The efficacy and safety of tadalafil: an update

OBJECTIVE: To provide an update on the efficacy and safety of tadalafil, a phosphodiesterase-5 inhibitor, in the treatment of erectile dysfunction (ED). PATIENTS AND METHODS: In all, 2102 men (mean age 56 years) with mild-to-severe ED of various causes were randomized to placebo or tadalafil, taken as needed with no food restrictions, at fixed 'on-demand' doses of 10 or 20 mg in 11 randomized, double-blind, placebo-controlled trials lasting 12 weeks. The three co-primary outcomes were changes from baseline in the erectile function domain of the International Index of Erectile Function (IIEF) and the proportion of 'yes' responses to questions 2 and 3 of the Sexual Encounter Profile (SEP). Additional efficacy instruments included a Global Assessment Question (GAQ). RESULTS: Compared with placebo, tadalafil gave significantly better outcomes. Patients receiving either dose of tadalafil had a significant mean improvement of 6.5 and 8.6, respectively, in the IIEF erectile function domain score from baseline (P < 0.001 vs placebo). At both doses the mean success rate for intercourse attempts (SEP-Q3) was 58% and 68%, respectively, compared with 31% in the placebo group (P < 0.001), and 71% and 84% reported improved erections at the endpoint (GAQ), vs 33% on placebo (P < 0.001). Tadalafil was effective up to 36 h after dosing and was effective regardless of disease severity and causes, and in patients of all ages. The most frequent adverse events were headache, dyspepsia, back pain and myalgia. CONCLUSION: Tadalafil was an effective and well-tolerated treatment for ED.     

Efficacy and safety of tadalafil taken as needed for the treatment of erectile dysfunction in Asian men： results of an integrated analysis

We evaluated the efficacy and safety of as-needed tadalafil in a diverse clinical population （with varying patient demographics, disease severity, and comorbid medical conditions） of Asian men with erectile dysfunction （ED）. An integrated analysis of five double-blind, placebo-controlled trials （N = 1 046） was performed. Patients were randomly assigned to receive 10 mg tadalafil （N = 185）, 20 mg tadalafil （N = 510）, or placebo （N = 351）. Efficacy assessments included the International Index of Erectile Function （IIEF）, Sexual Encounter Profile （SEP） diary and Global Assessment Question （GAQ）. Patients receiving 10 mg or 20 mg tadalafil showed significant improvement from baseline-to-end point on the Erectile Function domain of the International Index of Erectile Function （IIEF-EF） domain score in all clinical sub-populations analyzed, compared with patients receiving placebo （P 〈 0.001）. The 10-mg and 20-mg tadalafil groups showed a mean success rate of 64.1% and 70.5% for sexual intercourse attempts （SEP3, successful intercourse）, respectively, compared with 33.4% in the placebo group （P 〈 0.001）, and 85.5% and 85.4% reported improved erections at end point GAQ, respectively, versus 43.5% in the placebo group （P 〈 0.001）. Tadalafil was well tolerated across all groups studied. Headache and back pain were the most frequently reported adverse events. Overall, tadalafil was effective and well tolerated across a diverse clinical spectrum of Asian men with ED.     

Efficacy and treatment satisfaction with on-demand tadalafil (Cialis) in men with erectile dysfunction

