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Keywords:

  • control;
  • dapoxetine;
  • distress;
  • premature ejaculation;
  • treatment response

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

OBJECTIVE

To evaluate the overall treatment benefit of dapoxetine for premature ejaculation (PE), with specific emphasis on improvements in personal distress and interpersonal difficulty related to ejaculation. Although these factors are key elements of numerous sets of diagnostic criteria for PE, they have rarely been evaluated as outcome measures in clinical trials.

PATIENTS AND METHODS

In this randomized, double-blind, placebo-controlled, phase III trial we enrolled men aged ≥18 years, from the USA and Canada, who had a Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision, diagnosis of PE (1238 men). Men were randomized to receive placebo or dapoxetine 60 mg as needed or once daily for 9 weeks. The once-daily treatment arm was included for analysis of withdrawal symptoms (primary endpoint; presented elsewhere). Patients completed the Premature Ejaculation Profile (PEP) on day 1 (before dosing), and on days 28 and 63 (or study endpoint), which comprised the outcome measures for perceived control over ejaculation, satisfaction with sexual intercourse, and personal distress and interpersonal difficulty related to ejaculation. The patient-reported global impression of change in PE was reported on day 63 (or study endpoint). Treatment benefit measures included the composite criteria of at least a two-category increase in perceived control over ejaculation and at least a one-category decrease in personal distress related to ejaculation from baseline at study endpoint.

RESULTS

At baseline, ≈5% of patients in any treatment group reported ‘not at all’ or ‘a little bit’ of personal distress related to ejaculation, which increased to 54.3% of those receiving dapoxetine (vs 35.3% with placebo; P < 0.001). Similarly, 43.0% and 40.9% of men in the placebo and dapoxetine groups, respectively, reported ‘not at all’ or ‘a little bit’ of interpersonal difficulty related to ejaculation at baseline, which increased to 76.8% and 64.2% of those with dapoxetine and placebo, respectively (P < 0.001). The percentage of men who achieved the composite criteria with dapoxetine ‘as needed’ was 47.6%, vs 21.7% with placebo (difference from placebo, 25.9%; P < 0.001). The distribution of responses for the PEP among men who achieved the composite criteria was similar to that reported for men without PE in a previous observational study in the USA. The most common adverse events were nausea, dizziness, headache, diarrhoea and insomnia, which were more common with dapoxetine than with placebo.

CONCLUSION

Dapoxetine reduced the personal distress and interpersonal difficulty associated with PE, and was associated with patient-reported improvements in their condition. The percentage of patients who achieved a composite of a two-category or greater increase in perceived control over ejaculation and a one-category or greater decrease in personal distress related to ejaculation was substantially greater than with placebo, as were all outcome measures.


Abbreviations
AE

adverse event

DSM-IV-TR

Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision

IELT

intravaginal ejaculatory latency time

MITT

modified intent-to-treat

PE

premature ejaculation

PEP

Premature Ejaculation Profile

PRO

patient-reported outcome

SSRI

selective serotonin reuptake inhibitor

PGI

patient-reported global impression.

INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

Although premature ejaculation (PE) is a common sexual disorder among adult men, few men report seeking treatment [1,2]. This condition, defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR) [3], as ‘persistent or recurrent ejaculation with minimal sexual stimulation before, upon, or shortly after penetration and before the person wishes it, and is associated with marked distress or interpersonal difficulty’, affects numerous aspects of a man’s life, including sexual confidence, interpersonal relationships and the sexual satisfaction of both partners [4,5]. Although sexual function has been recognized to have a substantial impact on a man’s quality of life [6], no compounds are currently approved to treat PE.

Recent analyses with data from large, observational studies of men diagnosed with PE and men without PE conducted in the USA [7] and Europe [8] found that perceived control over ejaculation is a central mediator of PE, with a direct effect on the negative outcomes associated with PE, including personal distress related to ejaculation and satisfaction with sexual intercourse. Additional analyses of these data suggested that personal distress related to ejaculation is a key factor in determining PE status [9], and moreover, is the primary motivation for a man with PE to seek treatment. It follows then that these factors should be considered in evaluating the degree of therapeutic benefit of an agent such as dapoxetine in treating men with PE.

