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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15 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 Efficacy and safety. A Phase III, multicenter, randomized, vehicle-controlled, double-blind, parallel-group study in adults with mild-to- moderate plaque psoriasis was conducted to compare the safety and efficacy of BD spray 0.05% with that of a vehicle and with that of augmented BD lotion 0.05% (Diprolene® AF; Merck & Co., Inc., Kenilworth, New Jersey, USA). (ClinicalTrials.gov identifier: NCT01947491.) The first subject was enrolled on November 8, 2013, and the last subject completed the study on January 12, 2015. To participate, subjects had to be at least 18 years old; have a clinical diagnosis of stable (3 months or longer) plaque-type psoriasis involving 10 to 20-percent BSA (excluding the face, scalp, groin, axillae, and other intertriginous areas); and have a baseline Investigator's Global Assessment (IGA) grade of 3 (moderate). Subjects were excluded if they had a current diagnosis of unstable form(s) of psoriasis (including guttate, erythrodermic, exfoliative, or pustular); another inflammatory skin disease that might confound evaluation (e.g., atopic dermatitis, contact dermatitis, tinea corporis); pigmentation; extensive scarring; pigmented lesions; sunburn that might interfere with the rating of efficacy parameters; or a history of psoriasis unresponsive to topical treatments. Also excluded were those with a history of organ transplant requiring immunosuppression, human immunodeficiency virus, or another immunocompromised state. The use of biologic treatments within six months; systemic steroids, phototherapy, or systemic anti-inflammatory agents within 30 days; or topical antipsoriatic drugs, retinoids, or steroids within 14 days of baseline evaluation was prohibited. Subjects were randomized to receive BD spray 0.05%, vehicle spray, augmented BD lotion 0.05%, or vehicle lotion in a 4:2:2:1 ratio. Subjects in the BD spray 0.05%, vehicle spray, or vehicle lotion groups applied the study drug twice daily for 28 days. To comply with drug labeling restrictions and to maintain blinding, subjects in the augmented BD lotion 0.05% group applied treatment twice daily for 14 days, crossed over to the vehicle lotion group on Day 15, and applied the vehicle lotion twice daily for the subsequent 14 days. Subject visits occurred at screening to obtain informed consent, tentatively determine eligibility, or to initiate washout; Day 1 (baseline); Day 4 ±1 day; Day 8 ± 1 day; Day 15±1 day; and Day 29 ±3 days. The maximum number of days allowed between screening and baseline was 60; the screening and baseline visits could be combined when all required procedures for both visits were completed on the same day. The study duration from initial treatment to final evaluation was 29 days (± 3 days); the maximum duration of subject participation was 92 days (i.e., 60 days for screening plus 32 days after the initial treatment). Disease severity was assessed primarily by IGA and secondarily by using the Total Sign Score (TSS, the sum of individual scores for erythema, scaling, and plaque elevation) for a representative target lesion on Days 1, 4, 8, 15, and 29. Treatment success was defined as an IGA of 0 or 1 with at least a two-grade reduction from baseline at the Day 15 visit, and the primary efficacy endpoint was the proportion of subjects with treatment success at Day 15. Safety assessments included vital signs (blood pressure, pulse); urine pregnancy tests; local cutaneous safety evaluation of treated areas (atrophy, telangiectasia, itching, pain, and burning/stinging); and adverse events (AEs). Vital signs (blood pressure, pulse) were collected at each visit; urine pregnancy tests for women of childbearing potential were conducted on Days 1, 15, and 29. All statistical processing was performed using SAS software (SAS Institute, Cary, North Carolina, USA) unless otherwise stated. Two- sided hypothesis testing was conducted for all analyses using a significance level of 0.05. Type-1 error was controlled using a step-wise gatekeeping strategy. The primary efficacy analyses were performed on the intent-to-treat population; safety analyses were performed on the safety population. Detailed descriptions of the methods employed in this study are available elsewhere. 8,9 Adrenal suppression. This was a 15-day or 29-day randomized, multicenter, multi-dose, comparator-controlled, open-label study in adults with moderate to severe plaque psoriasis (ClinicalTrials.gov identifier: NCT02070965). Subjects were randomized in a 1:1:1 ratio to receive BD spray 0.05% for 15 days, BD spray 0.05% for 29 days, or augmented BD lotion 0.05% for 15 days. Study treatments were applied twice daily to the affected areas, excluding the face, scalp, groin, axillae, and other intertriginous areas. Subject visits were scheduled at screening; Day 1 (baseline); Days 8, 15, 29 (as appropriate); and Day 43 or 57 (if needed to confirm recovery from hypothalamic- pituitary-adrenal [HPA]-axis suppression). Clinical determinations of disease severity were conducted using the IGA for overall severity at each visit. No more than 60 days were permitted between screening and baseline. Local cutaneous safety evaluations (including atrophy, telangiectasia, pruritus, pain, and burning/stinging) were performed at each visit. Other safety assessments included vital signs (blood pressure, pulse), urine pregnancy tests, and collection of AEs. Subjects were tested for HPA-axis function using the adrenocorticotropic hormone (ACTH) stimulation test (intravenous or intramuscular cosyntropin) at least 14 days and no more than 28 days prior to the baseline visit and at the end of treatment visit. The screening ACTH stimulation test was conducted on the day of the screening visit (if timing was appropriate) or on a separate day (e.g., if washout was needed). An abnormal result was defined as a plasma cortisol level of 18μg/dl or less at 30 minutes after ACTH administration. If the HPA axis was suppressed at the end of treatment visit, another test was administered on Day 43 or 57, as appropriate, to confirm recovery, and the test was repeated until the HPA axis was stabilized or explained. At the screening ACTH stimulation test, a blood sample was taken to obtain a baseline value for blood levels (pharmacokinetics [PK]) of BD, betamethasone- 17-propionate, and betamethasone. At the end of treatment visit, subjects applied the last dose of the study product at the clinic up to 60 minutes after a pre-treatment PK blood sample was taken; samples were then collected at one, three, and six hours (±5 minutes) after application of the study product to assess the levels of BD, betamethasone- 17-propionate, and betamethasone. Plasma BD, betamethasone-17-propionate, and betamethasone were measured by a validated, liquid chromatography-mass spectrometry analytic method with a limit of quantitation of 5pg/mL. All statistical processing was performed using SAS software version 9.3 or later and all summaries were performed on the safety population. No inferential testing was performed, no interim analyses were planned,

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