Positron Emission Tomography (PET) Study to Evaluate Biodistribution of [11C]-GSK2256098 in Healthy Subjects and Idiopathic Pulmonary Arterial Hypertension (PAH) Patients

Exclusion Criteria

• •Presence or history, of any significant or uncontrolled medical condition which in the opinion of the investigator would increase the potential risk to the subject or affect the study outcomes.
• •Previous pulmonary embolus
• •Current or chronic history of intrinsic liver disease, or known hepatic or biliary abnormalities, including coagulation abnormalities (with the exception of Gilbert's syndrome).
• •Established diagnosis of systemic hypertension or known Left Ventricular Hypertrophy (LVH).
• •Estimated GFR \<60 milliliter/minute (mL/min) based on clinical chemistry.
• •Use of prohibited medication as mentioned in protocol.
• •Current smoker or a history of smoking within 6 months of Screening, or a total pack year history of \>5 pack years.
• •\[number of pack years = (number of cigarettes per day/20) x number of years smoked\]
• •Subjects that do not wish to consume alcohol by intravenous (IV) administration for personal reasons.
• •The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include cannabinoids, amphetamines, barbiturates, cocaine and opiates. The detection of drugs (e.g. benzodiazepines, opiates) taken for a legitimate medical purpose would not necessarily be an exclusion to study participation. The detection of alcohol would not be an exclusion at screening but would need to be negative pre-dose and during the study.
• •History of regular alcohol consumption within 6 months of the study defined as:
• •For United Kingdom (UK) sites: an average weekly intake of \>21 units for males or \>14 units for females. One unit is equivalent to 8 gram (g) of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
• •History of sensitivity to heparin or heparin-induced thrombocytopenia.
• •History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
• •Subject with QT duration corrected for heart rate by Fridericia's formula (QTcF) of \>450 milliseconds (msec) (or QTcF of \> 480 msec in subjects with Bundle Branch Block) or other 12-lead electrocardiogram (ECG) abnormalities (with the exception of right bundle-branch block) which, in the opinion of the investigator, is clinically significant (e.g. LVH) in that they may increase safety risk or affect study outcomes.
• •Have donated blood or have taken part in a study of an experimental medicine in the last 3 months, or plan to do so in the 3 months after this study.
• •Have had a serious reaction to any medicine .
• •Unable or unfit to undergo PET scans, or found to be unsuitable for PET scanning in the opinion of the Investigator.
• •History of or suffers from claustrophobia or subject feels unable to lie flat and still on their back for a period of up to 2 hours in the PET/CT scanner.
• •Previous inclusion in a research and/or medical protocol involving nuclear medicine, PET or radiological investigations or occupational exposure resulting in radiation exposure greater than 10 millisievert (mSv) over the past 3 years or greater than 10 mSv in a single year including the proposed study. Clinical exposure from which the subject receives a direct benefit is not included in these calculations
• •Presence of any uncontrolled co-morbid condition (e.g. unstable coronary artery disease or systemic hypertension) which in the opinion of the investigator would increase the potential risk to the subject.
• •Airways or interstitial lung disease, including adult asthma, chronic obstructive pulmonary disease (COPD), emphysema, bronchiectasis, pulmonary fibrosis orchronic thromboembolic disease.
• •Current or chronic history of intrinsic liver disease(with the exception of Gilbert's syndrome).
• •LVH on 2D-Echocardogram in the past 12 months
• •Estimated glomerular filtration rate (GFR) \<40 mL/min based on clinical chemistry.
• •Change in PAH medication within 28 days of scanning.
• •A syncopal episode within 28 days of scanning.
• •Subjects who require continuous oxygen.
• •Use of prohibited medication
• •Current smoker or a history of smoking within 6 months of Screening, or a total pack year history of \>5 pack years.
• •\[number of pack years = (number of cigarettes per day/20) x number of years smoked\]
• •Subjects that do not wish to consume alcohol by IV administration for personal reasons.
• •The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include cannabinoids, amphetamines, barbiturates, cocaine and opiates. The detection of drugs (e.g. benzodiazepines, opiates) taken for a legitimate medical purpose would not necessarily be an exclusion to study participation. The detection of alcohol would not be an exclusion at screening but would need to be negative pre-dose and during the study.
• •History of regular alcohol consumption within 6 months of the study defined as: For UK sites: an average weekly intake of \>21 units for males or \>14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
• •History of sensitivity to heparin or heparin-induced thrombocytopenia.
• •History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
• •Subject with QTcF of \>450 msec (or QTcF of \> 480 msec in subjects with Bundle Branch Block) or other 12-lead ECG abnormalities (with the exception of right bundle-branch block) which, in the opinion of the investigator is clinically significant in that they may increase safety risk.
• •Have donated blood or have taken part in a study of an experimental medicine in the last 3 months, or plan to do so in the 3 months after this study.
• •Have had a serious reaction to any medicine.
• •Unable or unfit to undergo PET scans, or found to be unsuitable for PET scanning in the opinion of the Investigator.
• •History of or suffers from claustrophobia or subject feels unable to lie flat and still on their back for a period of up to 2 hours in the PET/CT scanner.
• •Previous inclusion in a research and/or medical protocol involving nuclear medicine, PET or radiological investigations or occupational exposure resulting in radiation exposure greater than 10 mSv over the past 3 years or greater than 10 mSv in a single year including the proposed study. Clinical exposure from which the subject receives a direct benefit is not included in these calculations.