addiction alcoholism
Conditions
Interventions
Ethanol 10% w/v solution in 5% glucose will be delivered by intravenous
infusion to maintain blood ethanol concentration near 0.60 g/L for 300 minutes.
The target concentration of 0.60 g/L is expect
Sponsors
GlaxoSmithKline
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Healthy as determined by a responsible physician, based on a medical evaluation including medical history, psychiatric history, physical examination including mental status examination, laboratory tests and cardiac monitoring (12-lead ECG). 2. Male or female between 18 and 65 years of age. 3. A female subject is eligible to participate if she is of: * Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol
Exclusion criteria
Exclusion criteria: 1. The subject has a positive pre-study drug/alcohol screen. 2. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening. 3. A history of or findings on evaluation consistent with any Axis I or Axis II disorder as defined in the DSM IV. 4. A positive test for HIV antibody. 5. History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males), or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). 6. The subject has participated in a clinical trial and has received an investigational product within the 90 days prior to the first dosing day in the current study 7. Exposure to more than four new chemical entities within 12 months prior to the first dosing day. 8. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John*s Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication. 9. History of sensitivity to any of the study medications, or components thereof or a history of drug or other clinically significant allergies. 10. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 90 day period. 11. Pregnant females as determined by positive serum or urine beta-hCG test at screening and prior to dosing. 12. Lactating females or those who have lactated in last month. 13. Unwillingness or inability to follow the procedures outlined in the protocol. 14. History of sensitivity to heparin or heparin-induced trombocytopenia. 15. Subjects, who have asthma or a history of asthma, (e.g., for any FTIH where risk of bronchoconstriction is unknown, or compound specific where risk of bronchoconstriction). 16. Subjects who smoke on a daily basis. 17. Consumption of red wine, seville oranges, grapefruit or grapefruit juice [and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices] from 7 days prior to the first dose of study medication. 18. Any subject who is not prepared to eat the standard meals provided by the clinic. 19. Liver function tests (LFT) that are above the laboratory reference range at screening and that remain elevated when repeated.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary: * Safety and tolerability: * Vital Sign measurement * 12 Lead ECG and telemetry during dosing * Safety Laboratory sampling (Clinical Chemistry, Haematology and urinalysis) including Prolactin and lipid measurements. * Adverse Event monitoring. * Barnes Akathisia Scale (BAS) * Simpson-Angus Scale (SAS) * Abnormal Involuntary Movement Scale (AIMS). Pharmacokinetics: Concentrations will be measured at times specified in the study schedule, for the following: * Breath ethanol concentrations (BrAC), * Blood ethanol concentrations, * Main pharmacokinetic parameters of GSK598809 and its metabolite (GSK685249): AUC*, Cmax, Tmax and t*. Pharmacodynamic: * Saccadic eye movements (saccadic reaction time, saccadic peak velocity and saccadic accuracy), to assess sedation, * Smooth pursuit eye movements (percentage of time the subjects eyes are in smooth pursuit of the target), to assess attention and eye movement coordination, * Body sway (antero-posteral sway in mm/2min), to assess body movements in a single plane, providing a measure of postural (in)stability. During sway measurements, subjects will be instructed to keep their eyes closed for two minutes, * Adaptive tracking, to assess visuo-motor control and vigilance, * Visual Verbal Learning Test (VVLT), to assess memory. | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacodynamic/biomarker endpoints: * Saccadic eye movements (saccadic reaction time, saccadic peak velocity and saccadic accuracy), to assess sedation, * Visual Analogue Scales (VAS) according to Bond & Lader to assess mood, alertness and calmness, * Visual Analogue Scales for *alcohol effects* to assess the subjective effects of ethanol (VAS alcohol effects). | — |
Countries
Netherlands
Outcome results
None listed