Avanafil for the treatment of erectile dysfunction: A multicenter, randomized, double-blind study in men with diabetes mellitus

Objective: To prospectively assess the safety and effectiveness of the investigational phosphodiesterase 5 inhibitor avanafil to treat erectile dysfunction in men with diabetes mellitus. Patients and Methods: This 12-week, multicenter, double-blind, placebo-controlled study conducted between December 15, 2008, and February 11, 2010, randomized 390 men with diabetes and erectile dysfunction 1:1:1 to receive avanafil, 100 mg (n=129), avanafil, 200 mg (n=131), or placebo (n=130). Coprimary end points assessed changes in the percentage of sexual attempts in which men were able to maintain an erection of sufficient duration to have successful intercourse (Sexual Encounter Profile [SEP] 3), percentage of sexual attempts in which men were able to insert the penis into the partner\u27s vagina (SEP 2), and International Index of Erectile Function erectile function domain score. Results: Compared with placebo, least-squares mean change from baseline to study end in SEP 3, SEP 2, and International Index of Erectile Function erectile function domain score were significantly improved with both avanafil, 100 mg (P==.002), and avanafil, 200 mg (P\u3c.001). Additional analyses indicated that successful intercourse could be initiated in 15 minutes or less through more than 6 hours after avanafil dosing. Adverse events most commonly reported with avanafil treatment were headache, nasopharyngitis, flushing, and sinus congestion. Conclusion: Avanafil was safe and effective for treating erectile dysfunction in men with diabetes and was effective as early as 15 minutes and more than 6 hours after dosing. The adverse events seen with avanafil were similar to those seen with other phosphodiesterase 5 inhibitors. Trial Registration: clinicaltrials.gov Identifier NCT00809471. © 2012 Mayo Foundation for Medical Education and Research

An open-label, long-term evaluation of the safety, efficacy and tolerability of avanafil in male patients with mild to severe erectile dysfunction

Aim: Determine the long-term efficacy, safety and tolerability of avanafil, a highly specific, rapidly absorbed phosphodiesterase type 5 inhibitor in male patients with mild to severe erectile dysfunction (ED), with or without diabetes. Methods: This was a 52-week, open-label extension of two 12-week, randomised, placebo-controlled, phase 3 trials. Patients were assigned to avanafil 100 mg, but could request 200 mg (for increased efficacy; \u27100/200-mg\u27 group) or 50 mg (for improved tolerability). Primary end points included percentage of sexual attempts ending in successful vaginal penetration [Sexual Encounter Profile 2 (SEP2)] and intercourse (SEP3) and erectile function domain score per the International Index of Erectile Function (IIEF-EF). Results: Some 712 patients enrolled; 686 were included in the intent to treat population and contributed to the data. All primary end points showed sustained improvement. SEP2 and SEP3 success rates improved from 44% to 83% and from 13% to 68% (100-mg group) and from 43% to 79% and from 11% to 66% (100/200-mg group), respectively. Mean IIEF-EF domain scores improved from 13.6 to 22.2 (100-mg group) and from 11.9 to 22.7 (100/200-mg group). Avanafil was effective in some patients = 15 min and \u3e 6 h postdose. Sixty-five per cent (112/172) of \u27nonresponders\u27 to avanafil 100 mg responded to the 200-mg dose. The most common (= 2%) treatment-emergent adverse events were headache, flushing, nasopharyngitis and nasal congestion; \u3c 3% of patients discontinued therapy because of adverse events. Conclusions: The long-term tolerability and improvement in sexual function, coupled with rapid onset, suggest that avanafil is well suited for the on-demand treatment of ED. © 2013 Blackwell Publishing Ltd

Efficacy of Avanafil 15 Minutes after Dosing in Men with Erectile Dysfunction: A Randomized, Double-Blind, Placebo Controlled Study

