Loteprednol etabonate suspension 0.2% administered QID compared with olopatadine solution 0.1% administered BID in the treatment of seasonal allergic conjunctivitis: a multicenter, randomized, investigator-masked, parallel group study in Chinese patients.

BACKGROUND: Seasonal allergic conjunctivitis (SAC) is caused by seasonal allergens and usually manifests as ocular itching and bulbar conjunctival injection (redness). Treatment options for SAC include corticosteroids and dual-acting antihistamine and mast-cell stabilizers. OBJECTIVE: Our objective was to compare the efficacy and tolerability of loteprednol etabonate (LE), a C-20 ester-based corticosteroid, with those of olopatadine, a dual-acting antihistamine mast-cell stabilizer, in Chinese patients. METHODS: This was a multicenter, randomized, investigator-masked, parallel group study. Patients with acute SAC experiencing grade 4 ocular itching and grade 2 or higher bulbar conjunctival injection received either LE suspension 0.2% QID at 4-hour intervals or olopatadine solution 0.1% BID at 6- to 8-hour intervals bilaterally for 15 days. Primary efficacy end points included the change from baseline (CFB) in ocular itching and bulbar conjunctival injection at day 15. The primary analysis tested the noninferiority of LE suspension 0.2% to olopatadine solution 0.1%. Tolerability outcomes included the incidence of adverse events (AEs), biomicroscopy findings, visual acuity, and intraocular pressure. RESULTS: A total of 300 patients were randomly assigned, and 293 were included in the per-protocol population (LE, n = 147; olopatadine, n = 146). Mean (SD) CFB at day 15 in the LE and olopatadine treatment groups, respectively, was -3.74 (0.47) and -3.28 (0.91) for ocular itching and -1.91 (0.52) and -1.71 (0.59) for bulbar conjunctival injection. The 95% CI for the differences in CFB in ocular itching (-0.59 to -0.27) and bulbar conjunctival injection (-0.27 to -0.08) was less than the prespecified noninferiority limit of 0.3. Treatment differences in CFB were significantly better with LE compared with olopatadine for both end points (P ≤ 0.0006). Ocular AEs were few and similar between treatment groups. There were no clinically significant biomicroscopy or visual acuity findings, and no patient experienced a clinically significant increase in intraocular pressure (≥10 mm Hg). CONCLUSION: Results of this investigator-masked study with Chinese patients suggest LE suspension 0.2% was noninferior to olopatadine solution 0.1% for the treatment of SAC. Both LE suspension 0.2% and olopatadine solution 0.1% were well tolerated. ClinicalTrials.gov identifier: NCT01435460.

Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a 1-year, open-label extension study.

OBJECTIVE: • To evaluate the 1-year safety of 5 mg of tadalafil once daily in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH-LUTS); efficacy measures were included to evaluate the maintenance of efficacy after an additional year of treatment. PATIENTS AND METHODS: • In total, 427 men who completed a 12-week, placebo-controlled, dose- finding study assessing once-daily tadalafil (2.5, 5, 10 or 20 mg) or placebo elected to continue into the open-label extension period. Safety and efficacy parameters were assessed after 1 month and every 3 months. RESULTS: • In total, 299 patients (69.9%) completed the 1-year, open-label extension period. Treatment-emergent adverse events (TEAEs) were reported by 57.6% of patients, with most TEAEs being mild (44%) or moderate (45%) in severity; the most common TEAEs (≥ 2%) were dyspepsia, gastro-oesophageal reflux disease, back pain, headache, sinusitis, hypertension and cough. Twenty-two patients (5.2%) discontinued as a result of AEs. During the open-label extension period, mean prostate-specific antigen increased from 1.6 ± 1.3 ng/mL to 1.8 ± 1.4 ng/mL. • Mean post-void residual volume was 61.1 ± 60.4 mL at study entry and 42.2 ± 64.1 mL after the open-label extension period. Changes in the total International Prostate Symptom Score (IPSS), IPSS irritative and obstructive subscores, IPSS health-related quality of life and BPH Impact Index were maintained after 1 year. In sexually-active patients with erectile dysfunction, improvements in the International Index of Erectile Function-Erectile Function domain were maintained after 1 year. CONCLUSION: • In men with BPH-LUTS, 5 mg of tadalafil once daily during 1 year of treatment was well tolerated and efficacy changes were maintained.

Tadalafil Administered Once Daily for Treatment of Lower Urinary Tract Symptoms in Korean men with Benign Prostatic Hyperplasia: Results from a Placebo-Controlled Pilot Study Using Tamsulosin as an Active Control.

