Original Article

TADALAFIL IN CLINICAL TRIALS

SHABSIGH
et al.

Associate Editor
Michael G. Wyllie
Time from dosing to sexual
intercourse attempts in men taking
Editorial Board
Ian Eardley, UK
tadalafil in clinical trials
Jean Fourcroy, USA RIDWAN SHABSIGH, ARTHUR L. BURNETT*, IAN EARDLEY†, IRA D. SHARLIP‡,
Sidney Glina, Brazil PAMELA I. ELLSWORTH¶, CARMEN S. GARCIA§, FANNI NATANEGARA§ and
SANJEEV AHUJA§
Julia Heiman, USA Department of Urology, Columbia University, New York, NY, *Brady Urological Institute, Johns
Chris McMahon, Australia Hopkins Hospital, Baltimore, MD, †St. James University Hospital, Leeds, UK, ‡University of
Bob Millar, UK California, San Francisco CA, ¶University of Massachusetts Memorial Medical Center, Worcester,
Alvaro Morales, Canada MA and §Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA
Accepted for publication 29 April 2005
Michael Perelman, USA
Marcel Waldinger, Netherlands
OBJECTIVE attempt sexual intercourse at least once
during the 12-week treatment period at 4–36
To determine whether patients with erectile and 12–36 h, respectively, after taking
dysfunction (ED) and treated with tadalafil tadalafil. Regardless of previous experience
use the 36-h duration of effect of the drug, with sildenafil, about a third of patients using
and to discern if the timing of intercourse tadalafil attempted intercourse a mean of at
attempts is influenced by patient age, baseline least once per week at 4–36 h after the dose
severity of ED, or previous experience with over 12 weeks. Furthermore, 58% of patients
sildenafil citrate. attempted intercourse at least once during
two intervals (>1 to £ 4 h and >12 to £ 36 h)
PATIENTS AND METHODS after separate doses of tadalafil.

In 11 multicentre, double-blind, placebo- CONCLUSION

controlled studies, 2102 patients with ED were
randomized to a maximum of one dose per
day of tadalafil 10 or 20 mg (1464 men), or
placebo (638 men) with no time restrictions
before attempting sexual activity after the
dose. A post hoc analysis was used to
determine the proportion of men with ED who
attempted sexual intercourse during various
intervals (>0 to £ 1, >1 to £ 4, and >4 to £ 36,
including >12 to £ 36 h) after dosing with
tadalafil or placebo over a 12-week period.
Patients were stratified by age, baseline
severity of ED, and previous history of
sildenafil use.
RESULTS
Of patients in different age groups and
various ED severity, ≥ 79% and ≥ 53% chose to
Regardless of age, ED severity, or previous
experience with sildenafil, most patients
attempted sexual intercourse at least once at
12–36 h after one dose of tadalafil over a 12-
week treatment period. Furthermore, by
engaging in sexual intercourse at both earlier
and later intervals after separate doses, most
patients on treatment did not adhere to a
fixed schedule of intimacy and thus took
advantage of the 36-h duration.
KEYWORDS
phosphodiesterase inhibitors, erectile
function, timing of intercourse attempts,
Sexual Encounter Profile diary, duration of
effectiveness

