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

睾酮C-95-046研究是一项药物代动力学（PK）研究

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.