safety, tolerability and pharmacokinetics of gsk1034702 in healthy subjects

Conditions: Cognitive Disorders

Summary: this is a first time in human study to assess the safety, tolerability and pharmacokinetics of single doses of gsk1034702 in healthy subjects. it will be a single-blind, randomized, placebo-controlled, single oral dose, dose-rising, cross-over study in healthy male and female (of non-child bearing potential) subjects. subjects will be randomized into cohorts of 10 subjects and cohorts will be recruited until the pre-defined safety or pk stopping limits are reached. each subject will receive placebo and up to 4 doses of gsk1034702 in a randomized sequence on 5 separate study occasions.


Eligibility criteria:
inclusion criteria: * healthy as determined by a responsible physician, based on a medical evaluation including own and familial medical history, physical examination, laboratory tests and cardiac monitoring. * male or female between 18 and 55 years of age. * a female subject is eligible to participate if she is of non-childbearing potential * body weight \> 50 kg and bmi within the range 19 - 29.9 kg/m2 (inclusive). * capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. * capable of reading, comprehending and writing english at a sufficient level to complete study-related materials. * demonstrates no evidence of mental impairment. * no co-morbid psychiatric disorders as defined using the mini international neuropsychiatric interview exclusion criteria: * a positive pre-study drug/alcohol screen. * a positive pre-study hepatitis b , hepatitis c or hiv. * history of regular alcohol consumption. * the subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). * exposure to more than four new chemical entities within 12 months prior to the first dosing day. * use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements . * history of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy. * where participation in the study would result in donation of blood or blood products in excess of 500 ml within a 56 day period. * pregnant females, females planning pregnancy or lactating females. * unwillingness or inability to follow the procedures outlined in the protocol. * history of sensitivity to heparin or heparin-induced thrombocytopenia. * subjects with a current or a history of psychiatric illness. * subjects with any history of suicidal attempts or behavior. * urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products. * consumption of red wine, seville oranges, grapefruit or grapefruit juice (and pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices) from 7 days prior to the first dose of study medication.

Keywords: schizophrenia m1 receptor agonist safety pharmacokinetics gsk1034702