Clinical trial NCT00556478: Efficacy, Safety and Tolerability of PSD502 (a Topical Anesthetic) in the Treatment Premature Ejaculation
Official title: A Phase IIb, Multi-center, Randomized, Double-blind, Placebo-controlled Study, With Open-label Follow on, to Evaluate the Efficacy, Safety and Tolerability of PSD502 in Subjects With Premature Ejaculation (PE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Premature Ejaculation
Keywords: Premature Ejaculation
Lidocaine
Prilocaine
EMLA® cream
topical anesthetics
Lead sponsor: Plethora Solutions Ltd
Sponsor class: INDUSTRY
Collaborators: name: Shionogi Inc.
First posted: 2007-11-12
Enrollment: 256
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Mean Intravaginal Ejaculatory Latency Time (IELT): Change From Baseline to During 3 Month Double Blind-treatment
timeFrame: Baseline to 3 Months
measure: Index of Premature Ejaculation (IPE): Change From Baseline to End of Month 3
timeFrame: Baseline to 3 Months
Secondary outcomes:
measure: Percentage of Subjects With Mean Intravaginal Ejaculatory Latency Time (IELT) > 1 Minute and >2 Minutes During the 3 Months of Double-blind Treatment
timeFrame: 3 months
measure: Change in Mean Intravaginal Ejaculatory Latency Time (IELT) From Baseline to Month 3
timeFrame: 3 months
measure: Change in the Index of Premature Ejaculation (IPE) Domains of Ejaculatory Control, Distress and Sexual Satisfaction From Baseline to Month 1
timeFrame: 1 month
measure: Subject PEP at Month 1
timeFrame: 1 month
measure: Change in the Index of Premature Ejaculation (IPE) Domains of Ejaculatory Control, Distress and Sexual Satisfaction From Baseline to Month 2
timeFrame: 2 months
measure: Subject Premature Ejaculation Profile (PEP) at Month 2
timeFrame: 2 months
measure: Subject Premature Ejaculation Profile (PEP) at Month 3
timeFrame: 3 months
measure: Partner Premature Ejaculation Profile (PEP) at Month 3
timeFrame: 3 months
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: Department of Urology, University of North Carolina
state: North Carolina
Study officials:
affiliation: University of North Carolina
name: Culley Carson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dinsmore WW, Hackett G, Goldmeier D, Waldinger M, Dean J, Wright P, Callander M, Wylie K, Novak C, Keywood C, Heath P, Wyllie M. Topical eutectic mixture for premature ejaculation (TEMPE): a novel aerosol-delivery form of lidocaine-prilocaine for treating premature ejaculation. BJU Int. 2007 Feb;99(2):369-75. doi: 10.1111/j.1464-410X.2006.06583.x. Epub 2006 Nov 24.
citation: Morales A, Barada J, Wyllie MG. A review of the current status of topical treatments for premature ejaculation. BJU Int. 2007 Sep;100(3):493-501. doi: 10.1111/j.1464-410X.2007.07051.x. Epub 2007 Jul 3.
citation: Henry R, Morales A. Topical lidocaine-prilocaine spray for the treatment of premature ejaculation: a proof of concept study. Int J Impot Res. 2003 Aug;15(4):277-81. doi: 10.1038/sj.ijir.3901011.