Masayuki TAKEDA, 1 Osamu NISHIZAWA, 2 Takeshi IMAOKA, 3 Yoji MORISAKI, 3 and Lars VIKTRUP 4 ORIGINAL ARTICLE
|
|
- Vivian McCoy
- 6 years ago
- Views:
Transcription
1 LUTS (2012) 4, ORIGINAL ARTICLE Tadalafil for the Treatment of Lower Urinary Tract Symptoms in Japanese Men with Benign Prostatic Hyperplasia: Results from a 12-week Placebo-controlled Dose-finding Study with a 42-week Open-label Extension Masayuki TAKEDA, 1 Osamu NISHIZAWA, 2 Takeshi IMAOKA, 3 Yoji MORISAKI, 3 and Lars VIKTRUP 4 1 Department of Urology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Japan, 2 Department of Urology, Shinshu University School of Medicine, Matsumoto, Japan, 3 Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Kobe, Japan, and 4 Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, USA Objectives: To examine the efficacy, safety, and dose response of tadalafil once daily in Japanese men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH-LUTS). Methods: Men 45 years with moderate-to-severe BPH-LUTS were randomized to once-daily placebo (N = 140), tadalafil 2.5 mg (N = 142), or tadalafil 5.0 mg (N = 140), in a 12-week double-blind phase, followed by a 42-week, tadalafil 5.0 mg open-label extension (OLE) phase (N = 394). The primary outcome was total International Prostate Symptom Score (IPSS) change from baseline to last available observation in the double-blind phase. Results: The least squares (LS) mean difference between placebo and tadalafil in total IPSS change from baseline was 0.7 (P = 0.201) and 1.1 (P = 0.062) for tadalafil 2.5 and 5 mg, respectively (ANCOVA; a dose-dependent improvement in placebo-adjusted total IPSS for tadalafil 5 mg versus 2.5 mg of 57%). Repeated-measures analyses identified a significant total IPSS change for tadalafil 5 mg (LS mean difference between placebo and tadalafil 5mg: 1.2; P = 0.035), but not tadalafil 2.5 mg, at week 12. Significant improvements for tadalafil 5 mg were demonstrated (ANCOVA) for IPSS obstructive subscore (P = 0.033) and IPSS quality of life index (P = 0.022). Numerical improvements in IPSS scores were maintained over the OLE phase. Tadalafil was well tolerated with no unexpected adverse events. Conclusion: Tadalafil (5.0 mg) had a favorable benefit-to-risk profile, supporting further investigation of tadalafil (5.0 mg) in Japanese men with BPH-LUTS. Key words benign prostatic hyperplasia, Japanese, lower urinary tract symptoms, phosphodiesterase type 5 inhibitors, tadalafil 1. INTRODUCTION Benign prostatic hyperplasia (BPH) is a histological diagnosis characterized by the proliferation of stromal and epithelial cells leading to prostate enlargement. 1 The condition may be associated with storage, voiding, and postmicturition lower urinary tract symptoms (LUTS), including urinary frequency, urgency, nocturia, urinary hesitancy and intermittency, straining, weak urinary stream, incomplete bladder emptying, and postmicturition dribbles. 2 The term LUTS suggestive of BPH (or BPH-LUTS), even without the histological diagnosis of BPH, is recognized and continues to be used among clinicians 3 and as an indication for pharmacological treatment of LUTS associated with benign prostatic obstruction. Population-based studies conducted in Australia, Canada, France, the USA, and parts of Asia have shown that LUTS in men with BPH is common over the age of 50 years, and the prevalence significantly increases with increasing age. 4 In a Japanese community-based study, the prevalence of moderate-to-severe BPH-LUTS (defined as an International Prostate Symptom Score [IPSS] > 7) was 44, 52, and 63% for men aged 50 59, 60 69, and years, respectively. 5 Although BPH-LUTS is not life-threatening, the condition may have a significant impact on quality of life (QoL). 6,7 Pharmacotherapy is the first-line treatment for BPH- LUTS. In Japan, treatments approved for moderate-tosevere BPH-LUTS include α 1 -adrenoceptor blockers Correspondence: Lars Viktrup, MD, PhD, Lilly Research Laboratories, DC 1548, Lilly Corporate Center, Indianapolis, IN 46285, USA. Tel: ; Fax: viktrupla@lilly.com Trials registration: ClinicalTrials.gov NCT Received 9 October 2011; revised 8 December 2011; accepted 15 January DOI: /j x
2 Tadalafil for BPH-LUTS in Japanese men 111 (α-blockers; e.g. tamsulosin, prazosin, silodosin, naftopidil, and terazosin), antiandrogens (e.g. oxendolone, chlormadinone acetate, and allylestrenol), and the 5-α reductase inhibitor, dutasteride. 8,9 Although these treatments are effective in reducing symptoms caused by BPH, they have been associated with side-effects such as dizziness and hypotension (α-blockers), or sexual dysfunction (tamsulosin, silodosin, dutasteride, and antiandrogens), 3,8,10 15 which may impact treatment adherence. 16 In a retrospective assessment of Japanese men treated with silodosin, a low 1-year continuation rate (12.0%) was attributed in part to the occurrence of adverse events (AEs; 28.7%). 17 In the human prostate, nitric oxide (NO) plays a role in mediating contractile function, and lower urinary tract dysfunction in BPH might be associated with the lack of NO-related relaxation of prostate smooth muscle. 18 The effect of NO on prostate smooth muscle occurs via cyclic guanosine monophosphate production and phosphodiesterases (degrading enzyme of cyclic nucleotides) including phosphodiesterase type 5 (PDE5), which is present in the human prostate and other tissues of the urogenital tract. 19 Hence, PDE5 inhibitors may be effective in treating BPH-LUTS. Tadalafil, a selective PDE5 inhibitor, is currently approved in over 90 countries, including Japan, for the treatment of erectile dysfunction (ED). In a 24-month multinational extension study enrolling 1173 men with ED, tadalafil (up to 20 mg, as needed) treatment for up to 24 months was reported to be safe and well tolerated; most treatment-emergent AEs (TEAEs), such as headache, dyspepsia, flushing, back pain, myalgia, and nasal congestion, were mild or moderate in severity. 20 A similar safety profile for tadalafil (5 20 mg, as needed) has been reported in a 12-week randomized, double-blind, placebo-controlled study in Japanese men with ED. 21 We report the results of a randomized, placebocontrolled, dose-finding study examining the efficacy and safety of tadalafil once daily in Japanese men with BPH- LUTS. The study consisted of a 12-week, double-blind, placebo-controlled phase followed by a 42-week, openlabel extension (OLE) phase. 2. METHODS 2.1. Study design The study was a prospective, multicenter, double-blind, randomized, parallel-group, placebo-controlled, dosefinding study, which included a 4-week, single-blind, placebo run-in period, and a 12-week double-blind phase. The double-blind phase was followed by a 42-week OLE phase. The study was conducted at 19 sites in Japan. Eligible patients were randomized (1:1:1), using a computer-generated random sequence and an interactive voice response system, to receive once-daily placebo or tadalafil (2.5 mg or 5.0 mg) for 12 weeks. Randomization was stratified by baseline BPH-LUTS severity (moderate: IPSS < 20; severe: IPSS 20) and previous α-blocker therapy within 12 months of the first visit. The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines, and approved by the participating institutional review boards. All patients provided written informed consent before participating in the study Participant population The study enrolled Japanese men, aged 45 years, with moderate-to-severe BPH-LUTS (total IPSS 13) at the beginning of the 4-week placebo run-in period. At screening, physical examination included digital rectal examination. Histological verification of BPH was not required. Inclusion criteria included bladder outlet obstruction of intermediate severity, defined by a urinary peak flow rate (Qmax) of 4 15 ml/s (from a prevoid bladder volume of ml and a minimum voided volume 125 ml) and a prostate volume >20 ml. Major exclusion criteria were prostate-specific antigen (PSA) levels >10.0 ng/ml or between 4.0 and 10.0 ng/ml without clinical judgment of negative prostate cancer, postvoid residual volume (PVR) 300 ml, pelvic surgical procedures on the urinary tract including minimally invasive BPH therapies, clinical evidence of prostate cancer or any bladder or urinary tract conditions that may have affected LUTS, history of significant renal insufficiency, or received dutasteride within the previous 6 months. All participants agreed not to use any other treatments for BPH, ED, or overactive bladder (OAB), including α-blockers, 5-α reductase inhibitors, PDE5 inhibitors, or herbal preparations during the study Treatment protocol The first part of the study comprised a 2-week screening/wash-out period (if on BPH, OAB, or ED therapy), a 4-week placebo run-in period, and a 12-week double-blind phase (Fig. 1). Participants entering the double-blind phase were randomized to receive oral placebo, tadalafil 2.5 mg, or tadalafil 5.0 mg once daily. All participants who completed the double-blind phase entered the 42-week OLE phase and received tadalafil 5.0 mg once daily. The timing of all assessments is displayed in Figure Outcome measures The primary outcome measure was the total IPSS change from baseline (week 0) to the double-blind phase endpoint (week 12) or last available observation. The IPSS is a seven-item, self-administered questionnaire internationally validated to assess the severity of BPH-LUTS. 22,23 Each question is scored from 0 to 5 to give a total IPSS of 0 to 35 points; higher total scores represent greater symptom severity. Secondary efficacy outcome measures included: (i) IPSS obstructive subscore (IPSS questions 1, 3, 5, and 6); (ii) IPSS irritative subscore (IPSS questions 2, 4, and 7); (iii) IPSS QoL index; 24 and (iv) Qmax. Values obtained for Qmax were considered valid only if the prevoid bladder volume (assessed by ultrasound) was 150 ml and 550 ml, and the voided volume was 125 ml. Safety outcome measures included frequency and severity of