© 2 0 0 5 B J U I N T E R N A T I O N A L | 9 6 , 8 5 7 – 8 6 3 | doi:10.1111/j.1464-410X.2005.05750.x 857
S H A B S I G H ET AL.
INTRODUCTION
Tadalafil (Cialis®, Lilly ICOS LLC) is a potent
inhibitor of phosphodiesterase type 5 (PDE5)
indicated for the treatment of erectile
dysfunction (ED) [1]. Previously approved
PDE5 inhibitors, sildenafil citrate (Viagra®,
Pfizer Inc.) and vardenafil (Levitra, Bayer
Pharmaceuticals Corporation), have half-lives
of ª 4 h [2,3]. This has a direct bearing on
the duration of efficacy and patients are
instructed to have sexual intercourse about
an hour after taking the medication (sildenafil
can be taken from 0.5–4 h before attempting
sexual intercourse) [2]. The mean terminal
half-life of tadalafil is 17.5 h in healthy
subjects [1] and its duration of efficacy has
been shown to be up to 36 h after dosing
[4,5]. Consequently, tadalafil may provide
more flexibility in terms of timing of
intercourse attempts relative to the time of
dosing. However, unanswered questions
include whether patients use this interval and
whether the patient’s age, ED severity, or
previous use of oral therapies influence the
timing of intercourse attempts selected by
these patients over the 36-h period after
taking tadalafil.
The aim of this retrospective analysis was to
evaluate if patients with ED use the extended
period of effectiveness provided by tadalafil;
to determine if patients and their partners
show flexibility in selecting the time to
engage in sexual activity after dosing; and to
discern if the pattern of sexual activity
relative to timing after dosing was influenced
by age, severity of ED, or previous history of
sildenafil use.
PATIENTS AND METHODS
Eleven randomized, double-blind, placebo-
controlled, parallel-arm studies were
conducted at 174 centres worldwide to
evaluate the efficacy and safety of tadalafil at
doses of 2.5–20 mg over a 12-week period
(one of these studies had a 6-month duration,
but for the purpose of this analysis only data
from 12 weeks of treatment are included).
Details of these studies were previously
published in two integrated analyses of five
and 11 efficacy and safety trials of tadalafil
[6,7]. Briefly, patients enrolled in these studies
were aged ≥ 18 years, reported having a
history of ED of at least 3 months’ duration,
and were to report on their sexual attempts
with the same adult female partner. Nine of
the 11 studies excluded patients who, in the
858
opinion of the investigator, did not respond to
sildenafil. The study design included a 4-week
run-in period (no ED medication taken) to
establish baseline data, and a 12-week
treatment period with randomization to fixed
doses of tadalafil 10 mg (321 men) or 20 mg
(1143 men), or placebo (638 men). In these
analyses, except for the efficacy analysis
described below, patients on tadalafil 10 mg
and 20 mg are considered as one group (1464
men). An additional 225 patients were
randomized to tadalafil 2.5 mg or 5 mg;
efficacy and safety results from these latter
groups were reported previously [6].
Patients took the study medication as needed,
up to once daily before expected sexual
activity and with no restrictions on food
intake. Patients were free to choose the time
between taking the dose and the time of
sexual intercourse attempts. Dosing
instructions used in five of the 11 trials,
included detailed information about the
expected duration of efficacy of tadalafil up
to 36 h after the dose. The remaining six trials
used a simple dosing instruction without
mentioning the 36-h duration of efficacy.
Examples of dosing instructions are included
in the Appendix.
