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Dapoxetine for
premature ejaculation
Review:
Social anxiety disorder
US FDA requests further
information before approval of Indiplon tablets for insomnia
Source:
Lancet 2006; 368: 929-37, Comment 894-6
A phase-3 trial published that has had
wide media coverage shows dapoxetine, a short-acting SSRI in late stage
development, to be effective in the treatment of premature ejaculation (PE). The
authors note that PE is the most widespread male sexual dysfunction, with a
prevalence of 21-33%. While many men cope with it, for many it can have
significant adverse effects. Available SSRIs have been used for its treatment as
delayed ejaculation is a known adverse effect of these drugs, however they were
not developed for the purpose and generally have prolonged half-lives and
undesirable adverse effect profiles. Dapoxetine was developed specifically to
take advantage of this adverse effect, and has rapid absorption and a short half-life
(1.2 hr).
The paper published reports a pre-specified combined analysis of two identical
trials, carried out independently but in parallel. They involved men with more
severe PE than the general population of men reporting it, who were randomised
to receive dapoxetine 30mg, 60mg, or placebo, to be taken one to three hours
before expected intercourse. Study duration was fourteen weeks overall, with a
two-week baseline followed by twelve weeks treatment. Primary outcome was
intravaginal ejaculatory latency time (IELT) measured by partner-held stopwatch;
secondary outcomes measured changes in subjective effects of PE. Outcomes were
assessed at four, eight and twelve weeks.
A total of 2,614 men were randomised to the two trials. Around three-quarters of
the men in each group completed the study, and all three groups showed some
improvement in IELT. Those in the two dapoxetine groups showed significantly
greater improvements than placebo, however. Baseline IELT for all three groups
was less than a minute: at the end of the study, it was 1.75 minutes for
placebo, 2.78 minutes for 30mg, and 3.32 minutes for 60mg. The difference
between both strengths and placebo was highly significant (p<0.0001), as was the
difference between the two doses of dapoxetine (p=0.0007). Those in the
dapoxetine groups were also more likely to report improvements in secondary
outcomes. Minor adverse effects (nausea, diarrhoea, headache, and dizziness)
were fairly common, especially in the 60mg group, but few patients discontinued
because of them. Based on their results, the authors conclude that dapoxetine
effective in the treatment of PE, producing a 3 to 4-fold improvement in IELT.
These improvements were sufficient to be meaningful to the men involved and
their partners. They note that the study was restricted to men with moderate to
severe PE, and should therefore not be generalised to men less severely affected.
An accompanying editorial discusses the trial and its implications: the authors
briefly note their experience in dealing with patients with premature
ejaculation at their sexual medicine centre in Italy and indicate that current
therapeutic options are limited. They comment that the effect of dapoxetine is
less than chronic dosing with existing SSRI, but that patients are likely to
prefer an on-demand treatment to chronic therapy.
Link: http://www.thelancet.com/journals/lancet/article/PIIS0140673606693732/abstract (subscription required)
Source:
BioSpace.com Following
a meeting with the US FDA on the actions needed to bring
indiplon immediate-release (IR) capsules from
“Approvable” to “Approval” for the treatment of insomnia,
Neurocrine Biosciences has reported that the FDA has
made the following requests
• The FDA requested that the Company supplement the
pharmacokinetic/food effect profile of indiplon (IR)
capsules to include several meal types. The Company will
initiate such a study shortly after further consultation
with the FDA. No other clinical trials were requested
for the re-submission;
• The resubmission will also include further analyses
and modifications of analyses previously submitted which
address questions raised by the agency in the initial
review.
Indiplon is a non-benzodiazepine agent that acts on a
specific subtype of GABA-A receptors believed to be
responsible for promoting sleep.
Link: http://www.biospace.com/news_story.aspx?StoryID=28913&full=1
Boletín de Actualización en Neuropsicofarmacología (BAN)
