This is a repeat dose escalation study of GSK1349572 followed by a relative bioavailability
study comparing tablet and suspension formulations in healthy volunteers.
ING111322: A Double-Blind, Randomized, Placebo-Controlled, Repeat Dose Escalation Study to
Investigate the Safety, Tolerability and Pharmacokinetics of GSK1349572 Followed by A Single
Dose, Randomized, 3-Period, Balanced, Crossover Study to Assess the Relative Bioavailability
of Two Formulations and Food Effect on GSK1349572 in Healthy Male and Female Subjects
- Healthy as determined by a responsible physician, based on a medical evaluation
including medical history, physical examination, laboratory tests and cardiac
monitoring. 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) including any female who:
- Is pre-menopausal with a documented bilateral tubal ligation, bilateral
oophorectomy (removal of the ovaries) or hysterectomy, or
- Is post-menopausal defined as 12 months of spontaneous amenorrhea. A follicle
stimulating hormone (FSH) level will be performed to confirm a post-menopausal
status. For this study, FSH levels > 40 mlU/ml is confirmatory. Females on
hormone replacement therapy (HRT) and whose menopausal status is in doubt, HRT
should be discontinued for 2 weeks and then the subject rescreened, as HRT can
- Male subjects must agree to use one of the contraception methods listed in protocol.
This criterion must be followed from the time of the first dose of study medication
until 14 days after the last dose of study medication.
- Body weight >/ 50 kg for men and >/ 45 kg for women and BMI within the range
18.5-31.0 kg/m2 (inclusive).
- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.
- The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs
that will be screened for include amphetamines, barbiturates, cocaine, opiates,
cannabinoids and benzodiazepines.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening.
- A positive test for HIV antibody.
- History of regular alcohol consumption within 6 months of the study defined as:
- 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 effect of the
investigational product (whichever is longer).
- 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, unless in the opinion of the Investigator and GSK Medical
Monitor the medication will not interfere with the study procedures or compromise
- 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 GSK
Medical Monitor, contraindicates their participation.
- Where participation in the study would result in donation of blood or blood products
in excess of 500 mL within a 56 day period.
- Pregnant females as determined by positive serum or urine hCG test at screening or
prior to dosing.
- Lactating females.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- If heparin is used during PK sampling, subjects with a history of sensitivity to
heparin or heparin-induced thrombocytopenia should not be enrolled.
- Has a history or regular use of tobacco- or nicotine-containing products within 3
months prior to screening.
- Consumption of red wine, seville oranges, grapefruit or grapefruit juice from 7 days
prior to the first dose of study medication.
- 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.
- screening ECG within protocol parameters (a single repeat is allowed for eligibility
determination):• Evidence of previous myocardial infarction (Does not include ST
segment changes associated with repolarization).
- Any conduction abnormality (including but not specific to left or right complete
bundle branch block, AV block [2nd degree or higher], WPW syndrome).
- Sinus Pauses > 3 seconds.
- Any significant arrhythmia which, in the opinion of the principal investigator and
GSK medical monitor, will interfere with the safety for the individual subject.
- Non-sustained or sustained ventricular tachycardia (3 consecutive ventricular ectopic
- 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.
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), direct bilirubin or
creatinine values greater than the upper limit of normal. A single repeat is allowed
for eligibility determination.
- History of significant renal or hepatic diseases.