Outcome measures of the efficacy of tadalafil
included the International Index of Erectile
Function (IIEF) questionnaire, the Sexual
Encounter Profile (SEP) diary, and a Global
Assessment Question. In this paper, the
proportion of ‘yes’ responses to SEP question
3 (SEP3: ‘Did your erection last long enough
for you to have successful intercourse’? [yes/
no]) is presented as the efficacy variable. For
the efficacy analysis patients on tadalafil
10 mg and 20 mg were considered separately.
Assessments of individual sexual attempts
were obtained through the patient SEP diaries
throughout the 12-week treatment period.
Patients recorded the time of dosing and the
time and outcome of each sexual attempt.
Over this treatment period, we determined
the proportion of patients having at least
1, 4, 8 or 12 attempts during the following
intervals: >0 to £ 1 h, >1 to £ 4 h, and >4 to
£ 36 h (including >12 to £ 36 h) after dosing.
An individual patient could have attempted
intercourse during one interval after one
dose, and in a different interval after another
dose. The number of attempts (≥1, ≥ 4, ≥ 8 or
≥ 12) represents a cumulative value over a 12-
week treatment period. Flexibility relative to
the time selected to engage in sexual activity
after the dose was assessed by the percentage
of patients who attempted intercourse during
the >1 to £ 4-h interval after at least one dose
and during the >4 to £ 36-h or >12 to £ 36-h
intervals after another dose at least once
during the 12 weeks of study. The percentage
of patients who engaged in sexual activity at
least once during three given intervals (>1 to
£ 4 h, >4 to £ 12 h, and >12 to £ 36 h) after
separate doses of tadalafil or placebo was also
calculated.
Patients were stratified by age (£44, >44–64
and >64 years), severity of ED as defined by
the Erectile Function (EF) domain of the IIEF
questionnaire (mild 22–25, mild to moderate
17–21, moderate 11–16, and severe 1–10) and
previous history of sildenafil use (previous
users or not). Analyses by age and severity
only included data for at least one attempt at
sexual intercourse within a given interval over
the 12 weeks of treatment, while analyses
based on previous history of sildenafil use
included at least 1, 4, 8 or 12 attempts in the
various intervals.
The statistical analyses presented, except for
the efficacy during various intervals as
measured by SEP3, reflect a descriptive
behavioural observation. Stratification by
number of attempts, age, baseline ED severity,
or previous experience with sildenafil, each
yields 16 possible comparisons to test. These
multiple comparisons will inflate the type 1
error rate (probability of concluding that
some differences are significant when in fact
they are not). Thus, we made no attempt at
establishing statistical comparisons between
placebo- and tadalafil-treated patients based
on the percentage of patients having sexual
intercourse attempts in various intervals.
Analysis of covariance models were used to
evaluate treatment differences in changes
from baseline in the proportion of ‘yes’
responses to SEP3. The models included terms
for baseline value, study, treatment group,
and baseline by treatment group interaction
(if P < 0.1). Pairwise comparisons of tadalafil
vs placebo were based on least square means
adjusted by the Dunnett method.
RESULTS
Demographic and baseline characteristics are
shown in Table 1. In the nine trials (1804 men)
that excluded patients who, in the opinion of
the investigator, were not responders to
previous sildenafil treatment, 739 (41%) were
© 2005 BJU INTERNATIONAL
 TADALAFIL IN CLINICAL TRIALS

