Efficacy of tadalafil in men with erectile dysfunction naïve to phosphodiesterase 5 inhibitor therapy compared with prior responders to sildenafil citrate.
BACKGROUND
Tadalafil, an inhibitor of phosphodiesterase 5 (PDE5), is indicated for treatment of erectile dysfunction. Most tadalafil clinical trials excluded patients with unsuccessful prior treatment with sildenafil citrate (sildenafil).


OBJECTIVE
This retrospective analysis of pooled data from 14 tadalafil clinical trials examines the effect of this exclusion by comparing efficacy results in 1,349 patients without prior sildenafil use (naïve, presumably a mixture of potential responders and nonresponders) with efficacy results in 1,440 patients previously responsive to sildenafil (prior responders).


METHODS
Efficacy measures included the International Index of Erectile Function (IIEF) erectile function (EF) domain, overall satisfaction (OS), and intercourse satisfaction (IS) domain scores; Sexual Encounter Profile (SEP) diary questions 2 through 5 (SEP2 [successful penetration], SEP3 [successful intercourse], SEP4 (satisfaction with hardness of erection), and SEP5 [overall satisfaction with the sexual experience]); and a Global Assessment Question (GAQ1) (13/14 trials) about erection improvement. Efficacy was compared using analysis of covariance (IIEF and SEP) and logistic regression (GAQ1) models.


METHODS
After a 4-week, treatment-free, run-in period, patients in 14 double-blind, placebo-controlled, parallel-group trials were treated with tadalafil 10 mg, tadalafil 20 mg, or placebo for 12 weeks (dosed as needed before sexual activity, no more than once daily).


RESULTS
Tadalafil improved erectile function compared with placebo (P < 0.001) in naïve patients and sildenafil prior responders for all efficacy measures. For most efficacy outcomes, responses in the naïve group (probable mix of responders and nonresponders) were not statistically different from responses in the prior-responder group (P >or= 0.10).


CONCLUSIONS
The similar responses of these two patient groups observed in this post hoc analysis suggest, but do not confirm, that exclusion of sildenafil nonresponders in previously reported tadalafil clinical trials may not have substantially affected efficacy outcomes. Tadalafil improved erectile function in patients naïve to PDE5 inhibitor therapy and in patients who previously responded to sildenafil therapy.
Broderick
Gregory A
GA
Department of Urology, Mayo Clinic, Jacksonville, FL;. Electronic address: broderick.gregory@mayo.edu.
Donatucci
Craig F
CF
Medical Center, Duke University, Durham, NC, USA.
Hatzichristou
Dimitrios
D
Center for Sexual and Reproductive Health, Aristotle University of Thessaloniki, Thassaloniki, Greece.
Torres
Luiz O
LO
Clinica de Urologia e Andrologia, Belo Horizonte, Minas Gerais, Brazil.
Valiquette
Luc
L
Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
Zhao
Yanli
Y
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN.
Loughney
Kate
K
ICOS Corporation, Bothell, WA, USA.
Sides
Gregory D
GD
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN.
Ahuja
Sanjeev
S
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN.
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D002243:Carbolines / Q000627:therapeutic use*; D004311:Double-Blind Method; D007172:Erectile Dysfunction / Q000188:drug therapy*; D006801:Humans; D008297:Male; D017060:Patient Satisfaction; D010410:Penile Erection; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D011687:Purines; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D012720:Severity of Illness Index; D000068677:Sildenafil Citrate; D013450:Sulfones; D000068581:Tadalafil; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use*
D002243:Carbolines; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068581:Tadalafil; D000068677:Sildenafil Citrate; D015106:3',5'-Cyclic-GMP Phosphodiesterases