• Cumulative Irritation Potential and Contact Sensitization Potential of Tazarotene Foam 0.1% in 2 Phase 1 Patch Studies

    Jeffrey E. Berg, BSc, CCRA, James P. Bowman, MS; Alessandra B. Alio Saenz, MD, Cutis, Volume 90, pgs. 206-211, October 2012

    We performed 2 phase 1 patch studies to evaluate tazarotene foam 0.1% for cumulative irritation potential (study A) and contact sensitization potential (study B). Study A participants wore patches containing active study product, vehicle foam, and positive and negative controls for 24±1 hours for 21 consecutive days. Irritation scores were statistically higher with tazarotene foam 0.1% than vehicle foam and both controls. Fourteen participants (36%) experienced product-related, application-site adverse events (AEs); all of the AEs were mild and transient. Study B participants were exposed to active product and vehicle foam for an induction and challenge phase. At the investigator’s discretion, participants were administered a rechallenge to evaluate for contact sensitization. Three participants demonstrated questionable sensitization reactions and under-went a rechallenge; none of the participants displayed conclusive contact sensitization. Three application-site AEs were considered to be product related; none of the AEs led to study discontinuation. Tazarotene foam 0.1% showed potential to induce irritation but a low potential for contact sensitization and an acceptable tolerability and safety profile.

  • Pharmacokinetics and Safety of 0.5% Ivermectin Lotion for Head Louse Infestations

    Lydie Hazan, M.D., Jeffrey E. Berg, B.Sc., CCRA,  James P. Bowman, M.S., John V. Murray, M.D. and William G. Ryan, B.V.Sc., Pediatric Dermatology 1-6, 2012, available online

    The safety of a novel 0.5% ivermectin lotion (IVL) and potential for ivermectin absorption after application was investigated in an open-label study in young children, and a human repeat insult patch test (HRIPT) and cumulative irritation test (CIT) assessed any potential for cumulative dermal irritation and contact sensitization. In the pharmacokinetic and safety study, 30 head louse–infested children ages 6 months to 3 years received a 10-minute application of IVL on day 1. Blood was collected before application; 0.5, 1, and 6 hours after rinsing; and on days 2 and 8. Samples from 20 subjects were assayed for ivermectin (test sensitivity 0.05 ng/mL). Liver panel and complete blood counts were completed for all subjects. For the HRIPT/CIT, occlusive patches containing IVL or vehicle control lotion (CL) were repeatedly applied to 220 healthy adult subjects to assess contact sensitization; for cumulative dermal irritation testing, additional patches with normal saline and sodium dodecyl sulfate (SDS) were applied to 36 subjects. In the open-label study, all detected ivermectin plasma concentrations were <1 ng/mL. No safety signals emerged, and treatment was well tolerated. In the HRIPT/CIT, IVL was significantly less irritating than normal saline and SDS, with no evidence of dermal irritation or sensitization in human skin. IVL was safe when applied topically, absorption was de minimus, there was no evidence of irritation or sensitization from repeated exposures, and results support the safety of topical IVL use in children as young as 6 months.

  • The Differences of Human Cumulative Irritation Response to Positive and Negative Irritant Controls from Three Geographical Locations

    Mingyi W. Trimble, (Hill Top Research, OH) and Nalini Kaul, (Hill Top Research, CA), John E. Wild and James P. Bowman (Hill Top Research, OH). J Cosmet Sci 2007, Vol. 58 (Sep/Oct). PP 519-525.

    A retrospective analysis was conducted to evaluate whether studies from three geographically diverse locations have similar response profiles to the positive and negative controls in a standard 14-day cumulative irritation study (1). The positive irritant control (0.1% sodium lauryl sulfate, SLS) and the negative control (0.9% sodium chloride, saline) data from seventeen 14-day cumulative irritation studies were reviewed. The studies were compiled from three locations representing dry/hot, humid/hot, and dry/cold environments (Scottsdale, Arizona, St. Petersburg, Florida and Winnipeg, Manitoba, respectively). Irritation scores were generated by trained skin graders from a total of 442 completed subjects between 1999 and 2005. Cumulative irritation scores were reviewed and compared between study locations. The irritation scores for the positive and negative control were not significantly different between locations. Temperature and relative humidity (RH) variation did not correlate significantly with overall irritation. However, the dryer climate (i.e., negative or low dew point) had a tendency to induce a higher overall irritation level for both positive and negative controls.