3 112 Masayuki Takeda et al. Fig. 1 Study design. AEs, vital signs, clinical laboratory tests, PSA level, and PVR. Adverse events were summarized using the Medical Dictionary for Regulatory Activities (double-blind phase: version 12.0; OLE phase: version 13.0) preferred term. During the double-blind phase, TEAEs were defined as events that first occurred or worsened on or after the day of randomization (week 0) to the end of the double-blind phase. During the OLE phase, TEAEs were defined as events that first occurred or worsened on or after the day of enrollment (week 12) in the OLE phase to the end of the OLE phase Statistical analyses A sample size of 140 participants was planned for each treatment group based on outcomes from a previous similarly designed study. 25 This sample size was estimated to provide 90% power to detect an expected difference between the tadalafil 5 mg and placebo groups of 2.36 in total IPSS change from baseline to endpoint (week 12 or last available observation; based on a two-sided t-test at a significance level of 0.05). For the double-blind phase, efficacy and safety analyses included all participants who were randomized and started study medication, grouped by allocated treatment. For efficacy analyses only, participants were excluded if no postbaseline data were available. For the primary analysis, the change from baseline (week 0) to endpoint (week 12) was based on the last observation carried forward (LOCF). Treatment differences were assessed using analysis of covariance (ANCOVA) models, with treatment group and previous α-blocker therapy as fixed effects, and baseline total IPSS as a covariate. Changes in total IPSS were compared using least squares (LS) means and the corresponding 95% confidence intervals (CI). Prespecified mixed-effects models repeated measures (MMRM) analyses, with unstructured covariance matrices, were performed to evaluate the total IPSS change over time (weeks 2, 4, 8, and 12) from baseline. This model included treatment group, previous α-blocker use, time, and treatment-by-time interaction as fixed effects, and baseline total IPSS as a covariate. All data were analysed with a two-sided significance level of For the OLE phase, efficacy analyses were primarily descriptive and included the change in efficacy variables from baseline (week 0) and from the beginning of the OLE phase (week 12) to week 54, based on LOCF. Safety and efficacy analyses included all randomized participants who received at least one dose of tadalafil (5.0 mg) during the OLE phase. Statistical analyses were performed using SAS Drug Development (SAS Institute Inc., Cary, NC, USA). 3. RESULTS 3.1. Participant disposition A total of 422 participants were enrolled in the doubleblind phase (Fig. 2). Efficacy analyses included 421 participants; one participant was excluded from the analyses because no postbaseline data were available. Safety analyses included all 422 participants. Of the randomized participants, 394 (93.4%) completed the double-blind phase. During the double-blind phase, the number of participants who discontinued because of AEs was similar for all treatment groups (placebo: 5/140, 3.6%; tadalafil 2.5 mg: 4/142, 2.8%; tadalafil 5 mg, 5/140, 3.6%; Fig. 2). All 394 participants who completed the double-blind phase entered the OLE phase and received at least one dose of tadalafil. A total of 323 (82.0%) participants completed the OLE phase; AEs were the most common reason for discontinuation (n = 35, 8.9%; Fig. 2) Baseline characteristics The demographic and other baseline characteristics were similar among all treatment groups (Table 1). The median age of participants was 67.4 years (range: years) and the majority (n = 274; 64.9%) of participants were older than 65 years. At baseline, 302 (71.6%) participants had mild-to-moderate BPH-LUTS (IPSS < 20) with BPH-symptom duration of 4.2 ± 3.1 years (mean ± standard deviation [SD]). Most participants had received previous BPH therapy (α-blocker: 77.0%; other BPH therapy: 19.7%). Overall, the demographic and baseline characteristics of the participants enrolled in the OLE phase were similar to those in the double-blind phase (Table 1).
4 Tadalafil for BPH-LUTS in Japanese men 113 Fig. 2 Study flow diagram and participant disposition. DB, double-blind; OLE, open-label extension.
5 114 Masayuki Takeda et al. TABLE 1. Participant characteristics: double-blind and open-label extension (OLE) phase Double-blind phase OLE phase Characteristic Placebo n = 140 Tadalafil 2.5 mg n = 142 Tadalafil 5 mg n = 140 All n = 394 Age (years) Median Minimum, maximum 45.4, , , , 83.5 <65 years, n (%) 43 (30.7) 52 (36.6) 53 (37.9) 141 (35.8) Mean ± SD BMI (kg/m 2 ) 23.6 ± ± ± ± 2.6 BPH severity, n(%) Moderate 100 (71.4) 100 (70.4) 102 (72.9) 284 (72.1) Severe 40 (28.6) 42 (29.6) 38 (27.1) 110 (27.9) Mean ± SD duration of BPH (years) 4.1 ± ± ± ± 3.1 Previous BPH therapy, n (%) α-blocker 106 (75.7) 111 (78.2) 108 (77.1) 302 (76.6) Other 23 (16.4) 27 (19.0) 33 (23.6) 74(18.8) Previous OAB therapy, n (%) 7 (5.0) 10 (7.0) 12 (8.6) 26 (6.6) Mean ± SD Qmax (ml/s) 11.7 ± ± ± ± 4.8 Mean ± SD PVR (ml) 31.6 ± ± ± ± 42.9 IPSS, mean ± SD Total IPSS 16.5 ± ± ± ± 6.4 IPSS obstructive 10.3 ± ± ± ± 4.6 IPSS irritative 6.2 ± ± ± ± 2.6 IPSS QoL index 4.2 ± ± ± ± 1.4 Baseline (week 0) total IPSS score < 20; Baseline (week 0) total IPSS score 20; n = 136 (placebo), n = 140 (tadalafil 2.5 mg), n = 135 (tadalafil 5 mg), and n = 391 (all, OLE phase); Recorded at the beginning of the OLE phase (visit 7). BMI, body mass index; BPH, benign prostatic hyperplasia; IPSS, International Prostate Symptom Score; n, number of participants who were randomized and started study medication; OAB, overactive bladder; PVR, postvoid residual volume; Qmax, peak urine flow rate; QoL, quality of life; SD, standard deviation. TABLE 2. Change in efficacy from baseline (week 0) to endpoint (week 12 or last available observation) of treatment with placebo or tadalafilduring the double-blind phase Placebo Tadalafil 2.5 mg Tadalafil 5 mg N = 140 N = 142 N = 140 Variable n LS mean ± SE n LS mean ± SE P-value n LSmean± SE P-value Total IPSS ± ± ± IPSS obstructive ± ± ± IPSS irritative ± ± ± IPSS QoL index ± ± ± Qmax ± ± ± Analyses were based on last observation carried forward; Compared with placebo using ANCOVA. IPSS, International Prostate Symptom Score; LS, least squares; N, number of participants randomized; n, number of participants with nonmissing data at baseline and at least one postbaseline visit; Qmax, peak urine flow rate; QoL, quality of life; SE, standard error Efficacy: double-blind phase The LS mean difference between the placebo and tadalafil groups (placebo-adjusted LS mean) in total IPSS change from baseline was 0.7 (CI: 1.8, 0.4; P = 0.201; ANCOVA) for the tadalafil 2.5 mg group and 1.1 (CI: 2.2, 0.1; P = 0.062; ANCOVA) for the tadalafil 5 mg group. Although, there were no statistically significant differences in the total IPSS change between the placebo group and either tadalafil group, the placebo-adjusted total IPSS improvement was 57% greater in the tadalafil 5 mg group than the tadalafil 2.5 mg group (Table 2). Analyses using MMRM identified a statistically significant change in total IPSS for the tadalafil 5 mg group compared with the placebo group at week 12 (placeboadjusted LS mean change: 1.2; CI: 2.4, 0.1; P = 0.035), but not at weeks 2, 4, and 8 (Table 3). There were no statistically significant differences in the change in total IPSS at weeks 2, 4, 8, and 12, between the tadalafil 2.5 mg and the placebo groups (Table 3). There was a statistically significant difference between the tadalafil 5 mg and placebo groups in the change in IPSS obstructive subscore and IPSS QoL index from baseline to last available observation, but not for the IPSS irritative subscore (Table 2). There were no statistically significant differences between the tadalafil 2.5 mg and the placebo groups for any of the symptom scores (Table 2). A small improvement in Qmax was observed for all treatment groups during the double-blind phase, but there was no statistically significant difference in Qmax from baseline to last available observation in either tadalafil group compared with the placebo group (Table 2) Efficacy: open-label extension phase During the OLE phase, all participants showed numerical improvements in symptom scores, with the largest improvements in those who switched from placebo to tadalafil 5 mg (Table 4 and Fig. 3a). From the start of the
