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's 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<.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.

A randomized, double-blind, placebo-controlled evaluation of the safety and efficacy of avanafil in subjects with erectile dysfunction.

INTRODUCTION: Phosphodiesterase type 5 (PDE5) inhibitors have become standard treatment for erectile dysfunction (ED). AIM: To prospectively evaluate the safety and efficacy of avanafil, a novel PDE5 inhibitor, in men with mild to severe ED. METHODS: In this multicenter, double-blind, Phase 3 trial, 646 subjects were randomized to receive avanafil (50 mg, 100 mg, 200 mg) or placebo throughout a 12-week treatment period. Subjects were instructed to take study drug 30 minutes prior to initiation of sexual activity. At least a 12-hour separation time between doses was required; no restrictions were placed on food or alcohol intake. MAIN OUTCOME MEASURES: Improvement in erectile function (EF) was measured by Sexual Encounter Profile questions 2 and 3 (SEP2 and SEP3) and by the EF domain of the International Index of Erectile Function (IIEF) questionnaire. RESULTS: Mean change in percentage of successful sexual attempts (SEP2 and SEP3) and IIEF-EF domain score significantly favored all doses of avanafil over placebo (P ≤ 0.001). Secondary analyses demonstrated achievement of successful intercourse by subjects within 15 minutes of dosing. Of the 300 sexual attempts made during this interval, 64% to 71% were successful in avanafil-treated subjects compared with 27% in placebo-treated subjects. Successful intercourse was also demonstrated >6 hours post dosing, with 59% to 83% of the 80 sexual attempts successful in avanafil-treated subjects compared with 25% of placebo-treated subjects. The most commonly reported adverse events in subjects taking avanafil included headache, flushing, and nasal congestion; there were no drug-related serious adverse events. CONCLUSION: Following 12 weeks of avanafil treatment without food or alcohol restrictions, significant improvements in sexual function were observed with all 3 doses of avanafil compared with placebo. Successful intercourse was observed as early as 15 minutes and >6 hours after dosing in some subjects. Avanafil was generally well tolerated for the treatment of ED.

Clonality and phenotyping of canine lymphomas before chemotherapy and during remission using polymerase chain reaction (PCR) on lymph node cytologic smears and peripheral blood.

Polymerase chain reaction (PCR) assays for the immunoglobulin and T-cell receptor genes were utilized to determine phenotype and clonality from lymph node cytologic smears and peripheral blood lymphocytes from 10 dogs with lymphoma, before chemotherapy and during remission. Results were compared with those from 13 dogs with a cytologic diagnosis of lymph node hyperplasia. Clonality was identified in 7 of the lymphomas on the basis of either lymph node cytology or peripheral blood lymphocytes before treatment. No lymph node hyperplasia samples were clonal. In 6 of the dogs with lymphoma, clonality was demonstrated during clinical remission. Detection of PCR clonality during clinical remission is an effective means of identifying minimal residual disease in canine lymphoma and thus additional work is warranted to determine if molecular remission is prognostic or predictive for outcome in well-controlled and well-defined lymphoma subtypes.

Effects of inhalation exposure to a binary mixture of benzene and toluene on vitamin a status and humoral and cell-mediated immunity in wild and captive American kestrels.

Benzene and toluene are representative volatile organic compounds (VOC) released during production, storage, and transportation associated with the oil and gas industry and are chemicals of concern, as they are released in greater and possibly more biologically significant concentrations than other compounds. Most studies of air pollution in high oil and gas activity areas have neglected to consider risks to birds, including top-level predators. Birds can be used as highly sensitive monitors of air quality and since the avian respiratory tract is physiologically different from a rodent respiratory tract, effects of gases cannot be safely extrapolated from rodent studies. Wild and captive male American kestrels were exposed for approximately 1 h daily for 28 d to high (rodent lowest-observed-adverse-effect level [LOAEL] of 10 ppm and 80 ppm, respectively) or environmentally relevant (0.1 ppm and 0.8 ppm, respectively) levels of benzene and toluene. Altered immune responses characteristic of those seen in mammalian exposures were evident in kestrels. A decreased cell-mediated immunity, measured by delayed-type hypersensitivity testing, was evident in all exposed birds. There was no effect on humoral immunity. Plasma retinol levels as measured by high-performance liquid chromatography (HPLC) analysis were decreased in wild and captive kestrels exposed to the rodent LOAEL for combined benzene and toluene. This study indicates that American kestrels are sensitive to combined benzene and toluene. The study also illustrates the need for reference concentrations for airborne pollutants to be calculated, including sensitive endpoints specific to birds. Based on these findings, future studies need to include immune endpoints to determine the possible increased susceptibility of birds to inhaled toxicants.