Safety, efficacy, and pharmacokinetics of oral testosterone undecanoate in males with hypogonadism.

BACKGROUND: Testosterone deficiency results from insufficient testosterone production. Testosterone therapy may require dose titration to reach eugonadal serum testosterone concentrations. OBJECTIVE: The primary objective was the efficacy of oral testosterone undecanoate (TLANDO; Antares Pharma Inc.) in male patients with documented hypogonadism. Secondary objectives included a comparison of oral testosterone undecanoate safety and quality-of-life assessments to 1.62% topical testosterone gel (AndroGel 1.62%; AbbVie). MATERIALS AND METHODS: In this phase 3 study, 315 patients were randomized 2:1 to oral testosterone undecanoate or 1.62% topical testosterone gel (NCT02081300). Patients received 225 mg oral testosterone undecanoate twice daily, and doses were adjusted by 75 mg/dose at weeks 4 and 8 based on average serum total testosterone concentration and maximum observed serum concentration. The primary endpoint was the proportion of patients receiving oral testosterone undecanoate with serum total testosterone concentration within the eugonadal reference range (300-1140 ng/dL). Secondary endpoints included the proportion of patients with maximum serum total testosterone concentrations within predetermined limits, safety parameters, and quality-of-life endpoints including the Short Form-36v2 Health Survey, Psychosexual Daily Questionnaire, and International Prostate Symptom Score. RESULTS: Overall mean ± SD baseline testosterone was 205.7 ± 71.6 ng/dL. For patients receiving oral testosterone undecanoate, 87.4% demonstrated a 24-h average serum total testosterone concentration within the reference range following titration. Oral testosterone undecanoate demonstrated a nominal statistically significantly greater mean change from baseline than 1.62% topical testosterone gel for Short Form-36v2 Health Survey measures of mental health (2.91 vs. -0.10; p = 0.035), and mental component summary (3.82 vs. 0.55; p = 0.009); and Psychosexual Daily Questionnaire measure of weekly negative mood (-0.57 vs. -0.20; p = 0.021). Safety endpoints were comparable between therapies. No deaths or treatment-related serious adverse events were reported. DISCUSSION AND CONCLUSION: Male patients with hypogonadism receiving oral testosterone undecanoate 225 mg twice daily demonstrated improvements in libido and sexual frequency. Serum testosterone concentrations were within the reference range in 87% of patients without dose titration.

Ambulatory Blood Pressure Parameters Among Men With Hypogonadism Treated With Testosterone Transdermal Therapy.

OBJECTIVE: Studies are needed to examine the effects of testosterone replacement therapy on ambulatory blood pressure (BP) parameters. This study assessed a testosterone transdermal system (TTS) using 24-hour ambulatory BP monitoring. METHODS: In a single-arm, noninferiority trial conducted at 41 US sites, 168 men (mean age: 56.2 years) with hypogonadism not receiving testosterone replacement therapy in the past 6 months were enrolled and received ≥1 study drug dose. Nightly TTS treatment was administered for 16 weeks (starting dose: 4 mg/d; min, max dose: 2, 6 mg/d) to achieve testosterone concentration of 400-930 ng/dL. The primary endpoint was mean change from baseline to week 16 in 24-hour systolic BP (SBP). Noninferiority was determined based on the upper bound of the 2-sided 95% CI <3.0 mmHg. RESULTS: Sixty-two men had ≥85% study drug compliance and a valid week 16 ambulatory BP monitoring session. Mean change from baseline to week 16 in 24-hour average SBP was 3.5 mmHg (95% CI, 1.2-5.8 mmHg; n = 62). Since the upper limit of the CI was >3 mmHg, an effect of TTS could not be ruled out. Mean changes were larger at daytime vs nighttime and in subgroups of men with vs without hypertension. Cardiovascular adverse events were rare (<2%) and nonserious; no major cardiovascular adverse events were reported. CONCLUSION: A meaningful effect of 16-week TTS treatment on 24-hour average SBP among men with hypogonadism could not be ruled out based on the study's noninferiority criterion. The magnitude of mean changes observed may not be clinically meaningful regarding cardiovascular events.

