Cognitive Disorders
Conditions
Keywords
schizophrenia, M1 receptor agonist, safety, pharmacokinetics, GSK1034702
Brief 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.
Interventions
DRUGGSK1034702
Oral or liquid
DRUGPlacebo
To match GSK1034702
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| •Safety and tolerability determined by adverse events; ECG; Holter; blood pressure, heart rate, respiration rate; clinical laboratory evaluations, pupil size & temperature.•Blood concentrations of GSK1034702. | 20 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Assessment of the Bond-Lader Visual Analogue Scale. | 20 weeks |
| Assessment of exploratory PD markers: neuroendocrine markers, e.g. growth hormone. | 20 weeks |
| Relationship between GSK1034702 plasma concentrations and safety/tolerability or exploratory PD endpoints with selected pharmacodynamic and safety parameters. | 20 weeks |
Countries
United Kingdom
Outcome results
None listed