HYDRATION AND SPF TESTING OF LIP BALM FORMULATIONS 7 STUDY OUTCOMES Barrier function and moisturizing abilities study. The primary endpoint for study RH02116 was to determine the effect of fi ve lip balms (one test formulation and four comparator products) on barrier function 1, 3, and 6 h postapplication using the dry-skin leg model. The secondary endpoint was to determine the moisturizing abilities of the fi ve lip balms 1, 3, and 6 h postapplication, using the dry-skin leg model. Additional exploratory objectives included the following: to explore the effect of test product B on barrier function on dry lips during home use to explore the moisturizing abilities of test product B on dry lips using DMM, Corneometer, and clinical visual assessment of lip dryness during home use. SPF determination studies. The primary effi cacy endpoint for the four SPF studies was the individual SPF value (SPFi) of the test lip balm formulations 20–24 h after UV irradiation, determined by SPFi = MEDp/MEDu. An additional primary endpoint for studies RH02117 and RH01927 was label SPF, defi ned as the largest whole number less than SPF - (t* SE), where t is taken from the subjects’ t distribution table corresponding to the upper fi ve percent point with n - 1 degrees of freedom and SE is the standard error of the SPF value. The secondary endpoints were the safety and tolerability of the lip balm formulations. SAFETY ASSESSMENT In all fi ve studies, AEs were defi ned as any untoward medical occurrence in a patient or clinical investigation subject temporally associated with the use of an investigational product, whether or not considered related to the investigational product. Serious AEs (SAEs) were defi ned as any AE that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or sig- nifi cant disability/incapacity, or is a congenital anomaly/birth defect. In study RH02116, AEs and SAEs were collected from the start of investigational product use until 5 d fol- lowing last application of the investigational product. In the SPF studies, AEs and SAEs were recorded from the start of UV irradiation until 5 days following last application of the investigational product. SAEs related to study participation were recorded from the time the participant consented up to and including any follow-up contact. Subjects were asked about AEs at each study visit. In study RH02116, AEs were listed by treatment phase. Prior and concomitant medication use and concomitant nondrug treatment/proce- dures were recorded for each participant in all fi ve studies. Assessment of the relationship between the investigational product and the occurrence of each AE or SAE was performed by the respective investigator. STATISTICAL ANALYSES Barrier function and moisturizing abilities study. Study RH02116 was an exploratory study and no formal sample size calculation was undertaken however, 20 participants was considered adequate. All valid data from each of the four objective measurements (TEWL, Skicon, DMM, and Corneometer) of either barrier function or skin hydration were used in the intent-to-treat (ITT) analysis. All participants enrolled in this study were also considered evaluable for the determination of SPF. Statistical analyses included calculation of the mean,

JOURNAL OF COSMETIC SCIENCE 8 standard deviation (SD), median, minimum, and maximum for each assessment parameter for each of the products evaluated, in both the leg hydration phase and the home-use lip hydration phase of the study. Analysis of covariance (ANCOVA) was used to compare test product B with each of the four comparator products at each time point using TEWL, Skicon, and Corneometer measurements. The ANCOVA model included treatment as a fi xed effect, subject as a random effect, and baseline values on a site level and subject level for each measurement as covariates. SPF determination studies. In the SPF studies, data were rejected if irradiation did not achieve an MED or an erythemal response, if all subsites showed an erythemal response, or if re- sponses on the treatment site were absent 20–24 h postirradiation. The calculated SPF for a test product was considered valid if the SPF value of the positive control P2 fell within the SD range of the intended SPF, for either ISO 24444 (16.4 ± 2.4) or the FDA fi nal rule (16.3 ± 3.43). No formal statistical comparisons of calculated SPF values between the fi ve test products were conducted. In studies RH01927 and RH02117, sample size calculations determined that a minimum of 10 participants, and no more than 13, were required per product to produce valid test results for a screening study. Statistical analyses included calculation of the mean, SD, coeffi cient of variation (CV), and lower one-sided 95% confi dence interval (CI) of the SPF for each product. In study RH01928, sample size calculations determined that a minimum of 10 partici- pants and a maximum of 25 were required per product. A minimum of 10 valid partici- pant SPF results and a maximum of 20 were required to determine the mean SPF of each product. The number of valid SPF results was deemed suffi cient when the 95% CI was within ±17% of the mean SPF. If more than 20 results were needed to reach this criterion, the test was deemed invalid. Statistical analysis included calculation of the mean, SD, CV, SE, and 95% CI of the SPF for each product. In study RH02385, the safety population (SP) used for the safety analysis included all enrolled participants who received the fi rst irradiation for MEDu determination. The per- protocol population used for effi cacy analysis was defi ned per product and included all participants meeting the inclusion and exclusion criteria and who completed the study without protocol violations. A minimum of 10 participants were recruited as per the FDA fi nal rule (5) and ISO 24444 (6), with additional participants recruited if required for ISO 24444, up to a maximum of 25. The statistical analyses included calculation of the mean and 95% CI of the SPF for each product. RESULTS DISPOSITION AND BASELINE CHARACTERISTICS Barrier function and moisturizing abilities study. In study RH02116, a total of 39 individuals were screened, of whom 24 were randomized and included in the SP and ITT popula- tions 12 participants did not meet the study criteria and three participants decided not to participate before randomization. One individual did not complete the study because of failure to meet baseline criteria. All participants were female Caucasians with a mean age of 38.2 years (Table II). A subset of participants (n = 4) were enrolled into the home-use lip hydration phase of the study.