OBJECTIVES: Assess the efficacy and safety of once-daily tadalafil or tamsulosin versus placebo during 12 weeks on lower urinary tract symptoms (LUTS) in Korean men with benign prostatic hyperplasia (BPH). METHODS: Following a 4-week placebo run-in period, 151 Korean men were randomly assigned to receive once-daily tadalafil 5 mg, tamsulosin 0.2 mg, or placebo for 12 weeks. RESULTS: The International Prostate Symptom Score (IPSS) least squares mean changes from baseline to endpoint were numerically but not significantly improved in the tadalafil (-5.8) and tamsulosin (-5.4) groups compared with placebo (-4.2, P > 0.05). Decreases in IPSS obstructive and irritative subscores, IPSS Quality of Life score, and BPH Impact Index from baseline to endpoint were largest in the tadalafil group followed by tamsulosin, though none separated significantly from placebo. Increases in maximum urinary flow rate were small and not significantly different than placebo; the increase was largest in the tadalafil group (2.5 mL/sec), followed by the placebo (2.3 mL/sec) and tamsulosin (2.1 mL/sec) groups. The percentage of subjects reporting at least one treatment-emergent adverse event was 26.5, 13.7 and 3.9% in the tamsulosin, tadalafil and placebo groups, respectively. CONCLUSIONS: In this pilot study in Korean men, those with BPH and treated with tadalafil 5 mg or tamsulosin 0.2 mg once daily experienced a reduction in LUTS, which was numerically (but not statistically) significant compared with the placebo. Tadalafil was well tolerated and few subjects discontinued the study due to treatment-emergent adverse events. Larger studies in Asian men with BPH and LUTS treated with phosphodiesterase type 5 inhibitors are needed.

Effects of tadalafil on lower urinary tract symptoms secondary to benign prostatic hyperplasia in men with or without erectile dysfunction.

OBJECTIVES: To compare the safety and efficacy of the daily erectogenic therapy, tadalafil, on lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH-LUTS) in men with or without comorbid erectile dysfunction (ED). METHODS: Following a 4-week placebo run-in period, men with moderate-to-severe BPH-LUTS were randomized to placebo or tadalafil 2.5, 5, 10, or 20 mg once daily for 12 weeks. International Prostate Symptom Scores (IPSS), IPSS quality of life, and BPH Impact Index were measured every 4 weeks. Safety was mainly assessed via spontaneous reports of adverse events. Data from men with (n=716) or without (n=340) ED at baseline were compared in posthoc analyses. RESULTS: Men with ED were older and had more frequent hypertension, hyperlipidemia, coronary artery disease, and diabetes at baseline compared with men without ED. After 12 weeks, changes in IPSS in men with ED (least squares mean change from baseline, placebo: -2.4; tadalafil 2.5, 5, 10, 20 mg: -4.3, -4.8, -5.3, -5.6) and without ED (-2.4, -3.2, -5.3, -5.1, -4.5) were not significantly different (subgroup/interaction P values: .352/.644). Similar effects were observed for IPSS quality of life (with ED: -0.6, -0.9, -0.9, -1.0, -1.1; without ED: -0.6, -0.7, -0.9, -0.8, -0.8; 0.090/0.773) and BPH Impact Index (with ED: -0.7, -0.9, -1.3, -1.3, -1.4; without ED: -1.0, -0.7, -1.3, -1.3, -1.2; 0.753/0.852). Tadalafil was generally well tolerated, and men with or without ED had similar tolerability profiles. CONCLUSIONS: Changes in BPH-LUTS after 12 weeks of treatment with placebo or various doses of once daily tadalafil were similar in men with or without comorbid ED.

Changes in peak urinary flow and voiding efficiency in men with signs and symptoms of benign prostatic hyperplasia during once daily tadalafil treatment.