The PINNACLE Study: A Double-blind, Randomized, Sham-controlled Study Evaluating the Optilume BPH Catheter System for the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

PURPOSE: The Optilume BPH Catheter System is a novel drug/device combination minimally invasive surgical therapy for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. The PINNACLE study is a prospective, randomized, double-blind, sham-controlled clinical trial evaluating the safety and efficacy of Optilume BPH against a sham surgical procedure. MATERIALS AND METHODS: Eligible patients were men 50 years or older with symptomatic benign prostatic hyperplasia and a prostate size between 20 and 80 g. Subjects were randomized 2:1 to receive treatment with Optilume BPH or a sham surgical procedure. Blinding was maintained for subjects in both arms and evaluating personnel through 1 year postprocedure. Follow-up assessments included the International Prostate Symptom Score, uroflowmetry, and other quality-of-life and sexual function assessments. RESULTS: A total of 148 men were randomized (100 active, 48 sham) at 18 centers in the U.S. and Canada. Subjects randomized to receive Optilume BPH saw a reduction in International Prostate Symptom Score of 11.5±7.8 points at 1 year posttreatment, as compared to a reduction of 8.0±8.3 points at 3 months in the sham arm. Flow rate was dramatically improved after treatment with Optilume BPH, with an improvement of +10.3 mL/s from baseline to 1 year (+125%). CONCLUSIONS: Treatment with Optilume BPH provides immediate and sustained improvements in obstructive symptoms and flow rate while preserving erectile and ejaculatory function. Treatment is well tolerated and can be done in an office or ambulatory setting.

An Evaluation of Sexual Function in the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia in Men Treated with the Temporarily Implanted Nitinol Device.

Purpose: To document the effect of the temporarily implanted nitinol device (iTind; Medi-Tate Ltd, Israel) on sexual function from a multicenter, randomized, single-blinded, sham-controlled trial. Materials and Methods: Men were randomized 2:1 between iTind and sham procedure arms. The iTind was placed for 5-7 days and an 18F Foley catheter was inserted and removed for the iTind and sham group, respectively. Patients were assessed at baseline, 3, and 12 months postoperatively using the Sexual Health Inventory for Men (SHIM) and International Index of Erectile Function (IIEF). Unblinding occurred at 3 months. Results: We studied 185 men with a mean age of 61.1 ± 6.5 years. There was no difference in SHIM or total IIEF between iTind and sham at 3 months or in the iTind arm at 12 months compared with baseline. Men in the iTind arm without erectile dysfunction at baseline showed an improvement in total IIEF score of +6.07 ± 21.17 points (p = 0.034) at 12 months, in addition to an improvement in ejaculatory function. SHIM scores remained unchanged in all groups, regardless of age, prostate volume, or baseline erectile function. Conclusion: No changes were observed in sexual and ejaculatory function of patients with iTind regardless of a man's age, prostate volume, and baseline sexual function. Clinicaltrials.gov: NCT02506465.

IL-15 Superagonist NAI in BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer.

BACKGROUND: Patients with Bacillus Calmette­Guérin (BCG)­unresponsive non­muscle-invasive bladder cancer (NMIBC) have limited treatment options. The immune cell­activating interleukin-15 (IL-15) superagonist Nogapendekin alfa inbakicept (NAI), also known as N-803, may act synergistically with BCG to elicit durable complete responses (CRs) in this patient population. METHODS: In this open-label, multicenter study, patients with BCG-unresponsive bladder carcinoma in situ (CIS) with or without Ta/T1 papillary disease were treated with intravesical NAI plus BCG (cohort A) or NAI alone (cohort C). Patients with BCG-unresponsive high-grade Ta/T1 papillary NMIBC also received NAI plus BCG (cohort B). The primary end point was the incidence of CR at the 3- or 6-month assessment visit for cohorts A and C, and the disease-free survival (DFS) rate at 12 months for cohort B. Durability, cystectomy avoidance, progression-free survival, disease-specific survival (DSS), and overall survival were secondary end points for cohort A. RESULTS: In cohort A, CR was achieved in 58 (71%) of 82 patients (95% confidence interval [CI]=59.6 to 80.3; median follow-up, 23.9 months), with a median duration of 26.6 months (95% CI=9.9 months to [upper bound not reached]). At 24 months in patients with CR, the Kaplan­Meier estimated probability of avoiding cystectomy and of DSS was 89.2% and 100%, respectively. In cohort B (n=72), the Kaplan­Meier estimated DFS rate was 55.4% (95% CI=42.0% to 66.8%) at 12 months, with median DFS of 19.3 months (95% CI=7.4 months to [upper bound not reached]). Most treatment-emergent adverse events for patients receiving BCG plus NAI were grade 1 to 2 (86%); three grade 3 immune-related treatment-emergent adverse events occurred. CONCLUSIONS: In patients with BCG-unresponsive bladder carcinoma in situ and papillary NMIBC treated with BCG and the novel agent NAI, CRs were achieved with a persistence of effect, cystectomy avoidance, and 100% bladder cancer­specific survival at 24 months. The study is ongoing, with an estimated target enrollment of 200 participants (Funded by ImmunityBio.)