6 Tadalafil for BPH-LUTS in Japanese men 115 TABLE 3. Changes in total International Prostate Symptom Score (IPSS) from baseline (week 0) to weeks 2, 4, 8, and 12 in the double-blind phase Placebo Tadalafil 2.5 mg Tadalafil 5 mg N = 140 N = 142 N = 140 Timepoint n LS mean ± SE n LS mean ± SE P-value n LS mean ± SE P-value Week ± ± ± Week ± ± ± Week ± ± ± Week ± ± ± Compared with placebo using mixed-effects models repeated measures analyses. LS, least squares; N, number of participants randomized; n, number of participants with nonmissing data at baseline and at least one postbaseline visit; SE, standard error. TABLE 4. Mean change in efficacy variables from baseline (week 0) and from the start of the open-label extension phase (week 12) for all participants who entered the open-label extension phase Previous treatment Variable Placebo n = 131 Tadalafil 2.5 mg N = 135 Tadalafil 5 mg n = 128 All n = 394 Change in total IPSS Baseline to endpoint 6.2 ± ± ± ± 5.9 Week 12 to endpoint 2.3 ± ± ± ± 4.6 Change in IPSS obstructive Baseline to endpoint 4.3 ± ± ± ± 4.2 Week 12 to endpoint 1.8 ± ± ± ± 3.0 Change in IPSS irritative Baseline to endpoint 1.8 ± ± ± ± 2.6 Week 12 to endpoint 0.5 ± ± ± ± 2.1 Change in IPSS QoL index Baseline to endpoint 0.9 ± ± ± ± 1.4 Week 12 to endpoint 0.5 ± ± ± ± 1.0 Change in Qmax (ml/s) Baseline to endpoint 2.0 ± ± ± ± 4.6 Week 12 to endpoint 0.9 ± ± ± ± 4.4 Analyses were based on the last observation carried forward. Data are presented as mean ± SD. Previous treatment refers to the treatment received during the double-blind phase. All valuesare mean ± SD. IPSS, International Prostate Symptom Score; n, number of participants with nonmissing data at baseline and at least one postbaseline visit; Qmax, peak urine flow rate; QoL, quality of life; SD, standard deviation. OLE phase to endpoint (week 54 or last available observation), there was a reduction in total IPSS (mean ± SD) of 2.3 ± 4.4 and 0.9 ± 4.4 in participants who switched to tadalafil 5 mg from placebo and tadalafil 2.5 mg, respectively. A small positive change in Qmax was observed over the 42-week OLE phase irrespective of treatment during the double-blind phase (Table 4 and Fig. 3b). Analysis of the subgroup of participants (n = 128) who received tadalafil (5.0 mg) for 54 weeks showed a maintained reduction in total IPSS from baseline. At baseline, total IPSS (mean ± SD) was 16.5 ± 5.8. At week 12 and week 54, total IPSS was 11.4 ± 5.7 and 11.1 ± 6.8, respectively. For all other efficacy variables, including IPSS obstructive and irritative subscores, IPSS QoL index, and Qmax, the changes observed at the end of the doubleblind phase were maintained or numerically improved during the 42-week OLE phase Safety and tolerability Tadalafil (2.5 mg or 5.0 mg) treatment once daily was well tolerated, with few treatment-related AEs reported (Table 5). Generally, during the 12-week double-blind phase, the frequency and type of AEs were similar across all treatment groups, as was the percentage of participants discontinuing because of AEs (Table 5). The most frequent TEAEs were nasopharyngitis, diarrhea, back pain, and headache. In all treatment groups, most TEAEs (150/166; 90.4%) were mild in severity. Dyspepsia, reflux esophagitis, cataract, and hot flush were reported by at least four participants treated with tadalafil (2.5 mg or 5.0 mg), but were not reported for participants treated with placebo (Table 5). Nasopharyngitis was the most frequently occurring TEAE in the placebo group and occurred at a higher frequency than in either of the tadalafil groups. There was no apparent relationship between tadalafil dose and the frequency or type of AEs. Similar percentages of participants in each group experienced at least one treatment-related AE (placebo: 7.9%, 11/140; tadalafil 2.5 mg: 4.9%, 7/142; tadalafil 5 mg: 6.4%, 9/140). During the double-blind phase, five serious AEs (SAEs) were experienced by five participants (placebo: one participant; tadalafil 2.5 mg: two participants; tadalafil 5 mg: two participants). None of these SAEs were considered to be related to tadalafil treatment. Adverse events reported during the OLE phase were similar to those reported during the double-blind phase. During the 42-week OLE phase, 232/394 (58.9%) participants experienced at least one TEAE. The most frequent TEAEs were the same as those reported during the double-blind phase (Table 5). During the OLE phase, 12
7 116 Masayuki Takeda et al. (a) (b) hypertension and his death was considered unrelated to tadalafil treatment. There were 128 participants who received tadalafil (5.0 mg, once daily) during both the double-blind and OLE phases (54 weeks). Of these participants, 66.4% (85/128) reported one or more TEAEs during the doubleblind and OLE phases, and 57.0% (73/128) reported one or more TEAEs during the OLE phase only. For those participants who received tadalafil 5.0 mg during the double-blind and OLE phases, dyspepsia (five events; 3.9%) was the only AE with an incidence 2% that was considered to be possibly related to tadalafil treatment. During the double-blind and OLE phases, there were no clinically adverse changes in vital signs, laboratory values, or PVR (Fig. 4). There were two participants (placebo and tadalafil 2.5 mg group) in the double-blind phase and eight participants (previous treatment placebo: four participants; tadalafil 2.5 mg: two participants; tadalafil 5 mg: two participants) in the OLE phase who had PSA values 10 μg/l at either study discontinuation or endpoint. After further examination, all 10 participants had prostate malignancy ruled out by the investigators. The rise in PSA, which was transient in most participants, was not considered related to tadalafil treatment. Fig. 3 Change in mean total International Prostate Symptom Score (IPSS) (a) and mean Qmax (b) during the placebo run-in, double-blind, and open-label extension (OLE) phases. The figure legend refers to treatment group and dose of tadalafil administered during the double-blind phase (closed symbols) and the OLE phase (open symbols). Mean data were calculated from participants who entered the OLE phase (placebo, n = 131; tadalafil 2.5 mg, n = 135; tadalafil 5 mg, n = 128). SAEs were experienced by 11 participants. The percentage of participants experiencing an SAE was similar irrespective of the treatment received during the double-blind phase (placebo: 3.1%, four participants; tadalafil 2.5 mg: 2.2%, three participants; tadalafil 5 mg: 3.1%, four participants). One SAE (urinary retention) was considered possibly related to tadalafil treatment; this 74-year-old participant was catheterized because of prostatitis and urinary retention approximately 4.5 months after randomization and initiation of tadalafil (5.0 mg). Subsequent biopsy revealed prostate cancer and the participant underwent radical prostatectomy. One participant died of subarachnoid hemorrhage approximately 5 months into the OLE phase; this 69-year-old participant, initially randomized to the placebo group, had preexisting 4. DISCUSSION Tadalafil resulted in numeric, but insignificant, improvements in total IPSS with placebo-adjusted LS mean changes from baseline to last available observation of 0.7 and 1.1 in the tadalafil 2.5 and 5 mg groups, respectively. The magnitude of improvement was greater at the 5.0 mg dose compared with the 2.5 mg dose of tadalafil. Treatment with tadalafil 5.0 mg once daily during the OLE phase was associated with a further numeric reduction in total IPSS in participants who changed from placebo or tadalafil 2.5 mg. The improvement in total IPSS in participants who had previously received tadalafil 5.0 mg was maintained during the OLE phase. Over the 54-week treatment period, tadalafil (5.0 mg) was well tolerated and there were no unexpected TEAEs. Although there was no statistically significant difference between tadalafil treatment and placebo in the primary analysis (ANCOVA) with respect to the primary outcome (total IPSS change from baseline to last available observation), MMRM analyses showed that at week 12 there was a statistically significant change in total IPSS for the tadalafil 5 mg group compared with the placebo group. There was also a statistically significant difference between the tadalafil 5 mg and placebo groups in the change in the secondary outcome variables, IPSS obstructive subscore and IPSS QoL, from baseline to last available observation. The changes in other efficacy variables (IPSS irritative subscore and Qmax) were not statistically significant for tadalafil 5 mg versus placebo; however, the changes observed were maintained or numerically increased during the 42-week OLE phase. In addition, participants switching from placebo or tadalafil 2.5 mg to tadalafil 5.0 mg in the OLE phase experienced improvements in total IPSS and other efficacy variables, which
