PSD502 in Subjects With Premature Ejaculation

Study Overview
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Brief Summary
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This study is being done to test the effect of PSD502 (the study medication) compared to placebo in subjects with premature ejaculation. PSD502 is a topical (applied to skin) anesthetic spray containing a mixture of two drugs called lidocaine and prilocaine that will be applied to the penis. Half of the subjects will receive PSD502 and half will receive placebo.

Detailed Description
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The study will assess whether the bothersome symptoms of premature ejaculation (PE) are helped when treated with PSD502 by answering questionnaires such as the 'Premature Ejaculation Bothersome Evaluation Questionnaire' (PEBEQ) and 'Index of Premature Ejaculation© (IPE) and some additional questions about premature ejaculation. The study will also measure the effect of PSD502 on the Intravaginal Ejaculatory Latency Time (IELT). This is the time between when the penis enters the vagina and when the subject starts to ejaculate in the vagina. Subjects are stratified based on whether they are circumcised or uncircumcised and within each stratified group subjects are randomized to PSD502 (lidocaine prilocaine spray) or placebo in a 1:1 ratio.

Official Title
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A Pilot Multicenter, Randomized, Double-Blind Study Comparing The Proportion Of Responders to PSD502 and to Placebo Using the PEBEQ In Subjects With Premature Ejaculation

Conditions
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Premature Ejaculation

Intervention / Treatment
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* Drug: Placebo
* Drug: PSD502


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to provide written informed consent. Male and aged 18 years and over. Diagnosed with PE according to the ISSM definition, that is, he ejaculates always or nearly always prior to or within about one minute of vaginal penetration; and is unable to delay ejaculation on all or nearly all vaginal penetrations; and experiences negative personal consequences, such as distress, bother, frustration and/or the avoidance of sexual intimacy. Subject has lifelong PE from the first sexual experience. Subject must be in a stable heterosexual and monogamous relationship of at least 3 months' duration with this partner. Subject has at least documented 3 sexual encounters, each separated by an interval of at least 24 hours, in the baseline period. IELT ≤1 minute in all sexual encounters in the baseline period. The subject's partner must provide written informed consent, be aged 18 years or over and willing to comply with the study procedures. Subject indicates a level of Bother on Item 3 of the PEBEQ of either moderately, quite a bit or extremely on all encounters during the baseline period. Subject registers a level of bother at a score of 4 or greater on an 11-point NRS scale at Screening to ensure that subjects not bothered by the quickness of their ejaculation are not entered into the baseline period. Exclusion Criteria: Subject, or his sexual partner, has received an investigational (unapproved) drug within 30 days of Screening. Subject has erectile dysfunction, defined as an IIEF-5 score of 21, unless the low score is entirely related to PE symptoms in the opinion of the Investigator. The subject, or his sexual partner, has a physical or psychological condition that would prevent them from undertaking the study procedures, including, but not limited to, the following: Urological disease (e.g., prostatitis, urinary tract infection) or genitourinary surgery within 8 weeks of Screening. Ongoing significant psychiatric disorder (e.g., bipolar disease, depression / anxiety disorder or schizophrenia) not controlled by medication. Subject has safety testing abnormalities at the Screening Visit, in particular liver function tests or anemia, that are indicative of a medical condition that would preclude further participation in the opinion of the Investigator. Subjects taking tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs) or selective serotonin reuptake inhibitors (SSRIs), for indications other than PE, where the dose has been changed within 4 weeks of Screening or it is planned that the dose will change during the treatment period. Subject has received any treatment for PE e.g., anti-depressant therapy, local anesthetic spray, eutectic mixture of local anesthetics (EMLA®) cream, intra-cavernosal injection, tramadol or psychotherapy within 4 weeks of Screening Subject, or his sexual partner, has a current history of alcohol or drug abuse, in the opinion of the Investigator. The subject, or his sexual partner, is unlikely to understand or be able to comply with study procedures, for whatever reasons. Subject, or his sexual partner, has known drug sensitivity to amide-type local anesthetics. Subjects with pregnant partners. Subject with sexual partners of child-bearing potential and not using appropriate contraception (hormonal contraception or intra-uterine device [IUD]). Subject, or his sexual partner, has a history of glucose-6-phosphate dehydrogenase (G 6 PD) deficiency or currently using medications that would increase susceptibility to methemoglobinemia (e.g., anti-malarial agents) or has congenital or acquired methemoglobinemia, or is at risk of industrial exposure to agents causing methemoglobinemia. Subject, or his sexual partner, uses Class I (e.g., mexiletine, tocainide) or III (e.g., amiodarone, sotalol) anti-arrhythmic drugs, or cimetidine, beta blockers or local anesthetics. Subject has received PSD502 in a clinical study or has received Fortacin within 1 year of Screening.

