AbobotulinumtoxinA is effective in patients with urinary incontinence due to neurogenic detrusor overactivity regardless of spinal cord injury or multiple sclerosis etiology: Pooled analysis of two phase III randomized studies (CONTENT1 and CONTENT2).

BACKGROUND: Neurogenic detrusor overactivity incontinence (NDOI) is often inadequately managed with oral therapy. OBJECTIVE: To assess efficacy and safety of abobotulinumtoxinA (aboBoNT-A; Dysport®; Ipsen Ltd.) according to etiology of NDOI. DESIGN, SETTING, AND PARTICIPANTS: Two phase III, randomized, double-blind studies (CONTENT1 [NCT02660138] conducted in Asia, Europe and North America; CONTENT2 [NCT02660359] conducted in the Americas, Asia, Europe and Oceania) both included patients with spinal cord injury (SCI) or multiple sclerosis (MS), with inadequately managed NDOI, regularly performing clean intermittent catheterization (CIC). INTERVENTION: Patients in CONTENT1 and CONTENT2 received aboBoNT-A injections 600 U (n = 162)/800 U (n = 161), or placebo (n = 162) into the detrusor muscle. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary endpoint: mean change from baseline in number of NDOI episodes/week at Week 6. Secondary endpoints: proportion of patients with no NDOI episodes; incontinence-related quality of life (I-QoL); urodynamic parameters; and time-to-retreatment. Safety was also assessed. Statistical analyses were conducted for pooled populations by etiology (aboBoNT-A doses vs. placebo). RESULTS AND LIMITATIONS: Of 485 randomized patients, 341 (70%) and 144 (30%) had SCI and MS etiologies, respectively. A significant reduction was observed in mean NDOI episodes/week at Week 6 with both aboBoNT-A doses versus placebo in the SCI (all p < 0.001) and MS (all p < 0.01) groups, as well as significant improvements in I-QoL and urodynamic parameters. Median time-to-retreatment was longer in patients with MS (48-62 weeks across doses) than those with SCI (39-44 weeks). Safety data were similar between etiologies. Urinary tract infection was the most frequent adverse event; similar numbers were reported across treatment groups. CONCLUSIONS: AboBoNT-A was well tolerated and significantly improved continence and bladder function, and QoL, in patients with SCI or MS with NDOI performing regular CIC. PATIENT SUMMARY: AboBoNT-A injections improved QoL, symptoms, and bladder function in patients with SCI or MS with bladder muscle overactivity that causes incontinence.

Fexapotide triflutate: results of long-term safety and efficacy trials of a novel injectable therapy for symptomatic prostate enlargement.

PURPOSE: These studies were undertaken to determine if fexapotide triflutate 2.5 mg transrectal injectable (FT) has significant long-term (LT) safety and efficacy for the treatment of benign prostatic hyperplasia (BPH). METHODS: Two placebo controlled double-blind randomized parallel group trials with 995 BPH patients at 72 sites treated 3:2 FT:placebo, with open-label FT crossover (CO) re-injection in 2 trials n = 344 and long-term follow-up (LF) 2-6.75 years (mean 3.58 years, median 3.67 years; FT re-injection CO mean 4.27 years, median 4.42 years) were evaluated. 12 months post-treatment patients elected no further treatment, approved oral medications, FT, or interventional treatment. Primary endpoint variable was change in Symptom Score (IPSS) at 12 months and at LF. CO primary co-endpoints were 3-year incidence of (1) surgery for BPH in FT treated CO patients versus patients crossed over to oral BPH medications and (2) surgery or acute urinary retention in FT-treated CO placebo patients versus placebo patients crossed over to oral BPH medications. 28 CO secondary endpoints assessed surgical and symptomatic outcomes in FT reinjected patients versus conventional BPH medication CO and control subgroups at 2 and 3 years. RESULTS: FT injection had no significant safety differences from placebo. LF IPSS change from baseline was higher in FT treated patients compared to placebo (median FT group improvement - 5.2 versus placebo - 3.0, p < 0.0001). LF incidence of AUR (1.08% p = 0.0058) and prostate cancer (PCa) (1.1% p = 0.0116) were both reduced in FT treated patients. LF incidence of intervention for BPH was reduced in the FT group versus oral BPH medications (8.08% versus 27.85% at 3 years, p < 0.0001). LF incidence of intervention or AUR in placebo CO group with FT versus placebo CO group with oral medications was reduced (6.07% versus 33.3% at 3 years, p < 0.0001). 28/28 secondary efficacy endpoints were reached in LF CO re-injection studies. CONCLUSIONS: FT 2.5 mg is a safe and effective transrectal injectable for LT treatment of BPH. FT treated patients also had reduced need for BPH intervention, and reduced incidence of PCa and AUR.