8 TABLE 5. Treatment emergent adverse events in the double-blind and open-label extension (OLE) phases of the study Tadalafil for BPH-LUTS in Japanese men 117 Double-blind phase OLE phase Variable Placebo (n = 140) Tadalafil 2.5 mg (n = 142) Tadalafil 5 mg (n = 140) Tadalafil 5 mg (n = 394) One or more TEAE, n (%) 53 (37.9) 56 (39.4) 57 (40.7) 232 (58.9) TEAEs, n (%) Nasopharyngitis 18 (12.9) 12 (8.5) 14 (10.0) 42 (10.7) Diarrhea 5 (3.6) 3 (2.1) 2 (1.4) 24 (6.1) Back pain 2 (1.4) 2 (1.4) 2 (1.4) 17 (4.3) Headache 3 (2.1) 2 (1.4) 3 (2.1) 12 (3.0) Dyspepsia 0 (0.0) 2 (1.4) 4 (2.9) 10 (2.5) Eczema 3 (2.1) 0 (0.0) 0 (0.0) 9 (2.3) Insomnia 0 (0.0) 0 (0.0) 1 (0.7) 8 (2.0) Reflux esophagitis 0 (0.0) 3 (2.1) 2 (1.4) 8 (2.0) Cataract 0 (0.0) 1 (0.7) 3 (2.1) 5 (1.3) Gingivitis 0 (0.0) 3 (2.1) 0 (0.0) 3 (0.8) Hot flush 0 (0.0) 3 (2.1) 2 (1.4) 3 (0.8) Palpitations 0 (0.0) 3 (2.1) 0 (0.0) 2 (0.5) Discontinuation as a result of an AE, n (%) 5 (3.6) 4 (2.8) 5 (3.6) 36 (9.1) One or more SAE, n (%) 1 (0.7) 2 (1.4) 2 (1.4) 11 (2.8) Treatment-related AE, n (%) 11 (7.9) 7 (4.9) 9 (6.4) 57 (14.5) Reported by 2% of participants in any treatment group. For the double-blind phase, TEAEs were defined as events that first occurred or worsened from the day of randomization (Visit 3) to the end of the double-blind phase; for the OLE phase, TEAEs were defined as events that first occurred or worsened from the day of enrollment (Visit 7) in the OLE phase to the end of the OLE phase; Assessed by the investigator as possibly related to the study drug. AE, adverse event; n, number of participants who were randomized and started study medication; SAE, serious adverse event; TEAE, treatment-emergent adverse event. Fig. 4 Change in mean postvoid residual volume (PVR) during the placebo run-in, double-blind, and open-label extension (OLE) phases. The figure legend refers to treatment group and dose of tadalafil administered during the double-blind phase (closed symbols) and the OLE phase (open symbols). Mean data were calculated from participants who entered the OLE phase (placebo, n = 131; tadalafil 2.5 mg, n = 135; tadalafil 5 mg, n = 128). were similar to the improvements observed with the tadalafil 5 mg group in the double-blind phase. The observed safety and efficacy trends are similar to those from a previous phase-2/3 study conducted in 10 non-asian countries to examine the safety and efficacy of tadalafil in the treatment of BPH-LUTS. 25 This study by Roehrborn et al. 25 had a similar design to the current study, except that there was a longer wash-out period (4 weeks) and the inclusion criteria did not specify a minimum prostate volume. Roehrborn et al. 25 reported that during a 12-week double-blind phase, tadalafil (5.0 mg) was associated with a statistically significant improvement in total IPSS (LS mean ± SE) from baseline ( 4.9 ± 0.5) compared with placebo ( 2.3 ± 0.5). Although in the current study tadalafil (5.0 mg) was associated with a similar change in total IPSS from baseline ( 4.9 ± 0.4), this change was not statistically different from placebo. This may reflect the large placebo effect observed in the current study. In the placebo group, the total IPSS change from baseline (LS mean ± SE) was 3.8 ± 0.4 compared with 2.3 ± 0.5 reported by Roehrborn et al. 25 The apparent differences in efficacy may reflect differences in baseline characteristics of participants enrolled in the two studies. For example, the current study enrolled older participants ( 65 years: 274/422, 64.9% versus 394/1056, 37.3%) and fewer participants had severe BPH-LUTS (120/422, 28.4% versus 354/1056, 33.5%). In addition, a higher percentage of men had received previous α-blocker therapy (325/422, 77.0% versus 304/1056, 28.8%). Nevertheless, in the current study, the total IPSS change (mean ± SD) of 5.4 ± 6.3 during the 54-week treatment period (tadalafil 5.0 mg, once daily) was similar to changes observed in a 1-year tadalafil multinational study enrolling predominantly Caucasian participants (total IPSS change over 64 weeks: 5.0 ± 7.2). 26 In all treatment groups, there was a numeric improvement in Qmax that started at the beginning of the placebo run-in period and was maintained for the duration of the OLE phase. The changes in Qmax observed in the tadalafil groups were not significantly different from placebo. Improvements in Qmax that are not statistically different from placebo have previously been reported for
9 118 Masayuki Takeda et al. tadalafil. 25,27 Treatment with α-blockers, such as tamsulosin and silodosin, in Japanese men with BPH-LUTS, have also been associated with changes in Qmax that were insignificant compared with placebo. 28 The safety and tolerability profile of tadalafil observed in this study was similar to that previously reported for treatment with tadalafil (up to 20 mg, as needed) in Japanese men with ED. 21 In the current study, there was a higher incidence of nasopharyngitis in both the placebo and tadalafil groups, which may be associated with the study being conducted during winter. During the double-blind phase, the percentage of participants who discontinued because of AEs was low and similar among all treatment groups ( %). Of the participants treated with tadalafil (5.0 mg) during the double-blind and OLE phases, 57.0% (73/128 participants) reported one or more TEAEs during the OLE phase. This is similar to the percentage of participants (56.6%) reporting TEAEs during the OLE phase in the 1-year tadalafil multinational study enrolling predominantly Caucasian participants. 26 Over the 54-week treatment period, dyspepsia was the only AE with an incidence 2% that was considered to be possibly related to treatment. There were no clinically significant changes observed in vital signs, clinical laboratory tests, or PVR. In conclusion, this dose-finding study demonstrated that although there was no statistically significant difference between tadalafil treatment (2.5 or 5.0 mg) and placebo in the primary outcome (total IPSS change from baseline to last available observation), there was a dosedependent improvement in all efficacy variables over the 12-week double-blind placebo-controlled phase. These improvements were maintained over a 1-year treatment period with tadalafil 5.0 mg. Tadalafil, once daily, was generally well tolerated during both the 12-week, double-blind phase (2.5 or 5.0 mg) and the 42-week, OLE phase (5.0 mg). These results support further investigation of tadalafil (5.0 mg, once daily) in Japanese men with moderate-to-severe BPH-LUTS. Acknowledgments The study was funded by Eli Lilly and Company, the manufacturer of tadalafil. Medical writing services were provided by Narelle Bramich, PhD, and Serina Stretton, PhD, of ProScribe Medical Communications and were funded by Eli Lilly Japan K.K. Disclosure This study was sponsored by Eli Lilly and Company. The sponsor was involved in the study design, and in the collection, analysis and interpretation of data. T. Imaoka, Y. Morisaki, and L. Viktrup were involved in the study design. Y. Morisaki also completed the statistical analyses. All authors participated in the interpretation of the study results and in the drafting, critical revision, and approval of the final version of the manuscript. M. Takeda and O. Nishizawa have been advisory board members for Eli Lilly Japan K.K. T. Imaoka, and Y. Morisaki are employees of Eli Lilly Japan K.K., and L. Viktrup is an employee of Eli Lilly and Company. REFERENCES 1. Lepor H. Pathophysiology, epidemiology, and natural history of benign prostatic hyperplasia. Rev Urol 2004; 6(Suppl 9): S Abrams P, Cardozo L, Fall M et al. The standardisation of terminology in lower urinary tract function: report from the standardisation sub-committee of the International Continence Society. Urology 2003; 61: American Urological Association Practice Guidelines Committee. Chapter 1: Guideline on the management of benign prostatic