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

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.

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).