levels. Conclusion: In this population of subjects, luliconazole solution, 10% was well tolerated and safe with minimally absorbed systemic levels. The presence of luliconazole in the plasma 7 days after cessation of dosing implies that the nail is a reservoir for luliconazole allowing continual absorption through the nail bed into systemic circulation at very safe levels. Luliconazole Solution, 10% holds promise for reducing the need for daily applications in order to deliver efficacious levels of this antifungal to the nail bed. Commercial support: 100% is sponsored by Topica Pharmaceuticals.
Is monobenzylether of hydroquinone a safe depigmentation therapy in advanced vitiligo?
(Poster reference number 5304)
Saqib Bashir, MBBCh, MD, Dr. Saqib J Bashir, London, United Kingdom; Hui Min Liew, MBBCh, Hui Min Liew, London, United Kingdom; John Hawk, MBBCh, MD, Professor John Hawk, London, United Kingdom
The effect of laminaria saccharina extract on suppressing pigmentation in in-vitro system
Monobenzylether of hydroquionone (MBEH) is a permanent depigmenting agent for advanced vitiligo, involving 50% of body surface area. Risks include allergic or irritant dermatitis, depigmentation of distant untreated skin, potential patchy repigmentation and the social consequences of color change. Systemic consequences of treatment, and the development of cutaneous secondary ochronosis have not been convincingly established. The mechanism of MBEH is still not clearly understood but it is thought to induce melanocyte death. Aim To assess the safety of MBEH in the long term depigmentation of advanced vitiligo. Patients and Methods A retrospective study of patients receiving MBEH for advanced vitiligo was undertaken, based on a case notes review. Patients undergoing depigmentation were seen three monthly or more often in the photodermatology clinic. Patients underwent cutaneous examination and review of their general health. Some patients had a blood count, liver and renal function tests. After consent was obtained, a trial of topical MBEH at 10% was used and the concentration was gradually increased to 20% or 30% or decreased to 10% or 5% as tolerated. The treatment ceased once patients were satisfied with the outcome. Results 12 males and 32 females were treated, with a mean age of 44 (14-77). No significant adverse effects were reported; however, 7% (3 out of 44) reported irritation at 20% of MBEH, after a mean of 5 months, resolving with dose reduction. However, 68% of patients were able to tolerate 20% MBEH, and 23% tolerated 30%. There was no reported allergic contact dermatitis. No cases of exogenous ochronosis were identified. 20 out of 44 patients had blood tests done at some point during the therapy and 2 out of 20 had mildly deranged liver function tests, despite no preceding history of liver disease. No patients were required to discontinue therapy. Conclusion MBEH is a well-tolerated therapy, however some patients experience minor changes in liver function which may require monitoring.
(Poster reference number 5613)
Commercial support: None identified.
Commercial support: Supported by The Procter & Gamble Company.
AB172
J AM ACAD DERMATOL
Tomohiro Hakozaki, PhD, The Procter & Gamble Company, Cincinnati, OH, United States; Bin Fang, MS, The Procter & Gamble Company, Cincinnati, OH, United States; Deborah Finlay, PhD, The Procter & Gamble Company, Cincinnati, OH, United States; Heather Matheny, MS, The Procter & Gamble Company, Cincinnati, OH, United States; Jiazhen Wang, MS, The Procter & Gamble Company, Cincinnati, OH, United States; Steven Zhao, MS, The Procter & Gamble Company, Cincinnati, OH, United States; Timothy Laughlin, PhD, The Procter & Gamble Company, Cincinnati, OH, United States We evaluated the effect of Laminaria saccharina extract (LSE; Phlorogine) on melanogenesis in in vitro systems. In a B16 melanoma cell model, addition of LSE directly decreased melanin synthesis in a dose dependent manner. The effect on total glutathione was also determined in a chemical assay by using DNTB as a substrate and monitoring the 412 nm wavelength using a spectrophotometer. Increased glutathione affects melanogenesis by directing melanin production towards the lighter pheomelanin species. LSE significantly elevated the total glutathione concentration, and we confirmed addition of glutathione decreases melanin synthesis in a B16 cell culture model. We also tested LSE on the release of SCF (stem cell factor) and PGE2 (prostaglandin E2) from a human keratinocyte model. The results from the in vitro studies indicate LSE affects melanogenesis by directly reducing melanogenesis (via activation of glutathione) and reducing the release of melanogenic chemical mediators from keratinocytes. Taken all together, the results suggest that LSE is a promising ingredient to improve the appearance of skin color unevenness (eg, age spots) and skin lightness.