hyperplasia (BPH). American Urological Association Guideline: Management of Benign Prostatic Hyperplasia (BPH). American Urological Association Education and Research, Inc., [Cited 14 Feb 2012]. Available from URL: clinical-guidelines.cfm?sub=bph. 4. McVary KT. BPH: epidemiology and comorbidities. Am J Manag Care 2006; 12: S Tsukamoto T, Kumamoto Y, Masumori N et al. Prevalence of prostatism in Japanese men in a community-based study with comparison to a similar American study. JUrol 1995; 154: Calais Da Silva F, Marquis P, Deschaseaux P, Gineste JL, Cauquil J, Patrick DL. Relative importance of sexuality and quality of life in patients with prostatic symptoms. Results of an international study. Eur Urol 1997; 31: Yoshimura K, Arai Y, Ichioka K, Terada N, Matsuta Y, Okubo K. Symptom-specific quality of life in patients with benign prostatic hyperplasia. Int J Urol 2002; 9: Homma Y, Araki I, Igawa Y et al. Clinical guideline for male lower urinary tract symptoms. Int J Urol 2009; 16: Ishizuka O, Nishizawa O, Hirao Y, Ohshima S. Evidencebased meta-analysis of pharmacotherapy for benign prostatic hypertrophy. Int J Urol 2002; 9: Harnal D [prescribing information]. Tokyo: Astellas Pharma Inc., September URIEF [prescribing information]. Matsumoto: Kissei Pharmaceutical Co., Ltd, June Avolve [prescribing information]. Tokyo: GlaxoSmithKline K.K., December Prostatin [prescribing information]. Tokyo: ASKA Pharmaceutical Co., Ltd, July Perselin [prescribing information]. Tokyo: MSD K.K., October Prostal [prescribing information]. Tokyo: ASKA Pharmaceutical Co., Ltd, December Verhamme KM, Dieleman JP, Bleumink GS, Bosch JL, Stricker BH, Sturkenboom MC. Treatment strategies, patterns of drug use and treatment discontinuation in men with LUTS suggestive of benign prostatic hyperplasia: the Triumph project. Eur Urol 2003; 44: Furuya R, Masumori N, Furuya S et al. Investigation of adverse events and the continuance rate of silodosin in all patients who received silodosin for lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Nippon Hinyokika Gakkai Zasshi 2010; 101: Takeda M, Tang R, Shapiro E, Burnett AL, Lepor H. Effects of nitric oxide on human and canine prostates. Urology 1995; 45: Uckert S, Kuczyk MA. Cyclic nucleotide metabolism including nitric oxide and phosphodiesterase-related targets in the lower urinary tract. Handb Exp Pharmacol 2011; 202: Montorsi F, Verheyden B, Meuleman E et al. Long-term safety and tolerability of tadalafil in the treatment of erectile dysfunction. Eur Urol 2004; 45: Nagao K, Kimoto Y, Marumo K et al. Efficacy and safety of tadalafil 5, 10, and 20 mg in Japanese men with erectile dysfunction: results of a multicenter, randomized, doubleblind, placebo-controlled study. Urology 2006; 68:
10 Tadalafil for BPH-LUTS in Japanese men Barry MJ, Fowler FJ Jr, O Leary MP et al. The American Urological Association symptom index for benign prostatic hyperplasia. The Measurement Committee of the American Urological Association. JUrol1992; 148: Homma Y, Tsukamoto T, Yasuda K, Ozono S, Yoshida M, Shinji M. Linguistic validation of Japanese version of International Prostate Symptom Score and BPH impact index. Nippon Hinyokika Gakkai Zasshi 2002; 93: Barry MJ. Evaluation of symptoms and quality of life in men with benign prostatic hyperplasia. Urology 2001; 58: Roehrborn CG, McVary KT, Elion-Mboussa A, Viktrup L. Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a dose finding study. JUrol2008; 180: Donatucci CF, Brock GB, Goldfischer ER et al. Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a 1-year, openlabel extension study. BJU Int 2011; 107: Roehrborn CG, Kaminetsky JC, Auerbach SM, Montelongo RM, Elion-Mboussa A, Viktrup L. Changes in peak urinary flow and voiding efficiency in men with signs and symptoms of benign prostatic hyperplasia during once daily tadalafil treatment. BJU Int 2010; 105: Kawabe K, Yoshida M, Homma Y. Silodosin, a new α 1A -adrenoceptor-selective antagonist for treating benign prostatic hyperplasia: results of a phase III randomized, placebo-controlled, double-blind study in Japanese men. BJU Int 2006; 98:
H6D-MC-LVHR Clinical Study Report Synopsis Page LVHR Synopsis (LY450190)
H6D-MC-LVHR Clinical Study Report Synopsis Page 1 2. LVHR Synopsis H6D-MC-LVHR Clinical Study Report Synopsis Page 2 Clinical Study Report Synopsis: Study H6D-MC-LVHR Title of Study: A Randomized, Double-Blind,
More informationEVALUATION OF THE EFFICACY OF TADALAFIL IN IMPROVING LOWER URINARY TRACT SYMPTOMS IN PATIENTS WITH SYMPTOMATIC BENIGN PROSTATIC ENLARGEMENT
Basrah Journal Of Surgery EVALUATION OF THE EFFICACY OF TADALAFIL IN IMPROVING LOWER URINARY TRACT SYMPTOMS IN PATIENTS WITH SYMPTOMATIC BENIGN PROSTATIC ENLARGEMENT MB, ChB, FIBMS, Assistant Professor
More informationComparison of Silodosin versus Tadalafil in Patients with Lower Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasia
LUTS (2017) 9, 176 186 ORIGINAL ARTICLE Comparison of Silodosin versus Tadalafil in Patients with Lower Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasia Masaki YOSHIDA, 1, Hideki ORIGASA,
More informationJMSCR Vol 05 Issue 07 Page July 2017
www.jmscr.igmpublication.org Impact Factor 5.84 Index Copernicus Value: 83.27 ISSN (e)-2347-176x ISSN (p) 2455-0450 DOI: https://dx.doi.org/10.18535/jmscr/v5i7.47 Original Research Article Tadalafil therapy
More informationCorrespondence should be addressed to Yoshinori Tanaka;
Hindawi Advances in Urology Volume 2017, Article ID 4842025, 6 pages https://doi.org/10.1155/2017/4842025 Clinical Study The Persistence of Silodosin Monotherapy and the Reasons for Withdrawal from Treatment
More informationSilodosin versus naftopidil for the treatment of benign prostatic hyperplasia: A multicenter randomized trial
The study protocol was approved by the ethics committee and institutional review board of Nihon University School of Medicine. Written informed consent was obtained from all patients. From December 2007
More informationIncreasing Awareness, Diagnosis, and Treatment of BPH, LUTS, and EP
Introduction to Enlarged Prostate E. David Crawford, MD Professor of Surgery (Urology) and Radiation Oncology Head, Urologic Oncology E. David Crawford Endowed Chair in Urologic Oncology University of
More informationNew Treatment Modalities for Benign Prostatic Hyperplasia. Seung-June Oh, MD Department of Urology, Seoul National University Hospital
New Treatment Modalities for Benign Prostatic Hyperplasia Seung-June Oh, MD Department of Urology, Seoul National University Hospital Options for Treating BPH Pharmacotherapy blocker Agents for BPH + OAB
More informationVoiding Dysfunction. Hyo Serk Lee, Sae Woong Kim 1, Seung-June Oh 2, Myung-Soo Choo 3, Kyu-Sung Lee
www.kjurology.org http://dx.doi.org/10.4111/kju.2012.53.3.178 Voiding Dysfunction Efficacy and Safety of Tamsulosin for Treating Lower Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasia:
More informationLONG-TERM SAFETY AND EFFICACY OF TAMSULOSIN FOR THE TREATMENT OF LOWER URINARY TRACT SYMPTOMS ASSOCIATED WITH BENIGN PROSTATIC HYPERPLASIA
0022-5347/03/1702-0498/0 Vol. 170, 498 502, August 2003 THE JOURNAL OF UROLOGY Printed in U.S.A. Copyright 2003 by AMERICAN UROLOGICAL ASSOCIATION DOI: 10.1097/01.ju.0000076140.68657.fd LONG-TERM SAFETY
More informationMMM. Topic The use of Tadalafil 5mg daily for the treatment of BPH-LUTS
Dr Tan & Partners MMM Vol. 1 No. 1 Morbidity & Mortality Meeting 14 th November 2014 Introduction Topic The use of Tadalafil 5mg daily for the treatment of BPH-LUTS Tadalafil 5mg daily is a well established
More informationBenign Prostatic Hyperplasia. Jay Lee, MD, FRCSC Clinical Associate Professor University of Calgary
Benign Prostatic Hyperplasia Jay Lee, MD, FRCSC Clinical Associate Professor University of Calgary Copyright 2017 by Sea Courses Inc. All rights reserved. No part of this document may be reproduced, copied,
More informationMANAGING BENIGN PROSTATIC HYPERTROPHY IN PRIMARY CARE DR GEORGE G MATHEW CONSULTANT FAMILY PHYSICIAN FELLOW IN SEXUAL & REPRODUCTIVE HEALTH
MANAGING BENIGN PROSTATIC HYPERTROPHY IN PRIMARY CARE DR GEORGE G MATHEW CONSULTANT FAMILY PHYSICIAN FELLOW IN SEXUAL & REPRODUCTIVE HEALTH INTRODUCTION (1) Part of male sexual reproductive organ Size
More informationDiagnostic approach to LUTS in men. Prof Dato Dr. Zulkifli Md Zainuddin Consultant Urologist / Head Of Urology Unit UKM Medical Center
Diagnostic approach to LUTS in men Prof Dato Dr. Zulkifli Md Zainuddin Consultant Urologist / Head Of Urology Unit UKM Medical Center Classification of LUTS Storage symptoms Voiding symptoms Post micturition
More informationEUROPEAN UROLOGY 61 (2012)
EUROPEAN UROLOGY 61 (2012) 917 925 available at www.sciencedirect.com journal homepage: www.europeanurology.com Platinum Priority Benign Prostatic Hyperplasia Editorial by Christopher R. Chapple on pp.
