GSK2190915A - Bioavailability Study

Inclusion Criteria: INCLUSION CRITERIA FOR COHORTS 1, 2, 3, 5 and 6. A subject will be eligible for inclusion in cohorts 1, 2, 3, 5 and 6 of this study only if all of the following criteria apply: 1. Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase and bilirubin less than or equal to 1.5 times Upper Limit of Normal, ULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35 percent). 2.Healthy as determined by the Investigator, based on a medical evaluation including medical history, physical examination, laboratory tests and Electrocardiogram (ECG). A subject with a clinical abnormality or laboratory parameters 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 to introduce additional risk factors and will not interfere with the study objectives. 3.Male or female (of non child-bearing potential) between 18 and 65 years of age inclusive, at the time of signing the informed consent. A female subject is eligible to participate only if she is of: •Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation (in which case the male partner should use an acceptable form of contraception as specified in section 8.1) or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 million international units, MlU/ml and estradiol less than 40 picogrammes per millilitre (less than 140 picomoles per litre) is confirmatory]. [Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section 8.1 if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.] 4.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 5 terminal half-lives post-last dose. 5.Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. 6.12 lead ECG without any clinically significant abnormality as judged by the Investigator, and QTc intervals corrected for Bazett ror Fredericia (QTcB and QTcF) less than450 milliseconds (msec) 7.Body weight greater than or equal to 50 kilogrammes (kg) (110 pounds, lbs) for men and greater than or equal to 45 kg (99 lbs) for women and Body Mass Index, BMI within the range 18-30 kilogrammes per squared metre (kg/m2) inclusive. 8.Non-smokers only– Negative urine cotinine test at screening, no history of smoking within 6 months of the start of the study, and with a total pack year history of less than or equal to 1 pack years. INCLUSION CRITERIA FOR COHORT 4 A subject will be eligible for inclusion in cohort 4 of this study only if all of the following criteria apply: 1.Healthy as determined by the Investigator, based on a medical evaluation including medical history, physical examination, laboratory tests, ECG and Holter assessment at screening. A subject with a clinical abnormality or laboratory parameter 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 to introduce additional risk factors and will not interfere with the study objectives. A subject with a well controlled or mild medical condition (eg controlled hypertension, hypothyroidism adequately treated with replacement therapy, mild chronic obstructive pulmonary disease (COPD) requiring short acting bronchodilators only) may be included only if the Investigator and the GSK Medical Monitor agree that the condition is unlikely to introduce additional risk factors and will not interfere with the study objectives. 2.Male or female (of non child-bearing potential) over 65 years of age inclusive, at the time of signing the informed consent. A female subject is eligible to participate only if she is of: •Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation (in which case the male partner should use an acceptable form of contraception as specified in section 8.1) or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 million international units, MlU/ml and estradiol less than 40 picogrammes per millilitre (less than 140 picomoles per litre) is confirmatory]. [Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section 8.1 if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.] 3.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 5 terminal half-lives post-last dose. 4.Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. 5.12 lead ECG without any clinically significant abnormality as judged by the Investigator and QTcB and QTcF less than 450 msec 6.Body weight greater than or equal to 50 kg (110 lbs) for men and greater than or equal to 45 kg (99lbs) for women and BMI within the range 18-35 kg/m2 inclusive. 7.For non-smokers only