Pregabalin does not affect sperm production in healthy volunteers: a randomized, double-blind, placebo-controlled, noninferiority study.

OBJECTIVE: The primary objective of this study was to compare the effects of pregabalin and placebo on sperm concentration in healthy male subjects. Changes in follicle-stimulating hormone (FSH), testosterone, sperm motility, semen volume, and sperm morphology were also examined. METHODS: This was a phase 4, multicenter, double-blind, randomized, placebo-controlled, noninferiority study. A 12-week treatment period (placebo or 600 mg/day of pregabalin) was followed by a 1-week taper period and a 13-week washout period. The primary outcome measure was the percentage of subjects with a ≥ 50% reduction from baseline in sperm concentration at End of Study. RESULTS: One hundred and nine subjects received placebo and 111 subjects received pregabalin. The difference between placebo and pregabalin with respect to the percentage of subjects with a ≥ 50% reduction from baseline in sperm concentration at End of Study was 6% (95% CI: -2.29 to 14.3%). Noninferiority of pregabalin compared to placebo was declared as the upper bound of the 95% CI was less than the prespecified noninferiority margin of 20%. There were no significant differences between placebo and pregabalin groups with respect to their effects on FSH, testosterone, or sperm motility. Changes in semen volume and sperm morphology were numerically similar in both treatment groups. Adverse events were consistent with the known safety profile of pregabalin. Treatment with 600 mg/day pregabalin for 12 weeks does not adversely affect spermatogenesis or serum levels of FSH and testosterone in healthy males.

Onset of efficacy of tadalafil once daily in men with erectile dysfunction: a randomized, double-blind, placebo controlled trial.

PURPOSE: We evaluated the efficacy onset and safety of tadalafil 2.5 and 5 mg once daily for 14 days compared with placebo in men with erectile dysfunction. MATERIALS AND METHODS: In this randomized, double-blind, placebo controlled, parallel group study we randomized 372 men after a 4-week run-in period to receive placebo, or tadalafil 2.5 or 5 mg once daily for 14 days, followed by a 14-day open label extension period of tadalafil 5 mg once daily. Primary analysis focused on the cumulative percent of men with a successful intercourse attempt during the first 4 days of treatment. On secondary analysis we evaluated the percent of successful attempts during the study. The Sexual Encounter Profile diary question 3 was used to assess efficacy. Safety was assessed by monitoring adverse events and vital signs. RESULTS: Significantly more men in the tadalafil 5 mg group achieved successful intercourse, as indicated by a yes response to diary question 3, than those on placebo by day 2 (48.6% vs 36.6%, p < 0.025). The tadalafil 2.5 mg group did not separate from the placebo group on primary analysis. Secondary analysis showed that men on tadalafil 2.5 mg achieved a significantly higher percent of successful intercourse attempts than those on placebo by day 3 (35.5% vs 27.2%, p < 0.025). All groups further improved during the open label extension period. Tadalafil was well tolerated. CONCLUSIONS: This prospective trial shows the onset of efficacy of tadalafil 2.5 and 5 mg once daily within a few days of initiating therapy.

Daily vardenafil for 6 months has no detrimental effects on semen characteristics or reproductive hormones in men with normal baseline levels.

PURPOSE: Phosphodiesterase type 5 inhibitors are the first choice therapy in the treatment of erectile dysfunction. Many men in their reproductive years are now using phosphodiesterase type 5 inhibitors. The purpose of this study was to determine the effects of 6 months of treatment with 20 mg vardenafil, compared with 100 mg sildenafil and placebo, on semen characteristics and reproductive hormones in men with and without erectile dysfunction. MATERIALS AND METHODS: This was a randomized, double-blind, placebo controlled, parallel group, multicenter study. A total of 200 men with or without erectile dysfunction, able to produce semen samples without erectile dysfunction therapy, 25 to 64 years old, were randomized to daily treatment with vardenafil, sildenafil or placebo for 6 months. The primary variable was the percentage of vardenafil treated individuals with a 50% or greater decrease in mean sperm concentration from baseline to 6-month last observation carried forward, compared with placebo treated individuals. RESULTS: The between group difference (vardenafil minus placebo) in the percentage of patients with 50% or greater decrease in sperm concentration (baseline to 6 months last observation carried forward) was 0.07% (95% CI, -8.53% to 8.39%). Vardenafil also had no clinically significant effects on any other semen parameters, or on levels of reproductive hormones, when compared with placebo. Similar data were observed with sildenafil. CONCLUSIONS: This study demonstrated that vardenafil had no adverse effects on sperm concentration, compared with sildenafil and placebo, when administered daily at the maximum recommended dose for 6 months. Specifically, use of vardenafil for 6 months does not impair sperm concentration, total sperm count per ejaculate, or sperm morphology and motility. Levels of reproductive hormones were also unaffected.

Granulocyte macrophage colony-stimulating factor--secreting allogeneic cellular immunotherapy for hormone-refractory prostate cancer.

PURPOSE: This trial evaluated the safety, clinical activity, and immunogenicity of an allogeneic cellular immunotherapy in 55 chemotherapy-naïve patients with hormone-refractory prostate cancer (HRPC). The immunotherapy, based on the GVAX platform, is a combination of two prostate carcinoma cell lines modified with the granulocyte macrophage colony-stimulating factor (GM-CSF) gene. EXPERIMENTAL DESIGN: HRPC patients with radiologic metastases (n = 34) or rising prostate-specific antigen (PSA) only (n = 21) received a prime dose of 500 million cells and 12 boost doses of either 100 million cells (low dose) or 300 million cells (high dose) biweekly for 6 months. End points were changes in PSA, time to progression, and survival. RESULTS: Median survival was 26.2 months (95% confidence interval, 17, 36) in the radiologic group: 34.9 months (8, 57) after treatment with the high dose (n = 10) of immunotherapy and 24.0 months (11, 35) with the low dose (n = 24). The median time to bone scan progression in the radiologic group was 5.0 months (2.6, 11.6) with the high dose and 2.8 months (2.8, 5.7) with the low dose. In the rising-PSA group (n = 21) receiving the low dose, the median time to bone scan progression was 5.9 months (5.6, not reached), and median survival was 37.5 months (29, 56). No dose-limiting or autoimmune toxicities were seen; the most common adverse events were injection site reaction and fatigue. CONCLUSIONS: These results suggest that this GM-CSF-secreting, allogeneic cellular immunotherapy is well tolerated and may have clinical activity in patients with metastatic HRPC. Phase 3 trials to confirm these results are under way.