More informationThe Egyptian Journal of Hospital Medicine (January 2019) Vol. 74 (6), Page
The Egyptian Journal of Hospital Medicine (January 2019) Vol. 74 (6), Page 1377-1386 Evaluation of Silodosin in Comparison to Tamuslosin in Treatment of Benign Prostatic Hyperplasia with lower Urinary
More informationOriginal Article. Introduction. Methods. Abstract
Blackwell Science, LtdOxford, UKIJUInternational Journal of Urology0919-81722003 Blackwell Publishing Asia Pty LtdNovember 20031011587594Original ArticleUsefulness of a1-blockers in BPHI Ikemoto et al.
More informationEvaluation of Sexual Dysfunction in Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia Patients
Original Article Print ISSN: 2321-6379 Online ISSN: 2321-595X DOI: 10.17354/ijss/2018/10 Evaluation of Sexual Dysfunction in Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia Patients N. Narayanamoorthy,
More informationIntroduction. Original Article: Clinical Investigation
International Journal of Urology (2015) 22, 582--587 doi: 10.1111/iju.12741 Original Article: Clinical Investigation Treatment satisfaction and clinically meaningful symptom improvement in men with lower
More informationRole of silodosin in patients with LUTS/BPE non responding to medical treatment with tamsulosin: a prospective, open-label, pilot study
European Review for Medical and Pharmacological Sciences 2017; 21: 4941-4945 Role of silodosin in patients with LUTS/BPE non responding to medical treatment with tamsulosin: a prospective, open-label,
More informationINTRODUCTION MISCELLANEOUS
MISCELLANEOUS Comparing Monotherapy with Tadalafil or Tamsulosin and Their Combination Therapy in Men with Benign Prostatic Hyperplasia: A Randomized Clinical Trial Hossein Karami*, Amin Hassanzadeh-Hadad,
More informationLiterature Scan: Drugs for BPH
Copyright 2012 Oregon State University. All Rights Reserved Drug Use Research & Management Program Oregon State University, 500 Summer Street NE, E35 Salem, Oregon 97301-1079 Phone 503-947-5220 Fax 503-947-1119
More informationOriginal Research Article
International Surgery Journal Singh SN et al. Int Surg J. 218 May;():1866-1872 http://www.ijsurgery.com pissn 2349-33 eissn 2349-292 Original Research Article DOI: http://dx.doi.org/1.1823/2349-292.isj218199
More informationNational Institute for Health and Care Excellence. Lower Urinary Tract Symptoms Update Addendum Consultation Table 3 rd February 5 pm 3 rd March 2015
British Association of Urological Surgeons British Association of Urological Surgeons National Institute for Health and Care Excellence Lower Urinary Tract Symptoms Update Addendum Consultation Table 3
More informationKey words: Lower Urinary Tract Symptoms (LUTS), Prostatic Hyperplasia, Alpha-1 Adrenoceptor Antagonists, Tamsulosin, Terazosin.
The Professional Medical Journal DOI: 10.17957/TPMJ/17.4102 ORIGINAL PROF-4102 PROSTATIC HYPERPLASIA; COMPARISON BETWEEN TAMSULOSIN AND TERAZOSIN FOR EFFICACY IN MEDICAL MANAGEMENT OF LOWER URINARY TRACT
More informationNOTE: This policy is not effective until April 1, Transurethral Water Vapor Thermal Therapy of the Prostate
NOTE: This policy is not effective until April 1, 2019. Medical Policy Manual Surgery, Policy No. 210 Transurethral Water Vapor Thermal Therapy of the Prostate Next Review: December 2019 Last Review: December
More informationMonth/Year of Review: May 2014 Date of Last Review: November 2012 Source Document: OSU College of Pharmacy
Drug Use Research & Management Program Oregon State University, 500 Summer Street NE, E35, Salem, Oregon 97301-1079 Phone 503-947-5220 Fax 503-947-1119 Copyright 2012 Oregon State University. All Rights
More informationThe Evolution of Combination Therapy. US men eligible for BPH treatment * with projected population changes
The Management of BPH & The Impact of Combination Therapy Results Combination of Avodart and Tamsulosin (CombAT) Medical Therapy of Prostate Symptoms (MTOPS) Dr. Jack Barkin, md, fics, facs, dabu, Mcert
More informationManagement of LUTS. Simon Woodhams February 2012
Management of LUTS Simon Woodhams February 2012 The management of lower urinary tract symptoms (LUTS) in men Implementing NICE guidance May 2010 NICE clinical guideline 97 Background Lower urinary tract
More informationCialis. Cialis (tadalafil) Description
Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.06.02 Subject: Cialis Page: 1 of 5 Last Review Date: September 18, 2015 Cialis Description Cialis (tadalafil)
More informationChapter 4: Research and Future Directions
Chapter 4: Research and Future Directions Introduction Many of the future research needs listed in the 1994 Agency for Health Care Policy and Research (AHCPR) clinical practice guideline Benign Prostatic
More informationThe Journal of International Medical Research 2012; 40:
The Journal of International Medical Research 2012; 40: 899 908 Comparison of α-blocker Monotherapy and α-blocker Plus 5α-Reductase Inhibitor Combination Therapy Based on Prostate Volume for Treatment
More informationClinicalTrials.gov Identifier: sanofi-aventis. Sponsor/company:
These results are supplied for informational purposes only. Prescribing decisions should be made based on the approved package insert in the country of prescription Sponsor/company: sanofi-aventis ClinicalTrials.gov
More informationORIGINAL ARTICLE. Key words benign prostatic hyperplasia, bother, lower urinary tract symptoms, quality of life, tamsulosin
LUTS (2012) 4, 45 50 ORIGINAL ARTICLE Correlations among Lower Urinary Tract Symptoms, Bother, and Quality of Life in Patients with Benign Prostatic Hyperplasia and Associated Fluctuations with Tamsulosin
More informationeuropean urology 53 (2008)
european urology 53 (2008) 1236 1244 available at www.sciencedirect.com journal homepage: www.europeanurology.com Benign Prostatic Enlargement A Randomised, Placebo-Controlled Study to Assess the Efficacy
More informationIndex. urologic.theclinics.com. Note: Page numbers of article titles are in boldface type.
Index Note: Page numbers of article titles are in boldface type. A Ablative therapies, transurethral needle ablation, Adverse events, sexual side effects of BPH Aging, and incidence of BPH associated with
More informationThe Relationship between Prostate Inflammation and Lower Urinary Tract Symptoms: Examination of Baseline Data from the REDUCE Trial
european urology 54 (2008) 1379 1384 available at www.sciencedirect.com journal homepage: www.europeanurology.com Benign Prostatic Hyperplasia The Relationship between Prostate Inflammation and Lower Urinary
More informationBenign Prostatic Hyperplasia (BPH):
Benign Prostatic Hyperplasia (BPH): Evidence Based Guidelines for Primary Care Providers Jeanne Martin, DNP, ANP-BC Objectives 1. Understand the pathophysiology and prevalence of BPH 2. Select the appropriate
More informationj 727
Efficacy and Safety of the Coadministration of Tadalafil Once Daily with Finasteride for 6 Months in Men with Lower Urinary Tract Symptoms and Prostatic Enlargement Secondary to Benign Prostatic Hyperplasia
More informationProfile of Silodosin. Francesco Montorsi * Article info. Abstract
EUROPEAN UROLOGY SUPPLEMENTS 9 (2010) 491 495 available at www.sciencedirect.com journal homepage: www.europeanurology.com Profile of Silodosin Francesco Montorsi * Department of Urology, University Vita-Salute
More informationCialis. Cialis (tadalafil) Description
Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.40.22 Subject: Cialis Page: 1 of 5 Last Review Date: September 15, 2017 Cialis Description Cialis (tadalafil)
More informationVOIDING DYSFUNCTION IN ELDERLY MALE CURRENT STATUS
VOIDING DYSFUNCTION IN ELDERLY MALE CURRENT STATUS DR. FRANCIS LEE Voiding dysfunction Storage Emptying Common voiding dysfunction in elderly male Emptying BPH Storage Incontinence Overactive bladder Post-prostatectomy
More informationWho Would Benefit from Solifenacin Add-On Therapy to Tamsulosin for Overactive Bladder Symptoms Associated with Benign Prostatic Hyperplasia?
