Clinical trial NCT00659191 (phase 1, status: completed)
Conditions: hiv infection
ICD codes: Z21
Drugs: gsk1265744
SMILES: CC1=CC(=CC(C)=C1OC1=C(Br)C(N)=NC(NC2=CC=C(C=C2)C#N)=N1)C#N
Eligibility criteria:

        Inclusion Criteria:

          -  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.

        Exclusion Criteria:

          -  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.

          -  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 ECG as outlined in protocol.

               -  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 beats).

          -  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 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.

          -  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
             eligibility determination.

          -  History of significant renal or hepatic diseases.

          -  Exclusion Criteria for 24-Hour Screening Holter:

               -  Any symptomatic arrhythmia (except isolated extra systoles).

               -  Sustained cardiac arrhythmias (such as atrial fibrillation or flutter,
                  supraventricular tachycardia (>/10 consecutive beats), complete heart block).

               -  Non-sustained or sustained ventricular tachycardia (defined as >/ 3 consecutive
                  ventricular ectopic beats).

               -  Any conduction abnormality (including but not specific to left or right complete
                  bundle branch block, atrioventricular (AV) block [2nd degree or higher], WPW
                  syndrome etc.).

               -  Sinus Pauses > 3 seconds.

               -  300 or more supraventricular ectopic beats in 24 hours.

               -  250 or more ventricular ectopic beats in 24 hours.

        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.