OBJECTIVE: Tadalafil (Cialis) is an inhibitor of phosphodiesterase type 5, which mediates relaxation of vascular smooth muscle in the corpus cavernosum thus facilitating erection. The purpose of this multicentre, randomized, double-blind, parallel group, placebo-controlled study was to evaluate efficacy and treatment satisfaction of on-demand Cialis in men with mild-to-severe erectile dysfunction (ED). METHODS: Following a 4-week treatment-free run in period, patients stratified into three severity groups by the International Index of Erectile Function (IIEF) Erectile Function (EF) domain score were randomized to receive either placebo or Cialis 20 mg taken on demand over a 12-week period. Efficacy endpoints were change from baseline in IIEF EF domain scores, responses to Sexual Encounter Profile diary (SEP) questions, and responses to the Global Assessment Questions (GAQ). Treatment satisfaction was evaluated using the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire in two of seven participating countries where validated translations were available. RESULTS: Of the 443 men who entered the trial, 409 (mean age, 52 years) formed the intent-to-treat population. Mean baseline demographics and ED severity measures were balanced between treatment groups except for a higher percentage of patients na?ve to sildenafil in the tadalafil group compared to placebo (50% versus 36%). The percentage of patients in each IIEF EF severity class (mild, moderate and severe) was 47%, 30% and 23% for placebo patients and 48%, 29% and 23% for tadalafil patients, respectively. Tadalafil was significantly superior to placebo on all primary efficacy measures (IIEF EF domain scores, SEP15, GAQ1; p < 0.001); notably 64% of tadalafil patients achieved a normal IIEF EF domain score at endpoint compared to 16% of placebo patients (p < 0.001). Of the 185 patients completing the EDITS questionnaire (137 receiving Cialis and 48 receiving placebo), tadalafil-treated patients had a median EDITS score of 84 (95%CI 80, 86), which was significantly higher than the median score for placebo-treated patients of 41 (95%CI 32, 59; p < 0.001; Wilcoxon test). The proportion of patients satisfied with treatment (defined as final EDITS score greater than 50) was 87% for the tadalafil-treated group and 46% for the placebo-treated group (p < 0.001; exact test). Adverse events were significantly more common with tadalafil than placebo (p < 0.01) and included primarily headache (7.2% versus 1.9%) and flushing (4.6% versus 0%). One patient discontinued tadalafil treatment due to back pain. CONCLUSION: In men with mild-to-severe ED, tadalafil 20 mg significantly improves erectile function, demonstrates superior treatment satisfaction relative to placebo, and is well tolerated. This is the first study to yield efficacy data on tadalafil in an Eastern European population of men with erectile dysfunction, and the first to measure satisfaction with the EDITS questionnaire in any study population of men with this condition using tadalafil.     

Tadalafil is efficacious in Black American and Hispanic men with erectile dysfunction: results from multiple observations in men with erectile dysfunction in national tadalafil study in the US (MOMENTUS)

To show that tadalafil is efficacious in Black American and Hispanic men with erectile dysfunction (ED) and efficacy is noninferior to that in Caucasian men. Multiple observations in men with ED in national tadalafil study in the US, a multicenter, open-label study, assessed the efficacy of tadalafil 20 mg taken as needed (maximum one dose/day before sexual activity) for 12 weeks by patients with ED in various populations. This analysis focuses on three groups: Caucasian (Reference group), Black American, and Hispanic men. Primary measurement of efficacy was change from baseline in erectile function (EF) domain of the International Index of Erectile Function (IIEF) and the primary analysis was whether efficacy in Black American and Hispanic groups was noninferior to efficacy in the Caucasian group. Secondary efficacy measures included sexual encounter profile (SEP), IIEF intercourse satisfaction (IS) and overall satisfaction (OS) domains, Global Assessment Question (GAQ), and Psychological and Interpersonal Relationship Scale (PAIRS). Safety was assessed from adverse events (AEs) reported by all enrolled patients. The increase in IIEF EF domain score (>or=9.5) from baseline for each group was statistically significant (P<0.001) and clinically relevant. Efficacy of tadalafil in Black American and Hispanic patients was noninferior to the Caucasian group. IS and OS domains of IIEF had a statistically significant increase from baseline (P<0.001). Change from baseline in positive responses to SEP questions for each group was significant (P<0.001). At least 77% of intercourse attempts were successful over various time intervals up to 36 h postdose. At least 88% of patients in the various groups had a positive response to GAQ1. Improvement from baseline in Sexual Self-Confidence and Spontaneity domains of PAIRS was statistically significant (P<0.001). A low number of AEs and a low AE-related discontinuation rate (2.3%) were reported in all groups. Tadalafil 20 mg was as efficacious in Black American and Hispanic men with ED as in Caucasian patients and was well tolerated.     

