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Table 11






Efficacy Results of Tadalafil by ED Severity Groups.

Tadalafil (20 mg) versus tadalafil (10 mg) versus tadalafil (5 mg). The effects of both tadalafil doses 20 mg and 10 mg were evaluated in eight trials.215, 226230, 237, 238 In one of these trials, 238 there was an additional randomized arm in which patients received 5 mg tadalafil. Another trial221 evaluated dose-response models for different doses of tadalafil (e.g. 5, 10, 25 mg).

Harms. The incidence of most reported adverse events (e.g. myalgia, nausea, back pain, diarrhea, headache, dizziness, dyspepsia, nasal congestion, facial flushing, infection, flu syndrome) across the eight trials was numerically comparable in patients receiving 20 mg versus 10 mg of tadalafil. In three trials, 228, 230, 238 the incidence of headache was slightly higher in patients receiving 20 mg tadalafil as compared with those receiving 10 mg (or 5 mg) of tadalafil. For example, in the first trial, 228 the proportions of patients with headache in 20 mg and 10 mg tadalafil arms were 17.1 and 8.1 percent, respectively, with a statistically significant between-arm difference (p < 0.001).

In the same trial the incidence of serious adverse events (i.e., two cases of myocardial infarction) was numerically similar in the 20 mg and 10 mg tadalafil groups (two patients in each arm). In the second trial, 230 numerically more patients who received 20 mg tadalafil had headache compared with those who received a 10 mg dose (8.0 versus 4.1 percent). In one trial, 227 compared with those who received 10 mg of tadalafil, patients receiving a 20 mg dose experienced numerically higher rates of dyspepsia (22.0 versus 9.7 percent), vasodilation (6.0 versus 3.9 percent), and accidental injury (5.0 versus 1.0 percent). The incidence of back pain was numerically slightly higher in patients receiving 20 mg versus those receiving 10 mg of tadalafil in one trial (4.0 versus 0.8 percent, respectively).237 In another trial, 215 one patient died from an AMI after being randomly assigned to receive 20 mg tadalafil. Of the eight trials comparing the efficacy/safety profiles of 20 mg and 10 mg tadalafil, the absence or presence of serious adverse events could not be ascertained for six trials.221, 226, 227, 229, 230, 237

Efficacy. In five trials, 226, 227, 229, 237, 238 the degree of improvement in the mean change for IIEF “EF” domain and per-patient proportion of “yes” to SEP Q2–Q3 from baseline was numerically similar between 20 mg, 10 mg, and 5 mg tadalafil arms. The proportions of patients with improved erection (i.e., those who answered “yes” to GAQ) were also similar between the 10 mg and 20 mg tadalafil dose arms.226, 227, 229, 237, 238 In one trial, 215 the magnitude of improvement with respect to the mean change in per-patient proportion of “yes” responses to SEP-Q3 from baseline was numerically greater in the 20 mg than the 10 mg tadalafil arm 24 hours post-dose (46.3 versus 25.5 percent). Similarly, in another trial, 230 the cumulative proportion of patients with at least one successful intercourse attempt (“yes” to SEP-Q3) attempt 30 minutes post-dose was numerically improved in patients who received 20 mg relative to those who received 10 mg of tadalafil (34.0 versus 25.0 percent). In the same trial, patients on 20 mg tadalafil had a faster erectogenic response (starting 16 minutes post-dose) than those on 10 mg of tadalafil (starting 26 minutes post-dose).230

The results of one trial228 were slightly inconsistent with those of others.215, 226, 227, 229, 230 More specifically, patients on 10 mg (daily) of tadalafil experienced greater improvement in erectile function (based on responses to SEP-Q3, IIEF, GAQ-Q1) compared with those receiving 20 mg (on demand) of tadalafil. For example, there was a statistically significant higher mean per-patient proportion of successful intercourse attempts (i.e., based on “yes” answers to SEP-Q3) among patients receiving 10 mg tadalafil compared with those receiving 20 mg tadalafil (80 versus 67 percent, p < 0.05). Similarly, the proportion of patients who answered “yes” to GAQ Q1 was higher in the 10 mg arm compared with the 20 mg arm of tadalafil (88.0 versus 73 percent, p < 0.05). Furthermore, patients in the 10 mg tadalafil arm had a higher mean IIEF “EF” domain score than those in the 20 mg tadalafil arm (26.4 percent versus 23.3 percent, p < 0.05).

