Durability of Response Following

Cessation of Tadalafil Taken

Once Daily as Treatment for
Erectile Dysfunction
 INTRODUCTION
PDE5 inhibitors improve erectile
dysfunction (ED) while it is being
administered
Pilot study: PDE5 inhibitor
improvement in endothelial function
beyond discontinuation of treatment
Durability: sustainable improvements
in erectile function after treatment
cessation
 INTRODUCTION
Zumbe J, et al, 2008:
RCT: efficacy of vardenafil on-demand vs.
once daily in mild-to-moderate ED and
cardiovascular risk factors (dyslipidemia,
HT, DM) treated for 12 or 24 weeks
washout period 4 weeks
No statistically different changes in IIEF-EF
scores
Mean IIEF-EF scores for the vardenafil groups
at the end of washout period were higher
than at baseline
 INTRODUCTION
Montorsi F, et al, 2008:
RCT: effects of on-demand vs. nightly
administration of vardenafil on recovery of
erectile function in ED following bilateral
nerve-sparing radical prostatectomy
At the end of 9-month, double-blind treatment
period, proportions of patients with IIEF-EF
scores 22 were greater with vardenafil vs.
placebo
However, no significant differences between
the groups at the end of washout period
 INTRODUCTION
Porst H, et al, 2006:
268 men with ED received placebo,
tadalafil 5 mg, or tadalafil 10 mg once
daily for 12 weeks, followed by 1-year
open-label extension of tadalafil 5 mg
once daily and 4-week treatment-free
follow-up period
In double-blind period: changes in mean IIEF-
EF scores were significantly improved for
tadalafil 5 mg and 10 mg groups compared
to placebo
 INTRODUCTION
Porst H, et al, 2008:
After 1-year open-label extension
tadalafil 5 mg once daily:
Mean IIEF-EF scores improved from 13.7 at
baseline to 24.1 at the end of extension
After that, subjects entered a 4-week,
treatment-free, follow-up period:
Mean IIEF-EF scores returned to near-
baseline levels (16.0)
 AIMS
To examine the durability of response
(sustainability of erectogenic benefits
following treatment cessation) in
men with ED treated with long-term
tadalafil 5 mg once daily
METHODS
Study Procedures
 Study Procedures
160 patients 158 subjects with
complete IIEF-EF scores
Inclusion criteria:
Men 18 years
In a monogamous relationship with female
partner
Had at least 3-month history of ED
Entry into the study was based on
clinical diagnosis of ED, not IIEF-EF
scores
 Study Procedures
Some subjects have IIEF-EF scores in
the normal range (26)
Exclusion criteria:
Poor control of comorbidities (DM,
cardiovascular disease)
History of radical prostatectomy or other
pelvic surgery resulting in ED
Use of nitrates
 Study Procedures
Categorization of ED etiology (organic,
psychogenic, mixed):
was based on investigators clinical
opinion (by review of past medical
history, functional inquiry, physical
examination)
 Mean Outcome Measures
Primary measures: changes in efficacy
(IIEF-EF scores)
At baseline
At the end of the open-label extension
At the end of the 4-week, treatment-free,
follow-up period
ED severity:
Severe: 0-10
Moderate: 11-16
Mild: 17-25
Normal: 26-30
Mean Outcome Measures
Percentage of subjects who improved
at least one category (e.g. Moderate
to Mild), or stayed in Normal category,
from baseline to the end of open-label
period was calculated
Among those subjects who
improved/ remained Normal,
durability of response was assessed
 Statistical Methods
Subjects were categorized at the end
of open-label period compared with
baseline:
improved, remained the same,
worsened
No statistical comparisons because
of small sample sizes in some groups
 Statistical Methods
Durability of response:
If the subject had an improvement of
at least one category compared with
baseline (or maintained Normal) 4
weeks after cessation of treatment
No durability of response:
If the subjects had scores that were in
the same or lower than baseline 4
weeks after cessation of treatment
 Statistical Methods
Durability of response:
If the subject had an improvement of
at least one category compared with
baseline (or maintained Normal) 4
weeks after cessation of treatment
No durability of response:
If the subjects had scores that were in
the same or lower than baseline 4
weeks after cessation of treatment
 Statistical Methods
At the end of follow-up period compared
with the end of open-label period
Subjects with durability of response:
Maintained the improvement
Declined, but still had scores that remained
at least one category higher than baseline
Subjects with no durability of response:
Declined
Had scores that were in lower category
compared with baseline
 ETHICS
Approved by study center Ethical
Review Boards
All subjects provided written informed
consent