Two-Year Analysis of a New Oral Testosterone Undecanoate (TU) Formulation in Hypogonadal Men: Efficacy, Impact on Psychosexual Function, and Safety.

BACKGROUND: Long-term data evaluating the efficacy and safety of oral testosterone undecanoate (oral TU; JATENZO) in adult hypogonadal men provides important information for healthcare professionals who prescribe testosterone replacement therapy (TRT). AIM: To determine the efficacy and safety of long-term oral TU therapy, including its impact on total testosterone (T) levels and psychosexual functioning. METHODS: Hypogonadal men, between 18 and 75 years old, (mean age 56.2; 87.2% white) who completed a 12-month, open-label, multicenter, randomized, active-controlled trial were given the opportunity to enroll in a 12-month extension study. Among the 129 eligible TU-treated subjects, 86 chose this option, and 69 completed 24 months of uninterrupted oral TU therapy. OUTCOMES: The efficacy of oral TU was documented by measuring total serum T concentrations; sexual function was measured using the Psychosexual Daily Questionnaire (PDQ). For safety, liver function tests, cardiovascular endpoints, and prostate health were measured. RESULTS: Over 2 years, total serum T concentrations for patients treated with oral TU were in the eugonadal range (300-1,000 ng/dL [10-35 nmol/L]; mean ± SD: 617 ± 427 ng/dL [21 ± 15 nmol/L]) and increased significantly from baseline (P < .0001). For sexual function, mean score changes versus baseline for all PDQ domains at all time points were significantly improved (P < .0011 for all). For the sexual activity and sexual desire components, patient scores were consistently greater than validated thresholds for clinically meaningful change. Typical T-induced safety changes were observed, including a 3-6 mm Hg increase in systolic blood pressure (P < .05); a slight increase in hematocrit (P < .0001) that stayed <48% throughout the study; no clinically significant changes in prostate-specific antigen levels; and decreased high-density lipoprotein cholesterol (-9.8 ± 0.9 mg/dL from baseline; P < .0001). There were no clinically significant changes from baseline in liver function tests. CLINICAL IMPLICATIONS: Over 2 years of treatment, this novel oral TU formulation maintained total T concentrations in mideugonadal ranges, with improvements in sexual function and no clinically significant changes in liver function or other safety concerns previously associated with oral TRT. STRENGTHS & LIMITATIONS: These are the first long-term data to evaluate the efficacy and safety of a novel formulation of oral TU; the comparative long-term safety of oral TU would be strengthened by confirmatory studies versus other TRT formulations. CONCLUSION: Oral TU offers a safe and effective long-term treatment option for men with hypogonadism. Honig S, Gittelman M, Kaminetsky J, et al. Two-Year Analysis of a New Oral Testosterone Undecanoate (TU) Formulation in Hypogonadal Men: Efficacy, Impact on Psychosexual Function, and Safety. J Sex Med 2022;19:1750-1758.

