A Randomized Double-Blind, Placebo-Controlled Multicenter Study to Evaluate the Efficacy and Safety of Two Doses of the Tramadol Orally Disintegrating Tablet for the Treatment of Premature Ejaculation Within Less Than 2 Minutes.

Author(s): Bar-Or D, Salottolo KM, Orlando A, Winkler JV

Affiliation(s): Trauma Research Department, Swedish Medical Center, Englewood, CO, USA; Trauma Research Department, St. Anthony Hospital, Lakewood, CO, USA; Ampio Pharmaceuticals, Inc., Greenwood Village, CO, USA.

Publication date & source: 2011-08-30, Eur Urol., [Epub ahead of print]

BACKGROUND: Premature ejaculation (PE) is a widely observed male sexual dysfunction with a major impact on quality of life for many men and their sexual partners. OBJECTIVE: To assess the safety of tramadol orally disintegrating tablet (ODT) (Zertane) and its efficacy in prolonging intravaginal ejaculation latency time (IELT) and improving Premature Ejaculation Profile (PEP) scores. DESIGN, SETTING, AND PARTICIPANTS: We conducted an integrated analysis of two identical 12-wk randomized double-blind, placebo-controlled phase 3 trials across 62 sites in Europe. Healthy men 18-65 yr of age with a history of lifelong PE according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision, and an IELT </=120s were included. There were 604 intent-to-treat subjects included in the analysis. INTERVENTION: Subjects were randomized to receive 1:1:1 placebo (n=200), 62mg tramadol ODT (n=206), or 89mg tramadol ODT (n=198). MEASUREMENTS: We measured overall change and fold increase in median IELT and the mean change in all four measures of the PEP. Differences across treatment groups were analyzed using Wilcoxon rank-sum tests, analysis of variance, and chi-square analyses. RESULTS AND LIMITATIONS: Tramadol ODT resulted in significant increases in median IELT compared with placebo; increases were 0.6min (1.6 fold), 1.2min (2.4 fold), and 1.5min (2.5 fold) for placebo, 62mg tramadol ODT, and 89mg tramadol ODT, respectively (p<0.001 for all comparisons). Men saw significantly greater improvement in all four measures of the PEP in both doses compared with placebo (p<0.05 for all comparisons). Tramadol ODT was well tolerated; study discontinuation occurred in 0%, 1.0%, and 1.6% of subjects in placebo, 62mg, and 89mg tramadol ODT groups, respectively. Limitations include study inclusion for men with IELT up to 120s. CONCLUSIONS: On-demand 62mg tramadol ODT is an effective treatment for PE in a low and safe therapeutic dose and provides a new option for managing mild to severe PE. TRIAL REGISTRATION: ClinicalTrials.gov identifiers NCT00983151 and NCT00983736; http://clinicaltrials.gov/. Copyright (c) 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.