DERMALLY APPLIED T GEL PREPARATION IN HYPOGONADAL MALES

性腺机能减退男性的皮肤应用 T 凝胶制剂

• 批准号: 6415309
• 负责人: THOMAS J WEBER
• 金额: $ 29.31万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-12-01 至 2001-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6415309
• 关键词: androgens; clinical research; dosage; drug screening /evaluation; hormone therapy; human subject; human therapy evaluation; hypogonadism; male; testosterone; transdermal drug delivery

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.

目得：本研究的目的是评估睾酮1%水醇（T-凝胶）的安全性和有效性，作为一种手段，以提供雄激素替代性腺功能减退的男性后，每天给药六个月。待检验的假设是，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剂。方法：以前的研究表明，与肌肉注射睾酮相比，皮肤贴剂是一种上级递送系统。在这项研究中，将监测患者的睾酮变化和其他激素水平，包括促性腺激素、雌二醇、脱水睾酮、催乳素以及血脂、血液化学和血细胞计数。此外，将通过直肠检查和前列腺特异性抗原水平进行前列腺评价。将测量患者的骨形成和骨吸收标志物，并进行骨密度研究。此外，患者将填写有关情绪和性功能的问卷。有资格参加本研究的患者将是年龄在18至68岁之间的男性，他们已被诊断患有睾酮缺乏症，需要睾酮替代治疗。选定的患者应健康状况良好，无显著的全身性疾病，并且应无预先存在的前列腺异常。大多数患者将接受雄激素替代治疗，并且在进入方案之前将有一个洗脱期，对于肌肉内睾酮注射至少6周，对于经皮或口服雄激素至少4周。患者将接受筛选检查，以验证其雄激素缺乏综合征并确认其符合方案标准。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 mg T-凝胶或第三组，他们将服用目前可用的透皮睾酮贴剂。药物暴露持续时间为180天，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天监测患者。在第0、1、30、90和180天，将对患者进行采血，并在贴敷凝胶或贴剂后的-30、-15、0和2、4、8、12和24小时进行采血。第60、120和150天将在门诊进行单次上午采血。结果：入组期已结束。1例患者仍需完成研究。目前尚无结果。2例患者因不良事件提前终止研究。1例患者因皮肤对睾酮贴片不耐受而停药，并希望使用其他勃起增强疗法。1例患者因重度高血压退出研究，认为与研究药物无关。这项研究的意义和未来的计划：这项研究的意义在于，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。虽然这些是有效的，但它们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。这通常与深部肌肉注射的疼痛和注射部位臀部的一些疤痕有关。目前的补丁，Androderm，经常导致皮肤刺激。超过一半的患者尝试这种形式的替代品时会出现皮肤刺激，一旦出现这种问题，很少有人能忍受。新的凝胶制剂允许给予可由患者在皮肤上摩擦的测量剂量。本研究的结果将为今后的研究提供依据。