Final 5-Year Outcomes of the Multicenter Randomized Sham-Controlled Trial of a Water Vapor Thermal Therapy for Treatment of Moderate to Severe Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

PURPOSE: We present final 5-year outcomes of the multicenter randomized sham-controlled trial of a water vapor therapy (Rezum™) for treatment of moderate to severe lower urinary tract symptoms due to benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 197 subjects >50 years of age with International Prostate Symptom Score ≥13, maximum flow rate ≤15 ml/second and prostate volume 30 to 80 cc were randomized and followed for 5 years. From the control arm of 61 subjects, a subset of 53 subjects requalified and after 3 months received treatment as part of the crossover group and were also followed for 5 years. The total number of vapor treatments to each lobe of the prostate was determined by length of prostatic urethra and included middle lobe treatment per physician discretion. RESULTS: Significant improvement of lower urinary tract symptoms was observed at <3 months post-thermal therapy, remaining durable through 5 years in the treatment group (International Prostate Symptom Score reduced 48%, quality of life increased 45%, maximum flow rate improved 44%, Benign Prostatic Hyperplasia Impact Index decreased 48%). Surgical re-treatment rate was 4.4% with no reports of device or procedure related sexual dysfunction or sustained de novo erectile dysfunction. Results within the crossover group were similar through 5 years. CONCLUSIONS: Minimally invasive treatment with water vapor thermal therapy provides significant and durable symptom relief as well as flow rate improvements through 5 years, with low surgical re-treatment rates and without impacting sexual function. It is a versatile therapy, providing successful treatment to obstructive lateral and middle lobes.

A New Oral Testosterone Undecanoate Formulation Restores Testosterone to Normal Concentrations in Hypogonadal Men.

CONTEXT: A novel formulation of oral testosterone (T) undecanoate (TU) was evaluated in a phase 3 clinical trial. OBJECTIVE: Determine efficacy, short-term safety, and alignment of new oral TU formulation with current US approval standards for T replacement therapy. DESIGN: Randomized, active-controlled, open-label study. SETTING AND PATIENTS: Academic and private clinical practice sites; enrolled patients were clinically hypogonadal men 18 to 65 years old. METHODS: Patients were randomized 3:1 to oral TU, as prescribed (JATENZO®; n = 166) or a topical T product once daily (Axiron®; n = 56) for 3 to 4 months. Dose titration was based on average T levels (Cavg) calculated from serial pharmacokinetic (PK) samples. T was assayed by liquid chromatography-mass spectrometry/mass spectrometry. Patients had 2 dose adjustment opportunities prior to final PK visit. Safety was assessed by standard clinical measures, including ambulatory blood pressure (BP). RESULTS: 87% of patients in both groups achieved mean T Cavg in the eugonadal range. Sodium fluoride-ethylenediamine tetra-acetate plasma T Cavg (mean ± standard deviation) for the oral TU group was 403 ± 128 ng/dL (~14 ± 4 nmol/L); serum T equivalent, ~489 ± 155 ng/dL (17 ± 5 nmol/L); and topical T, 391 ± 140 ng/dL (~14 ± 5 nmol/L). Modeling/simulation of T PK data demonstrated that dose titration based on a single blood sample 4 to 6 h after oral TU dose yielded efficacy (93%) equivalent to Cavg-based titration (87%). Safety profiles were similar in both groups, but oral TU was associated with a mean increase in systolic BP of 3 to 5 mm Hg. CONCLUSION: A new oral TU formulation effectively restored T to mid-eugonadal levels in hypogonadal patients.

Safety of a New Subcutaneous Testosterone Enanthate Auto-Injector: Results of a 26-Week Study.

