Treatment of Premature Ejaculation in the Asia-Pacific Region:Results from a Phase III Double-blind, Parallel-group Study of Dapoxetine

McMahon et al. 2009Journal of Sexual Medicine

부천성모병원 김효신

Treatment of Premature Ejaculation with dapoxetine

• IntroductionDapoxetine is a short-acting SSRI that was recently approved for the on-demand treatment of premature ejaculation (PE).

• AimTo evaluate the efficacy and safety of dapoxetine 30 mg and 60 mg on demand (prn) in men with PE from the Asia-Pacific region.

중추신경계와 사정

사정관련 신경전달물질

사정의 병리학적 원인

중추신경계적 원인중추신경계적 원인

세로토닌 시스템의 이상> 5-HT2c receptor 기능저하> 5-HT1A receptor 기능과잉

세로토닌 시스템의 이상> 5-HT2c receptor 기능저하> 5-HT1A receptor 기능과잉

말초적 원인말초적 원인

음경의 감각 과민음경의 감각 과민

사정반사신경의 과도한 흥분사정반사신경의 과도한 흥분

Serotonin : 5-hydroxytryptamine, 5-HT, N-methyl-gammaSerotonin Transporter: 5-HTT

사정조절의 핵심 : 세로토닌

Selective serotonin reuptake inhibitors or serotonin-specific reuptake inhibitor: class of compounds typically used as

antidepressants in the treatment of depression,anxiety disorders, and some personality disorders. They are also typically effective and used in treating premature ejaculation problems as well as some cases of insomnia.

SSRIs increase the extracellular level of the neurotransmitter serotonin by inhibiting its reuptake into the presynaptic cell, increasing the level of serotonin available to bind to the postsynaptic receptor.

citalopram (Celexa, Cipramil, Cipram, Dalsan, Recital, Emocal, Sepram, Seropram, Citox) dapoxetine (no trade name yet; not yet approved by the FDA) escitalopram (Lexapro, Cipralex, Esertia) fluoxetine (Prozac, Fontex, Seromex, Seronil, Sarafem, Ladose, Fluctin (EUR), Fluox (NZ), Depress (UZB), Lovan (AUS)) fluvoxamine (Luvox, Fevarin, Faverin, Dumyrox, Favoxil, Movox) paroxetine (Paxil, Seroxat, Sereupin, Aropax, Deroxat, Rexetin, Xetanor, Paroxat) sertraline (Zoloft, Lustral, Serlain) zimelidine (Zelmid, Normud)

사정조절의 핵심 : 세로토닌

약물동력학

Peak plasma concentrations (Cmax) 은 복용후 1.3 시간 후 도달합니다 (Tmax).

initial half-life 는 90 minutes 이며 , 24 시간 후 peak concentration 대비 약 4%미만으로 농도가 떨어집니다 . 따라서 반복투여에 의한 체내 축적이 최소화되었습니다 .

음식 , 알코올 , PDE5I 와 약물상호작용이 적음

Methods

• Subjects– 18 years or older; monogamous, heterosexual relationship > 6 months

- Diagnostic and Statistical Manual of Mental Disorders 4th edit. text revision, criteria for PE for at least 6 months;

– intravaginal ejaculatory latency time (IELT) of 2 minutes or less in at least 75% of sexual intercourse episodes.

• Study design- Randomized, double-blind, parallel-group, placebo-controlled trial - 52 centers in Australia, China, Korea, Taiwan, Malaysia, Philippines,

Thailand, Singapore, and HongKong

Pre-randomization

Post-study telephone contact

12-week double-blind treatment

taking prn (1-3 hrs before intercourse)

placebo

Dapoxetine 30mg

Dapoxetine 60mgScreening visit

2wks after discontinuation of study

drug

Main Outcome Measures

Efficacy assessments• Stopwatch-measured Average IELT• Patient-reported outcome• the Premature Ejaculation Profile (PEP)

- Perceived control over ejaculation- Satisfaction with sexual intercourse- Ejaculation-related personal distress- Interpersonal difficulty

• Clinical Global Impression (CGI) of change in PE• Composite PRO definition of clinical benefit

Safety assessments• treatment-emergent adverse events (TEAEs)

Results_ subject disposition

Of the 1,067 subjects randomized, 858 completed the study.

Results

• 858/1067 pts. completed the study - 295 (83%), 284 (80%), and 279 (78%)

• Withdrawal: personal reasons, insufficient response, etc

• most common TEAEs: nausea, dizziness, somnolence, headache, vomiting, diarrhea, and nasopharyngitis

• baseline, mean Average IELT : 1.0±0.47,1.1±0.45, 1.1±0.48 minutes

• <0.5min 14%, 0.5~1min 45%, 1~2min 55%

Placebo Dapox. 30mg Dapox. 60mg

Withdrawal 11.8% 11.0% 12.1%

Lack of efficacy 1.7% 1.1% 0.6%

Side effects 0.3% 1.7% 5.1%

Results

• Increased Mean Average IELT • No differences between dapoxetine groups at any time point.

• Increased Geometric Mean Average IELT(Standard error)

• All PEP measures and the CGI of change were significantly improved with dapoxetine vs. placebo at study endpoint (P 0.005 for all).

Placebo Dapox. 30mg Dapox. 60mg

Initial IELT 1.0±0.47 1.1±0.45 1.1±0.48

First 1.8±1.71 2.7±2.68 3.0±3.19

12 week 2.4±2.05 3.9±3.95 4.2±3.97

Placebo Dapox. 30mg Dapox. 60mg

First 0.9(1.04) 1.0(1.03) 0.9(1.04)

12 week 1.8(1.05) 2.7(1.05) 3.1(1.05)

Results_ IELT, intravaginal ejaculatory latency time

Results_ Control over ejaculation during sexual intercourse

0.6

1.6

0.9

18.7

33.5 33.5

(P < 0.001)

Results_ Satisfaction with sexual intercourse

3.9

4.3

4.3

29.0

41.3 40.9

(P < 0.001)

Results_ ejaculation-related interpersonal difficulty of subjects

76.4

73.5

74.3

36.4

25.219.6

(P < 0.001)

Results_ ejaculation-related interpersonal difficulty of partners

48.8

51.9 50.

3

27.3

17.9

13.4

(P ≤ 0.005)

Safety_ TEAEs (Treatment-emergent adverse events)

The most common TEAEs with dapoxetine;nausea, dizziness, somnolence, headache, vomiting, diarrhea, and nasopharyngitis;

TEAEs ratio leading

discontinuation

요약

IELT 를 3-4 배 증가IELT 를 3-4 배 증가

초회 복용부터 효과 초회 복용부터 효과

사정에 대한 control 을 향상사정에 대한 control 을 향상

성행위에 대한 만족도를 향상 성행위에 대한 만족도를 향상

파트너의 성생활 만족도를 향상 파트너의 성생활 만족도를 향상

전반적으로 내약성이 우수 전반적으로 내약성이 우수

경청해 주셔서 감사합니다 .