APRIL 2012
(Poster reference number 4631)
Marjorie Biassette, Laboratoires Expanscience, Epernon, France; Bernard Chadoutaud, Clinreal Online, Toulouse, France; Franck Menu, Laboratoires Expanscience, Epernon, France; Nadege Lachmann, Laboratoires Expanscience, Epernon, France; Philippe Msika, Laboratoires Expanscience, Epernon, France Background: Early postnatal life is a period of active functional reorganization and cutaneous physiological adaptation to the extra uterine environment. Protection for baby’s skin must therefore be enhanced by the daily use of appropriate, welltolerated baby skin care products with a considered formulation rules as well as a specific evaluation of tolerance and nontoxicity. Following this process, a rinse cleansing gel for baby’s body and hair has been tested on babies. Protocol: An open multicenter study was conducted in Spain by 5 pediatricians and 2 dermatologists recruiting together 39 babies (mean age, 5.1 months; range, 10 days-2.5 years) with healthy skin. After clinical examination, the investigated product had to be daily use under normal conditions for 21 days. Evaluations were performed at D21 with a physical examination and evaluations questionnaires (mothers). Results: (1) Results were as follows for mothers: Efficacy 96%, gently cleanses the skin 100%, leaves the baby’s skin soft 100%, respects the body’s skin 95% and the scalp 92%, cosmetic qualities 96%, does not sting the eyes 92%, adapted for hygiene of baby’s skin/hair 100%/92%, global satisfaction 97%. (2) Results were as follows for clinicians: Gently cleanses the skin 100%, adapted for hygiene of baby’s skin/hair 100%/95%, global satisfaction 100%. Conclusion: The baby’s skin must be protected by using specific skin care products. This study proved that the product was perfectly tolerated and consequently validated our systemic process of raw material selection and tolerance evaluation as a predictive approach. Commercial support: None identified.
Results of a phase I/IIA maximal use pharmacokinetic study of luliconazole solution, 10% in subjects with moderate to severe distal subungual onychomycosis
(Poster reference number 5281)
Terry Jones, MD, J&S Studies, College Station, TX, United States; Jeremy Scott, J&S Studies, College Station, TX, United States; Mark W. Davis, MS, Topica Pharmaceuticals, Palo Alto, CA, United States Background: Onychomycosis affects 10% to 12% of adults worldwide. Luliconazole is a new imidazole with exceptional in-vitro activity against Trichophyton rubrum and Trichophyton mentagrophytes (MIC 90 of 0.001 g/mL). Luliconazole is being developed in a 10% solution formulation as a treatment for DSO based on its unique pharmacokinetic profile, excellent nail penetration, potent antifungal activity in in vitro human toenail models and excellent safety profile. Methods: This study assessed PK, tolerability, and preliminary safety. Subjects were 18 to 65 years and had[50% nail involvement with culture confirmed DSO. Subjects came to clinic each day for 29 days to receive 200 L applied to all ten toes and surrounding periungual tissue. Plasma samples were collected for 24 hours on days 1, 8, 15, and 29 and 2, 3 and 7 days after cessation of dosing. Application site tolerability was assessed throughout the study. A 24-hour Holter monitor recording was obtained on days 1, 8, and 29 and extractions were timed to align with plasma collections. Results: All 24 subjects enrolled completed the study with no alterations in dosing. Plasma levels were low and steady state was achieved by day 8; mean Cmax of 0.085 ng/mL, mean AUC of 1.288 ng*h/mL. The maximum observed plasma level was 0.307 ng/mL. These levels are [100 fold below levels at which toxicity occurred in toxicology studies and [100,000 fold less than levels that impact cardiac conduction based on IC50 determined in a hERG conduction study. Circulating plasma levels of luliconazole continued to be observed 7 days after cessation of dosing. There was no drug accumulation. Luliconazole solution, 10% was very well tolerated. Only one mild erythema was reported and resolved by the subsequent assessment. No serious adverse events occurred. ECG assessments showed no impact on cardiac safety. There was no prolongation of QTc intervals and no correlation of QTc with drug plasma levels. Conclusion: In this population of subjects, luliconazole solution, 10% was well tolerated and safe with minimally absorbed systemic levels. The presence of luliconazole in the plasma 7 days after cessation of dosing implies that the nail is a reservoir for luliconazole allowing continual absorption through the nail bed into systemic circulation at very safe levels. Luliconazole Solution, 10% holds promise for reducing the need for daily applications in order to deliver efficacious levels of this antifungal to the nail bed. Commercial support: 100% is sponsored by Topica Pharmaceuticals.
