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Efficacy and Safety Endpoints Reached for Long-Acting Injectable Testosterone Therapy
"I am extremely pleased to report the successful completion of our Nebido study and we are looking forward to the submission of our NDA later this summer," stated Glenn L. Cooper, M.D., chairman and chief executive officer of Indevus. "The market opportunity for Nebido is substantial. The results of our trial demonstrate the potential of Nebido , the only once every three month treatment for male hypogonadism, to dramatically improve the treatment options for men who suffer from this condition."
The study was designed to supplement the European clinical trial database (originally generated by Bayer Schering Pharma AG, Germany), which has formed the basis for the approval of Nebido in over 75 countries to date. Specifically, the purpose of the completed Phase III trial was to evaluate Nebido under U.S. Food and Drug Administration (FDA) pharmacokinetic guidelines for the approval of testosterone therapy products for male hypogonadism.
The Phase 3 pharmacokinetic trial was a randomized open-label (unblinded) study that included the evaluation of the pharmacokinetics of Nebido dosed as either 1000 mg every 12 weeks or as 750 mg every 12 weeks, both via intramuscular injection. The primary endpoints included a responder analysis (based on guidelines provided from the FDA for average testosterone concentrations over the steady state dosing interval) and an outlier analysis (based on the maximum testosterone concentrations during the steady state dosing interval). Specifically, a responder was defined (per the FDA) as a patient who, during steady state had an average concentration of serum total testosterone (Cavg) within the normal range (300 to 1000 ng/dL). The primary response endpoint was met if at least 75% of patients achieved a Cavg within this normal range. FDA also provided guidelines related to maximum testosterone (Cmax) levels, including thresholds that no patient should exceed a testosterone concentration of 2500 ng/dL, no more than 5% of patients should exceed a concentration of 1800 ng/dL, and no more than 15% of patients should exceed a concentration of 1500 ng/dL.
In addition, secondary outcomes included measurements evaluating the general health and well-being of the patients by questionnaires and assessment tools.
The trial randomized a total of 237 male hypogonadal patients (117 patients treated in the 1000 mg dose arm and 120 patients treated in the 750 mg dose arm). The patient completion rate of all 5 injections with Nebido was over 80%, demonstrating remarkably high treatment compliance for this one-year study. Reasons for discontinuation were similar between the treatment groups.
Of the 97 patients in the 1000 mg arm receiving their fourth injection, 94% had a Cavg over the course of the 12 week injection period that was within the normal range, demonstrating that treatment with Nebido was sufficient to maintain clinically therapeutic testosterone levels in hypogonadal men with injections given only once every 12 weeks (or just 4 to 5 times per year). Further, no patients in the 1000 mg arm exceeded a testosterone concentration of 2500 ng/dL; four of 97 (4.1%) patients had a peak level over 1800 ng/dL; and 11 of 97 (11.3%) patients had a peak level exceeding 1500 ng/dL. The duration of time any patient had a concentration over these Cmax thresholds was brief.
Of the 102 patients in the 750 mg arm receiving their fourth injection, 86% had a Cavg within the normal range. No patients in the 750 mg arm exceeded a testosterone level of either 2500 ng/dL or 1800 ng/dL, and only four of 102 (3.9%) patients had a peak level exceeding 1500 ng/dL. For those few patients exceeding the 1500 ng/dL threshold, the duration of time above the threshold was brief.
Both treatment arms demonstrated improvements from baseline in the key secondary clinical outcome variables.
Both doses of the drug were well-tolerated as indicated by the analysis of the safety measurements collected and the persistence with study treatment. Further, the spectrum of adverse events reported were comparable to other injectable hypogonadism treatments reported in the literature. There were no significant adverse changes in laboratory parameters with Nebido treatment.
Source: Indevus Pharmaceuticals