least once over 12 weeks. Importantly, 59% of

TABLE 1 The patients demographic and baseline characteristics
patients on tadalafil attempted intercourse at
least once during the 12–36-h interval after
Tadalafil Tadalafil
dosing. Also, over the duration of the study,
Variable Placebo 10 mg 20 mg Total
61%, 45% and 32% of patients on tadalafil
N 638 321 1143 2102
engaged in sexual intercourse at least 4, 8 or
Mean (range) age, years 57 (22–81) 58 (26–81) 56 (22–88) 56 (22–88)
12 times, at 4–36 h after the dose; 28%, 14%
Age > 65, n (%) 140 (22) 96 (30) 248 (22) 484 (23)
and 8% did so at least 4, 8 or 12 times at
Duration of ED ≥ 12 months, n (%) 572 (90) 280 (87) 1006 (88) 1858 (88)
12–36 h after tadalafil during the treatment
Cause of ED, n (%)
phase (Table 2). Overall, the percentage of
Organic 369 (58) 215 (67) 627 (55) 1211 (58)
patients who had at least one attempt within
Psychogenic 82 (13) 20 (6) 147 (13) 249 (12)
these intervals was numerically similar in the
Mixed 187 (29) 86 (27) 369 (32) 642 (31)
placebo group (Table 2).
IIEF EF severity, n (%)
Normal* (26–30) 33 (5) 16 (5) 39 (3) 88 (4)
The percentage of patients on tadalafil who
Mild (22–25) 76 (12) 34 (11) 157 (14) 267 (13)
attempted sexual intercourse at least once
Mild to moderate (17–21) 136 (21) 79 (25) 268 (23) 483 (23)
during the 12 weeks of treatment within the
Moderate (11–16) 171 (27) 84 (26) 303 (27) 558 (27)
interval >4–36 h (including >12–36 h) after
Severe (1–10) 220 (34) 107 (33) 376 (33) 703 (33)
dosing was similar in all age groups analysed
Medical history, n (%)
(Fig. 1a); 79% and 57% of patients aged
Coronary artery disease 33 (5) 17 (5) 62 (5) 112 (5)
>64 years attempted intercourse during the
Depression 23 (4) 15 (5) 53 (5) 91 (4)
>4–36 h and >12–36 h intervals, respectively,
Diabetes mellitus 130 (20) 68 (21) 223 (20) 421 (20)
on at least one occasion after dosing with
Hyperlipidaemia 110 (17) 51 (16) 166 (15) 327 (16)
tadalafil (Fig. 1a). Overall, there was a similar
Hypertension 189 (30) 90 (28) 337 (29) 616 (29)
pattern of timing of sexual activity, including
attempts at intercourse at >4 h after dose, in
*Patients were included based on a history of ED with the disease being a patient-reported condition.
the placebo group, regardless of age (Fig. 1b).
Subsequent assessment of EF by the IIEF at baseline showed that a small proportion of participants (4%)
had an EF domain score of ≥ 26. The cause of ED was determined by the investigators based on the
Regardless of ED severity, a similar proportion
patient history, findings from physical examination, and any previous diagnostic testing.
of patients attempted intercourse at least
once within the interval 4–36 h (83%, 85%,
82% and 79% of those with mild, mild-to-
moderate, moderate, and severe ED,
N attempts over 12 weeks TABLE 2
respectively) after dosing with tadalafil
≥1 ≥4 ≥8 ≥12 The percentage of patients
(Fig. 2a). In addition, ≥53% of patients with
Time of intercourse after dose, h who attempted sexual
any ED severity (64% mild, 63% mild to
Tadalafil 10 or 20 mg (1464), n (%)* intercourse during various
moderate, 60% moderate and 53% severe)
>0 to £1 1032 (71) 633 (43) 422 (29) 298 (20) intervals after treatment
chose to attempt sexual intercourse at least
>1 to £4 1303 (89) 1048 (72) 759 (52) 544 (37) with tadalafil or placebo
once during the 12–36-h interval. Figure 2b
>4 to £36 1201 (82) 897 (61) 658 (45) 475 (32)
shows the percentage of men, stratified by
>12 to £36 870 (59) 410 (28) 205 (14) 113 (8)
baseline ED severity, who attempted
Placebo (638), n (%)*
intercourse during various intervals in the
>0 to £1 466 (73) 300 (47) 199 (31) 130 (20)
placebo group.
>1 to £4 542 (85) 417 (65) 281 (44) 162 (25)
>4 to £36 480 (75) 301 (47) 200 (31) 125 (20)
A similar percentage of patients in the
>12 to £36 318 (50) 114 (18) 49 (8) 20 (3)
sildenafil-naïve and sildenafil-experienced
groups had ≥ 12 intercourse attempts (36% vs
*number of patients who attempted intercourse in the respective
31%) at 4–36 h after taking tadalafil,
interval. A particular patient could have attempted intercourse during
indicating that about a third of patients using
one interval after one dose, and in a different interval after another
tadalafil, irrespective of previous sildenafil
dose; therefore, the number of patients in each column is not
use, had intercourse a mean of at least once a
cumulative.
week during this interval (Table 3).

The results shown in Table 4 summarize the

sildenafil-naïve and 1065 (59%) were
previous users.
Table 2 summarizes the percentage of
patients who attempted intercourse at least 1,
4, 8 or 12 times during various intervals after
dosing with tadalafil or placebo over the
12 weeks of treatment. After dosing with
tadalafil, 82% of patients attempted
intercourse during the 4–36-h interval at
proportion of patients who had intercourse
during two or three given intervals after
separate doses of tadalafil or placebo over the
12 weeks of treatment. When assessing the
time selected to engage in sexual activity by

© 2005 BJU INTERNATIONAL 859

S H A B S I G H ET AL.

the same individual, 81% engaged in sexual a 100 FIG. 1.

