A Study To Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Two Oral Doses of GSK557296 in a Study in Men With Premature Ejaculation

Inclusion Criteria

• Males with primary PE, according to the ISSM Consensus Definition. Defined as, a male sexual dysfunction characterized by ejaculation which always or nearly always occurs prior to or within about one minute of vaginal penetration; and, inability to delay ejaculation on all or nearly all vaginal penetrations; and, negative personal consequences, such as distress, bother, frustration and/or the avoidance of sexual intimacy
• Stable heterosexual relationship, with a single non pregnant, nonlactating female partner using adequate contraception (as confirmed by oral questioning of male study subject) in a relationship of greater than >4 months duration. This same partner will be the one with whom the subject makes and records all IELT attempts during the duration of the study.
• Aged between 18 and 50 years (i.e. subjects must not have completed their 50th year birthday at the time of screening, but can turn 50 years during the course of the study).
• The subject must make at least four attempts at sexual intercourse on four separate days during the untreated run in period.
• The average intravaginal ejaculatory latency time must be 3 seconds, non-sustained ventricular tachycardia (3 consecutive ectopic beats), sustained ventricular tachycardia (30 consecutive ectopic beats), sustained supraventricular tachycardia (30 consecutive ectopic beats), accessory pathway tachycardia, bradycardia (heart rate 450msec at screening visit (Visit 1) using the Bazett formula.
• Mean systolic cuff BP > 140 mmHg, as assessed by three measurements taken in sequence within 5-10ming of last measure. Taken with the study subject in a supine position at the screening visit (Visit 1).
• Mean diastolic cuff BP >90 mmHg, as assess by three measurements taken in sequence within 5-10 minutes of the last measure. Taken with the study subject in a supine position at the screening visit (Visit 1).
• History of malignancy within the past five years (other than squamous or basal cell skin cancer).
• Any condition which would preclude sexual activity.

Concomitant Medications

• No concomitant medications maybe used within 7 days of Visit 1 and or at any time during the study including oral medications, vacuum devices, constrictive devices, injections, urethral suppositories, gels, any over-the-counter herbal or non-prescription medications, and products purchased via the internet or mail order pharmacies. During the course of the study concomitant medication use can be considered upon consultation and prior agreement with primary investigator and medical monitor. Specific exceptions for asthmatic patients and patients with allergic rhinitis, who are on stable doses of inhaled or intra nasal agents as prescribed by their health care providers, and who have had no adjustments in their prescribed and or actual use within the last 60 days. Agents which are known or expected to have significant systemic exposures as a result of inhaled or intra-nasal use or to have known CYP3A4 drug-drug interaction potential are not included in this exemption.
• Subjects who have received any investigational drug (including placebo) within 30 days of the screening visit or 5 half lives of the investigational drug whichever is longer (Visit 1).

Abnormal Laboratory Values

• Subjects who have a serum total testosterone level >25% below the lower limit of normal according to the range of the testing laboratory, when obtained in the morning versus in the afternoon, from screening lab which will need to be evaluated prior to randomization.
• Subjects with a clinically significant elevation of serum creatinine of > 2.0 when obtained from a screening lab which will need to be evaluated prior to randomization.
• Subject with a clinically significant elevation of AST of > 126 and/or ALT of > 144 when obtained from a screening lab which will need to be evaluated prior to randomization.
• Screening PSA > 4.0 ng/ml
• TSH outside the normal reference ra