To determine safety, tolerability and Pharmacokinetics of GSK706769
- Healthy as determined by a responsible physician, based on a medical evaluation
including medical history, physical examination, laboratory tests and cardiac
- 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 suppress FSH.
- 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 14 days after the last dose of study medication.
- Body weight ³ 50 kg for men and ³ 45 kg for women and BMI within the range 18.5-31.0
- 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:
- An average weekly intake of >14 drinks/week for men or >7 drinks/week for women. One
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.
- 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. This includes subjects with a history of known or
suspected sulfa related hypersensitivity.
- 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 grapefruit or grapefruit juice from 7 days prior to the first dose of
study medication until the last pharmacokinetic sample.
- 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.
- Exclusion criteria for screening as per protocol.
- 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
- History of significant renal or hepatic diseases.
- Exclusion Criteria for 24-Hour Screening Holter as per protocol.