The efficacy and safety of tadalafil in United States and Puerto Rican men with erectile dysfunction

PURPOSE: We evaluate the efficacy and safety of tadalafil, taken as needed, in men with mild to severe erectile dysfunction (ED) and assess sexual intercourse attempt patterns. MATERIALS AND METHODS: In this multicenter, double-blind, placebo controlled, parallel study conducted in the United States and Puerto Rico 207 men with ED were randomized to placebo or 20 mg tadalafil for 12 weeks. The primary efficacy variables were changes from baseline in the mean International Index of Erectile Function erectile function domain score and mean per patient percentage of "yes" responses to Sexual Encounter Profile (SEP) diary questions 2 (successful penetration) and 3 (successful intercourse). The Global Assessment Question was a secondary end point and post hoc analyses on sexual intercourse attempt patterns were conducted. RESULTS: Men treated with tadalafil compared with placebo reported greater mean changes from baseline on the erectile function domain score (9.3 vs 0.3 with placebo, p <0.001) and on the mean per patient percentage of successful penetration (SEP question 2, 31.6% vs 2.3% with placebo, p <0.001) and successful intercourse attempts (SEP question 3, 43.6% vs 3.5% with placebo, p <0.001). The per treatment group percentage of successful intercourse attempts during treatment was higher for tadalafil than placebo (67.6% vs 24.1%, respectively, p <0.001) and most successful intercourse attempts occurred between 4 and 36 hours after taking tadalafil. Of the men treated with tadalafil 82.8% reported improved erections versus 19.6% taking placebo (Global Assessment Question, p <0.001). The most common treatment emergent adverse events were headache (15.7% vs 6.3% with placebo), back pain (8.8% vs 0%), and dyspepsia (7.5% vs 0%). CONCLUSIONS: Tadalafil (20 mg) significantly improved erectile function and patients did not closely temporally link sexual intercourse attempts with taking tadalafil. Tadalafil was also well tolerated in both groups of men with mild to severe ED.     

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.     

Efficacy and safety of tadalafil in a Western European population of men with erectile dysfunction

Section Editor Michael G. Wyllie Panel of Advisors Ian Eardley, UK Jean Fourcroy, USA Sidney Glina, Brazil Julia Heiman, USA Chris McMahon, Australia Bob Millar, UK Alvaro Morales, Canada Michael Perelman, USA

OBJECTIVE

To evaluate, in a randomized, double‐blind, placebo‐controlled, multicentre trial, the safety and efficacy of on‐demand tadalafil (an oral phosphodiesterase type‐5 inhibitor approved in many countries for treating erectile dysfunction, ED) in a Western European population of men with mild‐to‐severe ED.

PATIENTS AND METHODS

Patients were randomized according to baseline severity of ED in a ratio of 3 : 1 to receive either tadalafil 20 mg or placebo for 12 weeks. Primary efficacy endpoints were mean changes from baseline to endpoint (12 weeks) in the erectile function (EF) domain of the International Index of Erectile Function (IIEF) and percentages of ‘Yes’ responses to Sexual Encounter Profile (SEP) diary Question 2 (‘Were you able to insert your penis into your partner's vagina?’) and Question 3 (‘Did your erection last long enough for you to have successful intercourse?’). Secondary endpoints included mean changes from baseline to endpoint in IIEF Intercourse Satisfaction and Overall Satisfaction domains, selected questions of the IIEF, and the percentage of ‘Yes’ responses to Global Assessment Questions (GAQ) at the last visit. Other analyses included the percentage of patients in each treatment group at endpoint with IIEF EF domain scores in the normal range (>26), the frequency of intercourse attempts and mean per‐patient intercourse success rate at various times after dosing.

