Lifelong versus Acquired PE 1. Palmer & Stuckey, 2008.

Estimated IELT Reported by Men with “ Normal ” Ejaculation and by their Partners Sotomayor M. J Sex Med 2 (Suppl 2): 110-114, 2005. Estimated IELT (minutes) Men Women USA 13.6 11.2 UK 9.9 8.5 France 9.3 8.4 Germany 6.9 7.4 Italy 9.6 8.6

A MultiNational Survey of IELT 500 couples >age 18 in Netherlands, UK, Spain, Turkey and US Not selected for ejaculatory status or co-morbidities IELT measured by stop-watch for 4 weeks ----------------------------------------------------------------------------------------------- RESULTS by Country (Median IELT in minutes) Netherlands UK Spain Turkey US ALL 5.1 7.6 5.8 3.7 7.0 5.4 ----------------------------------------------------------------------------------------------- ----------------------------------------------------------------------------------------------- Waldinger MD, Quinn P, Dilleen M et al. J Sex Med 2:492-7, 2005.

Prevalence of PE is similar across countries 1. Porst et al, 2007. 2. Janssen-Cilag Data On File 2009 PEPA (Premature Ejaculation Perceptions and Attitudes) Study * Men classified as having PE if low / absent control over ejaculation that is viewed as a problem by men or/ their partners ** Men classified as having PE or Probable PE by PEDT diagnosis ** ** * * * *

Normal Male Sexual Response Time Sexual interest/ stimulation Penile tumescence High arousal / penile erection Plateau Orgasm Ejaculation accompanied by orgasm Penile detumescence Resolution Adapted from Donatucci (2006) J Sex Med 3(suppl 4):303–308 Excitement Penetration

Premature Ejaculation Time Rapid ejaculation and associated orgasm with normal erection Normal response Adapted from Donatucci (2006) J Sex Med 3(suppl 4):303–308 Short plateau phase Steep excitement phase with normal erection PE

What percentage of men with PE might want treatment? Authors Percent Rowland et al ( JSexMed 1:225, 2004) 50% Carson et al ( JUrol 169 Suppl 2003) 24% Brock et al ( JUrol 177 Suppl 2007) 38%

Current Treatment Options ?

New topical penile spray using a combination of lidocaine and prilocaine to treat PE DB PC phase 2 study of 43 men with PE Drug Placebo Number of men 20 23 Baseline IELT (min) 1.0 0.9 Follow-up (min) 4.9 1.6 Dinsmore WW et al. BJU International 99:369-375, 2007 (Feb)

Efficacy of Sildenafil for Premature Ejaculation and Post-Ejaculatory Refractory Time Double-blind placebo-controlled study 157 men with PE ages 18-65 (mean 43 yrs) Compared flexible-dose sildenafil (50-100 mg) to placebo Results: No signficant difference between sildenafil and placebo in IELT Sildenafil-treated men had greater ejaculatory control and sexual satisfaction scores Sildenafil-treated men had decreased post-ejaculatory refractory time McMahon CG, Stuckey BGA, Andersen M, et al. J Sex Med 2: 368-375, 2005

FIG 1 The mechanism of ejaculation 2005 BJU International 95, 1181-1186 ejaculate

Neurophysiology of Ejaculation Motor supply to bulbospongiosus muscle Pudendal nerve Sensory inputs from genital areas Supraspinal Centres Spinothalamic cells L3-L4: Coordination of spinal nuclei Hypogastric Plexus ~ T12-L1: Emission Spinal Reflex S1-S3: Expulsion afferent efferent Giuliano & Clement (2005) Ann Rev Sex Res 16:190–216 Higher brain Centres Excitatory & inhibitory control Sympathetic supply to: Epididymis, Vas deferens Seminal Vesicles Prostate Pons: nPGi: Nucleus paragigantocellularis Dorsal nerve of penis

Dapoxetine (Priligy) A highly potent inhibitor of serotonin reuptake transporter Following oral administration, it is rapidly absorbed After reaching T max, serum concentration declines rapidly At 60 mg dose: 1 T max = 1.2 hr T ½ initial = 1.5 hr Single dose and multiple dose pharmacokinetics are similar 1 No interaction when used with food 2 , alcohol 3 or PDE5 inhibitors 4 1 Dresser M, et al. Clin Pharmacol Therap 32:2004. Abstract Pl-113 2 Dresser M, et al. J Sex Med 3 (Suppl 1):25, 2005. Abstract 37. 3 Modi N, et al. J Urol 173 (Suppl):239, 2005. Abstract 879. 4 Dresser M, et al. J Urol 173 (Suppl):201, 2005. Abstract 739.