INTRODUCTION: Patients with testosterone deficiency (TD) can be treated with exogenous testosterone (T) to achieve and maintain physiologic T levels and prevent negative clinical symptoms; with many testosterone replacement therapies currently available, this registration safety study was conducted to further characterize the clinical profile of chronically administered, concentration-guided subcutaneous testosterone enanthate (TE) dosing. AIM: The purpose of this study was to confirm the safety and characterize the pharmacokinetic (PK) profile of the subcutaneous TE auto-injector (SCTE-AI) in adult men with TD. METHODS: In this phase III, 26-week study, 133 men 18-75 years of age with symptomatic TD self-administered SCTE-AI 75 mg once weekly for 6 weeks from July 2015 to June 2016. Dosing was adjusted when indicated to 50 mg or 100 mg to maintain T trough levels between 350 and 650 ng/dL (12.1-22.5 nmol/L). PK data were collected from a subgroup of patients receiving 75 mg SCTE-AI through week 12. Safety, including ambulatory blood pressure monitoring (ABPM), lipid levels, and adverse drug reactions, and PK were assessed. MAIN OUTCOME MEASURES: The main outcomes were the documentation of the reproducibility of trough concentration-guided exposure to SCTE, 6-month safety profile, and PK data for the 75 mg dose SCTE. RESULTS: In total, 34 patients (25.6%) experienced adverse drug reactions; the most frequently reported were increased hematocrit (≥52%) in 10 patients (7.5%), injection-site hemorrhage in 6 patients (4.5%), injection-site bruising in 4 patients (3.0%), and increased prostate-specific antigen in 4 patients (3.0%). By week 26, mean systolic and diastolic blood pressure (BP) measured in the clinic increased by 3.4 mmHg (125.6-129.0 mmHg) and 1.8 mmHg (78.2-80.0 mmHg), respectively, from baseline. At week 12, ABPM showed 24-hour mean systolic and diastolic BP increases of 3.7 mmHg and 1.3 mmHg, respectively. All measured lipid fractions were below baseline levels at week 26. T, TE, dihydrotestosterone, and estradiol increased from weeks 1-12. T trough levels ranged from 300-650 ng/dL (10.4-22.5 nmol/L) in 82.4% and 83.2% of patients at weeks 12 and 26, respectively. Of the 965 assessed injections, mild pain was reported by 1 patient. CLINICAL IMPLICATIONS: Dosing with SCTE is well-tolerated overall, yet associated with a numerically small mean systolic BP increase. STRENGTHS & IMPLICATIONS: This study used a standardized ABPM protocol, confirming a numerically small systolic BP increase may be associated with reintroducing therapeutic T exposure in hypogonadal men. It is unknown at this time whether this applies with all routes of T supplementation. CONCLUSION: SCTE-AI has a favorable safety profile and is well-tolerated, with a stable PK profile. Gittelman M, Jaffe JS, Kaminetsky JC. Safety of a New Subcutaneous Testosterone Enanthate Auto-Injector: Results of a 26-Week Study. J Sex Med 2019;16:1741-1748. Clinicaltrials.gov Identifier: NCT02504541.

A 52-Week Study of Dose Adjusted Subcutaneous Testosterone Enanthate in Oil Self-Administered via Disposable Auto-Injector.

PURPOSE: In this open label, single arm, dose blinded, 52-week registration phase study we evaluated the efficacy and safety of a subcutaneous testosterone enanthate auto-injector administered weekly to men with hypogonadism. MATERIALS AND METHODS: A total of 150 patients were initiated on a 75 mg subcutaneous testosterone enanthate auto-injector self-administered weekly. Dose adjustments were made at week 7 to 50, 75 or 100 mg testosterone enanthate based on the week 6 total testosterone trough concentration. If required, dose adjustments continued through the extended treatment phase. Pharmacokinetic and clinical laboratory parameters, treatment emergent adverse events and injection site reactions were captured. RESULTS: The primary end point was met since 92.7% of patients achieved an average total testosterone concentration of 300 to 1,100 ng/dl (mean ± SD 553.3 ± 127.29) at week 12. A maximum concentration of less than 1,500 ng/dl was achieved by 91.3% of patients and no patient had a level greater than 1,800 ng/dl at week 12. The mean total testosterone trough concentration was 487.2 ± 153.33 ng/dl at week 52. Of the patients more than 95% reported no injection related pain. The most frequently reported treatment emergent adverse events were increased hematocrit, hypertension and increased prostate specific antigen, which led to discontinuation in 30 men. There were no study drug related serious adverse events. CONCLUSIONS: The dose adjusted subcutaneous testosterone enanthate auto-injector demonstrated a steady serum total testosterone pharmacokinetic profile with small peak and trough fluctuations. The device was safe, well tolerated and virtually painless, indicating that this subcutaneous testosterone enanthate auto-injector offers a testosterone delivery system that is a convenient weekly option to treat testosterone deficiency.

Summative Usability Evaluation of the SCTE-AI Device: A Novel Prefilled Autoinjector for Subcutaneous Testosterone Administration.