RESULTS

The mean age of the patients was 53 years and 80% had a history of ED of ≥ 1 year. The mean baseline EF domain score was 13.5, with 40.5% of patients in the severe category. Tadalafil improved mean EF domain scores by 11.1, vs 0.4 for placebo (P < 0.001). In addition, 73.9% of sexual intercourse attempts were successful (SEP‐Q3) in tadalafil‐treated patients, compared with 29.9% in placebo‐treated patients during the period after baseline (P < 0.001). Tadalafil significantly improved the mean IIEF intercourse satisfaction (5.1, tadalafil; 1.1, placebo) and overall satisfaction domain scores (3.9, tadalafil; 0.5, placebo), P < 0.001. GAQs used to assess the overall effect of the treatment indicated that tadalafil was superior to placebo (P < 0.001) in improving erections (82.1%, tadalafil; 23.1%, placebo) and sexual activity (78.6% and 17.3%). The most common treatment‐emergent adverse events more frequent (>2%) with tadalafil than placebo were headache, dyspepsia, flushing, back pain, pain in limb and myalgia. These adverse events were mostly mild to moderate.

CONCLUSIONS

Tadalafil improved erectile function and was well tolerated when taken by men from Western Europe with mild‐to‐severe ED.

     

Extended duration of efficacy of vardenafil when taken 8 hours before intercourse: a randomized, double-blind, placebo-controlled study

OBJECTIVES: This study explored the efficacy of vardenafil in men with erectile dysfunction (ED) when taken 8 hours before sexual intercourse. METHODS: A 10-week, randomized, double-blind, placebo-controlled, parallel-group, flexible-dose study of vardenafil (5, 10 or 20mg) was conducted in men with ED for >6 months who failed >or=50% of intercourse attempts during a 4-week treatment-free run-in period. Sexual Encounter Profile Question 3 (SEP3) was the primary efficacy measure; secondary measures included SEP2, International Index of Erectile Function-Erectile Function (IIEF-EF) domain score, Global Assessment Question (GAQ), Global Confidence Question (GCQ) and Erection Quality Scale (EQS). Adverse-event and safety monitoring were conducted throughout. RESULTS: 383 patients were randomized to vardenafil (n=194) or placebo (n=189). Patients treated with vardenafil 8 hours before sexual activity achieved clinically meaningful (>or=18%) and statistically significantly greater least-squares mean per-patient SEP3 and SEP2 success rates over weeks 2-10, compared with patients receiving placebo (SEP3 69% vs 34%; SEP2 81% vs 51%; both p<0.001). SEP3 and SEP2 measures demonstrated the significant superiority of vardenafil over placebo from week 2 onwards (p<0.001). Measurements of IIEF-EF domain score, GAQ, GCQ and EQS showed that vardenafil led to significantly greater improvements in erectile function, compared with placebo (all p<0.001). Vardenafil was generally well tolerated. CONCLUSIONS: The extended duration of efficacy of vardenafil up to 8 hours postdose may provide couples with more flexibility in their sexual life than anticipated.     

Efficacy and safety of on demand tadalafil in the treatment of East and Southeast Asian men with erectile dysfunction: a randomized double-blind, parallel, placebo-controlled clinical study

Aim:To assess the efficacy and safety of tadalafil in comparison to a placebo,when taken on demand for 12 weeksby East/Southeast Asian men with erectile dysfunction(ED).Methods:This multicenter,randomized,double-blind,parallel group,placebo-controlled study was conducted at 17 centers across East and Southeast Asia between August2002 and February 2003.Men more than 18 years of age with mild to severe ED of various etiologies were randomizedto receive a placebo or 20 mg of tadalafil taken as needed(maximum once daily).Efficacy assessments included theInternational Index of Erectile Function,the Sexual Encounter Profile diary and Global Assessment Questions.Results:Tadalafil significantly improved erectile function as compared to the placebo(P<0.001).At the endpoint,the pa-tients receiving 20 mg of tadalafil reported a greater mean per patient percentage of successful intercourse attempts(Sexual Encounter Profile question 3:70.9% compared to 33.5% in the placebo)and a greater proportion of improvederections(Global Assessment Question:86.2% compared to 30.1%).Most(≥3%)treatment emergent adverseevents were mild or moderate.The most common treatment emergent adverse events were headache,back pain,dizziness and dyspepsia.Conclusion:Tadalafil was an effective and well-tolerated treatment for ED in East andSoutheast Asian men.(Asian J Androl 2006 Nov;8:685-692)     

