Luger T, Van Leent E J, Graeber M, Hedgecock S, Thurston M, Kandra A, Berth-Jones J, Bjerke J, Christophers E, Knop J, Knulst A C, Morren M, Morris A, Reitamo S, Roed-Petersen J, Schoepf E, Thestrup-Pedersen K, Van Der Valk P G, Bos J D
Department of Dermatology, University of Muenster, Germany.
Br J Dermatol. 2001 Apr;144(4):788-94. doi: 10.1046/j.1365-2133.2001.04134.x.
SDZ ASM 981 is a selective inhibitor of the production of pro-inflammatory cytokines from T cells and mast cells in vitro. It is the first ascomycin macrolactam derivative under development for the treatment of inflammatory skin diseases.
This study was designed to determine the safety and efficacy of SDZ ASM 981 cream at concentrations of 0.05%, 0.2%, 0.6% and 1.0% in the treatment of patients with atopic dermatitis and to select the concentration to be used in phase III studies.
This was a double-blind, randomized, parallel-group, multicentre dose-finding study. A total of 260 patients were randomly assigned to treatment with SDZ ASM 981 cream at concentrations of 0.05%, 0.2%, 0.6%, or 1.0%, matching vehicle cream, or the internal control 0.1% betamethasone-17-valerate cream (BMV). Treatment was given twice daily for up to 3 weeks.
A clear dose-response relationship for SDZ ASM 981 was evident, with 0.2%, 0.6% and 1.0% SDZ ASM 981 creams all being significantly more effective than vehicle (P = 0.041, 0.001 and 0.008, respectively) in terms of baseline to end-point changes in the Eczema Area Severity Index (EASI) and pruritus score. The 1.0% cream was the most effective SDZ ASM 981 concentration. BMV was more effective than the SDZ ASM 981 creams tested in this study. It appears that the efficacy plateau was not reached with the SDZ ASM 981 creams within 3 weeks treatment. SDZ ASM 981 was well tolerated. Burning or a feeling of warmth were the only adverse events reported more frequently in the 0.6% and 1.0% SDZ ASM 981 treatment groups than in the vehicle treatment group (42.9%, 48.9% and 34.9%, respectively). Few systemic adverse events were reported during the study (headache was the most frequent systemic event reported by 15 of 252 patients) and none was considered to be related to treatment. The local tolerability profile of the 1.0% cream was similar to that of the lower concentrations.
1.0% SDZ ASM 981 cream, which was shown to be safe, well tolerated and the most effective concentration in this study, was selected as the concentration to be further developed in phase III studies.
SDZ ASM 981是一种在体外可选择性抑制T细胞和肥大细胞产生促炎细胞因子的抑制剂。它是首个正在研发用于治疗炎性皮肤病的子囊霉素大环内酯酰胺衍生物。
本研究旨在确定浓度为0.05%、0.2%、0.6%和1.0%的SDZ ASM 981乳膏治疗特应性皮炎患者的安全性和有效性，并选择用于III期研究的浓度。
这是一项双盲、随机、平行组、多中心剂量探索性研究。总共260例患者被随机分配接受浓度为0.05%、0.2%、0.6%或1.0%的SDZ ASM 981乳膏、对照赋形剂乳膏或内部对照0.1%倍他米松-17-戊酸酯乳膏（BMV）治疗。每天给药两次，持续3周。
SDZ ASM 981呈现明显的剂量-反应关系，就湿疹面积和严重程度指数（EASI）及瘙痒评分从基线到终点的变化而言，0.2%、0.6%和1.0%的SDZ ASM 981乳膏均显著优于赋形剂（P值分别为0.041、0.001和0.008）。含1.0%药物的乳膏是SDZ ASM 981最有效的浓度。BMV比本研究中测试的SDZ ASM 981乳膏更有效。在3周治疗期内，SDZ ASM 981乳膏似乎未达到疗效平台期。SDZ ASM 981耐受性良好。仅在0.6%和1.0%的SDZ ASM 981治疗组中，灼烧感或温热感这两种不良事件的报告频率高于赋形剂治疗组（分别为42.9%、48.9%和34.9%）。研究期间报告的全身性不良事件很少（头痛是252例患者中15例报告的最常见全身性事件），且无一例被认为与治疗有关。含1.0%药物的乳膏的局部耐受性与较低浓度的相似。
在本研究中显示安全、耐受性良好且为最有效浓度的1.0% SDZ ASM 981乳膏，被选为III期研究中进一步研发的浓度。
