Journal of Clinical and Aesthetic Dermatology

APR 2018

An evidence-based, peer-reviewed journal for practicing clinicians in the field of dermatology

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16 JCAD JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY April 2018 • Volume 11 • Number 4 O R I G I N A L R E S E A R C H and no statistical justification was made for the sample size. Potency. Two methodologically identical, single-point, randomized, evaluator-blinded, within-subject, single-center studies comparing the vasoconstrictive properties (potencies) of BD spray 0.05% with vehicle spray were conducted (1 pilot and 1 pivotal study). The vasoconstrictive properties were compared with six currently marketed topical steroid formulations of known potency (Table 1) in healthy, non-tobacco-using adults aged 18 to 65 years with a demonstrated blanching response to fluticasone propionate cream 0.05% (Fougera®; E. Fougera & Co., Melville, New York, USA) and a Fitzpatrick skin type of III or less. In both studies, 10μl of each formulation was applied to a single application site on the flexor surfaces of each subject's forearms (left and right) and kept in place for 16 hours; two untreated control sites were designated on each forearm. Konica Minolta CR-300 chroma meters (Konica Minolta Sensing Americas, Inc., Ramsey, New Jersey, USA; a-scale reading) were used to measure the degree of vasoconstriction at baseline and at 18 hours postdose using a rating scale in which 0 = no pallor, 1 = mild pallor, 2 = moderate pallor, and 3 = intense pallor. Assessments were performed under standard fluorescent lighting and at room temperature. The visual evaluators and the chroma meter operators had no knowledge of treatment locations at each site. Subjects were monitored throughout the studies for AEs, which were collected and subsequently coded in tabular form using the Medical Dictionary for Regulatory Activities version 16.1. The severity of AEs was determined by clinic staff based on the observation and questioning of the affected subjects; investigators judged the relationship of AEs to study treatments. Statistical analyses were performed separately for the visual and chroma meter data using SAS version 9.3 at a five-percent (two- tailed) significance level. Data were analyzed for mean differences among treatments using a randomized block analysis of variance or a nonparametric analog using the ranks of the scores, as deemed appropriate. The subject was the blocking variable. Within these analyses, pairwise comparisons of the mean assessment scores (chroma meter or visual) were performed using the Ryan–Einot–Gabriel–Welsch Multiple Range Test (REGWQ). The primary analyses were based on the visual scoring; the secondary analyses used data from the chroma meter corrected for both the average baseline readings and the average baseline-adjusted readings from the untreated sites. The relative potency of the test formulation of BD spray 0.05% was estimated by comparing it with the reference products of known potency. RESULTS Efficacy and safety. A total of 394 subjects were randomized: 174 to BD spray 0.05%, 87 to vehicle spray, 90 to augmented BD lotion 0.05%, and 43 to vehicle lotion. The majority of subjects (≥ 88%) in all treatment groups completed the study. The most common reason for early withdrawal was subjects being lost to follow-up (Table 2). Demographic and baseline characteristics are presented in Table 3. For the primary efficacy endpoint, the proportion of subjects with treatment success at Day 15, BD spray 0.05% was significantly superior to vehicle spray (19.0% vs. 2.3%, respectively, P<0.001). The Day 15 treatment success rate for augmented BD lotion 0.05% was 18.9 percent versus 9.3 percent for vehicle lotion. BD spray 0.05% also had significantly greater treatment success than did vehicle spray at Day 8 (10.0% vs. 1.2%, P = 0.003) and Day 29 (34.5% vs. 13.6%, P <0.001). Figure 1 shows the TABLE 1. Medications compared with BD Spray, 0.05% to evaluate relative potency STUDY 1 STUDY 2 Augmented BD ointment 0.05% a Augmented BD ointment 0.05% a Augmented BD lotion 0.05% a Augmented BD lotion 0.05% a Augmented BD cream 0.05% b Augmented BD cream 0.05% b Mometasone furoate ointment USP ointment 0.1% c Triamcinolone acetonide cream 0.1% Fluticasone propionate cream 0.05% Fluticasone propionate cream 0.05% Hydrocortisone cream 2.5% Hydrocortisone cream 2.5% BD: betamethasone dipropionate a Diprolene® b Diprolene® AF c Elocon® TABLE 2. Disposition of subjects in the efficacy and safety study (n=394) DISPOSITION BD SPRAY, 0.05% (n=174) VEHICLE SPRAY (n=87) AUGMENTED BD LOTION 0.05% (n=90) VEHICLE LOTION (n=43) Completed, n (%) 166 (95.4) 81 (93.1) 88 (97.8) 38 (88.4) Discontinued, n (%) 8 (4.6) 6 (6.9) 2 (2.2) 5 (11.6) AE-related 0 (0.0) 1 (1.1) 0 (0.0) 2 (4.7) Lack of efficacy 1 (0.6) 0 (0.0) 0 (0.0) 1 (2.2) Lost to follow-up 5 (2.9) 3 (3.4) 1 (1.1) 2 (4.7) Protocol violation 1 (0.6) 0 (0.0) 0 (0.0) 0 (0.0) Withdrawal not due to AE 1 (0.6) 1 (1.1) 1 (1.1) 0 (0.0) Worsening of condition 0 (0.0) 1 (1.1) 0 (0.0) 0 (0.0) n: number; BD: betamethasone dipropionate; AE: adverse event

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