Safety and efficacy of epelsiban in the treatment of men with premature ejaculation: a randomized, double-blind, placebo-controlled, fixed-dose study.
OBJECTIVE
To assess the efficacy and safety of the selective oxytocin receptor antagonist epelsiban in the treatment of premature ejaculation (PE).


METHODS
Double-blind, randomized, parallel-group, placebo-controlled, stopwatch-monitored, phase 2, multicenter study (GSK557296; NCT01021553) conducted in men (N=77) 18-55 years of age, with PE defined as per International Society for Sexual Medicine consensus definition. Patients provided informed consent prior to a 4-week un-medicated run-in to determine baseline intravaginal ejaculatory latency times (IELT) recorded in an electronic diary. Patients needed to make a minimum of four intercourse attempts and have a mean IELT<65 seconds to be considered for randomization. Men with moderate-to-severe erectile dysfunction were excluded from the study. Eligible patients were randomized to placebo, epelsiban 50 mg, or 150 mg, taken 1 hour before sexual activity. Active treatment IELT times were recorded in an electronic diary, along with subjective measures of intercourse satisfaction, over an 8-week treatment period. The Modified Index of Premature Ejaculation and International Index of Erectile Function were completed at study visits.


METHODS
Stopwatch timed IELT recordings and a modified version of the patient-reported outcome questionnaire the IPE were used in this study to determine the effect of epelsiban when taken orally prior to intercourse in subjects diagnosed with PE.


RESULTS
The baseline (mean) IELT for patients pretreatment was (0.52, 0.63, and 0.59 minutes) for placebo, epelsiban 50 mg and 150 mg, respectively. On-treatment, average geometric least squares means of the median IELT values (mean) were slightly higher in the 50 mg and 150 mg groups (0.72 and 0.69 minutes), respectively, vs. the placebo group (0.62 minutes). Headache was the most common adverse event, and rates were similar across all groups.


CONCLUSIONS
Epelsiban 50 mg and 150 mg were well tolerated, but did not result in a clinically or statistically significant change in IELT in men with PE, compared with placebo.
Santa Clara Valley Medical Center, Santa Clara, CA, USA.
Rajesh
R
Shinghal
Allison
A
Barnes
Kelly M
KM
Mahar
Brendt
B
Stier
Lisa
L
Giancaterino
Lynn D
LD
Condreay
Libby
L
Black
Stewart W
SW
McCallum
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000328:Adult; D054659:Diketopiperazines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004311:Double-Blind Method; D004542:Ejaculation / Q000187:drug effects*; D005838:Genotype; D006727:Hormone Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009426:Netherlands; D017060:Patient Satisfaction; D010597:Pharmacogenetics; D061686:Premature Ejaculation / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D011930:Reaction Time; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors / Q000378:metabolism; D012725:Sexual Behavior / Q000187:drug effects; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D054659:Diketopiperazines; D006727:Hormone Antagonists; D009025:Morpholines; C569600:OXTR protein, human; D018045:Receptors, Oxytocin; C571185:epelsiban
Epelsiban; Index of Premature Ejaculation; International Society for Sexual Medicine Consensus Definition; Intravaginal Ejaculatory Latency Time; Oxytocin Receptor Antagonist; Premature Ejaculation