BACKGROUND: The subcutaneous testosterone enanthate (TE) autoinjector (SCTE-AI) is a single-use, pre-filled, disposable autoinjector intended for testosterone (T) self-administration in adult males with T deficiency. AIM: To evaluate the usability of the market configuration of the SCTE-AI, including packaging and instructions for use (IFU), in order to identify and mitigate any preventable patterns of use errors that could result in harm. METHODS: 4 groups of participants (injection-naïve or injection-experienced patients or caregivers) were randomized to 1 of 3 doses (50, 75, and 100 mg) of TE and either trained (ie, reviewed the IFU and shown how to properly inject) or not trained (only given the IFU). After simulated at-home use, participants were asked questions regarding the comprehensibility of the IFU and the intuitiveness/usability of the device. All tasks were measured as success, use error, or close call (participant initiated an error but recovered in time). MAIN OUTCOME MEASURE: Usability (success rates, errors, and close calls) of the drug/device combination by adult males with T deficiency or their caregivers. RESULTS: 65 patients received 1 dose of TE, and 59 patients received 2 doses. Overall, 99 of 123 (80.5%) attempted injections resulted in administration of 1 full dose. Injection success rates were high and comparable among the various user groups. The most common use error (21 of 24) was due to not holding the autoinjector on the abdomen long enough (at least 8 seconds). Few critical drug delivery and safety errors or close calls were observed. No unmitigated use errors by patients or caregivers were apparent that could result in harm or have a negative impact on treatment. SCTE-AI was well tolerated. CLINICAL IMPLICATIONS: The SCTE-AI development process resulted in a subcutaneous, TE autoinjection device that is intuitive to use, with clear labeling and packaging and an easy-to-understand IFU, providing an option for T-deficient adult males to self-inject subcutaneously at home. STRENGTH & LIMITATIONS: The strengths of the study include use of a patient-ready drug/device combination for self-administration and inclusion of both injection-naïve and injection-experienced patients and caregivers. The main limitation of the study is the presence of observers/cameras that may have distracted or created performance anxiety, potentially contributing to errors. CONCLUSION: Results of this usability validation study indicate that the SCTE-AI device is safe and intuitive to use, with a low potential for harm and is associated with a high rate of injection success, regardless of prior training or experience. Arora S, Moclair B, Murphy K, et al. Summative Usability Evaluation of the SCTE-AI Device: A Novel Prefilled Autoinjector for Subcutaneous Testosterone Administration. J Sex Med 2018;15:1707-1715.

Efficacy and Safety of SER120 Nasal Spray in Patients with Nocturia: Pooled Analysis of 2 Randomized, Double-Blind, Placebo Controlled, Phase 3 Trials.

PURPOSE: SER120 desmopressin intranasal spray is the first U.S. Food and Drug Administration approved pharmacotherapy for nocturia. We evaluated its efficacy and safety in 2 randomized, double-blind, placebo controlled studies, DB3 and DB4. MATERIALS AND METHODS: A total of 1,333 intent to treat patients 50 years old or older with 2.16 or more nocturic voids per night during a 2-week screening period were randomized equally to SER120 intranasal spray 1.66 or 0.83 mcg, or placebo for a 12-week treatment. Co-primary end points were the mean change from baseline in nocturic episodes per night and the percent of patients with a 50% or greater reduction in mean nocturic episodes per night. Secondary end points were the validated INTU (Impact of Nighttime Urination) quality of life questionnaire in DB4, time to the first nocturic void and the percent of nights with 1 or fewer nocturic voids. RESULTS: Each SER120 dose showed statistical significance vs placebo for the 2 co-primary end points, including the mean nocturic episodes per night (-1.4 with 0.83 mcg and -1.5 with 1.66 mcg vs -1.2 with placebo, each p <0.0001), the percent of patients with a 50% or greater reduction in mean nocturic episodes per night (37.9% with 0.83 mcg and 48.7% with 1.66 mcg vs 30.3% with placebo, p = 0.0227 and <0.0001, respectively) as well as for all secondary end points in the pooled analyses. The 1.66 mcg dose demonstrated significant improvements in the INTU score (p = 0.0255). The incidence of hyponatremia, defined as serum sodium 125 mmol/l or less regardless of symptoms or less than 130 mmol/l with symptoms, was 1.1%, 0% and 0.2% in the 1.66 and 0.83 mcg, and placebo groups, respectively. Other adverse events were similar across treatment groups. CONCLUSIONS: SER120 demonstrated significant improvements over placebo for co-primary and secondary efficacy end points that corresponded with quality of life improvements. SER120 at each dose had an acceptable safety profile.

