Efficacy and Safety of MED2005, a Topical Glyceryl Trinitrate Formulation, in the Treatment of Erectile Dysfunction: A Randomized Crossover Study
Efficacy and Safety of MED2005, a Topical Glyceryl Trinitrate Formulation, in the Treatment of Erectile Dysfunction: A Randomized Crossover Study
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DOI：
10.1016/j.jsxm.2017.12.003
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发表时间：
2018-02-01
影响因子：
3.5
通讯作者：
Holland, Tim
中科院分区：
文献类型：
--
作者：
Ralph, David J.;Eardley, Ian;Holland, Tim
背景资料：目前勃起功能障碍（艾德）的治疗方法存在一定的局限性。目的：本研究评价MED 2005的疗效和耐受性，MED 2005是一种0.2%硝酸甘油酯外用凝胶，配制成一种增强吸收的外用给药系统（DermaSys），按需给药，用于治疗艾德。这项随机、双盲、安慰剂对照、II期交叉试验涉及232名艾德男性（231名接受治疗，230名接受疗效评估）及其伴侣。4周导入期后，患者被随机分配至2个治疗序列之一，MED 2005-安慰剂或安慰剂-MED 2005。每次治疗持续4周，间隔1周洗脱期。通过国际勃起功能指数（IIEF）、性接触概况、全球评估问卷（GAQ）以及关于行动和治疗偏好（患者和伴侣）的开始和抵消的具体问题来评估疗效。结局：主要结局指标是IIEF勃起功能领域（IIEF-EF）评分。结果：平均基线IIEF-EF评分为17.1（SD = 5.7），MED 2005治疗后增加至19.6（SD = 7.5），安慰剂治疗后增加至18.5（SD = 6.7）（P = 0.0132）。总体而言，23.1%的患者在仅接受MED 2005治疗后IIEF-EF评分出现临床相关（>= 4分）增加，相比之下，14.5%的患者在接受MED 2005和安慰剂治疗后有反应，14.0%的患者在仅接受安慰剂治疗后有反应，48.4%的患者在两种治疗后均无反应（P = 0.0272）。与安慰剂相比，MED 2005在其他IIEF领域也有显著改善，这与患者和伴侣对GAQ的反应一致。对于所有评估，MED 2005的显著效果主要见于轻度ED患者。在MED 2005的所有性交尝试中，分别有44.2%和69.5%的患者在5分钟和10分钟内开始勃起。患者和伴侣对MED 2005的偏好明显高于安慰剂。MED 2005治疗期间最常报告的不良事件为头痛（患者n = 18 [7.9%];伴侣n = 3 [1.3%]）和鼻咽炎（患者，n = 13 [5.7%];伴侣，n = 2 [0.9%]）。临床意义：这些发现表明，外用硝酸甘油可能是艾德的一种有用的治疗选择。优势和局限性：本研究的优势包括使用了经过验证的结果测量。局限性包括仅使用1个剂量。结论：需要进一步研究以调查局部三硝酸甘油的疗效，包括更高的剂量，从而提高临床意义，特别是在中度和重度ED的情况下。Copyright（C）2017，Futura Medical.爱思唯尔公司出版代表国际性医学协会
Background: Current treatments for erectile dysfunction (ED) have some limitations.Aim: This study evaluated the efficacy and tolerability of MED2005, a 0.2% glyceryl trinitrate topical gel, formulated into an enhanced absorption topical delivery system (DermaSys), administered on demand, in the treatment of ED.Methods: This randomized, double-blinded, placebo-controlled, phase II crossover trial involved 232 men with ED (231 treated, 230 assessed for efficacy) and their partners. After a 4-week run-in period, patients were randomized to 1 of 2 treatment sequences, MED2005-placebo or placebo-MED2005. Each treatment was given for 4 weeks, separated by a 1-week washout interval. Efficacy was assessed by the International Index of Erectile Function (IIEF), the Sexual Encounter Profile, a Global Assessment Questionnaire (GAQ), and specific questions about the onset and offset of action and treatment preferences (patients and partners).Outcomes: The primary outcome measure was the IIEF erectile function domain (IIEF-EF) score. Other efficacy assessments were secondary outcomes.Results: The mean baseline IIEF-EF score was 17.1 (SD = 5.7), and this increased to 19.6 (SD = 7.5) after MED2005 treatment and 18.5 (SD = 6.7) after placebo (P =.0132). Overall, 23.1% of patients showed a clinically relevant (>= 4-point) increase in IIEF-EF scores after treatment with MED2005 only compared with 14.5% who responded after MED2005 and placebo, 14.0% who responded after placebo only, and 48.4% who did not respond after either treatment (P =.0272). MED2005 also was associated with significant improvements compared with placebo in the other IIEF domains, and this was consistent with patients' and partners' responses to the GAQ. For all assessments, significant effects of MED2005 were seen primarily in patients with mild ED. The start of erection was noticed within 5 and 10 minutes in 44.2% and 69.5%, respectively, of all intercourse attempts with MED2005. Patients and partners showed significant preferences for MED2005 over placebo. The most commonly reported adverse events during MED2005 treatment were headache (patients, n = 18 [7.9%]; partners, n = 3 [1.3%]) and nasopharyngitis (patients, n = 13 [5.7%]; partners, n = 2 [0.9%]).Clinical Implications: These findings suggest that topical glyceryl trinitrate could be a useful treatment option in ED.Strengths and Limitations: Strengths of this study include the use of a validated outcome measure. Limitations include the use of only 1 dosage.Conclusion: Further studies are warranted to investigate the efficacy of topical glyceryl trinitrate to include higher doses, thereby improving clinical significance, especially in cases of moderate and severe ED. Copyright (C) 2017, Futura Medical. Published by Elsevier Inc. on behalf of the International Society for Sexual Medicine.