1. Overall Effectiveness of a Potentiatied 2% Micronized Platelet Pyrithione Zinc Shampoo Among Severe Dandruff/Seborrheic Dermatitis Sufferers INTRODUCTION Dandruff/seborrheic dermatitis of the scalp is characterized by flaking, irritation, itch, redness, and dryness. These conditions can be more severe when symptoms are heightened, more persistent, and/or do not respond to treatment. Previously we reported efficacy of micronized platelet PTZ can be potentiated in a shampoo with cosmetic excipients such as zinc carbonate to improve bioavailability of PTZ 1. Here, we report the effectiveness of a potentiated, 2% ZPT shampoo which provides strong symptom relief against a range of symptom severity (i.e., moderate to severe) and is effective at reducing Malassezia. The primary objective of this work was to assess the overall effectiveness of a potentiated 2% micronized platelet PTZ shampoo among severe dandruff/seborrheic dermatitis sufferers. HL Rocchetta, PhD, JR Schwartz, PhD, T Darcy, PhD, J Erb, K Grau, J Thomas, PhD, J Morgan, F Luo, PhD, M Copas The Procter & Gamble Company, Cincinnati, OH  The potentiated 2% micronized PTZ shampoo is effective at reducing dandruff/seborrheic dermatitis symptoms (i.e., flaking, itch and dryness) across a range of severities (moderate to severe).  In vitro and in vivo testing support the effectiveness of the potentiated 2% micronized PTZ shampoo at reducing Malassezia, the most effectively treated cause of dandruff/seborrheic dermatitis. Reference 1 J. R. Schwartz, Product pharmacology and medical actives in achieving therapeutic benefits. J. Invest. Dermatol. Symp. Proc., 2005. 10: p. 198-200 CONCLUSIONS RESULTS OBJECTIVE Clinical Studies Study A – 500 subjects participated in a dandruff/seborrheic dermatitis prevalence study. Endpoints – dermatologist graded Adherent Scalp Flaking Scores (ASFS) and self assessed symptom severity. Study B – 97 subjects participated in a 3 week, double-blinded, parallel design, placebo controlled, randomized clinical study. Subjects refrained from using any dandruff products 2 weeks prior to the treatment period (shampoo usage - at least 3X/week). Endpoints - dermatologist graded ASFS and self assessed symptom severity. Consumer Study 208 subjects participated in a single product, 2 week consumer test with self reported dandruff/seborrheic dermatitis symptoms. Post-usage consumers reported how well the product controlled symptoms. In Vitro and In Vivo Antifungal Testing In Vitro - Solution-based and zone of inhibition assays (ZOI) whereby product dilutions are tested for anti-Malassezia activity. In Vivo – Two week consumer usage test (shampoo usage 3X/week) whereby scalp swabs are taken, slides prepared/stained and Malassezia enumerated by fluorescent microscopy. METHODS Clinical Studies Pairwise comparisons of self assessed symptoms demonstrate that severe sufferers (based on ASFS), are statistically different (p≤0.05) than moderate and mild sufferers (Table 1). The potentiated 2% ZPT shampoo provided ASFS reductions to 90.1% of moderate and severe sufferers and 94.4% of severe sufferers (Table 2). This work was funded by P&G Beauty Self Assessment Dandruff/ Seborrheic Dermatitis Symptom Descriptors Severity of Flaking Severity of Scalp Itch Severity of Dry Scalp Mild (ASFS 16-24) Never Experienced67.8%36.9%40.7% Very Slight to Slight26.3%43.4%46.6% Moderate5.9%14.8%11.9% Somewhat Severe to Severe 0%4.9%0.85% Moderate (ASFS 25-34) Never Experienced42.8%19.3%21.4% Very Slight to Slight38.5%50%51.7% Moderate15.2%24%22.8% Somewhat Severe to Severe 3.5%6.7%4.2% Severe (ASFS 35-80) Never Experienced22.6%11.6%10.8% Very Slight to Slight49.5%50.5%46.2% Moderate17.2%15.8%21.5% Somewhat Severe to Severe 10.7%22.1%21.6% Percent of Subjects that Experienced ASFS Reductions from Baseline at Week 3 Dandruff/ Seborrheic Dermatitis Potentiated 2% ZPT Shampoo (n=71)Placebo Shampoo (n=25)p-values (Potentiated 2% ZPT vs. Placebo) Moderate & Severe (ASFS ≥ 24)90.1% (n=64) -19.9 ASFS units* 64% (n=16) -3.3 ASFS units* p=0.0026 p<0.0001 Severe (ASFS ≥ 34) 94.4% (n=34) -24.3 ASFS units* 78.6% (n=11) -8.6 ASFS units* p=0.0875 p<0.0001 Table 2. ASFS Response to the Potentiated 2% ZPT Shampoo (Study B). * LS Mean Change in ASFS from baseline at week 3 Table 3. Reduction in Dandruff Severity Following a Consumer Use Study. Symptom Descriptors How would you describe your dandruff severity before you tried this product? How would you describe your dandruff severity after 2 weeks of using this product? p-values Extremely Slight to Slight 50%89%p≤0.05 Moderate to More than Moderate 50%11%p≤0.05 Table 1. Mean Self Assessed Symptoms by ASFS Severity (Study A) Antifungal Assays In Vitro/In Vivo TestPotentiated 2% ZPT Shampoo Placebo Shampoo Solution-Based Growth Inhibition 0.978 ppm>31.3 ppm ZOI (1:10 dilution)30.47 mm0 mm Mean In Vivo Log Malassezia reduction from baseline at week 2 -1.28 (n=20) -0.053* (n=14) * Mean of 9 historical studies In Vitro & In Vivo Antifungal Tests In vitro and in vivo testing show potentiated 2% ZPT shampoo to be effective against Malassezia (Table 4). Table 4. In Vitro and In Vivo Malassezia reductions. Consumer Study Following 2 weeks of consumer usage, the potentiated 2% ZPT shampoo reduced dandruff symptoms reported to be ‘moderate to more than moderate’ from 50% to 11%.