In clinical studies, VIAGRA was assessed for its effect on the ability of men with
erectile dysfunction (ED) to engage in sexual activity and in many cases specifically
on the ability to achieve and maintain an erection sufficient for satisfactory sexual
activity. VIAGRA was evaluated primarily at doses of 25 mg, 50 mg and 100 mg in
21 randomized, double-blind, placebo-controlled trials of up to 6 months in duration,
using a variety of study designs (fixed dose, titration, parallel, crossover). VIAGRA
was administered to more than 3,000 patients aged 19 to 87 years, with ED of various
etiologies (organic, psychogenic, mixed) with a mean duration of 5 years. VIAGRA
demonstrated statistically significant improvement compared to placebo in all 21
studies. The studies that established benefit demonstrated improvements in success
rates for sexual intercourse compared with placebo.
The effectiveness of VIAGRA was evaluated in most studies using several assessment
instruments. The primary measure in the principal studies was a sexual function
questionnaire (the International Index of Erectile Function - IIEF) administered
during a 4-week treatment-free run-in period, at baseline, at follow-up visits,
and at the end of double-blind, placebo-controlled, at-home treatment. Two of the
questions from the IIEF served as primary study endpoints; categorical responses
were elicited to questions about (1) the ability to achieve erections sufficient
for sexual intercourse and (2) the maintenance of erections after penetration. The
patient addressed both questions at the final visit for the last 4 weeks of the
study. The possible categorical responses to these questions were (0) no attempted
intercourse, (1) never or almost never, (2) a few times, (3) sometimes, (4) most
times, and (5) almost always or always. Also collected as part of the IIEF was information
about other aspects of sexual function, including information on erectile function,
orgasm, desire, satisfaction with intercourse, and overall sexual satisfaction.
Sexual function data were also recorded by patients in a daily diary. In addition,
patients were asked a global efficacy question and an optional partner questionnaire
was administered.
The effect on one of the major end points, maintenance of erections after penetration,
is shown in Figure 3, for the pooled results of 5 fixed-dose, dose-response studies
of greater than one month duration, showing response according to baseline function.
Results with all doses have been pooled, but scores showed greater improvement at
the 50 and 100 mg doses than at 25 mg. The pattern of responses was similar for
the other principal question, the ability to achieve an erection sufficient for
intercourse. The titration studies, in which most patients received 100 mg, showed
similar results. Figure 3 shows that regardless of the baseline levels of function,
subsequent function in patients treated with VIAGRA was better than that seen in
patients treated with placebo. At the same time, on-treatment function was better
in treated patients who were less impaired at baseline.
Figure 3. Effect of VIAGRA and Placebo on Maintenance of Erection by Baseline Score.
The frequency of patients reporting improvement of erections in response to a global
question in four of the randomized, double-blind, parallel, placebo-controlled fixed
dose studies (1797 patients) of 12 to 24 weeks duration is shown in Figure 4. These
patients had erectile dysfunction at baseline that was characterized by median categorical
scores of 2 (a few times) on principal IIEF questions. Erectile dysfunction was
attributed to organic (58%; generally not characterized, but including diabetes
and excluding spinal cord injury), psychogenic (17%), or mixed (24%) etiologies.
Sixty-three percent, 74%, and 82% of the patients on 25 mg,
50 mg and 100 mg of VIAGRA, respectively, reported an improvement in their erections,
compared to 24% on placebo. In the titration studies (n=644) (with most patients
eventually receiving 100 mg), results were similar.
Figure 4. Percentage of Patients Reporting an Improvement in Erections.
The patients in studies had varying degrees of ED. One-third to one-half of the
subjects in these studies reported successful intercourse at least once during a
4-week, treatment-free run-in period.
In many of the studies, of both fixed dose and titration designs, daily diaries
were kept by patients. In these studies, involving about 1600 patients, analyses
of patient diaries showed no effect of VIAGRA on rates of attempted intercourse
(about 2 per week), but there was clear treatment-related improvement in sexual
function: per patient weekly success rates averaged 1.3 on 50-100 mg of VIAGRA vs
0.4 on placebo; similarly, group mean success rates (total successes divided by
total attempts) were about 66% on VIAGRA vs about 20% on placebo.
During 3 to 6 months of double-blind treatment or longer-term (1 year), open-label
studies, few patients withdrew from active treatment for any reason, including lack
of effectiveness. At the end of the long-term study, 88% of patients reported that
VIAGRA improved their erections.
Men with untreated ED had relatively low baseline scores for all aspects of sexual
function measured (again using a 5-point scale) in the IIEF. VIAGRA improved these
aspects of sexual function: frequency, firmness and maintenance of erections; frequency
of orgasm; frequency and level of desire; frequency, satisfaction and enjoyment
of intercourse; and overall relationship satisfaction.
One randomized, double-blind, flexible-dose, placebo-controlled study included only
patients with erectile dysfunction attributed to complications of diabetes mellitus
(n=268). As in the other titration studies, patients were started on 50 mg and allowed
to adjust the dose up to 100 mg or down to 25 mg of VIAGRA; all patients, however,
were receiving 50 mg or 100 mg at the end of the study. There were highly statistically
significant improvements on the two principal IIEF questions (frequency of successful
penetration during sexual activity and maintenance of erections after penetration)
on VIAGRA compared to placebo. On a global improvement question, 57% of VIAGRA patients
reported improved erections versus 10% on placebo. Diary data indicated that on
VIAGRA, 48% of intercourse attempts were successful versus 12% on placebo.
One randomized, double-blind, placebo-controlled, crossover, flexible-dose (up to
100 mg) study of patients with erectile dysfunction resulting from spinal cord injury
(n=178) was conducted. The changes from baseline in scoring on the two end point
questions (frequency of successful penetration during sexual activity and maintenance
of erections after penetration) were highly statistically significantly in favor
of VIAGRA. On a global improvement question, 83% of patients reported improved erections
on VIAGRA versus 12% on placebo. Diary data indicated that on VIAGRA, 59% of attempts
at sexual intercourse were successful compared to 13% on placebo.
Across all trials, VIAGRA improved the erections of 43% of radical prostatectomy
patients compared to 15% on placebo.
Subgroup analyses of responses to a global improvement question in patients with
psychogenic etiology in two fixed-dose studies (total n=179) and two titration studies
(total n=149) showed 84% of VIAGRA patients reported improvement in erections compared
with 26% of placebo. The changes from baseline in scoring on the two end point questions
(frequency of successful penetration during sexual activity and maintenance of erections
after penetration) were highly statistically significantly in favor of VIAGRA.
Diary data in two of the studies (n=178) showed rates of successful intercourse
per attempt of 70% for VIAGRA and 29% for placebo.
A review of population subgroups demonstrated efficacy regardless of baseline severity,
etiology, race and age. VIAGRA was effective in a broad range of ED patients, including
those with a history of coronary artery disease, hypertension, other cardiac disease,
peripheral vascular disease, diabetes mellitus, depression, coronary artery bypass
graft (CABG), radical prostatectomy, transurethral resection of the prostate (TURP)
and spinal cord injury, and in patients taking antidepressants/antipsychotics and
antihypertensives/diuretics.
Analysis of the safety database showed no apparent difference in the side effect
profile in patients taking VIAGRA with and without antihypertensive medication.
This analysis was performed retrospectively, and was not powered to detect any pre-specified
difference in adverse reactions.