OBJECTIVE: To determine, by post hoc analysis, the effects of tadalafil (a long-acting phosphodiesterase 5 inhibitor) on peak urinary flow (Q(max)), bladder capacity, voiding efficiency and the obstructive symptoms of benign prostatic hyperplasia (BPH) in men with lower urinary tract symptoms secondary to BPH (BPH-LUTS), compared with placebo. PATIENTS AND METHODS: After a 4-week placebo run-in period, 1058 men with BPH-LUTS were randomly allocated to receive once daily treatment with placebo or tadalafil (2.5, 5, 10, or 20 mg) for 12 weeks. Uroflowmetry, postvoid residual volume (PVR), and BPH symptom score measurements were assessed throughout the trial. RESULTS: Increases in Q(max) were numerically greater for tadalafil (2.5, 5, 10, and 20 mg with percentage changes of 15%, 16%, 17%, 22%, respectively) vs placebo (12%), but did not reach statistical significance. Age, baseline Q(max), erectile dysfunction history, sexual activity, and previous alpha-blocker therapy significantly influenced the Q(max) response. Tadalafil was not associated with significant changes in PVR. Tadalafil had its greatest effects on bladder capacity and voiding efficiency in men with a Q(max) of <10 mL/s at baseline, but these changes were not significantly different from placebo responses. Tadalafil treatment significantly improved the IPSS obstructive subscores (tadalafil 2.5, 5, 10, 20 mg with percentage changes of 24%, 31%, 33%, 33%, respectively) vs placebo (13%). CONCLUSIONS: Once daily tadalafil did not significantly change Q(max) or voiding efficiency compared with placebo in men with BPH-LUTS, although there were dose-dependent improvements. No subgroups were identified where tadalafil or placebo treatment had a deleterious effect on Q(max). Despite these minimal changes in uroflowmetric measures, tadalafil was associated with clinically meaningful and statistically significant improvements in the obstructive symptoms of BPH.

Effects of once-daily tadalafil on erectile function in men with erectile dysfunction and signs and symptoms of benign prostatic hyperplasia.

BACKGROUND: Lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH; BPH-LUTS) may be associated with erectile dysfunction (ED). OBJECTIVE: To evaluate the effects of once-daily tadalafil on erectile function in men with ED and BPH-LUTS. DESIGN, SETTING, AND PARTICIPANTS: Post hoc analysis of a phase 2-3, multinational, randomized, double-blind, placebo-controlled, parallel-group study of men with ED and moderate-to-severe LUTS secondary to BPH who reported being sexually active. In contrast to typical ED trials, no sexual activity threshold was required to participate. INTERVENTIONS: Screening and 4-wk washout period for patients taking BPH and/or ED treatments; 4-wk placebo run-in period; then once-daily placebo or tadalafil 2.5, 5, 10, or 20 mg for 12 wk. MEASUREMENTS: International Index of Erectile Function-Erectile Function (IIEF-EF) domain score, International Prostate Symptom Score (IPSS), peak urinary flow rate (Q(max)), and postvoid residual volume (PVR). Analyses were performed in men who reported being sexually active with a female partner and who expected to remain so throughout the study. IIEF-EF data are presented for the BPH/ED population overall and for subgroups stratified by baseline age group, body mass index, BPH-LUTS severity, prostate-specific antigen, prior alpha-blocker use, and prior ED therapy. RESULTS AND LIMITATIONS: Overall, 581 men were included (placebo, n=115; tadalafil 2.5 mg, n=113; tadalafil 5 mg, n=117; tadalafil 10 mg, n=120; tadalafil 20 mg, n=116). IIEF-EF domain score improvements from baseline to end point with tadalafil were 5.4 (2.5 mg), 6.8 (5 mg), 7.9 (10 mg), and 8.2 (20 mg) versus 2.0 with placebo (least-squares means; all p values <0.001). IIEF-EF domain score improvements were observed with tadalafil for all subgroup analyses, with no significant differences between subgroup or subgroup-by-treatment interaction terms. IPSS improvements from baseline to end point were significantly greater for all tadalafil doses versus placebo (all p values <0.05). Changes in Q(max) and PVR were small and not clinically meaningful. CONCLUSIONS: These data support the use of once-daily tadalafil in men with ED and BPH-LUTS. TRIAL REGISTRATION: http://www.clinicaltrials.gov: NCT00384930.

Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a dose finding study.

PURPOSE: Phosphodiesterase type 5 inhibitors are widely used to treat erectile dysfunction. Preliminary data have suggested phosphodiesterase type 5 inhibitor efficacy in men with lower urinary tract symptoms associated with clinical benign prostatic hyperplasia. MATERIALS AND METHODS: After a 4-week placebo run-in period 1,058 men with benign prostatic hyperplasia lower urinary tract symptoms were randomly allocated to receive 12-week, once daily treatment with placebo or tadalafil (2.5, 5, 10 or 20 mg). RESULTS: The International Prostate Symptom Score least squares mean change from baseline to end point was significantly improved for 2.5 (-3.9, p = 0.015), 5 (-4.9, p <0.001), 10 (-5.2, p <0.001) and 20 mg (-5.2, p <0.001) tadalafil compared to placebo (-2.3). International Prostate Symptom Score improvements at 4, 8 and 12 weeks were significant for all tadalafil doses and they demonstrated a dose-response relationship. Tadalafil (2.5 mg) significantly improved the International Prostate Symptom Score obstructive subscore and the International Index of Erectile Function-Erectile Function domain, the latter in sexually active men with a history of erectile dysfunction. Statistically significant improvements were noted for 5, 10 and 20 mg tadalafil compared to placebo, as assessed by the International Prostate Symptom Score irritative and obstructive subscores, International Prostate Symptom Score Quality of Life, Benign Prostatic Hyperplasia Impact Index (nonsignificant for 10 mg), Global Assessment Question and International Index of Erectile Function-Erectile Function domain. No statistically significant effect of treatment compared to placebo was noted for peak flow at any tadalafil dose. Treatment emergent adverse events were infrequent in all tadalafil groups. CONCLUSIONS: Once daily tadalafil demonstrated clinically meaningful and statistically significant efficacy and it was well tolerated in men with benign prostatic hyperplasia lower urinary tract symptoms. Of the doses studied 5 mg tadalafil appeared to provide a positive risk-benefit profile.