In one study, 221 authors who employed logistic regression models based on patient data obtained from a randomized placebo-controlled trial, showed a statistically significant dose-dependent effect of tadalafil on the patients' outcomes as defined by responses to SEP-Q2/3 and the IIEF “EF” domain questions; more specifically, the magnitude of response increased between the 10 mg and 25 mg doses of tadalafil. Furthermore, the baseline ED severity was an important covariate in these models, indicating that patients with severe ED at baseline experienced greater incremental improvement in erectile function compared with those with moderate or mild ED at baseline.

Tadalafil (20 mg; on-demand therapy) versus tadalafil (20 mg; scheduled therapy). Two trials214, 232 compared the efficacy/safety of two dosing regimens of 20 mg tadalafil (on demand therapy versus scheduled therapy).

Harms. In the first trial, 214 the rate of any adverse events (percentage of patients with at least one adverse event) did not differ between groups who were given tadalafil either on demand or 3 times per week (21.7 versus 25.3 percent, respectively). The most frequent events in both tadalafil arms were headache (7.5 percent), dyspepsia (6.5 percent), back pain (2.7 percent), flushing (2.6 percent), and myalgia (2.5 percent). The proportion of patients who withdrew from the on-demand and the 3 times per week dosing regimens were 4.0 percent and 5.1 percent, respectively. No deaths or serious adverse events occurred during the trial. In the second trial, 232 the most frequent adverse events were dyspepsia, headache, back pain and myalgia, observed in two of the 20 patients.

Efficacy. One crossover trial214 evaluated the relative effects of alternative dosing regimens of tadalafil (on demand versus 3 times per week) on the outcomes of ED (e.g. patient preference, mean change in IIEF “EF” domain scores and the per-patient proportion of successful intercourse attempts. The 3861 patients' responses to the treatment preference question (TPQ) showed that the on-demand regimen was preferred more frequently than the 3 times per week scheduled regimen, regardless of the sequence of the treatment regimens (57.8 versus 42.2 percent, p < 0.001). The on-demand and the scheduled 3 times per week dosing regimens were shown to be similarly efficacious with respect to the mean IIEF “EF” domain scores (24.6 versus 24.8, respectively). Similarly, the mean per-patient proportion of successful intercourse attempts (“yes” to SEP-Q3) did not differ between the on-demand and scheduled 3 times per week tadalafil groups(72.6 versus 74.4 percent).

The other trial evaluated whether 20 mg tadalafil dosing regimens (on demand versus scheduled on alternate days) differed in improving endothelium-dependent vasodilation of cavernous arteries (e.g. peak systolic velocity and flow-mediated dilation) and in producing morning erections in men diagnosed with ED as ascertained by one of the items of the SIEDY questionnaire (question: “ In the last four weeks, did it ever occur that you wake up with an erection? ”).232 After 4 weeks of therapy, the mean increase in flow-mediated dilation (FMD) from baseline in patients treated with scheduled dosing regimen on alternate days was statistically significant (1.2 versus 8.3 percent, p < 0.05), whereas the corresponding parameter for patients treated with the on-demand therapy schedule did not change (3.3 versus 2.1 percent, p ≥ 0.05). The improvement in FMD observed in patients who had received scheduled therapy was maintained 2 weeks after the discontinuation of the therapy. There was also a statistically significant improvement in regard to morning erections observed in patients treated with the scheduled dosing regimen (90 percent of the patients; p < 0.0001), but not in those treated with the on-demand dosing regimen.

