DERMALLY APPLIED T GEL PREPARATION IN HYPOGONADAL MALES

目的：本研究的目的是评估1%睾酮水酒精（t -凝胶）作为一种为性腺功能低下的男性提供雄激素替代的方法，每日给药6个月后的安全性和有效性。要测试的假设是凝胶制剂是一种有效的雄激素替代形式作为目前可用的皮肤贴片。方法：先前的研究表明，与肌肉注射睾酮相比，皮肤贴片是一种更好的给药系统。在这项研究中，将监测患者的睾丸激素变化和其他激素水平，包括促性腺激素、雌二醇、二氢睾酮、催乳素，以及血脂、血液化学和血细胞计数。此外，前列腺评估将通过直肠检查和前列腺特异性抗原水平进行。患者将接受骨形成和骨吸收标志物测量，并进行骨密度研究。此外，患者将填写关于情绪和性功能的问卷。有资格参加这项研究的患者将是年龄在18到68岁之间的男性，他们被诊断为睾酮缺乏，需要睾酮替代。入选的患者应身体健康，无明显的全身性疾病，且既往无前列腺异常。大多数患者将接受雄激素替代治疗，并且在方案开始前将有一段洗脱期，肌肉注射睾酮至少6周，透皮或口服雄激素至少4周。患者将接受筛选检查，以确认其雄激素缺乏综合征，并确认他们符合方案的标准。患者将被随机分配到两种剂量的凝胶制剂中的一种，接受50或100毫克的t -凝胶，或接受目前可用的透皮睾酮贴片的第三组。药物暴露时间为180天，患者将在第0天、第1天、第30天、第30天、第60天、第90天、第120天、第150天和第180天接受监测。在第0、1、30、90和180天，患者将抽血，并在使用凝胶或贴片后的第30、15、0、2、4、8、12和24小时，在第60、120和150天，在诊所进行单次上午抽血。结果：入组期结束。还有一名患者需要完成这项研究。目前还没有结果。2例患者因不良事件提前终止研究。一名患者因皮肤对睾酮贴片不耐受而停止治疗，并希望使用其他勃起增强疗法。一名患者因严重高血压而退出研究，这被认为与研究药物无关。本研究的意义和未来计划：本研究的意义在于，与目前可用的雄激素替代形式相比，这种凝胶将提供一种更容易的递送系统。虽然这些方法有效，但对患者来说相对不舒服。肌肉注射睾酮酯是标准的雄激素替代疗法，但需要每两周注射一次。这通常与深层肌肉注射的疼痛和臀部注射部位的一些疤痕有关。目前的贴片，Androderm，经常引起皮肤刺激。在尝试这种替代形式的患者中，超过一半的患者会出现皮肤刺激，一旦出现这种问题，很少有人能忍受。这种新的凝胶配方可以测量剂量，病人可以在皮肤上摩擦。本研究结果将为今后的研究提供依据。

PURPOSE: The purpose of this study is to assess the safety and effectiveness of a testosterone 1% hydroalcoholic (T-gel) as a means to provide androgen replacement in hypogonadal men following its daily administration for six months. The hypothesis to be tested is that the gel preparation is an effective a form of androgen replacement as the currently available cutaneous patch. Methods: Previous studies have shown cutaneous patches to be a superior delivery system compared to intramuscular injections of testosterone. In this study, patients will be monitored for testosterone changes and other hormonal levels including gonadotropins, estradiol, dyhydrotestosterone, prolactin, as well as lipid profiles, blood chemistry and blood count. In addition, prostate evaluation will be performed by rectal examination and prostate specific antigen levels. Patients will have bone formation and resorption markers measured, and bone density studies will be performed. In addition, questionnaires will be filled out by the patients regarding mood and sexual function. Patients eligible for the study will be males between the ages of 18 and 68 years of age who have been diagnosed with testosterone deficiency requiring testosterone replacement. Selected patients should be in good health without a significant systemic illness and should have no pre-existing prostate abnormalities. Most patients will be on androgen replacement and will have a wash-out period prior to protocol entry of at least six weeks for intramuscular testosterone injections and four weeks for transdermal or oral androgens. Patients will undergo a screening examination to validate their androgen deficiency syndrome and to confirm they meet criteria for protocol. Patients will be randomized to one of two doses of gel preparation, receiving either 50 or 100 mg T-gel or to a third group who will take the currently available transdermal testosterone patch. The duration of drug exposure will be 180 days and patients will be monitored on day 0, day 1, day 30, day 30, day 60, day 90, day 120, day 150 and day 180. On days 0, 1, 30, 90 and 180, patients will have blood drawn and minus30, minus15, 0, and 2, 4, 8, 12 and 24 hours after application of the gel or patch Days 60, 120 and 150 will be single a.m. blood draws in the clinic. Results: Enrollment period has ended. One patient remains to complete the study. Results are not available at this time. Two patients discontinued the study early due to adverse events. One patient discontinued due to skin intolerance of the testosterone patch, and a desire to use other erectile enhancing therapies. One patient was dropped from the study because of severe hypertension, which was not thought to be related to the study drug. Significance of the study and future plans: The significance of this study is that this gel will provide an easier delivery system compared to currently available forms of androgen replacement. While these are effective, they are relatively uncomfortable for patients. The intramuscular injection of testosterone esters is the standard androgen replacement therapy but requires injections every two weeks. This is frequently associated with the pain of a deep intramuscular injection and some scarring in the buttocks where the injection is given. The current patch, Androderm, frequently causes skin irritation. Skin irritation occurs in over half of the patients trying this form of replacement and few can tolerate this problem once it develops. The new gel formulation allows a measured dose to be given which can be rubbed on the skin by the patient. The results of this study will provide the basis for future studies.