Is monobenzylether of hydroquinone a safe depigmentation therapy in advanced vitiligo?
(Poster reference number 5304)
Saqib Bashir, MBBCh, MD, Dr. Saqib J Bashir, London, United Kingdom; Hui Min Liew, MBBCh, Hui Min Liew, London, United Kingdom; John Hawk, MBBCh, MD, Professor John Hawk, London, United Kingdom
The effect of laminaria saccharina extract on suppressing pigmentation in in-vitro system
Monobenzylether of hydroquionone (MBEH) is a permanent depigmenting agent for advanced vitiligo, involving 50% of body surface area. Risks include allergic or irritant dermatitis, depigmentation of distant untreated skin, potential patchy repigmentation and the social consequences of color change. Systemic consequences of treatment, and the development of cutaneous secondary ochronosis have not been convincingly established. The mechanism of MBEH is still not clearly understood but it is thought to induce melanocyte death. Aim To assess the safety of MBEH in the long term depigmentation of advanced vitiligo. Patients and Methods A retrospective study of patients receiving MBEH for advanced vitiligo was undertaken, based on a case notes review. Patients undergoing depigmentation were seen three monthly or more often in the photodermatology clinic. Patients underwent cutaneous examination and review of their general health. Some patients had a blood count, liver and renal function tests. After consent was obtained, a trial of topical MBEH at 10% was used and the concentration was gradually increased to 20% or 30% or decreased to 10% or 5% as tolerated. The treatment ceased once patients were satisfied with the outcome. Results 12 males and 32 females were treated, with a mean age of 44 (14-77). No significant adverse effects were reported; however, 7% (3 out of 44) reported irritation at 20% of MBEH, after a mean of 5 months, resolving with dose reduction. However, 68% of patients were able to tolerate 20% MBEH, and 23% tolerated 30%. There was no reported allergic contact dermatitis. No cases of exogenous ochronosis were identified. 20 out of 44 patients had blood tests done at some point during the therapy and 2 out of 20 had mildly deranged liver function tests, despite no preceding history of liver disease. No patients were required to discontinue therapy. Conclusion MBEH is a well-tolerated therapy, however some patients experience minor changes in liver function which may require monitoring.
(Poster reference number 5613)
Commercial support: None identified.
Commercial support: Supported by The Procter & Gamble Company.
AB172
J AM ACAD DERMATOL
Tomohiro Hakozaki, PhD, The Procter & Gamble Company, Cincinnati, OH, United States; Bin Fang, MS, The Procter & Gamble Company, Cincinnati, OH, United States; Deborah Finlay, PhD, The Procter & Gamble Company, Cincinnati, OH, United States; Heather Matheny, MS, The Procter & Gamble Company, Cincinnati, OH, United States; Jiazhen Wang, MS, The Procter & Gamble Company, Cincinnati, OH, United States; Steven Zhao, MS, The Procter & Gamble Company, Cincinnati, OH, United States; Timothy Laughlin, PhD, The Procter & Gamble Company, Cincinnati, OH, United States We evaluated the effect of Laminaria saccharina extract (LSE; Phlorogine) on melanogenesis in in vitro systems. In a B16 melanoma cell model, addition of LSE directly decreased melanin synthesis in a dose dependent manner. The effect on total glutathione was also determined in a chemical assay by using DNTB as a substrate and monitoring the 412 nm wavelength using a spectrophotometer. Increased glutathione affects melanogenesis by directing melanin production towards the lighter pheomelanin species. LSE significantly elevated the total glutathione concentration, and we confirmed addition of glutathione decreases melanin synthesis in a B16 cell culture model. We also tested LSE on the release of SCF (stem cell factor) and PGE2 (prostaglandin E2) from a human keratinocyte model. The results from the in vitro studies indicate LSE affects melanogenesis by directly reducing melanogenesis (via activation of glutathione) and reducing the release of melanogenic chemical mediators from keratinocytes. Taken all together, the results suggest that LSE is a promising ingredient to improve the appearance of skin color unevenness (eg, age spots) and skin lightness.
APRIL 2012