Dapoxetine, a short-acting selective serotonin reuptake inhibitor (SSRI) under development for the treatment of PE, was shown in two phase III, placebo-controlled clinical trials and their integrated analysis to significantly increase perceived control over ejaculation, satisfaction with sexual intercourse, and intravaginal ejaculatory latency time (IELT), when given ‘as needed’ to men with PE [10]. Here we present results from a randomized, double-blind, placebo-controlled phase III trial of dapoxetine 60 mg administered as needed or once daily, in which, for the first time, assessments of personal distress and interpersonal difficulty as treatment outcomes were investigated. The primary endpoint of this study was the evaluation of potential withdrawal effects after abrupt discontinuation of dapoxetine in the once-daily arm (for which results are presented elsewhere) [11]. In the current analysis we evaluated the treatment benefit of dapoxetine 60 mg as needed vs placebo, based on its effects on personal distress and interpersonal difficulty related to ejaculation, perceived control over ejaculation, and satisfaction with sexual intercourse, as well as the patient-reported global impression (PGI) of change in PE. In addition, a composite patient-reported outcome (PRO) definition of treatment benefit, comprising increased perceived control over ejaculation and decreased personal distress related to ejaculation, was used to assess treatment benefit. Safety analyses are also reported.

PATIENTS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

Men enrolled in the study were aged ≥18 years; in a stable, monogamous, heterosexual relationship for ≥6 months; and expected to maintain the relationship for the duration of the study. Men were required to meet the DSM-IV-TR criteria for PE, to have had PE for ≥6 months and to have reported at least ‘moderate’ distress or interpersonal difficulty related to their PE at baseline. As noted above, the DSM-IV-TR criteria require an ejaculatory latency that is ‘before, upon, or shortly after penetration’; a threshold IELT was not an inclusion criterion, and IELT was not reported or assessed in this study. Exclusion criteria included the presence of a serious condition that affected overall physical or mental health status, a previous event or condition associated with PE (such as spinal trauma or pelvic surgery), the presence of another sexual dysfunction in the man (such as erectile dysfunction) or his partner, a known allergy to SSRIs, or a history of drug abuse within the past 2 years. Patients were required to limit alcohol consumption to two drinks per day.

This was a 9-week, placebo-controlled, double-blind, parallel-group, randomized clinical trial conducted at 91 centres in the USA and Canada. There were four phases to the trial: pre-randomization (days −7 to −1), double-blind treatment (days 1–62), withdrawal assessment (days 63–69), and follow-up (days 70–84).

During the pre-randomization phase, baseline responses were collected for the Premature Ejaculation Profile (PEP), a validated tool for assessing men with PE that includes items for perceived control over ejaculation, satisfaction with sexual intercourse, and personal distress and interpersonal difficulty related to ejaculation (Table 1) [12]. Analyses of data (published elsewhere [13]) from observational studies in men with and without PE, as well as phase III studies of dapoxetine, showed that the PEP has acceptable reliability, validity and the ability to detect changes in PE, which are requirements of the USA Food and Drug Administration for PRO measures [14]. During the double-blind treatment phase, patients were randomized (2:2:1) to one of three treatment groups: (i) dapoxetine 60 mg once daily and placebo as needed (i.e. ‘dapoxetine once daily’); (ii) dapoxetine 60 mg as needed and placebo once daily (i.e. ‘dapoxetine as needed’); and (iii) placebo once daily and placebo as needed (i.e. placebo). Dosing was carried out in a double-blind, double-dummy fashion: once daily dosing was to occur at the same time each day, in the evening before bedtime; as needed dosing was to occur 1–3 h before intercourse. Patients completed a treatment event log to answer questions for each time they had sexual intercourse. Patients were expected to attempt sexual intercourse at least six times per month. They completed the PEP and reported their PGI of change in PE (Table 1) on days 28 and 63 or at study endpoint.