activity at least once during both the >1 to The percentage of patients in
90
£ 4-h and >4 to £ 36-h intervals, and 58% different age groups who
80
during both the >1 to £ 4-h and >12 to £ 36- attempted sexual intercourse

Percentage of men, %
h intervals, after separate doses of tadalafil; 70 during various intervals after
54% of patients attempted intercourse at 60 treatment with tadalafil (a) or
least once during each of the following 50 placebo (b); >0 to £ 1, green; >1 to
intervals: >1 to £ 4, >4 to £ 12 and >12 to 40 £ 4, light green; >4 to £ 36, red;
£ 36 h, after separate doses of tadalafil. 30 >12 to £ 36 h, light red. The
20 percentage is for men making at
Tadalafil was statistically superior to placebo 10
least one attempt in any of the
in the percentage of successful intercourse intervals over the 12 weeks. The
0
attempts at all intervals after dosing, as £44 (195) >44–64 (895) >64 (374) numbers in parenthesis indicate
measured by SEP3 (P < 0.001 vs placebo; b 100 the number of men in each age
Fig. 3). The mean per-patient percentages of 90 group.
sexual intercourse attempts that were 80
Percentage of men, %

successful on tadalafil 10 mg during the >0 to 70

£ 1, >1 to £ 4, >4 to £ 36, and >12 to £ 36 h 60
intervals were 57%, 59%, 60% and 66%, 50
respectively, and on tadalafil 20 mg 65%, 40
69%, 70% and 71%, vs 31%, 32%, 36% and 30
39% for placebo-treated patients (Fig. 3). 20
10
0
£44 (77) >44–64 (405) >64 (156)
DISCUSSION Age, years

Consistent with a mean terminal half-life of

17.5 h, tadalafil is effective for treating ED up
to 36 h after dosing [1,4,5], but few reports TABLE 3 Percentage of patients who attempted sexual intercourse at > 4 h after the dose, based on their
address the question of whether patients with previous experience with sildenafil
ED use this period to engage in sexual activity.
This retrospective analysis shows that a high N attempts at intercourse at No previous use of
proportion of patients treated with tadalafil interval (h) after dosing, % of sildenafil* Previous use of sildenafil*
10 or 20 mg engaged in sexual intercourse men Placebo Tadalafil Placebo Tadalafil
during the 4–36-h (including 12–36 h)
>4 to £36
interval after dose, at least once over
N 207 532 286 779
12 weeks of treatment (Table 2). The mean
≥1 77 84 74 81
(range) per-patient success rate for
≥4 50 63 46 61
intercourse attempts completed during
≥8 33 49 31 44
the 4–36 and 12–36 h intervals after the
≥12 20 36 22 31
tadalafil dose was ≥ 60 (60–71)% (Fig. 3).
>12 to £36
Importantly, to the best of our knowledge, this
N 207 532 286 779
is the first detailed report to show this pattern
≥1 48 63 51 58
of timing of sexual activity at >4 h after the
≥4 14 31 21 27
tadalafil dose in a high percentage of patients,
≥8 7 16 11 13
regardless of their age, severity of ED, or
≥12 3 8 5 8
previous history of sildenafil use. The results
presented in Table 4 also support the novel
*Based on 9 studies; the data presented are limited to a descriptive behavioural observation. The number
hypothesis that patients with ED use the
of attempts (≥1, ≥4, ≥8 or ≥12) represents a cumulative value over a 12-week treatment period.
flexibility provided by tadalafil in the timing of
intercourse relative to time of dosing, as
indicated by the high proportion who
engaged in sexual activity during the earlier
(1–4 h) and later (4–36 and 12–36 h) intervals [7] showed that during 12 weeks of treatment and 24–36 h after the dose, respectively [7].
after separate doses of tadalafil. a large percentage of patients on tadalafil These data seem to indicate that, when given
attempted intercourse at least once at 4–36 h the opportunity, patients with ED tend to use
A recently published retrospective analysis of after dosing, with 50% and 33% of patients the extended period of efficacy provided by a
11 integrated phase 3 clinical trials of tadalafil engaging in sexual intercourse during 12–24 longer-acting PDE5 inhibitor. The present data

