To determine safety, tolerability and Pharmacokinetics of GSK1247303
- The subject is healthy. Healthy as determined by a responsible physician, based on a
medical evaluation including medical history, physical examination, laboratory tests
and 12-lead 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 procedures.
- Male or female between 18 and 50 years of age.
- A female subject is eligible to participate if she is of non-childbearing potential
(i.e., physiologically incapable of becoming pregnant):
- A male is eligible to enter and participate in the study if he is surgically sterile
OR if he either agrees to abstain from sexual intercourse with a female partner or
agrees to use a condom/spermicide, in addition to having his female partner use
another form of contraception as outlined in Section 8.1.
- Body weight >=50 kg (110 lbs.) for men and >= 45 kg (99 lbs) for women and body mass
index (BMI) within the range 18.5-31.0 kg/m2 (inclusive).
- A signed and dated written informed consent is obtained from the subject or the
subject's legal representative prior to screening.
- Subject must be capable of giving written informed consent, which includes compliance
with the requirements and restrictions listed in the consent form.
- As a result of the medical interview, physical examination, or screening
investigations, the Investigator considers the subject unfit for the study.
- The subject's systolic blood pressure is outside the range of 90-140mmHg, or
diastolic blood pressure is outside the range of 45-90mmHg or heart rate is outside
the range of 50-100bpm for female subjects or 45-100 bpm for male subjects.
- History/evidence of symptomatic arrhythmia, angina/ischemia, coronary artery bypass
grafting surgery or percutaneous transluminal coronary angioplasty or any clinically
significant cardiac disease.
- History/evidence of clinically significant pulmonary disease.
- Has a positive pre-study Hepatitis B surface antigen; positive hepatitis C (HCV)
antibody or detectable HCV ribonucleic acid (RNA); or positive HIV-1 antibody result.
- Has a history of regular alcohol consumption averaging >7 drinks/week for women or
>14 drinks/week for men within 6 months of the screening visit.
Note: 1 drink is equivalent to 12 g alcohol = 5 ounces (150 ml) of wine or 12 ounces (360
ml) of beer or 1.5 ounces (45 ml) of 80 proof distilled spirits.
- Unwilling to abstain from alcohol for 48 hours prior to the start of dosing until
collection of the final pharmacokinetic sample during each treatment period.
- Has a history of regular use of tobacco- or nicotine-containing products within 3
months of the screening visit.
- The subject has a positive pre-study drug and/or alcohol screen.
- Unwilling to refrain from the use of illicit drugs and adhere to other
protocol-stated restrictions while participating in the study.
- The subject has received an investigational drug or participated in any other
research trial within 30 days or 5 half-lives, or twice the duration of the
biological effect of any drug (whichever is longer) prior to the first dose of
current study medication.
- Participation in the study would result in donation of blood in excess of 500 mL
within a 56 day period. Note: This does not include plasma donation.
- History or presence of allergy or intolerance to the study drug or its components or
drugs of its class, or a history of drug or other allergy that, in the opinion of the
physician responsible, contraindicates their participation. In addition, if heparin
is used during PK sampling, subjects with a history of sensitivity to heparin or
heparin-induced thrombocytopenia should not be enrolled. Note: "Study" or
"investigational" drugs include GSK1247303 or placebo.
- Use of prescription or non-prescription drugs, including antacids, vitamins, herbal
and dietary supplements (including St John's Wort and iron supplements) 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, unless in the opinion of the
Investigator and sponsor the medication will not interfere with the study procedures
or compromise subject safety.
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin
values greater than the upper limit of normal. A single repeat is allowed for
- Subjects with a pre-existing condition interfering with normal gastrointestinal
anatomy or motility, hepatic and/or renal function, that could interfere with the
absorption, metabolism, and/or excretion of the study drugs. Subjects with a history
of cholecystectomy should be excluded.
- History of significant renal or hepatic diseases.
- History of Gilbert's syndrome.
- Exclusion Criteria for 24-Hour Screening Holter as per protocol.
- Exclusion criteria for screening ECG as per protocol (a single repeat is allowed for