Table 1.  Outcome measures
Outcome measureDomainQuestionScores and response options
PEPPerceived control over ejaculation‘Over the past month, was your control over ejaculation during sexual intercourse:’0: Very poor 1: Poor 2: Fair
Satisfaction with sexual intercourse‘Over the past month, was your satisfaction with sexual intercourse:’3: Good 4: Very good
Personal distress related to ejaculation‘Over the past month, how distressed were you by how fast you ejaculated during sexual intercourse?’0: Not at all 1: A little bit 2: Moderately
Interpersonal difficulty related to ejaculation‘Over the past month, to what extent did how fast you ejaculated during sexual intercourse cause difficulty in your relationship with your partner?’3: Quite a bit 4: Extremely
PGIChange in PE‘Compared to the start of the study, would you describe your premature ejaculation problem as:’−3: Much worse −2: Worse −1: Slightly worse 0: No change 1: Slightly better 2: Better 3: Much better

Adverse events (AEs) were reported spontaneously by patients when they occurred and were actively solicited by the investigator at each study visit. Safety was also monitored using standard laboratory tests, vital signs, 12-lead electrocardiograms, and at initial dosing, 3-h Holter monitoring and orthostatic vital sign measurements.

At the end of the double-blind treatment phase, patients taking dapoxetine were re-randomized in a double-blind fashion to continue taking the same treatment or to switch to placebo for an additional 7 days, during which withdrawal symptoms were assessed using the 43-item Discontinuation-Emergent Signs and Symptoms checklist [15]. A detailed description of and results from the withdrawal and follow-up phases of this study are presented elsewhere [11].

All efficacy analyses were conducted based on the modified intent-to-treat (MITT) population, defined as patients who took one or more doses of study medication and answered either or both of the perceived control and satisfaction PRO questions at baseline, and at one or more sample times after baseline. Efficacy assessments and analyses were conducted only during the treatment phase. Change from baseline during each treatment period was assessed using an anova model that included factors for treatment group and pooled centre. For PGI of change, the day-63 or the last observed scores were assessed with an anova model that included factors for treatment group and pooled centre. Based on the importance of perceived control over ejaculation and personal distress related to ejaculation in determining PE status [9], patients reporting at least a two-category increase in perceived control over ejaculation and at least a one-category decrease in personal distress related to ejaculation from baseline to study endpoint were evaluated.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

Of 1238 patients enrolled, 1099 (89%) were included in the MITT analysis population; 811 men (66%) completed the treatment phase. The demographic and baseline characteristics were similar for the placebo and dapoxetine ‘as needed’ groups (Table 2). Discontinuation because of AEs during the treatment phase occurred in 2.0% of men who received placebo and 10% of men who received dapoxetine as needed (Table 2; discussed in more detail later).

Table 2.  The demographic characteristics of the patients
CharacteristicPlaceboDapoxetine 60 mg as needed
  • *

    All randomized patients who took at least one dose of study medication and answered the PRO question for perceived control over ejaculation or satisfaction with sexual intercourse at baseline and at least once after baseline.

  • Includes patients who were discontinued from the study because of noncompliance (i.e. not compliant with protocol and/or procedures), insufficient compliance (i.e. missing >20% of doses), use of concomitant medications, and other reasons.

Total, n (%)
 randomized  245 (100.0)   491 (100.0)
 MITT*   221 (90.2)   431 (87.8)
 completed treatment phase  167 (68.2)   313 (63.7)
All randomized patients
Reasons for discontinuation, n (%)
 patient’s request   24 (9.8)   59 (12.0)
 lost to follow-up   32 (13.1)   44 (9.0)
 AE    5 (2.0)   47 (9.6)
 Other   17 (6.9)   28 (5.7)
Mean (sd) age, years 41.8 (9.80) 40.9 (9.71)
Race, n (%)
 White  199 (81.2)  390 (79.4)
 Black   28 (11.4)   62 (12.6)
 Asian    9 (3.7)   22 (4.5)
 Other    9 (3.7)   17 (3.5)
Ethnicity, n (%)
 Hispanic/Latino   16 (6.5)   34 (6.9)
 Non-Hispanic  229 (93.5)  457 (93.1)
Mean (sd)
 height, cm178.3 (7.6)178.4 (7.3)
 weight, kg 90.1 (16.1) 92.4 (18.2)

