Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a significant clinical aboonnality or laboratory finding significantly outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely lo introduce additional risk factors and will not interfere with the study integrity.
boolean
C1512693 (UMLS CUI [1])
Inclusion criteria
Item
AST, ALT, alkaline phosphatase and bilirubin =< I .5xULN (isolated bilirubin > I .5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
boolean
C1512693 (UMLS CUI [1])
Inclusion criteria
Item
Male or female between 18 and 50 years of age inclusive, at the time of signing the informed consent. Males between 18 and 50 years of age inclusive, at the time of signing the informed consent will be eligible for the PET portion of the study.
boolean
C1512693 (UMLS CUI [1])
Inclusion criteria
Item
Male subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until 90 days after last dose.
boolean
C1512693 (UMLS CUI [1])
Inclusion criteria
Item
A female subject is eligible to participate if she is: • Of child-bearing potential and agree to use one of the contraception methods listed in Section 8.1 Female subjects currently on oral, patch or depot honnonal contraception must agree to the additional contraceptive measures listed in Section 8.1 Female subjects must agree to use contraception ulllil 90 days after last dose.; • Of non-childbearing potential defined as pre-menopausal females with a documented tuba! ligation or hysterectomy; or postmenopausal defined as at least 12 consecutive months of spontaneous amenorrhea [In questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MIU/ ml and estradiol < 40 pg/ml (< 140 pmol/L) is confinnatory.]. Females on honnone replacement therapy (HRT) and whose menopausal stan1s is in doubt will be required to use one of the contraception methods in Section 8.1.
boolean
C1512693 (UMLS CUI [1])
Inclusion criteria
Item
Body weight=> 50 kg and BMI within the range 19.0 to 30.0 kg/m2 (inclusive).
boolean
C1512693 (UMLS CUI [1])
Inclusion criteria
Item
Capable of giving wrinen infonned consent, which includes compliance with the requirements and restrictions listed in the consent form.
boolean
C1512693 (UMLS CUI [1])
Exclusion Criteria
Item
A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
boolean
C0680251 (UMLS CUI [1])
Exclusion Criteria
Item
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
boolean
C0680251 (UMLS CUI [1])
Exclusion Criteria
Item
The subject has personal or family history of prolonged QTc, a personal history of arrhythmia, a history of sudden unexplained death in a first degree relative, or unexplained syncope in a first degree relative.
boolean
C0680251 (UMLS CUI [1])
Exclusion Criteria
Item
Pulse rate <SO or > I 00 bpm OR a systolic blood pressure > 140 or <95 OR a diastolic blood pressure >90 or <50tnmHg at screening and/or baseline. These maybe repeated af'ter discussion with the GSK medical monitor.
text
C0680251 (UMLS CUI [1])
Exclusion Criteria
Item
A screening ECG with a QTc (QTcB and/or QTcF) value of>450msec or a PR interval outside the range 120 to 200msec or an ECG that is not suitable for QT measurements (e.g. poorly defined termination of the Twave) at screening or baseline. These maybe repeated once after discussion with the GSK medical monitor.
boolean
C0680251 (UMLS CUI [1])
Exclusion Criteria
Item
A positive pre-study drug/alcohol screen.
boolean
C0680251 (UMLS CUI [1])
Exclusion Criteria
Item
A positive test for HIV antibody.
boolean
C0680251 (UMLS CUI [1])
Exclusion Criteria
Item
History of regular alcohol consumption within 6 months of the study defined as: An average weekly i11take of>2 I units for males or > 14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (- 240 ml) of beer, I glass (125 ml) of wine or I (25 ml) measure of spirits.
boolean
C0680251 (UMLS CUI [1])
Exclusion Criteria
Item
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 effoct of the investigational product (whichever is longer).
boolean
C0680251 (UMLS CUI [1])
Exclusion Criteria
Item
Exposure to more than four new chemical entities within 12 months prior to the first dosiug day.
boolean
C0680251 (UMLS CUI [1])
Exclusion Criteria
Item
Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St Johns Wort) within 7 days ( or 14 days if the drug is a potential enzyme inducer) or 5 hali~ lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the stl1dy procedures or compromise subject safety.
boolean
C0680251 (UMLS CUI [1])
Exclusion Criteria
Item
History of sensitivity to any of tbe study medications, or components thereof or a bistory of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
boolean
C0680251 (UMLS CUI [1])
Exclusion Criteria
Item
Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
boolean
C0680251 (UMLS CUI [1])
Exclusion Criteria
Item
Pregnant females as determined by positive serum hCG test at screening or prior to dosing.
boolean
C0680251 (UMLS CUI [1])
Exclusion Criteria
Item
Lactating females or those who were lactating in the month preceding enrolment.
text
C0680251 (UMLS CUI [1])
Exclusion Criteria
Item
Unwillingness or inability to follow the procedures outlined in the protocol.
boolean
C0680251 (UMLS CUI [1])
Exclusion Criteria
Item
Subject is mentally or legally incapacitated.
boolean
C0680251 (UMLS CUI [1])
Exclusion Criteria
Item
Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
boolean
C0680251 (UMLS CUI [1])
Exclusion Criteria
Item
Consumption ofred wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic c itrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication and throughout the duration of the study.
boolean
C0680251 (UMLS CUI [1])
Exclusion Criteria
Item
Subjects, who in the investigator's judgement, pose a significant suicide risk. Evidence of serious suicide risk may include any history of suicidal behavior and/or any suicidal ideation of type 4 or 5 on the C-SSRS in the last 6 months.
boolean
C0680251 (UMLS CUI [1])
Exclusion Criteria
Item
Previous inclusion in a research and/or medical protoco I involving nuclear medicine, PET or radiological investigations with significant radiation burden (a significant radiation burden being defined as ICRP category lib or above i.e. No more than 10 rnSv in addition to the natural background radiation) in the previous 3 years u1cluding the dose from the study.
boolean
C0680251 (UMLS CUI [1])
Exclusion Criteria
Item
History of or suffers from claustrophobia or feels that he will be unable to lie still on his back in the PET camera for a period of 90 minutes.
boolean
C0680251 (UMLS CUI [1])
Exclusion Criteria
Item
History of a neurological/psychiatric diagnosis (not limited to but including for example, stroke, traumatic brain injury, epilepsy, space occupying lesions, multiple sclerosis, Parku1sons disease, vascular dementia, transient ischemic attack, schizophrenia, majo r depressiou etc) that may influence the outcome or analysis of the scan results.
boolean
C0680251 (UMLS CUI [1])
Exclusion Criteria
Item
Presence of a cardiac pacemaker or other electronic device or potential for ferromagnetic metal foreign bodies, such as staples, as assessed by a standard pre- MRI questionnaire.