- Parts A and B: 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 55 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.
- 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 in protocol
- 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.
- Part C: HIV-infected cohort only: CD4 cell count >/ 200 cells/mm3 and plasma HIV-1 RNA >/ 5,000 copies/mL.
- Part C: HIV-infected cohort only: A pre-baseline viral load measurement will be obtained 7-14 days after the screening visit. The pre-baseline viral load must be within 0.7 log of the screening HIV-1 RNA and must meet the screening HIV-1 RNA (i.e., > 5000) requirements for the subject to be included.
- As a result of the medical interview, physical examination, or screening investigations, the Investigator considers the subject unfit for the study.
- 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. NOTE that a positive HIV-1 antibody result is acceptable for those entering the study as a subject infected with HIV-1 (Part C)
- 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.
- 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 GSK1265744 or placebo.
An HIV-infected subject will not be eligible for inclusion in this study if any of the following criteria apply:
- An active Center for Disease Control (CDC) Category C disease [see Appendix 6], except cutaneous Kaposi's sarcoma not requiring systemic therapy during the trial.
- Prior treatment with an integrase inhibitor (>/ 1 dose).
- Serum alanine aminotransferase (ALT) >2 times the upper limit of normal at screening. A single repeat is allowed for eligibility determination.
- Absolute neutrophil counts <1000/uL, hemoglobin <10 g/dL, platelet count <50,000/uL or creatinine clearance <50 mL/minute. A single repeat is allowed for eligibility determination.
- History of clinically relevant pancreatitis or hepatitis within the previous 6 months.
- Treatment with radiation therapy or cytotoxic chemotherapeutic agents within 30 days of study drug administration or anticipated need for such treatment within the study.
- Treatment with immunomodulating agents (such as systemic corticosteroids, interleukins, interferons) or any agent with known anti-HIV activity (such as hydroxyurea or foscarnet) within 30 days of study drug administration
- Treatment with any vaccine within 30 days prior to receiving study medication.
- The subject has a positive pre-study drug screen including amphetamines, barbiturates, cocaine, or PCP.
- Use of multivitamins or antacids within 7 days prior to the first dose of investigational product.