Efficacy of vardenafil in men with erectile dysfunction: a flexible-dose community practice study

OBJECTIVE: To determine the efficacy and tolerability of flexible dosing with vardenafil in a broad population of men with erectile dysfunction (ED). METHODS: 10-week, open-label, flexible-dose study starting with vardenafil 10 mg, titrating to 5 mg or 20 mg at weeks 2 and 6 based on efficacy and tolerability, set in 78 community practice centers in Germany and France. Participants comprised 398 men aged > or =18 years with ED. Main outcome measures were self-reported improvement in erections according to a Global Assessment Question (GAQ), diary questions from the Sexual Encounter Profile (SEP2 and SEP3), and the erectile function domain score from the International Index of Erectile Function (IIEF) questionnaire. RESULTS: In a last observation carried forward (LOCF) analysis, a total of 92% (336/366) of men with ED reported an improvement of erections according to the GAQ. Per-patient success rates for penetration (SEP2) and maintenance (SEP3) of erection for intercourse were 89% (348/390) and 78% (303/390), respectively. Mean erectile function domain scores increased from 13.9 at baseline to 25.9 at LOCF. Vardenafil was generally well tolerated; headache (6%, 25/398) and flushing (6%, 24/398) were the most frequent adverse events. CONCLUSIONS: In this community practice setting, vardenafil was shown to be a highly effective and generally well-tolerated treatment for men with ED when dosing was titrated by the physician to individual patient requirements.     

The efficacy and tolerability of vardenafil, a new, oral, selective phosphodiesterase type 5 inhibitor, in patients with erectile dysfunction: the first at-home clinical trial

Vardenafil, a novel selective phosphodiesterase type 5 inhibitor, was evaluated in its first large-scale at-home trial. A total of 601 men with mild to severe erectile dysfunction (ED) were enrolled in this multi-centre, randomized, double-blind, placebo-controlled trial of 12 weeks of treatment with either placebo or 5, 10 and 20 mg of vardenafil. Primary endpoints were Q3 (vaginal penetration) and Q4 (maintenance of erection) of the International Index of Erectile Function (IIEF). In the intent-to-treat population (n=580), the changes from baseline for 5, 10 and 20 mg vardenafil (1.2, 1.3 and 1.5, respectively) were all improved (P<0.001) over placebo (0.2) for Q3 and were similarly improved for Q4 (1.4, 1.5 and 1.7) compared to placebo (0.5) (P<0.001). All vardenafil doses improved all IIEF domains compared to placebo (P<0.001). The percentage of successful intercourses was between 71 and 75% for the three vardenafil doses. For the 20 mg dose, 80% of the patients experienced improved erections (GAQ) compared to 30% for placebo. Most frequent treatment-emergent adverse events were headache (7-15%), flushing (10-11%) and up to 7% for dyspepsia or rhinitis. Vardenafil treatment resulted in a high efficacy and low adverse-event profile in a population with mixed ED etiologies.     

Evaluation of an alternative dosing regimen with tadalafil, three times per week, for men with erectile dysfunction： SURE study in Italy

Aim： To examine the preference for two dosing regimens of 20 mg of tadalafil, on demand or three times per week, in men affected with erectile dysfunction （ED） in Italy. Methods： Scheduled Use versus on demand Regimen Evaluation （SURE） is a multicenter, crossover and open-label study, involving 94 urology centers in Italy. Patients aged 18 years or older affected with ED for at least 3 months were enrolled and randomized to 20 mg of tadalafil treatment on demand or three times per week for 5-6 weeks. After a 1-week washout, patients were crossed over to the alternate regimen for 5-6 weeks. A treatment preference question was used to determine the preferred treatment regimen. International Index of Erectile Function （IIEF） and Sexual Encounter Profile （SEP） questionnaire were used as efficacy measures. Results： A total of 1 058 men （mean age 54.8 years）, were randomized to treatment. Overall, 59.1% of patients preferred the on-demand regimen and 41.9% preferred the three times per week dosing. Both regimens were efficacious and well tolerated. Although a statistically higher improvement of the IIEF erectile function （IIEF-EF） domain score and the SEP questionnaire was reported for the three times per week compared to the ondemand treatment regimen, this difference was numerically minimal and lacking in clinical significance. Conclusion： Tadalafil is effective and well tolerated whether used on demand or three times per week. Patients should be given the option to choose the best treatment regimen according to personal needs and preferences.     

