A Study Of GSK189254 And Duloxetine In The Electrical Hyperalgesia Model Of Healthy Volunteers

Inclusion criteria

• He/she is a healthy subject.
• Women of child bearing potential must have a negative pregnancy test at screening and have undergone, or confirm regular use of one of the following:

Female sterilisation Sterilisation of male partner Practising a clinically accepted method of contraception during the study and for at least one month prior to baseline and one month following completion of the study.

• Has Caucasian skin colour.
• Body weight > 50kg and BMI within the range 18.5 to 29.9kg/m2 inclusive.
• Non smoker.
• Satisfactory pre-study medical within 28 days prior to the start of the study.
• No abnormality on clinical examination
• No abnormality on clinical chemistry or haematology.
• Negative pre-study urine drug screen and cotinine test.
• Signed and dated written informed consent prior to admission to the study.
• The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
• Available to complete the study.

Exclusion criteria

• The subject has a positive pre-study urine drug/alcohol screen. A minimum list of drugs that will be screened for include Amphetamines, Barbiturates, Cocaine, Opiates, Cannabinoids, Methadone and Benzodiazepines.
• The subject has a history of drug or other allergy, that, in the opinion of the responsible physician, contraindicates their participation.
• A positive pre-study Hepatitis B surface antigen, positive Hepatitis C antibody or positive HIV results.
• History of clinically significant psychiatric disease, or presence of depressive disorder as defined by HAD depression score >8, or presence of anxiety disorder as defined by HAD anxiety score >8.

History or presence of insomnia or other sleep disorders.

• A QTcB interval < 430msec (men) or < 450msec (women).
• The subject has donated >500 mls of blood within 56 days prior to the first dose.
• Abuse of alcohol defined as an average daily intake of greater than 3 units for men and 2 units for the women.
• The subject has a history or presence of drug/substance abuse as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria.
• The subject has participated in a study with a new molecular entity during the previous 112 days or any other trial during the previous 84 days.
• The subject is currently taking regular (or a course of) medication whether prescribed or not. Such a subject may be included if the Investigator considers that this does not compromise safety or study procedures.
• Has received prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days or 5 half-lives whichever is the longer, prior to the first dose of study medication
• The subject has a history of chronic pain before screening.
• The subject has ingested or used a topical preparation containing aspirin or other non-steroidal anti-inflammatory drugs or paracetamol or other analgesic medication in the 7 days prior to the screening visit.
• The subject has used any topical steroid in the previous 30 days.
• The subject has used any topical capsaicin preparations on the forearms in the previous 30 days.
• The subject suffers from eczema, psoriasis or any other acute or chronic dermatological problem.
• The subject does not produce an area of allodynia or hyperalgesia to the EH model at screening
• The subject is unable to tolerate the EH model, including anxiety or atypical response to the model.
• The subject has any abnormality on diagnostic EEG at screening, or a history or presence of seizures or risk factors for seizure.
• The subject has any other medical condition that in the opinion of the Investigator would compromise the safety of the subject or the subject's ability to complete the study.