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.

Multicenter Clinical Evaluation of the Alere i Respiratory Syncytial Virus Isothermal Nucleic Acid Amplification Assay.

The Alere i respiratory syncytial virus (RSV) assay is an isothermal nucleic acid amplification test capable of detecting RSV directly from respiratory specimens, with results being available in ≤13 min after test initiation. The objective of this study was to evaluate the performance characteristics of the Alere i RSV assay in a point-of-care setting by using direct nasopharyngeal (NP) swab specimens (direct NP) and nasopharyngeal swab specimens eluted and transported in viral transport medium (VTM NP). The study was a prospective, multicenter, clinical trial conducted at 9 sites across the United States to evaluate the clinical performance of the Alere i RSV assay with respiratory specimens obtained from both children (age, <18 years) and older adults (age, >60 years). The performance of the Alere i RSV assay was compared with that of the reference method, the Prodesse ProFlu+ real-time reverse transcriptase PCR (RT-PCR) assay. All specimens with discrepant test results were tested further by a second FDA-cleared PCR assay (the Verigene respiratory virus plus nucleic acid test; Luminex Inc., TX). A total of 554 subjects with signs and symptoms of respiratory infections were enrolled, and respiratory samples were collected in this study. In comparison with the ProFlu+ real-time RT-PCR, the overall sensitivity and specificity of Alere i RSV assay for the detection of RSV were 98.6% (95% confidence interval [CI], 94.4 to 99.7%) and 98.0% (95% CI, 95.8 to 99.1%), respectively, for direct NP and 98.6% (95% CI, 94.4 to 99.7%) and 97.8% (95% CI, 95.5 to 98.9%), respectively, for VTM NP. The Alere i RSV is a highly sensitive and specific molecular assay ideal for rapid RSV detection in patients in the point-of-care setting due to its minimal hands-on time and rapid result availability.

Quality of erections by age group in men with erectile dysfunction.

AIMS: The aim of this study was to assess erection quality with sildenafil vs placebo and adverse events (AEs) according to age (≤45, 46-55 and ≥56 years) in 997 men with erectile dysfunction (ED) using pooled data from four randomized, double-blind, placebo-controlled, flexible-dose trials. METHODS: The trials included 6- to 10-week treatment periods. The starting sildenafil dose was 50 mg, taken ~1 hour before sexual activity but not more than once daily, with subsequent adjustment to 100 or 25 mg based on efficacy and safety. Exclusion criteria included blood pressure <90/50 or >170/110 mmHg, taking nitrate therapy or nitric oxide donors, severe cardiac failure/unstable angina or recent stroke or myocardial infarction. Changes from baseline in Quality of Erection Questionnaire (QEQ), International Index of Erectile Function (IIEF) and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) scores were analysed. RESULTS: Improvements in QEQ scores with sildenafil vs placebo were significant (P<.0001) for the overall sample (33.7 sildenafil; 8.1 placebo) and each age group (≤45 years: 38.5 sildenafil, 13.9 placebo; 46-55 years: 34.9 sildenafil, 5.8 placebo; ≥56 years: 26.9 sildenafil, 4.9 placebo). IIEF Erectile Function domain (P<.0001), question 3 (achieving erection; P<.003), and question 4 (maintaining erection; P<.001) scores also improved significantly for the overall sample and each age group. Treatment satisfaction was significantly greater (P<.0001) with sildenafil vs placebo for the overall sample and each age group. The most common AEs with sildenafil were headache, flushing and nasal congestion in all age groups. CONCLUSIONS: Sildenafil significantly improved erection quality across all age groups of men with ED. Efficacy improvements with sildenafil were consistent with the QEQ, IIEF, and EDITS. AEs were comparable across age groups. ClinicalTrials.gov ID: NCT00159900, NCT00147628, NCT00301262, NCT00343200.