Men with PE who were treated with dapoxetine reported significant improvements in perceived control over ejaculation and satisfaction with sexual intercourse compared with placebo at study endpoint (P < 0.001 for both; Table 3) and at all sample times after baseline (P < 0.001 for all; data not shown), similar to that reported previously [10]. Although almost no patients in any treatment group rated their perceived control over ejaculation as ‘good’ or ‘very good’ at baseline (dapoxetine as needed, 0.2%; placebo, 0%), 39.7% of patients in the dapoxetine group rated their control over ejaculation as ‘good’ or ‘very good’ at study endpoint (compared with 20.4% with placebo; Fig. 1A). Similarly, only a small percentage of patients rated their satisfaction with sexual intercourse as ‘good’ or ‘very good’ at baseline (dapoxetine 7.9%; placebo 9.5%); by study endpoint, 54.7% of patients who were treated with dapoxetine rated their satisfaction with sexual intercourse as ‘good’ or ‘very good’, compared with only 34.0% of those in the placebo group (Fig. 1B).

Table 3.  Responses to the PEP at study endpoint (MITT population; endpoint based on last observation carried forward after baseline) in patients receiving placebo and dapoxetine
PEP measureTimePlaceboDapoxetine 60 mg as needed
  • *

    P < 0.001 vs placebo.

No. of patients 221431
Mean (sd):
Personal distress related to ejaculation
 Baseline  2.8 (0.82)  2.8 (0.81)
Endpoint  2.0 (1.05)  1.5 (1.05)*
Interpersonal difficulty related to ejaculation
 Baseline  1.8 (1.14)  1.7 (1.06)
Endpoint  1.1 (1.04)  0.8 (1.00)*
Perceived control over ejaculation
 Baseline  0.6 (0.59)  0.6 (0.61)
Endpoint  1.6 (1.02)  2.1 (1.13)*
Satisfaction with sexual intercourse
 Baseline  1.5 (0.79)  1.4 (0.83)
Endpoint  2.0 (1.01)  2.5 (1.11)*
image

Figure 1. Effect of placebo and dapoxetine 60 mg as needed (prn) on (A) perceived control over ejaculation; (B) satisfaction with sexual intercourse; (C) personal distress related to ejaculation; (D) interpersonal difficulty related to ejaculation; (E) PGI of change in PE.

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Patients receiving dapoxetine also had a significantly greater decrease in the mean score for personal distress related to ejaculation at study endpoint than those receiving placebo (Table 3, P < 0.001). At baseline, ≈5% of patients in any treatment group reported that they were ‘not at all’ or only ‘a little bit’ distressed by the timing of their ejaculation (Fig. 1C). By study endpoint, this improved to 54.3% of those receiving dapoxetine, vs 35.3% with placebo (Fig. 1C).

The mean scores for interpersonal difficulty related to ejaculation improved significantly from baseline to study endpoint with dapoxetine as needed compared with placebo (Table 3, P < 0.001). At baseline, 43.0% and 40.9% of men in the placebo and dapoxetine groups, respectively, reported ‘not at all’ or ‘a little bit’ for the level of interpersonal difficulty related to ejaculation (Fig. 1D). At study endpoint, 76.8% of men who received dapoxetine reported ‘not at all’ or ‘a little bit’ of interpersonal difficulty, compared with 64.2% who received placebo (Fig. 1D). Notably, this difference was due largely to the greater percentage of patients who reported ‘not at all’ for the level of interpersonal difficulty related to ejaculation with dapoxetine.

