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Premature Ejaculation
Table 1: Design of Dapoxetine Phase III Clinical Trials
Country or Region Trial Population (n) Trial Duration Trial Medication Outcome Measures Reference
US (two trials of 2,614 12 weeks Dapoxetine 30mg prn IELT 23
identical design) Dapoxetine 60mg prn Control over ejaculation
Placebo prn Satisfaction with sexual intercourse
CGI
Asia-Pacific 1,067 12 weeks Dapoxetine 30mg prn IELT 43
Dapoxetine 60mg prn PEP
Placebo prn CGI
International 1,162 24 weeks and a 1-week Dapoxetine 30mg prn IELT 42
randomised withdrawal period Dapoxetine 60mg prn PEP
Placebo prn CGI
DESS
North America 1,238 9 weeks and a 1-week Double-dummy: PEP 44
(Canada and US) randomised withdrawal period Dapoxetine 60mg qd CGI
Dapoxetine 60mg prn DESS
Placebo prn
Placebo qd
CGI = Clinical Global Impression of change in premature ejaculation; DESS = Discontinuation-Emergent Signs and Symptoms questionnaire; IELT = intravaginal ejaculatory latency time;
PEP = premature ejaculation profile; prn = on demand.
45
Source: Hellstrom, 2009. Adapted with permission from Dove Press Ltd and Hellstrom WJG, Emerging treatments for premature ejaculation: Focus on dapoxetine, Neuropsychiatr Dis Treat,
2009;5:37–46. © 2009 Dove Medical Press Ltd.
Figure 1: Increases in Intravaginal Ejaculatory Latency Dapoxetine has been evaluated for the treatment of PE in five phase III
Time with Dapoxetine Treatment in the International
randomised, double-blind, parallel-group, placebo-controlled clinical
Clinical Trial
trials that enrolled more than 6,000 individuals (see Table 1). These trials
included: two in the US of identical design (for which an integrated
4.0
analysis was published);
23
an international trial conducted in Europe,
3.5
3.5
North and South America, Israel and South Africa;
42
a withdrawal trial
3.1
3.0
conducted in North America;
43
and a trial conducted in men from the
2.8
2.5
Asia-Pacific region.
44,45
All five trials were similar in design, involving a
2.5
T (min)
baseline period (one to four weeks) and a double-blind treatment
2.0
1.9
1.8 period (nine to 24 weeks); two trials also included a one-week
1.5
randomised withdrawal period for the evaluation of discontinuation
Mean IEL
1.5
1.3
syndrome.
42,43
All trials enrolled men ≥18 years of age with a DSM-IV-TR
1.0
0.9 0.9 0.9
0.8
0.6
diagnosis of PE who had been in a stable, monogamous, heterosexual
0.5
0.5 0.5
0.3 0.3 0.3
relationship for a minimum of six months;
23,42–44
four of the trials also
0
required a stopwatch-measured IELT of ≤2 minutes in ≥75% of sexual
≤0.5 min ≤1 min ≤2 min
encounters at baseline.
23,42,44
Although these trials were conducted prior
Baseline IELT
to the development of the ISSM definition and subsequent proposals
Placebo Dapoxetine 30mg Dapoxetine 60mg
for ideal PE trial design,
46
these trials meet many of the required
All comparisons with placebo are statistically significant (p<0.002).
evaluation criteria. Additional evaluations included each participant’s
IELT intravaginal ejaculatory latency time.
Clinical Global Impression of change in PE (CGI; evaluated in all studies).42
Source: Buvat et al., 2009.
Safety evaluations were also extensive, and included the use of
potentially resulting in a reduced risk of adverse events (AEs) and less validated tools to evaluate sexual side effects, anxiety, changes in
likelihood of drug–drug interactions. Therefore, a serotonergic agent mood or affect and the potential for SSRI discontinuation syndrome
with a rapid onset and rapid clearance could be effective and following abrupt treatment discontinuation.
42,43
maximise convenience, while improving safety and tolerability
compared with SSRIs with longer half-lives. Efficacy of Dapoxetine
In comparison with placebo, dapoxetine treatment significantly
Dapoxetine, a short-acting SSRI, is the first oral agent to be approved increased IELT above baseline at all time-points, including after the
for the treatment of PE. Dapoxetine has recently been approved in first dose and at each four-week interval up to 12 or 24 weeks of
several European countries.
39
In contrast to the longer-acting SSRI treatment, with consistent and reproducible results observed across
antidepressants,
40
the pharmacokinetic profile of dapoxetine is all clinical trials.
23,42,44
Among participants in the 24-week international
better suited to the on-demand treatment of PE.
41
Peak plasma trial, significant increases in the mean IELT compared with placebo
concentrations of dapoxetine were observed 1.01 and 1.27 hours were observed after the first dose and at every four-week interval
after the administration of single doses of dapoxetine 30 and 60mg, through to the end of the trial (p≤0.001 for both doses at all time-
respectively.
41
The plasma concentrations of dapoxetine decreased to points).
42
At the 24-week end-point, the mean IELT increased from
5% of the peak concentrations for both doses 24 hours after 0.9 minutes (mean for each treatment group) at baseline to 3.1 and
administration (initial half-life 1.3 and 1.4 hours for the 30 and 60mg 3.5 minutes with dapoxetine 30 and 60mg, respectively, compared
doses, respectively).
41
with 1.9 minutes for placebo
42
(see Figure 1). The results for the
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EUROPEAN UROLOGICAL REVIEW
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