Vardenafil improves ejaculation success rates and self-confidence in men with erectile dysfunction due to spinal cord injury.

STUDY DESIGN: Multicenter, double-blind, placebo-controlled, parallel-group study. OBJECTIVE: To assess the effect of the oral phosphodiesterase type-5 inhibitor, vardenafil, on ejaculation rates and self-confidence in men with spinal cord injury (SCI). SUMMARY OF BACKGROUND DATA: Spinal command of male sexual functions is often seriously impaired by traumatic spinal cord injury (SCI). A high proportion of men with SCI cannot ejaculate during sexual intercourse. SCI-related ejaculatory disorders are often responsible for male infertility. Sexual dysfunction associated with SCI can also affect men's self-confidence. METHODS: In this 12-week study, 418 men aged >or=18 years with erectile dysfunction >6 months resulting from a traumatic SCI were randomized to vardenafil (n = 207) or placebo (n = 211) 10 mg for 4 weeks, then maintained or titrated to 5 or 20 mg at weeks 4 and 8. Assessments included questions of the International Index of Erectile Function (IIEF) about ejaculation success and orgasmic perception; the Global Confidence Question; and quality-of-life scales to measure psychological well-being, self-esteem, depression, and mental health status. RESULTS: Overall per patient ejaculation success rates were significantly greater with vardenafil than placebo over 12 weeks of treatment (19% vs. 10%; P < 0.001). At last observation carried forward, the IIEF "orgasmic function" score increased from 2.9 at baseline to 4.0 for vardenafil and from 3.0 at baseline to 3.4 for placebo. Sixteen percent of men receiving vardenafil and 8% receiving placebo felt orgasm "almost always" or "always" at weeks 8-12, compared with 4% and 6%, respectively, at baseline. Significant improvements in confidence scores were observed with vardenafil compared with placebo (P < 0.0001). There were no clinically significant differences between vardenafil and placebo in the quality-of-life measures at the study endpoint, but these had been in the normal range at baseline. CONCLUSION: Vardenafil significantly improved ejaculation and self-confidence in men with erectile dysfunction due to SCI.

Tadalafil relieves lower urinary tract symptoms secondary to benign prostatic hyperplasia.

PURPOSE: We assessed the efficacy and safety of tadalafil dosed once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia. MATERIALS AND METHODS: Following a 4-week, single-blind, placebo run-in 281 men were randomly assigned (1:1) to 5 mg tadalafil for 6 weeks, followed by dose escalation to 20 mg for 6 weeks or 12 weeks of placebo. RESULTS: Tadalafil significantly improved the mean change from baseline in International Prostate Symptom Score at 6 weeks (5 mg tadalafil -2.8 vs placebo -1.2) and at 12 weeks (5/20 mg tadalafil -3.8 vs placebo -1.7). Larger changes were observed with inclusion of the placebo run-in at 12 weeks (5/20 mg tadalafil -7.1 vs placebo -4.5). Significant improvements were also seen in the International Prostate Symptom Score irritative and obstructive domains, the International Prostate Symptom Score quality of life index, a question about urinary symptom improvement and the Benign Prostatic Hyperplasia Impact Index (significant at 12 weeks) vs placebo. International Prostate Symptom Score and International Index of Erectile Function erectile function domain scores significantly improved in the 56% of men with lower urinary tract symptoms/benign prostatic hyperplasia who were sexually active and had erectile dysfunction. Changes in uroflowmetry parameters were similar in the placebo and tadalafil groups. Commonly reported (2% or greater) treatment emergent adverse events were "erection increased," dyspepsia, back pain, headache, nasopharyngitis and upper respiratory tract infection (each 5.1% or less). No change in post-void residual volume was seen with tadalafil treatment. CONCLUSIONS: Tadalafil once daily was well tolerated and demonstrated clinically meaningful and statistically significant symptomatic improvement for lower urinary tract symptoms/benign prostatic hyperplasia. Tadalafil also improved erectile function in men with lower urinary tract symptoms and erectile dysfunction.