Men reported an improvement in their condition with dapoxetine on the PGI of change in PE measure. At study endpoint, twice as many men reported that their PE was ‘better’ or ‘much better’ with dapoxetine than with placebo (41.3% and 20.8%, respectively; P < 0.001; Fig. 1E).

Previous analyses suggested that perceived control over ejaculation and personal distress related to ejaculation are integral components of PE [7,9] and are important to assessing the condition [16–18]; therefore, changes in these variables might be appropriate indicators of treatment benefit in men with PE. Results from another analysis indicated that the assessment of substantial therapeutic benefit in men being treated for PE could be based on a two-category or greater increase in perceived control over ejaculation, assuming a five-point scale [19]. As shown in Table 4, nearly four-fifths of patients (79.8%) receiving dapoxetine reported at least a one-category increase in perceived control over ejaculation at study endpoint (vs 64.7% with placebo), and more than half (51.0%) reported at least a two-category increase (vs 25.8% with placebo), which would represent, e.g. an improvement in perceived control over ejaculation from ‘very poor’ to at least ‘fair’, or from ‘poor’ to at least ‘good.’ At study endpoint, 74.8% of men receiving dapoxetine reported a one-category or greater decrease in personal distress related to ejaculation (vs 56.1% with placebo; Table 4).

Table 4.  Patients reporting specific improvements in perceived control over ejaculation and personal distress related to ejaculation
Extent of therapeutic responsePlaceboDapoxetine 60 mg as needed
  • *

    432 men.

N221431
n (%):
Perceived control over ejaculation:
≥1 category increase143 (64.7)344 (79.8)
≥2 category increase 57 (25.8)220 (51.0)
Personal distress related to ejaculation:
≥1 category decrease124 (56.1)323 (74.8)*

Because it was shown that both of these factors are integral to PE and personal distress related to ejaculation is the driving force behind treatment-seeking behaviour [20], it might be desirable to evaluate treatment benefit using a composite PRO approach. Improvements in both measures taken together might distinguish patients with a marked treatment benefit from those with lesser degrees of improvement by coupling functional improvement (at least a two-category increase in perceived control over ejaculation) with a reduction in the negative consequences of the condition (at least a one-category decrease in personal distress related to ejaculation; Fig. 2). Approximately twice as many patients reported this degree of benefit with dapoxetine than with placebo (47.6% and 21.7%, respectively; difference vs placebo of 25.9%, 95% CI, 18.3–33.4%; P < 0.001). Most men who met these composite PRO criteria for clinical benefit reported ‘good’ or ‘very good’ perceived control over ejaculation and satisfaction with sexual intercourse (Fig. 3A,B), as well as ‘not at all’ or ‘a little bit’ of personal distress or interpersonal difficulty related to ejaculation (Fig. 3C,D). Furthermore, nearly all patients (>96%) who met these composite criteria reported that their PE had improved from baseline to study endpoint, as assessed by the PGI of change in PE (‘slightly better’, ‘better’, or ‘much better’; Fig. 3E). The distribution of responses to the PEP measures among men who met the composite criteria approached those of men without PE in a USA observational study [12]; in that study, 75.2% and 85.1% of men without PE reported ‘good’ or ‘very good’ perceived control over ejaculation and satisfaction with sexual intercourse, respectively, and 84.8% and 93.9% of men without PE reported ‘not at all’ or ‘a little bit’ of personal distress and interpersonal difficulty related to ejaculation, respectively.

image

Figure 2. Percentage of patients with substantial clinical benefit, based on a composite of a two-category or greater increase in perceived control over ejaculation and a one-category or greater decrease in personal distress related to ejaculation after treatment with dapoxetine 60 mg as needed (prn) or placebo. aP < 0.001.

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image

Figure 3. Response distributions among patients with substantial clinical benefit and others who did not achieve this level of response for (A) perceived control over ejaculation; (B) satisfaction with sexual intercourse; (C) personal distress related to ejaculation; (D) interpersonal difficulty related to ejaculation; (E) PGI of change in PE.

