Efficacy and Safety of Dapoxetine for the Treatment of Premature Ejaculation: Integrated Analysis of Results from Five Phase 3 Trials

Abstract

Introduction Dapoxetine has been evaluated for the on-demand treatment of premature ejaculation (PE) in five phase 3 studies in various populations worldwide and has recently been approved in several countries. Aim To present integrated efficacy and safety data from phase 3 trials of dapoxetine. Methods Data were from five randomized, multicenter, double-blind, placebo-controlled studies conducted in over 25 countries. Men (N = 6,081) ≥18 years who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision criteria for PE; four studies required a baseline intravaginal ejaculatory latency time (IELT) of ≤2 minutes. Dapoxetine 30 and 60 mg on demand (prn; 1–3 hours before intercourse) were evaluated for either 12 or 24 weeks in four studies; one study evaluated dapoxetine 60 mg daily (qd; included in safety assessments only) or prn for 9 weeks. Main Outcome Measures End points included stopwatch-measured IELT, Premature Ejaculation Profile (PEP) items, clinical global impression of change (CGIC) in PE, and adverse events (AEs). Results Average IELT (mean [standard deviation], geometric mean [standard error]) increased from baseline (across groups, 0.9 [0.49] minutes, 0.8 [1.01] minutes) to a significantly greater extent with dapoxetine 30 (3.1 [3.91] minutes, 2.0 [1.03] minutes) and 60 mg (3.6 [3.85] minutes, 2.3 [1.03] minutes) vs. placebo (1.9 [2.43] minutes, 1.3 [1.02] minutes; P < 0.001 for all) at week 12 (geometric mean fold increase, 2.5, 3.0, and 1.6, respectively). All PEP items and CGIC improved significantly with both doses of dapoxetine vs. placebo (P < 0.001 for all). The most common AEs included nausea, dizziness, and headache, and evaluation of validated instruments demonstrated no anxiety, akathisia, suicidality, or changes in mood with dapoxetine use and no discontinuation syndrome following abrupt withdrawal. Conclusions In this diverse population, dapoxetine significantly improved all aspects of PE and was generally well tolerated.

Results from a Prospective Observational Study of Men with Premature Ejaculation Treated with Dapoxetine or Alternative Care: The PAUSE Study

“…An important strength of this study was the thorough and comprehensive collection of adverse event data. Compared with former studies, fewer patients were lost to follow-up (6.2% vs 3.9%, respectively) and fewer patients prematurely withdrew from the study because of the onset of a side effect induced by the drug (approximately 31% vs approximately 11%, respectively) [2].…”

“…Among a total of 6081 subjects in the phase 3 studies, of whom 4224 subjects were treated with dapoxetine, the incidence of syncope was similar in patients receiving placebo and in those treated with dapoxetine 30 mg (0.05% vs 0.06%, respectively), although greater in subjects treated with the 60-mg dose (0.23%) [2]. In comparison, based on this large observational study of 6128 patients treated with dapoxetine, it was observed that the incidence of syncope was zero, with the upper bound of the 95% confidence limit around 2.0 per 1000 person-years.…”

“…syncope observed in phase 3 studies (0.23%) [2]. In addition, this sample size would result in an 80% probability of observing at least one infrequent adverse event (0.027%).…”

“…An integrated analysis from five phase 3 trials concluded that dapoxetine 30 mg and 60 mg significantly improved all aspects of PE compared to placebo, including intravaginal ejaculatory latency time, PE profile questionnaire items, and Clinical Global Impression of Change in PE [2]. The geometric mean fold increases were 2.5, 3.0, and 1.6 with dapoxetine 30 mg, 60 mg, and placebo, respectively.…”

“…The safety assessment currently available for dapoxetine is based on data from the clinical development program that included >6000 patients [3]. In phase 3 studies, several well-recognized side effects of SSRIs (ie, akathisia, withdrawal syndrome, and mood-related changes) were not reported for dapoxetine use [2]. A low rate of vasovagal syncope was reported in phase 3 studies, and the premarketing safety profile did not show evidence of serious cardiovascular (CV) events or arrhythmias [4,5].…”