Dapoxetine Phase III Studies Summary © J & J Pharmaceutical Services LLC, 2007 Study number Description Subjects enrolled Sites 012 & 013 12 week phase III trials of dapoxetine in men with moderate to severe premature ejaculation (completed 2004) 2614 121 sites in USA 014 9 month open label extension of studies 012 & 013 (completed 2005) 1774 121 sites in USA 3001 24 week phase III trial of dapoxetine in men with moderate to severe premature ejaculation (completed 2007) 1162 143 sites in Europe, South Mexico, America, Canada, Israel and South Africa 3002 Withdrawal effects of chronic daily and as-needed dosing with dapoxetine in the treatment of PE (completed 2005) 1238 91 sites in USA and Canada 3003 12 week phase III trial of dapoxetine in men with moderate to severe premature ejaculation (completed 2007) 1349 52 sites in Asia and Australia

Dapoxetine IELT for ≤1min & ≤0.5min Pooled IELT values at endpoint for baseline IELT ≤1min & ≤0.5min † McMahon et al. (2008) Presented at ESSM/ISSM IELT≤Imin IELT≤0.5min * Fold-increase=geometric endpoint/geometric baseline, not model based. Values are unadjusted. † Week 12 (012, 013, 3001, 3003) or last observation carried forward Fold Increase=4.3 Fold Increase=3.4 Fold Increase=2.7 Fold Increase=3.4

Dapoxetine Mean IELT Results Over Time (3x, NOT 3 hours) *P<0.001 vs. placebo ANCOVA * * * * * * * * Pooled study data: C-2002-012, C-2002-013, PRE-3001, PRE-3003 * * Pooled Studies

Dapoxetine: Most adverse events mild to moderate in severity and occurred within first 4 weeks of treatment 1. McMahon et al., 2008 2. Casey et al., 2008 3. Giuliano et al., 2008 SSRI Class Effects are not evident: No deleterious effects on mood and anxiety symptoms, suicidal ideation or withdrawal syndrome, erectile function or libido

Dapoxetine - Most Common Adverse Events Phase III Data - Pooled Discontinuation due to Nausea: 0.1% placebo, 0.9% 30 mg, 3.0% 60 mg Pooled data: C-2002-012, C-2002-013, PRE-3001, PRE-3002, PRE-3003

Thank you ! (Damai Lagoon KUCHING)

Medical Therapy Options for Treatment of PE - AUA Guidelines Oral Therapies Trade Names Recommended Dose Nonselective serotonin reuptake inhibitor Clomipramine Anafranil ® 25 to 50 mg/day or 25 mg 4 - 24 hr pre-intercourse Selective serotonin reuptake inhibitors Fluoxetine Prozac ® , Sarafem ® 5 to 20 mg/day Paroxetine Paxil ® 10, 20, 40 mg/day or 20 mg 3 to 4 hr pre-intercourse Sertraline Zoloft ® 25 to 200 mg/day or 50 mg 4 to 8 hr pre-intercourse Topical Therapies Trade Name Dose Lidocaine/prilocaine cream EMLA ® Cream Lidocaine 2.5%, prilocaine 2.5% 20 to 30 minutes pre-intercourse

Slow onset of effect of SSRIs in PE sertraline washout placebo IELT (min) Weeks McMahon CG. J Urol 159:1935-8, 1998

Evaluating the Patient on Dapoxetine Evaluating patient responses - Does the patient want to continue on treatment? - somewhat worse, the same, somewhat better or much better? What is a successful treatment? - A 3-fold increase in IELT is considered clinically significant and adequate for patient satisfaction Managing nausea and somnolence - Antacid - Timing of sexual activity