Efficacy, Safety and Tolerability of PSD502 (a Topical Anesthetic) in the Treatment Premature Ejaculation

Phase 2

Completed

Conditions: Premature Ejaculation

Interventions: Drug: PSD502, contains a mixture of lidocaine and prilocaine
Drug: Placebo

Registration Number: NCT00556478

Lead Sponsor: Plethora Solutions Ltd

Brief Summary: The purpose of this study is to evaluate the effectiveness, safety and tolerability of the investigational drug, PSD502 in subjects with premature ejaculation (PE) The study drug, PSD02, is a metered dose (measured dose), topical (applied to the skin surface) anesthetic (numbing) spray containing a mixture of lidocaine and prilocaine. The study drug will be applied in a spray to the penis prior to intercourse in order to decrease sensitivity in an attempt to delay ejaculation.

Detailed Description: Most studies evaluating treatments PE include intravaginal ejaculatory latency time (IELT) in the definition of PE. It has been estimated that PE affects 30-40% of the male population, but is paradoxically a condition for which they are least likely to seek help.

Men with PE exhibit abnormal autonomic reflex pathways for the ejaculatory process. These include lower vibratory threshold to ejaculation, shorter bulbocavernous latency time and higher bulbocavernous evoked potentials. Reducing the heightened sensitivity of the glans penis with topical anesthetics might therefore be a way of improving IELT, without adversely affecting the sensation of ejaculation.

Although IELT is an objective measure of ejaculatory function it does not address the impact of therapy on patients' well being and confidence in their sexual performance, which are important markers of treatment benefit. Therefore, if IELT is used as a sole efficacy measure it may not fully characterise the treatment benefit to the patient. For this reason, a patient reported outcome (PRO) known as the Index of Premature Ejaculation (IPE) will be used in this study in conjunction with IELT to evaluate efficacy. Thus the combination of the objective measure of ejaculatory latency with the PRO of IPE should be able to provide efficacy data which are representative of clinical benefit to the patient.

The use of lidocaine, prilocaine and EMLA® cream as topical anesthetics is well established. Many years of experience of use in large numbers of patients, as well as comprehensive non-clinical safety testing programs for various formulations of lidocaine and prilocaine exist, to support their safety and tolerability. This information, together with the clinical data from 3 studies with PSD502 (ANAE-059-00, PSD502-PE-001, and PSD502-PE-003), suggest that PSD502 may have beneficial effects in reducing penile sensation and prolonging IELT, and its use is unlikely to be associated with significant clinical safety or tolerability concerns.

The aim of this study is to provide additional placebo-controlled efficacy data to establish the clinical utility of PSD502 in the treatment of PE. In addition, long term open-label efficacy and safety data will be collected, to further support the registration package for PSD502 in the indication of treatment of PE.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 256

Inclusion Criteria

Willing and able to provide written informed consent.
Male and aged 18 years and over.
Diagnosed with PE according to DMS-IV criteria and ISSM definition
Diagnosed with lifelong PE
Acceptable response to Baseline PEP
Subject must be in a stable heterosexual and monogamous relationship and the partner must provide consent
Acceptable sexual encounters in the Baseline period.

Exclusion Criteria

Subject, or his sexual partner, has received an investigational (non-registered) drug within 30 days of Screening.
Subject has erectile dysfunction
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
- Ongoing significant psychiatric disorder not controlled by medication.
Subject has safety testing abnormalities at the Screening Visit
Subjects taking excluded medications or receiving any treatment for PE
Subject, or his sexual partner, has a current history of alcohol or drug abuse,
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
Subject, or his sexual partner, has a history of Glucose-6-Phosphate Dehydrogenase (G-6-PD) deficiency or use of medications that would increase susceptibility to methemoglobinemia (e.g. anti-malarial agents).

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Double-Blind Active	PSD502, contains a mixture of lidocaine and prilocaine	Double-blind Phase: Subjects will be randomised to PSD502 respectively if the patient meets all the entry criteria.
Double-Blind Placebo	Placebo	Double-blind Phase: Subjects will be randomised to Placebo respectively if the patient meets all the entry criteria.
Open Label Phase	PSD502, contains a mixture of lidocaine and prilocaine	Subjects will all receive PSD502 if they wish to continue in the trial.