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Treatment-emergent AEs in the double-blind treatment phase were reported by 44.1% and 61.3% of patients who received placebo and dapoxetine as needed, respectively; the AE profile of dapoxetine once daily was similar to that of dapoxetine as needed (data not shown; presented elsewhere [11]). The most frequently reported AEs (≥5%) during the double-blind treatment phase were nausea, dizziness, headache, diarrhoea and insomnia, which were more common with dapoxetine than with placebo (Table 5).

Table 5.  Treatment-emergent AEs reported by ≥2% of patients
AE, n (%)PlaceboDapoxetine 60 mg as needed
N patients245491
Total with AEs108 (44.1)301 (61.3)
Nausea  4 (1.6) 75 (15.3)
Dizziness  7 (2.9) 50 (10.2)
Headache 15 (6.1) 40 (8.1)
Diarrhoea  5 (2.0) 30 (6.1)
Fatigue  7 (2.9) 22 (4.5)
Insomnia  9 (3.7) 32 (6.5)
Orthostatic hypotension  8 (3.3) 22 (4.5)
Somnolence  2 (0.8) 18 (3.7)
Nasopharyngitis  7 (2.9)  6 (1.2)
Dry mouth  7 (2.9) 20 (4.1)
Disturbance in attention  2 (0.8)  7 (1.4)
Blood pressure orthostatic  7 (2.9) 10 (2.0)
Influenza  2 (0.8) 13 (2.6)
Irritability  4 (1.6)  11 (2.2)
Upper respiratory tract infection  9 (3.7) 14 (2.9)
Anxiety  4 (1.6) 12 (2.4)
Erectile dysfunction  6 (2.4)  4 (0.8)
Flushing  0 10 (2.0)

Discontinuation because of AEs was more common with dapoxetine than with placebo (10% and 2%, respectively); the most common AEs that led to discontinuation were nausea and insomnia with dapoxetine as needed, and dizziness, diarrhoea and insomnia with placebo.

Serious AEs were reported during the treatment phase by one patient (0.5%) receiving placebo (optic neuritis secondary to Lyme disease on day 58; led to discontinuation) and two (0.5%) receiving dapoxetine 60 mg as needed (malignant melanoma on day 9; renal cyst on day 14); all of these events were considered unrelated to study drug by the investigators. Serious AEs were reported by seven patients receiving dapoxetine 60 mg once daily; of these, only two had serious AEs that were judged by investigators as related to study drug (syncope, sinus arrest, and sinus bradycardia, each of which resolved spontaneously, after dose on day 1 in both).

Syncope, defined as a sudden temporary loss of consciousness, was reported during the treatment period for two patients receiving dapoxetine as needed (one of whom experienced loss of consciousness) and two receiving dapoxetine once daily. With dapoxetine as needed, both syncopal episodes occurred on day 1, 40 min and 1 h after the first dose of dapoxetine, and were classified as moderate and mild AEs, respectively; both men discontinued the study. Prodromal symptoms included a cold sensation over the entire body, pallor, diaphoresis, weakness and slow heart rate. With dapoxetine once-daily, both syncopal episodes also occurred on day 1, at 40 and 45 min after the first dose of dapoxetine, and were both classified as serious AEs (see previous paragraph); both men discontinued the study. Prodromal symptoms included light-headedness, dizziness, pallor and nausea.

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

Based on the present findings, treatment with dapoxetine significantly improves the condition of men with PE. All outcome measures assessed, including perceived control over ejaculation, satisfaction with sexual intercourse, personal distress related to ejaculation, interpersonal difficulty related to ejaculation, and PGI of change, improved significantly with dapoxetine vs placebo. In addition, a large percentage of men treated with dapoxetine (47.6%) had a composite PRO-defined treatment benefit, based on at least a two-category increase in perceived control over ejaculation and at least a one-category decrease in personal distress related to ejaculation, which was about double that observed with placebo (21.7%). The clinical relevance of this two-fold difference is supported by responses to the PEP measures in these men, which approached those of men without PE from a USA observational study [12]. Furthermore, >96% of these patients reported an improvement in their PE status from baseline to endpoint, as measured by the PGI of change in PE.