Long-term therapy with the dual 5alpha-reductase inhibitor dutasteride is well tolerated in men with symptomatic benign prostatic hyperplasia.

OBJECTIVE: To examine the long-term (4-year) safety and tolerability of dutasteride in the treatment of symptomatic benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Patients who completed the double-blind phase of three dutasteride Phase III studies were eligible to enter a 2-year open-label extension, during which all patients received dutasteride 0.5 mg. Safety was assessed, including adverse-event reporting, clinical laboratory assessments, yearly physical examinations, and vital sign assessments. RESULTS: In all, 2340 patients entered the open-label phase, 1188 of whom previously received dutasteride during the double-blind phase of the study. The most common drug-related adverse events (occurring in > or = 1%) were effects on sexual function, which decreased with a longer duration of therapy. Gynaecomastia was reported in a small percentage of men throughout the 4-year study period. The incidence of individual sexual functional adverse events that led to withdrawal was < or = 1% (0.3-1.0%) during the 4-year study period. Dutasteride had no relevant effects on vital signs or clinical laboratory variables. CONCLUSION: These data show that dutasteride is well tolerated during long-term use for the treatment of symptomatic BPH.

A six-month, open-label study assessing a new formulation of leuprolide 7.5 mg for suppression of testosterone in patients with prostate cancer.

OBJECTIVE: The safety, efficacy, and pharmacokinetics of monthly subcutaneous injections of a new leuprolide acetate (LA) depot formulation were investigated in patients with advanced prostate cancer. METHODS: The 2-part, 6-month (168-day), open-label, multicenter study enrolled male patients diagnosed with adenocarcinoma of the prostate (Jewett stage C or D). LA-2500 7.5-mg (a new subcutaneous depot formulation containing 7.5 mg of LA) injections were administered at monthly (28-day) intervals. The primary efficacy parameter was total serum testosterone level. A breakthrough response was defined as a single testosterone measurement > 50 ng/dL after achieving castration testosterone levels. Testosterone was isolated from sera by alumina column chromatography and measured by radioimmunoassay (RIA). LA was purified by solid-phase extraction and high-performance liquid chromatography and was then quantitated by RIA. RESULTS: One hundred seventeen of the 120 enrolled patients completed the 6-month study. Three patients withdrew for reasons not related to treatment. LA had a mean (SD) maximal concentration of 26.3 (12.6) ng/mL at 4.66 (1.44) hours and was detected for a mean of 37 days (range, 28-49 days). By day 28, 94.1% (112/119) of the patients achieved medical castration (serum testosterone < or = 50 ng/dL). By day 42, 100.0% (118/118) of the patients remaining in the study had serum testosterone levels < or = 50 ng/dL and 97.5% (115/118) had levels < or = 20 ng/dL. At study completion, the mean (SD) serum testosterone level was 6.12 (4.3) ng/dL (range, 3.0-27.0 ng/dL). No breakthrough or acute-on-chronic responses were reported throughout the study. From baseline to month 6, mean (SD) luteinizing hormone level decreased from 8.0 (7.3) mIU/mL to 0.09(0.1) mIU/mL, and mean (SD) prostate-specific antigen level decreased from 32.9 (86.3) ng/mL to 3.2 (12.0) ng/mL. Treatment-related adverse events were reported by 74.2% (89/120) of patients, the most common being hot flashes (56.7%). CONCLUSION: This 6-month, open-label, noncontrolled study showed LA-2500 7.5-mg depot was well tolerated and maintained testosterone suppression (< or = 50 ng/dL) in the patients completing the study without any testosterone breakthrough responses.