Primary Outcome Measures

Name	Time	Method
Mean Intravaginal Ejaculatory Latency Time (IELT): Change From Baseline to During 3 Month Double Blind-treatment	Baseline to 3 Months	To evaluate efficacy of treatment with PSD502 compared with placebo in subjects with PE as measured by: • change in mean IELT from baseline to during the 3 month double-blind treatment Results provide are ratio (over the 3 months/baseline).
Index of Premature Ejaculation (IPE): Change From Baseline to End of Month 3	Baseline to 3 Months	To Evaluate Efficacy of Treatment With PSD502 Compared With Placebo in Subjects With PE as measured by: • changes in all 3 IPE domains from baseline to month 3 Ejaculatory control scores range from 4 to 20 with a higher score indicating greater ejaculatory control Sexual satisfaction scores range from 4 to 20 with a higher score indicating greater sexual satisfaction Distress scores range from 2 to 10 with a higher score indicating less distress

Secondary Outcome Measures

Name	Time	Method
Percentage of Subjects With Mean Intravaginal Ejaculatory Latency Time (IELT) > 1 Minute and >2 Minutes During the 3 Months of Double-blind Treatment	3 months	Percentage of subjects with mean IELT \> 1 minute and \>2 minutes during the 3 months of double-blind treatment as measured by the proportion of subjects
Change in Mean Intravaginal Ejaculatory Latency Time (IELT) From Baseline to Month 3	3 months	Summary of mean IELT at Baseline and at month 3 during double-blind treatment
Change in the Index of Premature Ejaculation (IPE) Domains of Ejaculatory Control, Distress and Sexual Satisfaction From Baseline to Month 1	1 month	Change in the IPE domains of ejaculatory control, distress and sexual satisfaction from Baseline to month 1. Ejaculatory control scores range from 4 to 20 with a higher score indicating greater ejaculatory control Sexual satisfaction scores range from 4 to 20 with a higher score indicating greater sexual satisfaction Distress scores range from 2 to 10 with a higher score indicating less distress
Subject PEP at Month 1	1 month	Scores for perceived control over ejaculation, personal distress related to ejaculation, satisfaction with sexual intercourse and interpersonal difficulty related to ejaculation based on the subject PEP at month 1. Percentage of subjects with at least a 1 point category improvement in subject PEP domain scores at month 1.
Change in the Index of Premature Ejaculation (IPE) Domains of Ejaculatory Control, Distress and Sexual Satisfaction From Baseline to Month 2	2 months	Change in the IPE domains of ejaculatory control, distress and sexual satisfaction from Baseline to month 2 Ejaculatory control scores range from 4 to 20 with a higher score indicating greater ejaculatory control Sexual satisfaction scores range from 4 to 20 with a higher score indicating greater sexual satisfaction Distress scores range from 2 to 10 with a higher score indicating less distress
Subject Premature Ejaculation Profile (PEP) at Month 2	2 months	Scores for perceived control over ejaculation, personal distress related to ejaculation, satisfaction with sexual intercourse and interpersonal difficulty related to ejaculation based on the subject PEP at month 2. Proportion of subjects with at least a 1 point category improvement in subject PEP domain scores from baseline to month 2.
Subject Premature Ejaculation Profile (PEP) at Month 3	3 months	Scores for perceived control over ejaculation, personal distress related to ejaculation, satisfaction with sexual intercourse and interpersonal difficulty related to ejaculation based on the subject PEP at month 3. Proportion of subjects with at least a 1 point category improvement in subject PEP domain scores from baseline to month 3.
Partner Premature Ejaculation Profile (PEP) at Month 3	3 months	Scores for perceived control over ejaculation, personal distress related to ejaculation, satisfaction with sexual intercourse and interpersonal difficulty related to ejaculation based on the partner PEP at month 3. Proportion of partners with at least a 1 point category improvement in partner PEP domain scores from baseline to month 3.