860 © 2005 BJU INTERNATIONAL

 TADALAFIL IN CLINICAL TRIALS

FIG. 2. The percentage of patients, stratified by baseline ED severity, who attempted sexual intercourse during show that across the 12-week treatment
various intervals after treatment with tadalafil (a) or placebo (b). Key as for Fig. 1. The percentage is for men period, 82% and 59% of patients had at
making at least one attempt in any of the intervals over the 12 weeks. The numbers in parenthesis indicate least one sexual intercourse attempt during
the number of men in each age group. the 4–36 and 12–36-h intervals, respectively,
after a single dose of tadalafil (Table 2).
a Furthermore, the percentage of patients
100
on tadalafil who attempted intercourse at
90 least once over the treatment period at
80 >4 h after dosing (4–36 h, including 12–36 h)
was generally similar irrespective of
Percentage of men, %

70 patient age (Fig. 1), baseline ED severity

60 (Fig. 2), or previous history of sildenafil
use (Table 3).
50
40 Although there is a higher prevalence of ED in
ageing men [8,9], it is known that those aged
30
≥60 years remain sexually active [10]. The
20 present analysis of the timing of sexual
intercourse by men of various ages (Fig. 1)
10
shows that a large percentage of patients in
0 all age groups analysed, including those aged
Mild (191) Mild to Mod (347) Moderate (387) Severe (483)
>64 years, engaged in sexual activity at >4 h
b after the tadalafil dose (4–36 h, including
100
12–36 h). These results might indicate that
90 regardless of age the patients’ timing of
80 sexual activity extends to >4 h after the
tadalafil dose. This might appear to contradict
70
Percentage of men, %

results from previous research [11], which

60 suggested in a cohort of British men aged
>40 years that the average time from
50
first thinking of intercourse to beginning
40 intercourse was <1 h. However, we think
that these two studies are not necessarily
30
incompatible. The present data suggest that
20 for many men there is a considerable delay
between taking the medication and having
10
intercourse, while the period alluded to in the
0 previous research [11] was from thinking
Mild (76) Mild to Mod (136) Moderate (171) Severe (220)
about intercourse to having intercourse. It
seems reasonable to suggest that the
Baseline ED Severity
prolonged duration of action of tadalafil
allows a man to use the medication with
no concerns about time limitations,
TABLE 4 Intra-individual flexibility of the timing of sexual intercourse after separate doses of tadalafil or while allowing him to have spontaneous
placebo intercourse within the context of the timings
reported by the previous research. For
Interval, h Tadalafil 10, 20 mg, n (%) Placebo, n (%) patients and their partners, this flexibility may
N 1403 611 translate into a dissociation between taking
>1 to £4 and >4 to £36 1130 (80.5) 440 (72.0) the medication and timing intercourse at a
>1 to £4 and >12 to £36 814 (57.8) 288 (47.0) fixed time after dosing.
N* 1395 606
>1 to £4 and >4 to £12 and 12 to £36 749 (53.7) 245 (40.4) A large percentage of patients in the present
analysis chose to have intercourse at 4–36 h
N, number of patients having at least two, or N* three, intercourse attempts after baseline during the (including 12–36 h) after dosing, regardless of
study; n, number of patients having intercourse attempts after baseline in the respective intervals after ED severity (Fig. 2). Patients on tadalafil had a
separate doses. Data shown represent attempts made by the same patient at one interval after one dose higher success rate for intercourse attempts
and at a different interval after another dose (any two or three separate doses are shown). Multiple made at all intervals evaluated up to 36 h
attempts after a single dose of tadalafil or placebo were not analysed. after dose than those on placebo (P < 0.001;
Fig. 3). Importantly, the high proportion of

© 2005 BJU INTERNATIONAL 861

S H A B S I G H ET AL.