This is the first large clinical trial of a treatment for PE to incorporate measures of personal distress and interpersonal difficulty related to ejaculation as specific treatment outcomes, which are criteria included in commonly used definitions of PE, such as the DSM-IV-TR [3] and the new definition proposed by the International Society of Sexual Medicine [21]. Previous smaller studies have used various proxies for ejaculation-related personal distress and interpersonal difficulty. For example, results from a study [22] of 14 men with PE treated with clomipramine showed significant improvements in happiness with the relationship compared with eight men with PE treated with placebo (P value not given). In a separate study [23], treatment with clomipramine resulted in reductions in patient-reported measures of guilt/embarrassment and anger/annoyance in 27 men with PE, although these values were still higher than those of 13 men without PE (P ≤ 0.05 for both). In another study [24], nine men with PE treated with fluoxetine had better PRO scores for happiness with their relationship than 15 men with PE treated with placebo (5.6 vs 4.5, respectively, on a scale of 1–7). In a study [25] of 78 men with PE treated with the phosphodiesterase-5 inhibitor sildenafil, patient-reported measures of sexual relationship satisfaction, sense of control over ejaculation, and enjoyment of sexual intercourse did not change significantly compared with 79 men on placebo. The current study is the largest (1238 men) reported to date to evaluate the effect of treatment on personal distress and interpersonal difficulty related to ejaculation in men with PE. Results from this study are notable because they show not only that dapoxetine 60 mg as needed significantly reduced both forms of distress associated with PE, but also that substantially more patients achieved responses to the PEP measures that approached those of men without PE. These men showed improvements in all measures of the PEP.

Results from previous studies [10] showed that dapoxetine 30 and 60 mg significantly increased the IELT compared with placebo. The present study was designed to further explore other measures of PE, and IELT was not assessed. The treatment effects in the present study are informative for the performance of dapoxetine in the absence of a stopwatch-based diagnosis or outcome assessment, which might not be practical during routine care. In addition, the absence of IELT evaluations might more closely mimic ‘real-world’ use and avoid distracting the patient and his partner by issues related to the stopwatch, as well as a possible bias related to the patient and partner being aware of the patient’s IELT. This study was designed and conducted before recent proposals for a new definition of PE that include a diagnostic threshold for IELT [26], such as those recently proposed by the International Society of Sexual Medicine [21]. The present results for perceived control over ejaculation, satisfaction with sexual intercourse, and PGI of change in PE are similar to those reported in studies that included IELT [10], suggesting that dapoxetine provides benefits in the absence of accompanying stopwatch data.

In conclusion, dapoxetine significantly improved personal distress and interpersonal difficulty related to ejaculation in men with PE, perceived control over ejaculation and satisfaction with sexual intercourse, and the PGI of change in PE measure. Furthermore, twice as many men receiving dapoxetine versus placebo met the composite PRO definition for clinical benefit. When considered together with previously reported results [10], these findings show that dapoxetine is generally well tolerated and significantly improves all variables that assess the different constructs included in the DSM-IV-TR definition of PE.

ACKNOWLEDGEMENTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

This study was funded by Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Raritan, NJ. The authors thank J. McDonough, PhD, of MedErgy for editorial assistance. This study is registered in ClinicalTrials.gov (Identifier: NCT00210613).

CONFLICT OF INTEREST

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES

This study was funded by Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Raritan, NJ, USA. Drs Mudumbi, Tesfaye and Rivas are employees of Johnson & Johnson; Dr Hashmonay was an employee of Johnson & Johnson at the time of the study. Dr Kaufman is an investigator for Johnson & Johnson. Dr Rosen is an investigator/consultant for Johnson & Johnson.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. CONFLICT OF INTEREST
  9. REFERENCES