To compare plasma GSK706769 PK following repeat administration of GSK706769 QD with and
without KALETRA (LPV 400 mg/RTV 100mg) q12h
- 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 females with a documented bilateral tubal ligation, bilateral
oophorectomy (removal of the ovaries), or hysterectomy;
- 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. Following
confirmation of their post-menopausal status, they can resume use of HRT.
- 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 medication.
- Body weight >= 50 kg (110 lbs.) for men and >=45 kg (99 lbs) 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.
- As a result of the medical interview, physical examination, or screening
investigations, the Investigator considers the subject unfit for the study.
- 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.
- Unwilling to refrain from the use of illicit drugs and adhere to other protocol-stated
restrictions while participating in the study.
- 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.
Note: 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.
- 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.
- History or regular use of tobacco- or nicotine-containing products within 3 months
prior to screening.
- History/evidence of symptomatic arrhythmia, angina/ischemia, coronary artery bypass
grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PCTA) or
any clinically significant cardiac disease.
- History/evidence of clinically significant pulmonary disease.
- History of significant renal or hepatic diseases.
- 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.
- 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).
- The subject has received GSK706769 in a previous clinical trial.
- 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. 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 GSK706769 or Kaletra
- Where participation in the study would result in donation of blood or blood products in
excess of 500 mL within a 56 day period.
Note: this does not include plasma donation.
- 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.
- 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.
- Exclusion criteria for screening ECG per protocol.
- Exclusion Criteria for 24-Hour Screening Holter per protocol (conducted only if
telemetry is warranted from findings on telemetry from an ongoing repeat dose study):