PHASE I STUDY OF TESTODERMR-TTS IN HYPOGONADAL MALES WITH/WITHOUT AIDS

在患有/未患有艾滋病的性腺机能减退男性中进行 TestodeMR-TTS 的 I 期研究

• 批准号: 6243971
• 负责人: CAROL S DUKES-HAMILTON
• 金额: $ 3.24万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1975
• 资助国家: 美国
• 起止时间: 1975-10-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6243971
• 关键词: AIDS therapy; HIV infections; basal metabolism; body weight; clinical research; clinical trial phase I; drug screening /evaluation; hormone regulation /control mechanism; hormone therapy; human subject; human therapy evaluation; hypogonadism; male; quality of life; testosterone; transdermal drug delivery

The Testoderm C-95-046 Study was a pharmacokinetic (PK) study of a transdermal patch containing the male hormone, testosterone, in HIV- positive and HIV-negative males, who were hypogonadal by measurement of serum testosterone. The PK study was a companion study designed to measure the serum testosterone at baseline, and at the end of a 28 day time period during which participants wear the transdermal patch. A second part of the study measured serum testosterone after another 28 days of medication usage. The drug was given as a transdermal patch worn on the scrotum, and changed daily. The first 2 days of the study (baseline and day one of therapy) were spent as an inpatient in the GCC, during which time a careful physical examination was performed, and 12 blood samples were obtained, as part of the pharmacokinetic data collection. Patients were then instructed in use of the patches and sent home for self-administration. Patients returned to clinic on days 7, 14 and 21 for more blood tests. Patients were again admitted to the GCC on day 27 of the study, for urine and blood testing (16 blood samples). A quality of life questionnaire was filled out at both the first and the second GCC inpatient stay. Clinic evaluations, consisting of a brief evaluation and blood sampling, occurred in the outpatient clinic on days 42 and 56. On day 56, the final day of the study, a physical exam was also performed. The study's potential significance lies in the fact that testosterone, unlike other hormonal manipulations and patient-independent nutrition (e.g., TPN), adds lean body mass to HIV-infected and wasted patients, rather than fat. This is important as we become aware of the need to address the dysfunctional metabolism that studies have now shown to be common in advanced HIV-infection and AIDS. In addition, testosterone appears to contribute to an increased sense of well-being. Results of C-95-012: Nationally, 124 men, with a mean weight loss of 7% of body mass, were enrolled. The Testoderm patches effectively increased serum testosterone levels, with concomitant decrease in FSH and LH levels, as expected. Unfortunately, changes in weight or lean body mass did not reach statistical significance. Quality of life measures and measures of sexual function were also not different between placebo and treatment. There were no differences in HIV viral load between placebo and treatment groups, and no relevant differences in adverse events. Sample size calculations were done to provide 90% power to detect a difference of 2.0 kg in the change in body cell mass from baseline. Co-variate and subgroup analyses were performed for body cell mass using the variables CD4, total and free testosterone, use of protease inhibitor, and history of opportunistic infections. No effects were observed in the co-variate analysis and no differences in the subgroups were observed. Analysis of the continuation, unblinded study (C-95-013) and the PK study are underway.

Testoderm C-95-046 研究是一项药代动力学 (PK) 研究 含有男性荷尔蒙、睾酮的透皮贴剂，可用于 HIV- HIV 阳性和阴性男性，通过测量发现性腺功能减退 血清睾酮。 PK 研究是一项配套研究，旨在 测量基线和 28 天结束时的血清睾酮 参与者佩戴透皮贴剂的时间段。 一个 研究的第二部分在另外 28 名患者之后测量了血清睾酮水平 药物使用天数。 该药物以透皮贴剂形式给药 戴在阴囊上，每日更换。 研究的前2天 （基线和治疗第一天）在海湾合作委员会住院治疗， 在此期间进行了仔细的身体检查，12 获取血液样本，作为药代动力学数据的一部分 收藏。 然后指导患者使用贴剂和 送回家进行自我管理。 患者几天内返回诊所 7、14 和 21 日进行更多血液检查。 患者再次被收治入院 GCC 在研究第 27 天进行尿液和血液检测（16 次血液检测） 样品）。 双方均填写了生活质量调查问卷 第一次和第二次 GCC 住院。 临床评估，包括 在门诊进行的简短评估和血液采样 第 42 天和第 56 天到诊所。第 56 天，即研究的最后一天， 还进行了身体检查。 这项研究的潜在意义在于睾酮， 与其他激素控制和患者独立营养不同 （例如，TPN），为艾滋病毒感染者和消瘦的患者增加瘦体重， 而不是脂肪。 这很重要，因为我们意识到有必要 解决目前研究表明的代谢功能失调问题 常见于晚期艾滋病毒感染和艾滋病。 此外，睾酮 似乎有助于增加幸福感。 C-95-012 的结果：全国 124 名男性，平均体重减轻 7% 体重，被登记。 睾丸有效地修补 血清睾酮水平升高，同时 FSH 降低 和 LH 水平，如预期。 不幸的是，体重或瘦肉的变化 体重未达到统计学显着性。 生活质量 性功能的测量和测量之间也没有差异 安慰剂和治疗。 HIV病毒载量没有差异 安慰剂组和治疗组之间没有相关差异 不良事件。 样本量计算提供 90% 的功效 检测体细胞质量变化 2.0 kg 的差异 基线。 对体细胞进行协变量和亚组分析 使用变量 CD4、总睾酮和游离睾酮、使用 蛋白酶抑制剂和机会性感染史。 不 在协变量分析中观察到效果，并且没有差异 观察亚组。 连续性分析，非盲法 研究（C-95-013）和 PK 研究正在进行中。