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: PSD502<br>PSD502 spray contains a eutectic-like mixture of lidocaine and prilocaine, and a propellant (norflurane) which also serves as a solvent. Each spray contains 7.5 mg lidocaine and 2.5 mg prilocaine. A single dose consists of 3 sprays applied to the glans penis. | Drug: PSD502<br>* For each sexual encounter during the 4-week treatment period the study spray will be applied 5 minutes before intercourse and any excess will be wiped off prior to penetration. Study subjects should leave at least 24 hours between each dosing.<br>|
| Placebo Comparator: Placebo<br>The placebo is a metered dose spray, identical in appearance to the active treatment and contains the same propellant (norflurane) but has no lidocaine or prilocaine (instead it contains PEG600 and Povidone). | Drug: Placebo<br>* For each sexual encounter during the 4-week treatment period the study spray will be applied 5 minutes before intercourse and any excess will be wiped off prior to penetration. Study subjects should leave at least 24 hours between each dosing.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change between Baseline and 4 weeks : Success on the Premature Ejaculation Bothersome Evaluation Questionnaire PEBEQ Item 3 (event-specific bother) | Success is defined as having a 1-point or greater improvement between the mean response over the treatment period and the mean response during the baseline period | Baseline and 4 week treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Global Impression of Change | Patient-reported global impression of change in the quickness of their ejaculation. Subjects will be asked to provide a response to the question 'Compared to when you started the study, how would you describe any change in how quickly you ejaculate now?' on a 7-point scale of: 'A great deal better', 'Moderately better', 'A little better', 'About the same', 'A little worse', 'Moderately worse' and 'A great deal worse'. Subjects will also be asked to provide a 'Yes' or 'No' response to the question 'Was this a meaningful or important change for you?' | 4 weeks post treatment | 
| Patient Global Impression of Severity | Change from baseline in patient-reported impression of severity of the quickness of their ejaculation.Subjects will be asked to answer the question 'Overall, how severe is the quickness of your ejaculation?' using a 5-point scale of 'Not Severe', 'Mildly Severe', 'Moderately Severe', 'Very Severe' and 'Extremely Severe'. | Baseline and 4 week treatment period | 
| Patient Global Impression of Change-Bother | Patient-reported global impression of change in the bother resulting from the quickness of their ejaculation. Subjects will be asked to provide a response to the following question 'Compared to when you started the study, how would you describe any change in how much you are bothered by the quickness of your ejaculation now?' on a 7-point scale of: 'Bothered a great deal less', 'Bothered moderately less', 'Bothered a little less', 'Bothered about the same', 'Bothered a little worse', 'Bothered moderately worse' and 'Bothered a great deal worse'. Subjects will also be asked to provide a 'Yes' or 'No' response to the question 'Was this a meaningful or important change for you?'. | 4 weeks post treatment | 
| Intravaginal ejaculatory latency time | Change from baseline in intravaginal ejaculatory latency time | Baseline and 4 week treatment period | 
| Independent Ejaculation Quickness Item | Change from baseline in patient-reported impression of how quickly they ejaculated during each attempt of sexual intercourse | Baseline and 4 week treatment period | 
| Index of Premature Ejaculation Control Domain Score | Change from baseline in the Index of Premature Ejaculation Control Domain Score. The domain is based on 4 items (score range 4-20). Low scores represent a worse value. | 4 weeks post treatment | 
| Index of Premature Ejaculation Distress Domain Score | Change from baseline in the Index of Premature Ejaculation Distress Domain Score. The domain is based on two items (score range 2-10). Low scores represent a worse value. | 4 weeks post treatment | 
| Index of Premature Ejaculation Satisfaction Domain Score | Change from baseline in the Index of Premature Ejaculation Satisfaction Domain Score. The domain is based on 4 items (score range 4-20). Low scores represent a worse value. | 4 weeks post treatment | 
| Independent Numeric Response Scale Bother Item | Change from baseline in patient-reported assessment of bother during each attempt of sexual intercourse | Baseline and 4 week treatment period | 
| Psychometric properties of the Premature Ejaculation Bothersome Evaluation Questionnaire Item 3 (event-specific bother) | Patient-reported impression of how bothered they were by how quickly they ejaculated during each attempt of sexual intercourse. Subjects will be asked to provide a response to the question 'How bothered were you by how quickly you ejaculated during the sexual intercourse you just engaged in?' on a 5-point scale of 'Not at All', 'A Little Bit', 'Moderately', 'Quite a Bit' and 'Extremely' | 4 weeks post treatment |