LUTS (2013) 5, 145 149 ORIGINAL ARTICLE Who Would Benefit from Solifenacin Add-On Therapy to Tamsulosin for Overactive Bladder Symptoms Associated with Benign rostatic Hyperplasia? Jun OBATA, Kazuhiro
More informationCombination Drug Therapy for Benign Prostatic Hyperplasia (BPH)
The Annals of African Surgery www.sskenya.org Combination Drug Therapy for Benign Prostatic Hyperplasia (BPH) Author: Oliech J.S. FRCS, Affiliation: Department of Surgery, University of Nairobi. P.O. Box
More informationOriginal Article - Voiding Dysfunction
www.kjurology.org http://dx.doi.org/10.4111/kju.2014.55.5.335 Original Article - Voiding Dysfunction http://crossmark.crossref.org/dialog/?doi=10.4111/kju.2014.55.5.335&domain=pdf&date_stamp=2014-05-16
More informationClinical Trial Results Database Page 1
Clinical Trial Results Database Page 1 Sponsor Novartis Pharmaceuticals Corporation Generic Drug Name Therapeutic Area of Trial Major Depressive Disorder (MDD) Approved Indication Treatment of major depressive
More informationLast Review Status/Date: December Summary
Section: Surgery Effective Date: January 15, 2016 Subject: Prostatic Urethral Lift Page: 1 of 9 Last Review Status/Date: December 2015 Summary Benign prostatic hyperplasia (BPH) is a common condition in
More informationInvestigation of ejaculatory disorder by silodosin in the treatment of prostatic hyperplasia
Sakata and Morita BMC Urology 2012, 12:29 RESEARCH ARTICLE Open Access Investigation of ejaculatory disorder by silodosin in the treatment of prostatic hyperplasia Koichi Sakata 1* and Tatsuo Morita 2
More informationISSN: (Print) (Online) Journal homepage:
Archives of Andrology Journal of Reproductive Systems ISSN: 0148-5016 (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/iaan19 CHANGE IN INTERNATIONAL PROSTATE SYMPTOM SCORE AFTER TRANSURETHRAL
More informationKeywords: Lower urinary tract symptoms; Phosphodiesterase 5 Inhibitors; Prostatic hyperplasia; Safety; Tadalafil
Original Article pissn: 2287-4208 / eissn: 2287-4690 World J Mens Health 2018 May 36(2): 161-170 https://doi.org/10.5534/wjmh.17017 Safety and Effectiveness of Once-Daily Tadalafil (5 mg) Therapy in Korean
More informationBenign Prostatic Hyperplasia. Management of Benign Prostatic Hyperplasia. Goals of Therapy
Benign Prostatic Hyperplasia Management of Benign Prostatic Hyperplasia Goals of Therapy Improve or abolish lower urinary tract symptoms (LUTS) Prevent or delay clinical progression of benign prostatic
More informationEfficacy of Silodosin for Relieving Benign Prostatic Obstruction: Prospective Pressure Flow Study
Efficacy of Silodosin for Relieving Benign Prostatic Obstruction: Prospective Pressure Flow Study Yoshihisa Matsukawa,* Momokazu Gotoh, Tomonori Komatsu, Yasuhito Funahashi, Naoto Sassa and Ryohei Hattori
More informationAlpha antagonists from initial concept to routine clinical practice
european urology 50 (2006) 635 642 available at www.sciencedirect.com journal homepage: www.europeanurology.com Editorial 50th Anniversary Alpha antagonists from initial concept to routine clinical practice
More informationSummary ID# Clinical Study Summary: Study B4Z-MC-LYBX
CT Registry ID#7068 Page 1 Summary ID# 7068 Clinical Study Summary: Study B4Z-MC-LYBX A Randomized, Double-Blind Comparison of Hydrochloride and Placebo in Child and Adolescent Outpatients with Attention-
More informationThe clinical trial information provided in this public disclosure synopsis is supplied for informational purposes only.
The clinical trial information provided in this public disclosure synopsis is supplied for informational purposes only. Please note that the results reported in any single trial may not reflect the overall
More informationTzu Chi Medical Journal
Tzu Chi Medical Journal 25 (2013) 98e102 Contents lists available at SciVerse ScienceDirect Tzu Chi Medical Journal journal homepage: www.tzuchimedjnl.com Original Article First-line antimuscarinic monotherapy
More informationDOWNLOAD OR READ : TREATMENT OF BENIGN PROSTATIC HYPERPLASIA PDF EBOOK EPUB MOBI
DOWNLOAD OR READ : TREATMENT OF BENIGN PROSTATIC HYPERPLASIA PDF EBOOK EPUB MOBI Page 1 Page 2 treatment of benign prostatic hyperplasia treatment of benign prostatic pdf treatment of benign prostatic
More informationSystematic Review of Combination Drug Therapy for Non-neurogenic Male Lower Urinary Tract Symptoms
EUROPEAN UROLOGY 64 (2013) 228 243 available at www.sciencedirect.com journal homepage: www.europeanurology.com Platinum Priority Collaborative Review Benign Prostatic Hyperplasia Editorial by Herbert
More informationPROSTATIC EMBOLIZATION FOR BENIGN HYPERPLASIA
St. Louis Hospital PROSTATIC EMBOLIZATION FOR BENIGN HYPERPLASIA INITIAL CLINICAL RESULTS Faculty of Medical Sciences New University of Lisbon JOÃO PISCO LUÍS CAMPOS PINHEIRO TIAGO BILHIM HUGO RIO TINTO
More informationSYNOPSIS 2/198 CSR_BDY-EFC5825-EN-E02. Name of company: TABULAR FORMAT (For National Authority Use only)
SYNOPSIS Title of the study: A randomized, double-blind, placebo-controlled, parallel-group, fixed-dose (rimonabant 20 mg) multicenter study of long-term glycemic control with rimonabant in treatment-naïve
More informationfor ED and LUTS/BPH Pierre Sarkis, M.D. Assistant Professor Fellow of the European Board of Urology
Tadalafil 5 mg once daily for ED and LUTS/BPH Pierre Sarkis, M.D. Assistant Professor Fellow of the European Board of Urology Why this conference? Not promotional but educational The pharmacist regularly
More informationEvaluation of Tadalafil effect on lower urinary tract symptoms of benign prostatic hyperplasia in patients treated with standard medication
ORIGINal article Vol. 38 (1): 33-39, January - February, 2012 Evaluation of Tadalafil effect on lower urinary tract symptoms of benign prostatic hyperplasia in patients treated with standard medication
More informationThe Enlarged Prostate Symptoms, Diagnosis and Treatment
The Enlarged Prostate Symptoms, Diagnosis and Treatment MAC00031-01 Rev G Financial support for this seminar has been provided by NeoTract, Inc., the manufacturer of the UroLift System. 1 Today s Agenda
More informationDiagnosis and Mangement of Nocturia in Adults
Diagnosis and Mangement of Nocturia in Adults Christopher Chapple Professor of Urology Sheffield Teaching Hospitals University of Sheffield Sheffield Hallam University UK 23 rd October 2015 Terminology
More informationLower Urinary Tract Symptoms K Kuruvilla Zachariah Associate Specialist
Lower Urinary Tract Symptoms K Kuruvilla Zachariah Associate Specialist Lower Urinary Tract Symptoms Storage Symptoms Frequency, urgency, incontinence, Nocturia Voiding Symptoms Hesitancy, poor flow, intermittency,
More informationOriginal Article. J Fac Med Baghdad 119. Nibbras I. AL-Hamdani* Ali W. Zeki*** Introduction:
Original Article The Efficacy of Solifenacin Added to Α-Adrenergic Antagonists in the Treatment of Lower Urinary Tract Symptoms in Males with Benign Prostate Hyperplasia (The Iraqi Experience) Nibbras
More informationThe population of subjects which was statistically analyzed was the Intent-to-Treat population
Study No.: ARIB3003 (Year 1) Title: A Randomized, Double-Blind, Placebo-Controlled, Two-Year Parallel-Group Study of the Efficacy and Safety of GI198745 in the Treatment and Modification of Progression
More informationPRABHAKAR SINGH*, MANOJ INDURKAR, AMITA SINGH, PALLAVI INDURKAR
Academic Sciences International Journal of Current Pharmaceutical Research ISSN- 0975-7066 Vol 5, Issue 1, 2013 Research Article COMPARISON OF THE EFFICACY AND SAFETY OF TAMSULOSIN (0.4 V/S (and) FINASTERIDE
More informationThe patient, your co-pilot in assessing LUTS
The patient, your co-pilot in assessing LUTS Frank Van der Aa Leuven, Belgium This symposium is supported by Astellas Pharma Europe Ltd., including speaker honoraria and production of materials the slides
More informationImpact of Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia Treatment with Tamsulosin and Solifenacin Combination Therapy on Erectile Function
www.kjurology.org DOI:10.4111/kju.2011.52.1.49 Sexual Dysfunction Impact of Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia Treatment with Tamsulosin and Solifenacin Combination Therapy on Erectile
More informationProstate Disease. Chad Baxter, MD
Prostate Disease Chad Baxter, MD Managing BPH and LUTS Chad Baxter, MD Department of Urology cbaxter@mednet.ucla.edu 33 nd Annual UCLA Intensive Course in Geriatric Medicine & Board Review Prevalence of
More informationThe potential for NX-1207 in benign prostatic hyperplasia: an update for clinicians
Therapeutic Advances in Chronic Disease Review The potential for NX-1207 in benign prostatic hyperplasia: an update for clinicians Neal Shore and Barrett Cowan Ther Adv Chronic Dis (2011) 2(6) 377 383
More informationThe clinical trial information provided in this public disclosure synopsis is supplied for informational purposes only.