patients who had intercourse during both the
earlier (1–4 h) and later (4–36, 12–36 h)
intervals after dosing (Table 4), highlights
the flexibility that patients had to choose
the time to engage in sexual activity
according to their individual needs and
circumstances.
FIG. 3. Mean per-patient percentages of successful intercourse attempts over time by patients on tadalafil
(10 mg, red; 20 mg, light red) or placebo (green), as measured by SEP3. * P < 0.001 vs placebo. Numbers at base
of bars indicate the number of patients who had at least one attempt at intercourse in any of the intervals
over 12 weeks.
100
90

Percentage of ‘yes’ answers to SEP3, %

The present analyses of sildenafil-naive vs
sildenafil-experienced patients showed that a
high proportion engaged in intercourse at
least once over 12 weeks at 4–36 h (84% and
81%, respectively) and 12–36 h (63% and
58%, respectively). In addition, about a third
of patients attempted intercourse a mean of
at least once a week (≥12 attempts over
12 weeks) during the 4–36-h interval,
regardless of their previous history of
sildenafil use. These findings suggest that
regardless of previous experience with
sildenafil, patients understood the tadalafil
dosing instructions and used the time
available to them to engage in sexual activity
(Table 3).
Some limitations of the present analyses
include: (i) the integration of 11 clinical
studies with two distinctive dosing
instructions (see Appendix) limits the direct
correlation of patients’ behavioural pattern of
timing of sexual intercourse relative to time of
dosing, with their clear understanding of
tadalafil’s duration of effectiveness; (ii) the
nature of the analyses does not allow for a
statistical comparison between tadalafil- and
placebo-treated patients, restricting the
results to a descriptive behavioural
observation of the timing of sexual activity
after dosing.
In summary, the overall results suggest that
patients with ED used the 36-h period of
effectiveness of tadalafil regardless of their
age, baseline ED severity or previous
experience with sildenafil. Importantly, the
behavioural observations reported here
clearly indicate that patients not only used
the extended time available to them, but also
had the flexibility to engage in sexual activity
after the tadalafil dose at the most convenient
time to them.
ACKNOWLEDGEMENTS
Funding for this study was provided by Lilly
ICOS LLC (Bothell, Washington, and
Indianapolis, Indiana).
80
70
* *
60 * *
*
50
40
30
20
10
0
n= 466 208 824 542 282 1021
>0–£1 >1–£4
Time of intercourse postdose, h
CONFLICT OF INTEREST
R. Shabsigh is a paid consultant and speaker
for Bayer Pharmaceuticals, Lilly ICOS LLC, and
Pfizer Inc., and a study investigator for Bayer
and Pfizer. I. Sharlip is a paid consultant, study
investigator, and speaker for Bayer, Lilly ICOS,
and Pfizer. C. Garcia, F. Natanegara and S.
Ahuja are employees and stockholders for Eli
Lilly and Company. I. Eardley is a paid
consultant, study investigator and speaker for
Lilly ICOS, Pfizer, Bayer, GSK and J&J. P.
Ellsworth is a study investigator and speaker
for Eli Lilly, paid consultant for Pfizer, and
speaker for Bayer. Source of funding: Lilly
ICOS LLC.
REFERENCES
1 Lilly ICOS LLC. Tadalafil Prescribing
Information. November, 2003
2 Pfizer Inc. Sildenafil Citrate Prescribing
Information. Revised August 2003
3 Bayer Healthcare. Levitra® Vardenafil
Hydrochloride Summary of Product
Specifications 2003
4 Porst H, Padma-Nathan H, Giuliano F,
Anglin G, Varanese L, Rosen R. Efficacy
of tadalafil for the treatment of erectile
dysfunction at 24 and 36 hours after
dosing: a randomized controlled trial.
Urology 2003; 62: 121–6
* *
*
480 248 953 318 172 698
>4–£36 >12–£36
5 Young JM, Feldman RA, Auerbach SM
et al. Tadalafil improved erectile function
at twenty-four and thirty-six hours after
dosing in men with erectile dysfunction:
US trial. J Androl 2005; 26: 310–8
6 Brock GB, McMahon CG, Chen KK et al.
Efficacy and safety of tadalafil in the
treatment of erectile dysfunction: results
of integrated analyses. J Urol 2002; 168:
1332–6
7 Carson CC, Rajfer J, Eardley I et al. The
efficacy and safety of tadalafil: an update.
BJU Int 2004; 93: 1276–81
8 Feldman HA, Goldstein I, Hatzichristou
DG, Krane RJ, McKinlay JB. Impotence
and its medical and psychosocial
correlates: results of the Massachusetts
Male Aging Study. J Urol 1994; 151: 54–
61
9 Bacon CG, Mittleman MA, Kawachi I,
Giovannucci E, Glasser DB, Rimm EB.
Sexual function in men older than 50
years of age: results from the Health
Professionals Follow-up Study. Ann Intern
Med 2003; 139: 161–8
10 Braun M, Wassmer G, Klotz T,
Reifenrath B, Mathers M, Engelmann
U. Epidemiology of erectile dysfunction:
results of the ‘Cologne Male Survey’. Int J
Impot Res 2000; 12: 305–11
11 Eardley I, Dean J, Barnes T, Kirby M,
Glasser D, Solanki J. The sexual habits of
British men and women over 40 years old.
BJU Int 2004; 93: 563–7

