Articles

Letter to the Editor

Reply to Christopher C.K. Ho's Letter to the Editor re: David Bar-Or, Kristin M. Salottolo, Alessandro Orlando, James V. Winkler. 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. Eur Urol 2012;61:736–43

By: Kristin M. Salottoloa b c

European Urology, Volume 61 Issue 1, April 2012, Pages e25-e26

Published online: 01 April 2012

Abstract Full Text Full Text PDF (74 KB)

Refers to article:

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

David Bar-Or, Kristin M. Salottolo, Alessandro Orlando and James V. Winkler for the Tramadol ODT Study Group1.

Accepted 18 August 2011

April 2012 (Vol. 61, Issue 4, pages 736 - 743)

Refers to article:

Re: David Bar-Or, Kristin M. Salottolo, Alessandro Orlando, James V. Winkler. 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. Eur Urol 2012;61:736–43

Christopher C.K. Ho

Accepted 6 September 2011

April 2012 (Vol. 61, Issue 4, pages e23 - e24)

We read with interest the letter to the editor by Dr. Ho. In his letter, Dr. Ho raises a few pertinent issues we would like to address.

We did not originally report the increase in median intravaginal ejaculatory latency time (IELT) at each time interval during the double-blind treatment phase for tramadol ODT (Zertane) versus placebo [1]. There was a significant increase (p<0.025) in median IELT at the first visit during the double-blind period for both doses of tramadol ODT versus placebo and at each subsequent visit during the double-blind period for 89mg tramadol ODT versus placebo. Furthermore, results from the premature ejaculation profile (PEP) questionnaire show significant improvements (p<0.05) in all four aspects of the PEP at the first visit and at each subsequent visit during the double-blind period for 89mg tramadol ODT versus placebo and significant improvements (p<0.05) in ejaculation-related control and distress at the first visit and at each subsequent visit during the double-blind period for 62mg tramadol ODT versus placebo.

These results demonstrate that no conditioning is necessary to achieve improvements in IELT with tramadol ODT after initiating treatment. Conversely, selective serotonin reuptake inhibitors (SSRIs), whether taken chronically or on demand, require conditioning to demonstrate the desired effect. This conditioning may be a reason why studies using SSRIs report a last-observation-carried-forward approach rather than utilizing all available data during the treatment period, as we reported in our study [1].

We did not report the findings of the 12-wk open-label extension period of our phase 3 study, in which all subjects received the higher dose of tramadol ODT (89mg, n=101), and safety was assessed at additional 3-wk intervals. Six subjects experienced an adverse event (5.9%) with only one treatment-related adverse event (anxiety or erectile dysfunction [ED]), demonstrating that even the higher dose of tramadol ODT was safe with longer follow-up. The abuse potential and tolerance of tramadol, the active ingredient of tramadol ODT, has been studied extensively [2] and [3]. These reports show little or no development of drug dependence because the opioid effect of tramadol is mediated through the mu-opioid receptor.

We excluded men with ED from our study because ED treatment may lead to therapy-related premature ejaculation (PE). As Dr. Ho states, ED and PE can co-occur in up to 30% of patients. We recently began designing a phase 3 clinical trial for a combination drug, tramadol ODT and phosphodiesterase type 5 inhibitor (PDE5-I), that targets the population of men in whom ED and PE co-occurs. Preliminary data show no untoward interaction between tramadol ODT and PDE5-Is. The combination drug will simultaneously treat PE and ED and alleviate therapy-related sexual dysfunction and comorbid conditions.

We are equally pleased to report that tramadol ODT is at least as efficacious as and safer than dapoxetine for the treatment of PE. We believe that cost will not be a barrier to utilization. We expect this unique formulation of tramadol ODT (Zertane) to be commercially available in the very near future, providing significant therapeutic benefit to men with PE and their sexual partners.

Conflicts of interest

I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/ affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: David Bar-Or: Board membership, Ampio Pharmaceuticals, Inc.; Salaried employee, Ampio Pharmaceuticals, Inc.; Stock/stock options, Ampio Pharmaceuticals, Inc.; Inventor of patents belonging to Ampio Pharmaceuticals, Inc. (not paid for patents). Kristin Salottolo: Salaried employee, Ampio Pharmaceuticals, Inc.; Stock/stock options, Ampio Pharmaceuticals, Inc.

References

  • [1] D. Bar-Or, K.M. Salottolo, A. Orlando, J.V. Winkler. 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 2minutes. Eur Urol. 2012;61:736-743 Abstract, Full-text, PDF, Crossref.
  • [2] P. Dayer, J. Desmeules, L. Collart. Pharmacology of tramadol [in French]. Drugs. 1997;53(Suppl 2):18-24 Crossref.
  • [3] D.H. Epstein, K.L. Preston, D.R. Jasinski. Abuse liability, behavioral pharmacology, and physical-dependence potential of opioids in humans and laboratory animals: lessons from tramadol. Biol Psychol. 2006;73:90-99 Crossref.

Footnotes

a Trauma Research Department, Swedish Medical Center, Englewood, CO, USA

b Trauma Research Department, St. Anthony Hospital, Lakewood, CO, USA

c Ampio Pharmaceuticals, Inc., Greenwood Village, CO, USA

lowast Corresponding author. Trauma Research Department, Swedish Medical Center, 501 E. Hampden Ave., Room 4–454, Englewood, CO 80113, USA.

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