Concomitant Use of PriLigy in Men Treated for Erectile Dysfunction

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of dapoxetine compared to placebo in men with premature ejaculation and erectile dysfunction who are currently being treated with a phosphodiesterase-5 inhibitor (ie, sildenafil, vardenafil, or tadalafil) for erectile dysfunction.

Detailed Description
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Premature ejaculation (PE) and erectile dysfunction (ED) are forms of sexual dysfunction in men. An objective measurement of PE in clinical studies is the intravaginal ejaculatory latency time (IELT), which is the time it takes for a man to ejaculate during sexual intercourse (as measured by stopwatch). This is a multicenter, double-blind (neither the physician or the study participant will know the identity of the treatment assigned), randomized (study drug assigned by chance) efficacy and safety study of dapoxetine compared with placebo (a sugar pill) in men with premature ejaculation who are currently being treated for ED with a phosphodiesterase 5 (PDE-5) inhibitor such as sildenafil, vardenafil, or tadalafil. A maximum of 656 men 18 years or older (hereafter referred to as study participants) who have received treatment with a PDE-5 inhibitor for at least 3 months prior to study entry will be enrolled. The study will last approximately 18 weeks and includes a 4-week screening period, a 12-week treatment period, and a follow-up telephone contact approximately 2 weeks after the end of treatment. Both the study participant and his partner will be required to attend the screening visit and to sign an informed consent form documenting that they understand and agree to the requirements for the study. After initial screening procedures are completed, study participants who qualify for the study will enter a 4-week screening period. During the 4 weeks, the study participant and his partner will be provided with a stopwatch to time and record the IELT during all attempts at sexual intercourse. At the next scheduled clinic visit which is Day 1 of the double-blind treatment period, study participants who continue to qualify for the study will be assigned by chance (like flipping a coin) to receive 1 of 2 study treatments (dapoxetine or placebo) for 12 weeks in addition to prescribed treatment with a PDE-5 inhibitor. Study participants will be instructed to take study drug with or without food with at least 1 full glass of water approximately 1 to 3 hours before sexual activity (no more than 1 dose should be taken within a 24-hour period). During the 12-week treatment period, the study participant and his partner will be asked to time and record the IELT during all attempts at sexual intercourse on Treatment Event Logs provided. Study participants will return to the clinic after 4, 8 and 12 weeks of treatment for routine safety assessments (including review of Treatment Event Logs returned) and to be dispensed study drug. Following 12 weeks of treatment (or at the time of early withdrawal from the study) end-of-treatment safety and efficacy evaluations will be performed at the final clinic visit. Approximately 2 weeks later, a follow up telephone call will be made to the study participant to collect information on any adverse events that may have occurred or concomitant therapy received since the time of the last clinic visit. The primary outcome measure in the study is the average IELT, as measured by stopwatch, during sexual intercourse at the end of the treatment period (Week 12). Safety will be monitored during the study by evaluating adverse events, physical examination findings, results from clinical laboratory tests, and concomitant medication usage. An Independent Data Monitoring Committee (IDMC) will be established to monitor the safety and efficacy of study participants during the study. In addition, an interim (preliminary) analysis will be performed during the study to monitor safety and efficacy after approximately 268 men have completed 12 weeks of treatment (also includes any study participants who did not complete treatment and were withdrawn early from the study). Study participants will receive either dapoxetine or matching placebo tablets at a dose of 30 mg prn (as needed) taken orally (by mouth) with or without food with at least 1 full glass of water approximately 1 to 3 hours before sexual activity (not to be taken more than once every 24 hours). At Weeks 4 or 8, the dose of dapoxetine or matching placebo may be increased to a maximum of 60 mg prn if specific predefined criteria are met or be subsequently decreased from 60 to 30 mg at Weeks 4 or 8.

Official Title
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A Prospective, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study of the Efficacy and Safety of Dapoxetine in Men With Premature Ejaculation and Concomitant Erectile Dysfunction Treated With a Phosphodiesterase-5 Inhibitor

Conditions
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Erectile Dysfunction, Sexual Dysfunction