The clinical trial information provided in this public disclosure synopsis is supplied for informational purposes only. Please note that the results reported in any single trial may not reflect the overall
More informationTamsulosin sustained release preparation in patients of lower urinary tract symptoms due to benign prostatic hyperplasia
J. Acad. Indus. Res. Vol. 1(11) April 2013 679 RESEARCH MANUSCRIPT ISSN: 2278-5213 Tamsulosin sustained release preparation in patients of lower urinary tract symptoms due to benign prostatic hyperplasia
More informationNaoki Wada, Seiji Matsumoto, Masafumi Kita, Kazumi Hashizume and Hidehiro Kakizaki
bs_bs_banner International Journal of Urology (1) 1, 15 1 doi: 1.1111/iju.157 Original Article: Clinical Investigation Decreased urinary nerve growth factor reflects prostatic volume reduction and relief
More informationTadalafil 5 mg Once Daily Improves Lower Urinary Tract Symptoms and Erectile Dysfunction: A Systematic Review and Meta-analysis
LUTS (2018) 10, 84 92 ORIGINAL ARTICLE Tadalafil 5 mg Once Daily Improves Lower Urinary Tract Symptoms and Erectile Dysfunction: A Systematic Review and Meta-analysis Yilin WANG, 1 Yiping BAO, 2, Jie LIU,
More informationStudy Center(s): The study was conducted at 39 study sites in Japan.
SYNOPSIS Issue Date: 20 NOVEMBER 2012 Name of Sponsor/Company Janssen Pharmaceutical K. K. Name of Finished Product CONCERTA Name of Active Ingredient(s) Methylphenidate HCl Protocol No.: JNS001-JPN-A01
More informationAll about the Prostate
MEN S HEALTH Dr Nick Pendleton January 16 th 2018 All about the Prostate 1 What does it do? Functions of the Prostate 1. Secretes Prostatic Fluid slightly alkaline fluid, 30% of volume of seminal fluid,
More informationMedical Policy An independent licensee of the Blue Cross Blue Shield Association
Prostatic Urethral Lift Page 1 of 19 Medical Policy An independent licensee of the Blue Cross Blue Shield Association Title: Prostatic Urethral Lift Professional Institutional Original Effective Date:
More informationThe Journal of International Medical Research 2005; 33:
The Journal of International Medical Research 2005; 33: 562 573 A Comparative Study on the Safety and Efficacy of Tamsulosin and Alfuzosin in the Management of Symptomatic Benign Prostatic Hyperplasia:
More informationBPH: a present and future perspective on health impact
BPH: a present and future perspective on health impact Burden of disease in men with moderate LUTS Dalibor Pacík This presentation is financially supported by GlaxoSmithKline. CZ/DUTT/0019/12 Men with
More informationL ower urinary tract symptoms (LUTS) are a major health problem and are prevalent in men aged.45 years1 3.
OPEN SUBJECT AREAS: UROGENITAL DISEASES DRUG DEVELOPMENT Received 23 October 2013 Accepted 15 January 2014 Published 4 February 2014 Correspondence and requests for materials should be addressed to P.H.
More informationMini-Invasive Treatment in Urological Diseases Dott. Alberto Saita Responsabile Endourologia Istituto Clinico Humanitas - Rozzano
Dipartimento di Urologia Direttore Prof. Giorgio Guazzoni Mini-Invasive Treatment in Urological Diseases Dott. Alberto Saita Responsabile Endourologia Istituto Clinico Humanitas - Rozzano alberto.saita@humanitas.it
More informationEfficacy and safety of daily mirabegron 50 mg in male patients with overactive bladder: a critical analysis of five phase III studies
702797TAU0010.1177/1756287217702797Therapeutic Advances in UrologyA. Tubaro research-article2017 Therapeutic Advances in Urology Original Research Efficacy and safety of daily mirabegron 50 mg in male
More informationClinical Study Treatment Strategy According to Findings on Pressure-Flow Study for Women with Decreased Urinary Flow Rate
Advances in Urology Volume 2009, Article ID 782985, 5 pages doi:10.1155/2009/782985 Clinical Study Treatment Strategy According to Findings on Pressure-Flow Study for Women with Decreased Urinary Flow
More informationCan men with prostates sized 80 ml or larger be managed conservatively?
Original Article - Lower Urinary Tract Dysfunction Investig Clin Urol 2017;58:359-364. pissn 2466-0493 eissn 2466-054X Can men with prostates sized 80 ml or larger be managed conservatively? Alvin Lee,
More informationAs man draws near the common goal Can anything be sadder Than he who, master of his soul Is servant to his bladder LUTS 2. Prevalence of BPH LUTS 5
BPH / LUTS Dr Jonny Coxon MA MD MRCS MRCGP DRCOG Beaconsfield Medical Practice, Brighton As man draws near the common goal Can anything be sadder Than he who, master of his soul Is servant to his bladder
More informationRole of herbal drugs in the management of benign prostatic hyperplasia: Clinical trial to evaluate the efficacy and safety of Himplasia
[Medicine Update (2003): 11(2), 55-58] Role of herbal drugs in the management of benign prostatic hyperplasia: Clinical trial to evaluate the efficacy and safety of Himplasia Arora, R.P., CMO, Rajiba L.
More informationPROSTATIC ARTERY EMBOLISATION (PAE) FOR BENIGN PROSTATIC HYPERPLASIA. A Minimally Invasive Innovative Treatment
PROSTATIC ARTERY EMBOLISATION (PAE) FOR BENIGN PROSTATIC HYPERPLASIA A Minimally Invasive Innovative Treatment What is the prostate? The prostate is an accessory organ of the male reproductive system.
More informationStudy No. 178-CL-008 Report Final Version, 14 Dec 2006 Reissued Version, 18 Jul 2011 Astellas Pharma Europe B.V. Page 13 of 122
Page 13 of 122 3 SYNOPSIS Title of study: (International) Study No: A randomized, double-blind, parallel group, proof-of-concept study of in comparison with placebo and tolterodine in patients with symptomatic
More informationManagement of male LUTS in general practice
17 Management of male LUTS in general practice MARK J. SPEAKMAN AND FAITH MCMEEKIN The initial management of lower urinary tract symptoms in men is usually carried out in primary care. The authors explain
More informationUV-2005/01. Chronic Prostatitis and Chronic Pelvic Pain Syndrom (CP/CPPS) Karl-Bickleder-Str. 44C Straubing - Germany
SYNOPSIS UV-2005/01 Title: Short Title: Indication: Phase: Study Code: Study Director Co-ordinating Investigator: Study Centres: Multicentre, randomised, double-blind, placebo-controlled clinical study
More information50% of men. 90% of men PATIENT FACTSHEET: BPH CONDITION AND TREATMENTS. Want more information? What are the symptoms?
PATIENT FACTSHEET: BPH CONDITION AND TREATMENTS What is Benign Prostatic Hyperplasia (enlarged prostate)? Benign prostatic hyperplasia (BPH) is a noncancerous enlargement of the prostate, the gland that
More informationRELATIONSHIPS BETWEEN AMERICAN UROLOGICAL ASSOCIATION SYMPTOM INDEX, PROSTATE VOLUME, PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA
American Urological Association symptom index for BPH RELATIONSHIPS BETWEEN AMERICAN UROLOGICAL ASSOCIATION SYMPTOM INDEX, PROSTATE VOLUME, AND DISEASE-SPECIFIC QUALITY OF LIFE QUESTION IN PATIENTS WITH
More informationSexual dysfunction in male LUTS. M. Gacci Department of Urology, University of Florence
Sexual dysfunction in male LUTS M. Gacci Department of Urology, University of Florence Roma, 25-26 June, 2015 Cross-sectional population-based study of 4800 men (40 79 yr of age) UK, Netherlands, France,
More informationSingle Technology Appraisal (STA) Tadalafil for the treatment of symptoms associated with benign prostatic hyperplasia
Comment 1: the draft remit Appendix D - NICE s response to consultee and commentator comments on the draft scope and provisional matrix National Institute for Health and Clinical Excellence Single Technology
More informationNATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE Centre for Clinical Practice Surveillance Programme
NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE Centre for Clinical Practice Surveillance Programme Clinical guideline CG97: The management of lower urinary tract symptoms in men Publication date May
More informationLower Urinary Tract Symptoms (LUTS) and Nurse-Led Clinics. Sean Diver Urology Advanced Nurse Practitioner candidate Letterkenny University Hospital
Lower Urinary Tract Symptoms (LUTS) and Nurse-Led Clinics Sean Diver Urology Advanced Nurse Practitioner candidate Letterkenny University Hospital 01/02/2018 Lower Urinary Tract Symptoms LUTS - one of
More informationα-blocker Monotherapy and α-blocker Plus 5-Alpha-Reductase Inhibitor Combination Treatment in Benign Prostatic Hyperplasia; 10 Years Long-Term Results
www.kjurology.org http://dx.doi.org/10.4111/kju.2012.53.4.248 Voiding Dysfunction α-blocker Monotherapy and α-blocker Plus 5-Alpha-Reductase Inhibitor Combination Treatment in Benign Prostatic Hyperplasia;
More information