Performance of a palladium-103 line source for prostate brachytherapy implants: A Phase I trial.

PURPOSE: To evaluate the use of a polymer-encapsulated palladium-103 (103 Pd) source with a unique linear radioactive distribution in prostate brachytherapy. This feasibility study assessed dosimetry, ease and efficiency of use, and side effects. The number of needles required for adequate coverage was the primary end point. METHODS AND MATERIALS: CivaString 103 Pd Model CS10 implants were preplanned for 25 patients. CivaStrings were custom manufactured according to plan. CivaStrings were implanted with 18 gauge needles. Post-implant dosimetry was performed at 3-6 weeks. RESULTS: Monotherapy (125 Gy) was prescribed for 11 implants. External beam radiation with CivaString boost (100 Gy) was prescribed for 14 implants. The mean time to implant the sources was 23.5 min. The number of planned needles and prostate sizes ranged from 14 to 25 and 21-101 cm3, respectively. 70% of implants in prostates less than 50 cm3 required ≤17 needles. Planned source strength ranged from 2.8 U/cm to 3.9 U/cm. Total source strength averaged 216 U (130-323 U) for monotherapy and 154 U (92.4-245 U) for boost. Nomograms were generated at both prescription dose levels. CONCLUSIONS: The linear 103Pd source provides good dose coverage to the prostate. Prostate volume changes were minimal suggesting minimal swelling using the CivaString device.

Convective Thermal Therapy: Durable 2-Year Results of Randomized Controlled and Prospective Crossover Studies for Treatment of Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia.

PURPOSE: We report 2-year outcomes of a multicenter randomized controlled trial plus 1-year results of a crossover trial after treatment with convective radiofrequency water vapor thermal energy for lower urinary tract symptoms due to benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 197 men at least 50 years old with I-PSS (International Prostate Symptom Score) 13 or greater, maximum flow rate 15 ml per second or less and prostate size 30 to 80 cc were randomized 2:1 to thermal therapy with the Rezum® System or a control group. Rigid cystoscopy with simulated active treatment sounds served as the control procedure. After unblinding at 3 months control subjects could requalify for crossover study. Convectively delivered radiofrequency thermal energy was delivered into obstructive prostate tissue, including the median lobe as needed. The primary efficacy end point was a change in severity of symptom scores. RESULTS: Convective radiofrequency thermal therapy improved urinary symptoms significantly over controls at 3 months and provided a sustained 51% reduction from baseline at 24 months (p <0.0001). This produced a 5 and 8-point or greater score decrease in 84% and 74% of subjects, respectively, at 24 months. Crossover subject symptoms, flow rate and quality of life measures were markedly improved after thermal therapy compared to after the control procedure (p = 0.024 to <0.0001). No de novo erectile dysfunction was reported. CONCLUSIONS: Convective radiofrequency water vapor thermal therapy is a minimally invasive office or outpatient procedure that provides early effective symptom relief that remains durable for 2 years and is applicable to the median lobe.

Bremelanotide for female sexual dysfunctions in premenopausal women: a randomized, placebo-controlled dose-finding trial.

AIM: Evaluate efficacy/safety of bremelanotide (BMT), a melanocortin-receptor-4 agonist, to treat female sexual dysfunctions in premenopausal women. METHODS: Patients randomized to receive placebo or BMT 0.75, 1.25 or 1.75 mg self-administered subcutaneously, as desired, over 12 weeks. Primary end point was change in satisfying sexual events/month. Secondary end points included total score changes on female sexual function index and female sexual distress scale-desire/arousal/orgasm. RESULTS: Efficacy data, n = 327. For 1.25/1.75-mg pooled versus placebo, mean changes from baseline to study end were +0.7 versus +0.2 satisfying sexual events/month (p = 0.0180), +3.6 versus +1.9 female sexual function index total score (p = 0.0017), -11.1 versus -6.8 female sexual distress scale-desire/arousal/orgasm total score (p = 0.0014). Adverse events: nausea, flushing, headache. CONCLUSION: In premenopausal women with female sexual dysfunctions, self-administered, as desired, subcutaneous BMT was safe, effective, and well tolerated (NCT01382719).