Intervention / Treatment
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* Drug: Placebo
* Drug: Dapoxetine
* Drug: PDE5I (phosphodiesterase-5 inhibitor)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of erectile dysfunction (ED), International Index of Erectile Function (IIEF) score >=21 at screening and baseline, and receiving treatment with a stable regimen of a phosphodiesterase 5 (PDE 5) inhibitor (ie, sildenafil, vardenafil, or tadalafil) for the treatment of ED for at least 3 months before screening Study participant in a stable, monogamous sexual relationship with the same woman for at least 6 months before screening and plan to maintain this relationship for the duration of the study Study participant medically stable (ie, in good general health) on the basis of physical examination, medical history, vital signs, 12 lead ECG, and clinical laboratory tests performed at screening Exclusion Criteria: History suggestive of syncope (a condition characterized by a loss of consciousness) History of medical events such as surgical interventions or neurologic conditions (eg, multiple sclerosis), trauma, or infections that are associated with the development of symptoms of premature ejaculation (PE) and considered a potential cause of PE Current major psychiatric disorder such as mood disorder, anxiety disorder, schizophrenia, mania, suicidal ideation, other psychotic disorder, or alcoholism Known allergy, hypersensitivity, or intolerance to selective serotonin reuptake inhibitors (SSRIs) or selective noradrenaline reuptake inhibitors (SNRIs) Taken another investigational drug (or vaccine) within 30 days or used an investigational medical device within 6 months before screening, or enrolled in another investigational study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dapoxetine + PDE5I<br>Dapoxetine 30 mg to 60 mg tablets 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks + a PDE5I (phosphodiesterase-5 inhibitor) prescribed prior to study entry for the treatment of erectile dysfunction. | Drug: Dapoxetine<br>* 30 mg to 60 mg tablets 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks.<br>Drug: PDE5I (phosphodiesterase-5 inhibitor)<br>* Patients were to be using a stable regimen of a PDE5-I (i.e., sildenafil, vardenafil, or tadalafil), as reported by the patient for the treatment of erectile dysfunction (ED) for at least 3 months before screening and up to 12 weeks during treatment in the study.<br>|
| Placebo Comparator: Placebo + PDE5I<br>Placebo tablets identical in appearance to dapoxetine taken 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks + a PDE5I (phosphodiesterase-5 inhibitor) prescribed prior to study entry for the treatment of erectile dysfunction. | Drug: Placebo<br>* Tablets identical in appearance to dapoxetine taken 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks.<br>Drug: PDE5I (phosphodiesterase-5 inhibitor)<br>* Patients were to be using a stable regimen of a PDE5-I (i.e., sildenafil, vardenafil, or tadalafil), as reported by the patient for the treatment of erectile dysfunction (ED) for at least 3 months before screening and up to 12 weeks during treatment in the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Average Intravaginal Ejaculatory Latency Time (IELT) at Week 12 | The intravaginal ejaculatory latency time (IELT) is the time it takes for a man to ejaculate during sexual intercourse (as measured by stopwatch). The data below show the average IELT measured in minutes at Baseline (before treatment) to Endpoint (after 12 weeks of treatment). In this study, patients took placebo or dapoxetine along with a stable dose of a phosphodiesterase-5 inhibitor (PDE5I) prescribed prior to study entry for the treatment of erectile dysfunction. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Patients Reporting At Least a 2-category Increase in Control Over Ejaculation | The Premature Ejaculation Profile (PEP), a patient-reported outcome measure was used to rate the patient's control over ejaculation on a 5-point scale from Very poor, Poor, Fair, Good, to Very Good. The percentage of patients who reported at least a 2-category increase in control over ejaculation is provided in the table below. | At the end of treatment (Week 12) | 
| The Percentage of Patients Who Achieved 1-category or Greater Decrease (Improvement) in Personal Distress Related to Ejaculation | The Premature Ejaculation Profile (PEP), a patient-reported outcome measure was used to rate the patient's level of distress related to the speed of ejaculation on a 5-point scale from Very poor, Poor, Fair, Good, to Very Good. The percentage of patients who achieved 1-category or greater decrease (improvement) in personal distress related to the speed of ejaculation is provided in the table below. | At Endpoint (After 12 weeks of treatment) | 
| The Percentage of Patients Reporting a Composite Score of At Least a 2-category Increase in Control Over Ejaculation and At Least a 1-category Decrease in Personal Distress | The Premature Ejaculation Profile (PEP), a patient-reported outcome measure was used to rate the patient's level of distress related to the speed of ejaculation and control over ejaculation on a 5-point scale from Very poor, Poor, Fair, Good, to Very Good. The percentage of patients who reported a composite score of at least a 2-category increase in control over ejaculation and at least a 1-category decrease (improvement) in personal distress is provided in the table below. | At the end of treatment (Week 12) | 
| The Percentage of Patients Who Achieved a 1-category or Greater Increase in Satisfaction With Sexual Intercourse | The Premature Ejaculation Profile (PEP), a patient-reported outcome measure was used to rate the patient's level of satisfaction with intercourse on a 5-point scale from Very poor, Poor, Fair, Good, to Very Good. The percentage of patients who achieved 1-category or greater increase in satisfaction with sexual intercourse is provided in the table below. | Endpoint (After 12 weeks of treatment) | 
| The Percentage of Patients Reporting At Least a Better Response to Treatment | The Clinical Global Impression of Change (CGIC) was used to assess the degree of improvement the patient experienced with premature ejaculation (PE) since initiating treatment with study drug on a 7-point scale from Much worse, Worse, Slightly worse, No change, Slightly better, Better, to Much better. The percentage of patients who reported improvement in PE of at least better at Endpoint (after 12 weeks of treatment) is provided in the table below. | Endpoint (After 12 weeks of treatment) | 
| The Percentage of Patients Who Reported At Least a 1-category Decrease (Improvement) in Interpersonal Difficulty Related to Ejaculation | The Premature Ejaculation Profile (PEP), a patient-reported outcome measure was used to rate the patient's level of interpersonal difficulty related to ejaculation on a 5-point scale from Very poor, Poor, Fair, Good, to Very Good. The percentage of patients who reported at least a 1-category decrease (improvement) in interpersonal difficulty related to ejaculation is provided in the table below. | Endpoint (After 12 weeks of treatment) | 
| The Percentage of Patients Reporting At Least a Slightly Better Response to Treatment | The Clinical Global Impression of Change (CGIC) was used to assess the degree of improvement the patient experienced with premature ejaculation (PE) since initiating treatment with study drug on a 7-point scale from Much worse, Worse, Slightly worse, No change, Slightly better, Better, to Much better. The percentage of patients who reported improvement in PE of at least slightly better at Endpoint (after 12 weeks of treatment) is provided in the table below. | Endpoint (After 12 weeks of treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Erectile Dysfunction, Sexual Dysfunction, Dapoxetine hydrochloride, PRILIGY, Premature ejaculation, Serotonin Uptake Inhibitors, Sildenafil (Viagra), Vardenafil (Levitra), Tadalafil (Cialis)