Efficacy and safety of tadalafil in men with erectile dysfunction following spinal cord injury.

OBJECTIVE: To determine the efficacy and safety of tadalafil when taken on demand by men with erectile dysfunction (ED) secondary to traumatic spinal cord injury (SCI). DESIGN AND SETTING: Multicenter, randomized, double-blind, placebo-controlled, flexible dose-titration, parallel-group study in clinical practices in Europe. Patients Enrolled patients had ED secondary to SCI (all spinal levels) and sustained 6 months or longer before visit 1. INTERVENTIONS: After a 4-week run-in period, patients were randomly assigned to tadalafil, 10 mg, (n = 142) or placebo (n = 44) for a 12-week, on-demand treatment period with assessments at 4-week intervals. The dose of tadalafil was maintained or titrated (10 or 20 mg) at 4 and 8 weeks. MAIN OUTCOME MEASURES: Efficacy was measured using the International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP), and Global Assessment Question (GAQ). Treatment-emergent adverse events and vital signs were collected at each visit. RESULTS: Mean age was 38 years. Mean baseline IIEF erectile function domain score was 13.4, and following 12 weeks of treatment, 22.6 for tadalafil and 13.6 for placebo (P < .001). After treatment, the tadalafil group compared with the placebo group was significantly greater (P < .001) in mean per-patient percentage of successful penetration attempts (SEP question 2; 75.4% vs 41.1%) and intercourse attempts (SEP question 3; 47.6% vs 16.8%); percentage of improved erections (GAQ question 1; 84.6% vs 19.5%); and ejaculatory frequency (IIEF question 9; P = .03). The 2 most common treatment-emergent adverse events in the tadalafil group compared with placebo were headache (8.5% vs 4.5%) and urinary tract infection (7.7% vs 6.8%). CONCLUSIONS: Tadalafil (10 mg and 20 mg) improved erectile function and was well tolerated by men with ED secondary to traumatic SCI.

Evaluation of the efficacy and safety of once-a-day dosing of tadalafil 5mg and 10mg in the treatment of erectile dysfunction: results of a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Erectile dysfunction (ED) is a chronic disease; however, therapy is currently administered as needed with oral phosphodiesterase 5 (PDE5) inhibitors like tadalafil. Because the 17.5-h half-life of tadalafil enables therapeutic plasma levels to be sustained with daily administration, tadalafil is a good candidate for once daily dosing therapy. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group, 12-week study enrolled 268 men 1:2:2 to placebo, tadalafil 5mg, and tadalafil 10mg taken once daily. Primary efficacy measures included changes in the International Index of Erectile Function Erectile Function domain (IIEF EF), Sexual Encounter Profile diary Questions 2 (SEP2: successful penetration), and 3 (SEP3: successful completion of intercourse), and tolerability. Secondary measures included percentage of patients at endpoint who reported improved erectile function (EF), and percentage who reported "no ED" (IIEF EF score 26-30). RESULTS: For patients who took placebo, tadalafil 5mg, and tadalafil 10mg, changes from baseline to endpoint were, respectively, 0.9, 9.7, and 9.4 for IIEF EF; 11.2, 36.5, and 39.4 for SEP2; and 13.2, 45.5, and 50.1 for SEP3. At endpoint, 28.3%, 84.5%, and 84.6% reported improved erections, and 8.3%, 51.5%, and 50.5% reported "no ED," respectively. All comparisons between tadalafil and placebo were significant (p<0.001). Adverse events that occurred in at least 5% of patients were dyspepsia, headache, back pain, upper abdominal pain, and myalgia; nine patients (3.4%) discontinued because of adverse events. CONCLUSIONS: Once-a-day tadalafil 5mg or 10mg was well tolerated and significantly improved EF in men with ED.