Tadalafil improved erectile function at twenty-four and thirty-six hours after dosing in men with erectile dysfunction: US trial

In a previous study assessing tadalafil for the treatment of erectile dysfunction (ED), tadalafil 20 mg was shown to improve erectile function for up to 36 hours vs placebo. This study sought to demonstrate the effectiveness of both 10- and 20-mg tadalafil vs placebo at 2 prespecified assigned times of 24 and 36 hours postdosing. This double-blind, placebo-controlled, parallel-group study randomized 483 men with ED into 6 groups according to a combination of treatment (placebo, tadalafil 10 or 20 mg) and assigned time (24 or 36 hours) for intercourse attempts. Patients were stratified by baseline ED severity based on Erectile Function Domain scores. The study had 4 phases: a 4-week run-in (no ED medication taken); a 2- to 4-week equilibration (dosing as needed); a 4- to 6-week assessment; and a 6-month open-label extension. During the assessment phase, men took a total of 4 doses of study medication, each dose separated by more than or equal to 7 days. Efficacy was measured as the mean per-patient percentage of successful intercourse attempts (Sexual Encounter Profile Diary Question 3: SEP3) during the assessment phase. Men taking either 10- or 20-mg tadalafil had a significant increase in SEP3 from baseline scores vs placebo at both 24 hours (P = .038 and <.001 for 10 and 20 mg, respectively) and 36 hours (P < .001 for both doses) postdose. The mean per-patient percentages of successful intercourse attempts for the 24-hour time point were 41.8%, 55.8%, and 67.3% for placebo and tadalafil 10 and 20 mg, respectively; for the 36-hour time point, the mean per-patient percentages were 32.8%, 56.2%, and 61.9% for placebo and tadalafil 10 and 20 mg, respectively. The most common treatment-emergent adverse events were headache, back pain, dyspepsia, and nasopharyngitis. Both 10- and 20-mg tadalafil improved erectile function for up to 36 hours postdosing in men with ED of varied severity.     

Efficacy and safety of oral SK3530 for the treatment of erectile dysfunction in Korean men: a multicenter, randomized, double-blind, placebo-controlled, fixed dose, parallel group clinical trial

Aim： To evaluate the efficacy and safety of SK3530, a newly developed type 5 phosphodiesterase inhibitor （PDE5I）, in Korean men with erectile dysfunction （ED）. Methods： A total of 119 patients were randomized at 10 centers in Korea to receive either SK3530 （50, 100, or 150 mg; n = 89） or placebo （n = 30） taken 1 h before anticipated sexual activity for an 8-week period. The patients were evaluated at baseline and 4 and 8 weeks after beginning therapy. Efficacy was assessed using the International Index of Erectile Function （IIEF）, Sexual Encounter Profile （SEP）, and the Global Assessment Question （GAQ）. Safety was analyzed by adverse events, laboratory values and vital signs. Results： At the end of the study, all the primary and secondary efficacy end-points were statistically significantly improved by SK3530 compared with placebo （P 〈 0.05）. Of the 89 patients in the treatment arm, 36 （42.3 %） achieved normal erectile function after treatment, including six patients with severe ED. Treatment-related adverse events occurred in 32 patients. The most common adverse events were flushing, headache, dizziness and eye redness （10.9%, 7.6%, 2.5% and 2.5%, respectively）, and most were mild. Only two patients discontinued treatment during the study period because of adverse events. Conclusion： The results of our phase Ⅱ study have confirmed the efficacy and safety of SK3530 in a broad population of men with ED of various etiologies and severity. The optimal doses in terms of efficacy and safety were determined to be 50 mg and 100 mg, respectively.     