Purpose: We examined the therapeutic effects of avanafil 15 minutes after dosing in men with mild to severe erectile dysfunction. Materials and Methods: This randomized, double-blind, placebo controlled, 12-week study (4-week run-in and 8-week treatment) randomized 145 men to placebo, 147 to avanafil 100 mg and 148 to avanafil 200 mg on demand. The primary efficacy variable was the per subject proportion of sexual attempts during the treatment period in which subjects achieved erection sufficient for vaginal penetration within approximately 15 minutes after dosing as measured by a stopwatch. The attempt had to enable successful completion of sexual intercourse according to SEP question 3. Results: Significantly greater mean per subject percentages of successful intercourse attempts within approximately 15 minutes after dosing were observed for avanafil 100 mg (mean 25.9%, LS mean ± SE 24.7% ± 2.9%) and 200 mg (mean 29.1%, LS mean 28.2% ± 2.9%) vs placebo (mean 14.9%, LS mean 13.8% ± 2.9%, p= 0.001 and \u3c0.001, respectively). After treatment we noted a statistically significant difference between avanafil and placebo in the average per subject proportion of successful intercourse attempts according to SEP question 3 as early as 10 minutes in the 200 mg group and 12 minutes in the 100 mg group. Treatment emergent adverse events included headache, upper respiratory tract infection andnasal congestion, and most such events were mild or moderate in severity. Conclusions: Avanafil was efficacious within approximately 15 minutes of dosing compared to placebo. Astatistically significant treatment difference in the percentage of successful sexual attempts was demonstrated as early as 10 minutes after treatment. © 2015 American Urological Association Education and Research, Inc

Selective estrogen receptor alpha agonist GTx-758 decreases testosterone with reduced side effects of androgen deprivation therapy in men with advanced prostate cancer

Background A need remains for new therapeutic approaches for men with advanced prostate cancer, particularly earlier in the disease course. Objective To assess the ability of an oral selective estrogen receptor a agonist (GTx-758) to lower testosterone concentrations compared with leuprolide while minimizing estrogen deficiency-related side effects of androgen-deprivation therapy. Design, setting, and participants Hormone-naive advanced prostate cancer patients were randomized to oral GTx-758 1000 mg/d, 2000 mg/d, or leuprolide depot. Intervention GTx-758 and leuprolide. Outcome measurements and statistical analysis The primary end point was the proportion of patients achieving total testosterone =50 ng/dl by day 60. Secondary end points included serum free testosterone, prostate-specific antigen (PSA), sex hormone-binding globulin, hot flashes, bone turnover markers, and insulin-like growth factor (IGF)-1 levels. Results and limitations Of 159 randomized patients, leuprolide reduced total testosterone to =50 ng/dl in a greater proportion of patients than GTx-758 by day 60 (43.4%, 63.6%, and 88.2% of subjects receiving GTx-758 1000 mg [p \u3c 0.001], GTx-758 2000 mg [p = 0.004], and leuprolide, respectively). GTx-758 reduced free testosterone and PSA earlier and to a greater degree than leuprolide. GTx-758 led to fewer hot flashes, decreases in bone turnover markers, and alterations in IGF-1 compared with leuprolide. A higher incidence of venous thromboembolic events (VTEs) was seen with GTx-758 (4.1%) compared with leuprolide (0.0%). Conclusions Although leuprolide reduced total testosterone to =50 ng/dl in a greater proportion of patients compared with GTx-758, GTx-758 was superior in lowering free testosterone and PSA. GTx-758 reduced estrogen deficiency side effects of hot flashes, bone loss, and insulin resistance but with a higher incidence of VTEs. Patient summary This paper reports findings that leuprolide lowered total testosterone more than GTx-758 but that GTx-758 lowered free testosterone and prostate-specific antigen more than leuprolide. GTx-758 also reduced estrogen deficiency side effects, albeit at a higher rate of vascular events. Trial registration Clinicaltrials.gov identifier NCT01615120. © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved

Acute pulmonary hemorrhage associated with metastatic testicular choriocarcinoma in a 46-year-old incarcerated male

Pure testicular choriocarcinoma is a rare histological subtype of germ cell tumor (GCT) and typically presents with distant metastases and aggressive features leading to a generally poor prognosis. Unique to choriocarcinoma among GCT histological subtypes is the propensity of spontaneous hemorrhage into metastatic lesions. We report a case of pure testicular choriocarcinoma in a 46-year-old male with postoperative acute pulmonary hemorrhage secondary to tumor invasion of the lungs, and the subsequent management of his disease with a discussion of relevant literature