862 © 2005 BJU INTERNATIONAL


Correspondence: Ridwan Shabsigh, Columbia
University, 161 Fort Washington Avenue, New
York, NY 10032, USA.
e-mail: RShabsigh@urology.columbia.edu
Abbreviations: PDE5, phosphodiesterase type
5; ED, erectile dysfunction; IIEF, International
Index of Erectile Function; EF, erectile
function (domain); SEP, Sexual Encounter
Profile.
APPENDIX
Simple dosing instructions listed in the
study protocol for LVBN, LVCE, LVCO,
LVCQ, LVCR, and LVDJ Clinical Studies.
Patients will be instructed to take one dose of
medication with water prior to expected
sexual activity. The patients will also be
instructed to take no more than one (1) dose
daily.
Detailed dosing instructions listed in the
study protocol for LVEF, LVEG, LVDZ, LVEL,
and LVDW clinical studies.
© 2005 BJU INTERNATIONAL
Patients will be instructed to take one dose of
study drug with water prior to the potential
for sexual activity. In clinical studies, IC351
(tadalafil) has shown to be effective up to
36 h after dosing and, in some patients, as
early as 16 min after dosing. Patients may
initiate sexual activity at various times after
dosing in order to determine their own
optimal window of responsiveness. They will
be instructed to take no more than one dose
per day.
Patient dosing instruction sheet given to
patients participating in LVEF, LVEG, LVDZ,
LVEL, and LVDW clinical studies.
In clinical studies, IC351 (tadalafil) has
shown to be effective up to 36 h after dosing
and, in some patients, within 30 min after
dosing. You may initiate sexual activity at
varying time points after dosing in order
to determine your own optimal window of
responsiveness.
The 36 h of potential intimacy provides
considerable flexibility in how you may
choose to take your study drug and does not
TADALAFIL IN CLINICAL TRIALS
require that you closely link dosing to sexual
activity. You may find your sex life to be more
flexible and spontaneous by taking IC351
(tadalafil) well in advance of anticipated
sexual activity.
The following are some possible ways you
might choose to take study drug:
• Consider taking study drug in the morning
if you feel the potential exists for sexual
intimacy later in the day, in the evening, or
even early the next day.
• Consider taking study drug the evening
prior to sexual activity if you prefer to engage
in sexual activity in the morning.
• While IC351 (tadalafil) has been shown
to be effective for 36 h, the maximum
dosing frequency is once per day. Hence,
you may take a dose at the same time of
day on several consecutive days if you so
desire in order to be able to engage in sexual
activity over that period whenever the mood
strikes.
• Study drug can be taken with or without
food. Hence, you may take a dose with any
meal, if you choose.
863