title: Comparative efficacy of tadalafil once daily in men with erectile dysfunction who demonstrated previous partial responses to as-needed sildenafil, tadalafil, or vardenafil.
abstract: OBJECTIVE
  Phosphodiesterase type-5 inhibitors (PDE5Is) are first-line therapies for erectile dysfunction (ED). Sildenafil (SIL) and vardenafil (VAR) are approved for as-needed (PRN) dosing; tadalafil (TAD) is approved for both PRN and once-a-day (OaD) dosing for ED. Recent evidence suggests that TAD-OaD may be effective as therapy in men with an incomplete response to PRN-PDE5I therapy. This study evaluated whether TAD-OaD provides similar efficacy in men with ED who had previously demonstrated a partial response to PRN-PDE5I therapy.
  
  
  METHODS
  In this randomized, double-blind, placebo-controlled trial, men with a ≥3 month ED history received SIL 100 mg, TAD 20 mg, or VAR 20 mg during a 4 week open-label lead-in period. Those with International Index of Erectile Function - Erectile Function (IIEF-EF) domain scores <26 following lead-in treatment completed a 4 week washout period, then randomized to TAD 2.5 mg up-titrated to 5 mg, TAD 5 mg, or placebo (PBO) OaD for 12 weeks. MAIN OUTCOME MEASURES obtained from patients treated with TAD-OaD were compared to PBO-treated patients. Additionally, results of treatment with TAD-OaD were compared to results obtained from 4 week PRN-PDE5I therapy to determine whether OaD and PRN regimens provided comparable efficacy.
  
  
  BACKGROUND
  NCT01130532.
  
  
  METHODS
  International Index of Erectile Function (IIEF) domain scores; Sexual Encounter Profile (SEP) questions 2-5.
  
  
  RESULTS
  Endpoint data was obtained from 590 men (391 TAD; 199 PBO). RESULTS for all IIEF and SEP measures were significantly better for TAD-OaD (p < 0.001 for all) compared to PBO and were comparable to those observed during PRN-PDE5I treatment. TAD 2.5 mg and TAD 5 mg OaD therapy were safe and generally well tolerated.
  
  
  CONCLUSIONS
  Tadalafil once daily is a viable alternative to as-needed PDE5I therapy in men with ED. Key limitations include the lack of a PRN PDE5I study group during the double-blind period, and that many more patients took tadalafil than sildenafil or vardenafil during the PRN period.
authors.affiliation: University of Tennessee Graduate School of Medicine , Knoxville, TN , USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Kim
authors.forename: Allen
authors.initials: A
authors.lastname: Seftel
authors.forename: Evan
authors.initials: E
authors.lastname: Goldfischer
authors.forename: Simin
authors.initials: S
authors.lastname: Baygani
authors.forename: Patrick
authors.initials: P
authors.lastname: Burns
mesh_terms: D000328:Adult; D002243:Carbolines / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016903:Drug Monitoring / Q000379:methods; D007172:Erectile Dysfunction / Q000188:drug therapy / Q000209:etiology / Q000523:psychology; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D057240:Patient Preference; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage; D010879:Piperazines / Q000008:administration & dosage*; D011687:Purines / Q000008:administration & dosage; D000068677:Sildenafil Citrate; D013449:Sulfonamides / Q000008:administration & dosage*; D013450:Sulfones / Q000008:administration & dosage; D000068581:Tadalafil; D016896:Treatment Outcome; D014227:Triazines / Q000008:administration & dosage; D000069058:Vardenafil Dihydrochloride
chemical_list: D002243:Carbolines; D007093:Imidazoles; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013449:Sulfonamides; D013450:Sulfones; D014227:Triazines; D000069058:Vardenafil Dihydrochloride; D000068581:Tadalafil; D000068677:Sildenafil Citrate
keywords: As-needed dosing; Erectile dysfunction; Once daily dosing; Sildenafil; Tadalafil; Vardenafil