Assessment of the Effect of Mirodenafil on the Hemodynamics of Healthy Male Korean Volunteers Administered Tamsulosin: A Randomized, Double-Blind, Placebo-Controlled, 2-Period Crossover Study

Background: Both mirodenafil, a phosphodiesterase type 5 inhibitor for the treatment of erectile dysfunction, and tamsulosin, a selective α_1A-adrenergic receptor antagonist for the treatment of benign prostatic hyperplasia, have mild vasodilational effects. Objective: The aim of this study was to investigate the effect of mirodenafil on the hemodynamics of healthy volunteers who were administered tamsulosin. Methods: Healthy, Korean normotensive male volunteers were enrolled in a randomized, placebo-controlled, double-blind, 2-sequence, 2-period crossover study. Mirodenafil 100 mg or placebo was administered orally after pretreatment with tamsulosin 0.2 mg once daily for 7 days in each period, with a 1-week washout period. Blood pressure (BP) and pulse rate (PR) in supine and standing positions were measured repeatedly before and until 24 hours after the administration of mirodenafil or placebo. The mean differences from the baseline values of the maximum changes of BP and PR, which were measured at 4 and 24 hours, were analyzed by using a mixed-effects model. Results: Eighteen subjects (mean [SD] age, 26.8 [3.9] years; weight, 65.5 [7.0] kg) were administered any trial medication, and 16 of them completed the study. For 4 hours/24 hours after mirodenafil administration, the mean maximal changes from baseline versus placebo in supine systolic BP, diastolic BP, and PR were -1.0 mm Hg (95% CI, -4.2 to 2.2) (P = 0.53)/-1.2 mm Hg (95% CI, -5.3 to 2.9) (P = 0.56), -2.1 mm Hg (95% CI, -4.6 to 0.4) (P = 0.10)/-1.1 mm Hg (95% CI, -3.9 to 1.6) (P = 0.39), and 7.2 beats/min (95% CI, 4.7 to 9.6) (P < 0.05)/4.8 beats/min (95% CI, 1.4 to 8.1) (P < 0.05), respectively. Those changes in a standing position were -4.0 mm Hg (95% CI, -8.9 to 0.9) (P = 0.10)/-4.3 mm Hg (95% CI, -10.0 to 1.5) (P = 0.13), -1.1 mm Hg (95% CI, -4.9 to 2.7) (P = 0.54)/-1.9 mm Hg (95% CI, -5.5 to 1.7) (P = 0.27), and 10.7 beats/min (95% CI, 4.4 to 16.9) (P < 0.05)/6.0 beats/min (95% CI, 0.7 to 11.3) (P < 0.05), respectively. A total of 33 adverse events (AEs) were reported in 9 of 18 subjects. The number of subjects with AEs (P = 0.13) and the number of AEs (P = 0.26) were not significantly different between the 2 groups. The most common AEs were vasodilational symptoms, such as nasal congestion, headache, and flushing. Conclusions: The coadministration of mirodenafil 100 mg did not induce a significant decrease in BP when associated with an increase in PR in these healthy male Korean volunteers administered tamsulosin 0.2 mg compared with placebo. (Clinical Trial Registry, http://cris.cdc.go.kr/cris/en/: KCT0000117).