Testosterone Gel 1% was evaluated in a multi-center, randomized, parallel-group, active-controlled, 180-day trial in 227 hypogonadal men. The study was conducted in 2 phases. During the Initial Treatment Period (Days 1 to 90), 73 patients were randomized to Testosterone Gel 1% 50 mg daily, 78 patients to Testosterone Gel 1% 100 mg daily, and 76 patients to a non-scrotal testosterone transdermal system. The study was double-blind for dose of Testosterone Gel 1% but open-label for active control. Patients who were originally randomized to Testosterone Gel 1% and who had single-sample serum testosterone concentrations above or below the normal range on Day 60 were titrated to 75 mg daily on Day 91. During the Extended Treatment Period (Days 91 to 180), 51 patients continued on Testosterone Gel 1% 50 mg daily, 52 patients continued on Testosterone Gel 1% 100 mg daily, 41 patients continued on a non-scrotal testosterone transdermal system (5 mg daily), and 40 patients received Testosterone Gel 1% 75 mg daily. Upon completion of the initial study, 163 enrolled and 162 patients received treatment in an open-label extension study of Testosterone Gel 1% for an additional period of up to 3 years.

Mean peak, trough and average serum testosterone concentrations within the normal range (298 to 1043 ng/dL) were achieved on the first day of treatment with doses of 50 mg and 100 mg of Testosterone Gel 1%. In patients continuing on Testosterone Gel 1% 50 mg and 100 mg, these mean testosterone concentrations were maintained within the normal range for the 180-day duration of the original study. Figure 2 summarizes the 24-hour pharmacokinetic profiles of testosterone administered as Testosterone Gel 1% for 30, 90 and 180 days. Testosterone concentrations were maintained as long as the patient continued to properly apply the prescribed Testosterone Gel 1% treatment. 

Figure 2: Mean Steady-State Testosterone Concentrations in Patients with Once-Daily Testosterone Gel 1% Therapy

Table 4 summarizes the mean testosterone concentrations on Treatment Day 180 for patients receiving 50 mg, 75 mg, or 100 mg of Testosterone Gel 1%. The 75 mg dose produced mean concentrations intermediate to those produced by 50 mg and 100 mg of Testosterone Gel 1%.

Table 4: Mean (± SD) Steady-State Serum Testosterone Concentrations During Therapy (Day 180)

Of 129 hypogonadal men who were appropriately titrated with Testosterone Gel 1% and who had sufficient data for analysis, 87% achieved an average serum testosterone concentration within the normal range on Treatment Day 180.

In patients treated with Testosterone Gel 1%, there were no observed differences in the average daily serum testosterone concentrations at steady-state based on age, cause of hypogonadism, or body mass index.

DHT concentrations increased in parallel with testosterone concentrations at Testosterone Gel 1% doses of 50 mg/day and 100 mg/day, but the DHT/T ratio stayed within the normal range, indicating enhanced availability of the major physiologically active androgen. Serum estradiol (E2) concentrations increased significantly within 30 days of starting treatment with Testosterone Gel 1% 50 or 100 mg/day and remained elevated throughout the treatment period but remained within the normal range for eugonadal men. Serum levels of SHBG decreased very slightly (1 to 11%) during Testosterone Gel 1% treatment. In men with hypergonadotropic hypogonadism, serum levels of LH and FSH fell in a dose- and time-dependent manner during treatment with Testosterone Gel 1%.