Tadalafil dosed once a day in men with erectile dysfunction: a randomized, double-blind, placebo-controlled study in the US

The efficacy and safety of tadalafil, dosed once a day for the treatment of erectile dysfunction, was assessed in a randomized, double-blind, placebo-controlled, parallel-design study at 15 US centers. Following a 4-week treatment-free run-in period, patients (>or=18 years of age) were randomly assigned to 24 weeks treatment with tadalafil 2.5 mg, tadalafil 5 mg or placebo. Primary efficacy endpoints were change at 24 weeks in International Index of Erectile Function Erectile Function (EF) Domain score and mean per-patient percentage 'yes' responses to Sexual Encounter Profile diary questions 2 and 3. Tadalafil significantly improved erectile function compared with placebo for all three co-primary efficacy endpoints. Few patients discontinued because of adverse events (2.1%, placebo; 6.3%, tadalafil 2.5 mg; 4.1%, tadalafil 5 mg). Common treatment-emergent adverse events (>or=5%) were nasopharyngitis, influenza, viral gastroenteritis and back pain. Tadalafil 2.5 mg and 5 mg, dosed once a day for 24 weeks, was well tolerated and significantly improved erectile function.     

Efficacy and safety of long‐term tadalafil 5 mg once daily combined with sildenafil 50 mg as needed at the early stage of treatment for patients with erectile dysfunction

This study aimed to evaluate the efficacy and safety of long‐term and low‐dose tadalafil combined with sildenafil as needed at the early stage of treatment for erectile dysfunction (ED). We enrolled 180 patients with ED 1 : 1 to tadalafil 5 mg once daily or once‐a‐day tadalafil 5 mg combined with sildenafil 50 mg as needed. The efficacy measures included the 5‐item version of the International Index of Erectile Function (IIEF‐5) and the Sexual Encounter Profile (SEP). The safety was assessed by observing drug tolerability and adverse events. Total IIEF‐5 scores of patients with severe ED in combined medication group were significantly higher than in tadalafil alone group. Question 2 scores of IIEF‐5 of patients with moderate and severe ED in combined medication group were significantly higher than in tadalafil alone group. The significant improvement in question 3 scores of IIEF‐5 existed only in patients with severe ED receiving combined medication. The percentage of ‘yes’ responses to SEP4, SEP5 and partner's SEP3 were improved significantly in combined medication group. There was no difference between two groups in the incidence of adverse events. Our results suggest that combined medication can better improve erectile function, especially for patients with severe ED.     

Tadalafil relieves lower urinary tract symptoms secondary to benign prostatic hyperplasia

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

Tadalafil in the treatment of erectile dysfunction following bilateral nerve sparing radical retropubic prostatectomy: a randomized, double-blind, placebo controlled trial

PURPOSE: We evaluated the efficacy and safety of tadalafil 20 mg, taken on demand, in men with erectile dysfunction following bilateral nerve sparing radical retropubic prostatectomy (BNSRRP). MATERIALS AND METHODS: This randomized, double-blind, placebo controlled multicenter study consisted of a 4-week treatment-free run-in period (baseline) followed by 12 weeks of treatment. A total of 303 men (mean age 60 years) with preoperative normal erectile function who had undergone a BNSRRP 12 to 48 months before study were randomized (2:1) to tadalafil (201) or placebo (102). The 3 co-primary end points were changes from baseline in the International Index of Erectile Function erectile function domain score, and the percentage of positive responses to Sexual Encounter Profile questions 2 (successful penetration) and 3 (successful intercourse). The Global Assessment Question and the Erectile Dysfunction Inventory of Treatment Satisfaction questionnaire were secondary end points. We defined a priori a subgroup of 201 patients reporting evidence of postoperative tumescence, defined as 50% or greater "yes" responses to Sexual Encounter Profile question 1 (ability to achieve at least some erection) during baseline intercourse attempts and stratified randomization based on this criterion. RESULTS: Patients receiving tadalafil reported greater improvement on all primary and secondary end points (p <0.001) compared to placebo. For all randomized patients and for the subgroup with evidence of postoperative tumescence, the mean International Index of Erectile Function erectile function domain score increased for patients receiving tadalafil (mean +/- SEM 5.3 +/- 0.5 and 5.9 +/- 0.7, respectively, p <0.001 vs placebo for both). For all randomized patients who received tadalafil, the mean percentage of successful penetration attempts was 54% and the mean percentage of successful intercourse attempts was 41%. For the subgroup with evidence of postoperative tumescence these values were 69% and 52%, respectively. Of all patients randomized to tadalafil 62% and of the subgroup patients randomized to tadalafil 71% reported improved erections. Patients receiving tadalafil reported greater treatment satisfaction on the Erectile Dysfunction Inventory of Treatment Satisfaction than those receiving placebo. Headache (21%), dyspepsia (13%) and myalgia (7%) were the most commonly reported adverse events. CONCLUSIONS: Tadalafil 20 mg, taken on-demand, was an efficacious and well tolerated treatment for erectile dysfunction following BNSRRP.     