Tadalafil versus sildenafil versus vardenafil. Four crossover trials compared efficacy/safety of tadalafil (20 mg) and sildenafil (25–100 mg, 50 mg, or 100 mg) in treating patients with ED.103, 118, 121, 163 One of these163 additionally evaluated the efficacy/safety profile of vardenafil (20 mg).

Harms. In general, in these trials, all three therapies were well tolerated and had similar safety profiles. There were no statistically significant differences in the incidence of any adverse events between tadalafil- and sildenafil-treated groups of patients. In the tadalafil arms the proportion of patients with at least one adverse event across the four trials ranged from 27.7 percent163 to 34.9 percent.103 The corresponding proportion in the sildenafil arms ranged from 23.8 percent121 to 34.1 percent.103 In the vardenafilgroup, about 26.6 percent patients had at least one adverse event.163 Most common events in the three therapy groups were: headache (7.8–12.2 percent), dyspepsia (3.0–6.4 percent), flushing (2.5–7.4 percent), back pain (1.8–4.8 percent), and nasal congestion (1.1–4.7 percent).

In one trial, 103 the incidence of serious adverse events did not differ between the tadalafil (5 patients had prostate cancer, purpura, pulmonary edema, gastric cancer) and sildenafil groups (4 patients had cardiac biopsy, chest pain, perianal abscess). Three remaining trials118, 121, 163 did not report the occurrence or absence of serious adverse events.

The total number of withdrawals due to adverse events across the four trials ranged from two121 to 12 patients.103, 163 The proportion of patients who withdrew from tadalafil groups ranged from one121 to seven.103, 241 The respective proportion of patients who withdrew from the sildenafil arms ranged from one121 to five.103, 163 Two patients withdrew due to adverse events in thevardenafil group.163

Efficacy. In one trial, 103 the IIEF mean changes from baseline to endpoint were greater in the tadalafil than in the sildenafil arm for the domains of “Orgasmic Function” (difference between the mean changes: 0.28, 95 percent CI: 0.02–0.53) and “Sexual Desire” (difference between the mean changes: 0.19, 95 percent CI: 0.02–0.35).

In general, results of the four trials103, 118, 121, 163 regarding the measures of erectile function (i.e., mean IIEF-“EF domain” scores) were not consistent.

For example, in one trial the difference between the mean changes for IIEF “EF” domain scores did not reach statistical significance (0.51, 95 percent CI: -0.07 to 1.09).103 In another trial, 163 there was a statistically significant higher median (percentile range 10–90) IIEF score in the tadalafil group in comparison with the vardenafil group: 30 (25–30) versus 28 (23.1–30.0), p = 0.00022. In the same trial, the differences in the mean IIEF score between the sildenafil/tadalafil and sildenafil/vardenafil groups were not statistically significant.163

In one trial, 118 the proportion of men who had at least one successful intercourse attempt 12 or more hours post-dose was greater among patients receiving 20 mg tadalafil than in patients receiving 50 mg sildenafil (55.0 versus 29.0 percent, p < 0.001). In another trial, 103 the mean change in per-patient proportion of successful intercourse attempts (“yes” to SEP Q3) was slightly greater in patients receiving tadalafil compared with those receiving sildenafil (difference between the mean changes: 5.2 percent, 95 percent CI: 1.8–8.6). The mean time (in hours) between dosing and sexual attempt was found to be longer for tadalafil than for sildenafil (5.6 versus 2.7, p < 0.001).118, 121

In the four trials, the proportion of patients preferring tadalafil (range 52.2 to 73.0 percent) was statistically significantly greater than the proportion of patients preferring sildenafil (27.0–33.7 percent) or vardenafil (20.0 percent). In one trial, 118 73 percent of the patients preferred tadalafil and 27 percent preferred sildenafil (p < 0.001). Similarly, the results from the two other trials121, 163 also indicated that more patients preferred tadalafil (66.3 and 52.2 percent, respectively) compared with those preferring sildenafil (33.7 and 27.7 percent, respectively) or vardenafil (20 percent). In one trial, 163 the reason for 25 percent of men preferring tadalafil to sildenafil was that they could have intercourse again the next day post-dose.


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