夜间勃起功能监测结果与他达拉非治疗勃起功能障碍疗效的相关性研究

目的:评价夜间勃起功能监测(NPT)结果与他达拉非疗效的相关性。方法:188例ED患者,根据NPT结果分为NPT正常组(n=136)和NPT异常组(n=52),2组患者均给予他达拉非治疗,3次/周,每次20mg。治疗前及治疗1个月后,分别评价IIEF-5评分、阴茎插入成功率(SEP2)、完成性交成功率(SEP3)以及总体评价问卷(GAQ),比较2组间治疗前后各项指标的变化。结果:2组患者用药后其IIEF-5评分、SEP2、SEP3均显著高于用药前(P<0.01)。NPT正常组患者治疗后的IIEF-5评分、SEP2、SEP3及GAQ均显著高于NPT异常组患者治疗后结果(P<0.05,P<0.01)。结论:经过他达拉非治疗1个月后,NPT正常组患者勃起功能(包括IIEF-5评分、SEP2及SEP3)较NPT异常组改善更为显著,即NPT正常组患者行他达拉非治疗疗效更佳。     

An open-label,multicenter, randomized,crossover study comparing sildenafil citrate and tadalafil for treating erectile dysfunction in Chinese men na?ve to phosphodiesterase 5 inhibitor therapy

The study was to compare treatment preference, efficacy, and tolerability of sildenafil citrate (sildenafil) and tadalafil for treating erectile dysfunction (ED) in Chinese men naïve to phosphodiesterase 5 (PDE5) inhibitor therapies. This multicenter, randomized, open-label, crossover study evaluated whether Chinese men with ED preferred 20-mg tadalafil or 100-mg sildenafil. After a 4 weeks baseline assessment, 383 eligible patients were randomized to sequential 20-mg tadalafil per 100-mg sildenafil or vice versa for 8 weeks respectively and then chose which treatment they preferred to take during the 8 weeks extension. Primary efficacy was measured by Question 1 of the PDE5 Inhibitor Treatment Preference Questionnaire (PITPQ). Secondary efficacy was analyzed by PITPQ Question 2, the International Index of Erectile Function (IIEF) erectile function (EF) domain, sexual encounter profile (SEP) Questions 2 and 3, and the Drug Attributes Questionnaire. Three hundred and fifty men (91%) completed the randomized treatment phase. Two hundred and forty-two per 350 (69.1%) patients preferred 20-mg tadalafil, and 108/350 (30.9%) preferred 100-mg sildenafil (P < 0.001) as their treatment in the 8 weeks extension. Ninety-two per 242 (38%) patients strongly preferred tadalafil and 37/108 (34.3%) strongly the preferred sildenafil. The SEP2 (penetration), SEP3 (successful intercourse), and IIEF-EF domain scores were improved in both tadalafil and sildenafil treatment groups. For patients who preferred tadalafil, getting an erection long after taking the medication was the most reported reason for tadalafil preference. The only treatment-emergent adverse event reported by > 2% of men was headache. After tadalafil and sildenafil treatments, more Chinese men with ED naïve to PDE5 inhibitor preferred tadalafil. Both sildenafil and tadalafil treatments were effective and safe.