Study to Compare the Safety and Anti-HIV Effect of GSK1265744 Versus Placebo in HIV-1 Infected Adults (ITZ112929)
Condition: Infection, Human Immunodeficiency Virus
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Intervention: GSK1265744 30mg; Placebo; GSK1265744 5mg
Intervention description: GSK1265744 30 mg; Placebo to match GSK1265744; GSK1265744 5mg
Intervention MeSH terms: Cabotegravir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: HIV; naive; Phase II; integrase inhibitor; GSK1265744; newly diagnosed; pharmacokinetics; AIDS; integrase; HIV Infections; Treatment naive

Summary:

      The purpose of this randomized, double-blinded study is to test the safety of GSK1265744 and
      how well it works on reducing the amount of HIV in the blood. It will also look at how people
      react to and how a human body uses GSK1265744. This study will compare the effects of
      GSK1265744 and placebo.

      The study will consist of 1 or 2 parts to look at doses of GSK1265744. About 8 people will
      take part in Part 1 of the study receiving dose A. If additional dosing information is needed
      after Part 1, about 6 people will take part in Part 2 of the study receiving dose B.
    

Eligibility criteria:

        Inclusion Criteria:

        A subject will be eligible for inclusion in this study only if all of the following
        criteria apply:

          -  Male or female between 18 and 65 years of age inclusive, at the time of signing the
             informed consent.

          -  A female subject is eligible to participate if she is of non-childbearing potential,
             defined as:

          -  Pre-menopausal females with a documented bilateral oophorectomy, tubal ligation or
             hysterectomy; or

          -  Postmenopausal defined as 12 months of spontaneous amenorrhea. A follicle stimulating
             hormone level will be performed to confirm post-menopausal status. For this study, FSH
             levels > 40 MlU/ml and estradiol < 40 pg/ml (<140 pmol/L) is confirmatory.

          -  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.

          -  CD4+ cell count greater than or equal to 200 cells/mm3 and plasma HIV-1 RNA greater
             than or equal to 5000 copies/mL at Screening.

          -  No current antiretroviral therapy and have not received any in the 12 weeks prior to
             first dose.

          -  For subjects who have received antiretroviral treatment in the past, adequate
             treatment options to construct HAART therapy with at least 3 active antiretrovirals
             for Optimized Therapy, as selected by the Investigator.

          -  Capable of giving written informed consent, which includes compliance with the
             requirements and restrictions listed in the consent form.

        Exclusion Criteria

        A subject will not be eligible for inclusion in this study if any of the following criteria
        apply:

          -  A positive screening Hepatitis B surface antigen; positive screening hepatitis C virus
             (HCV) antibody and detectable HCV ribonucleic acid (RNA) on subsequent testing. If the
             hepatitis C antibody is positive but the HCV RNA is undetectable, the subject may be
             included in the study.

          -  AST and ALT > 3ULN at Screening. A single repeat is allowed for eligibility
             determination.

          -  Inadequate renal function at Screening, defined as either a serum creatinine >1.5
             mg/dL or a calculated creatinine clearance (CrCl) ≤ 50 mL/min. A single repeat serum
             creatinine is allowed to determine eligibility.

          -  Any acute laboratory abnormality at screening which, in the opinion of the
             investigator, should preclude the subject's participation in the study of an
             investigational compound. Any grade 4 laboratory abnormality at screening, with the
             exception of CPK, will exclude a subject from study participation unless the
             investigator can provide a compelling explanation for the laboratory result(s) and has
             the assent of the sponsor. A single repeat is allowed for eligibility determination.

          -  A positive drug screen at screening and baseline. A minimum list of drugs that will be
             screened for include amphetamines, barbiturates, cocaine or PCP.

          -  History of regular alcohol consumption, defined as an average weekly intake of >14
             drinks for males or >7 drinks for females, within 6 months of Screening.

        Note: One drink is equivalent to 12 g of alcohol: 12 ounces (360 ml) of beer, 5 ounces (150
        ml) of wine or 1.5 ounces (45 ml) of 80 proof distilled spirits.

          -  Any condition (including alcohol or drug abuse) which, in the opinion of the
             investigator, could interfere with the subject's ability to comply with the dosing
             schedule and protocol evaluations or which might compromise the safety of the subject.

          -  Prior treatment with an integrase inhibitor (greater than or equal to 1 dose).

          -  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.

          -  An active Center for Disease Control and Prevention (CDC) Category C disease, except
             cutaneous Kaposi's sarcoma not requiring systemic therapy during the trial.

          -  Pregnant females as determined by positive serum or urine hCG test at screening or
             prior to dosing.

          -  Lactating females.

          -  Use of multivitamins or antacids within 24 hours prior to the first dose of
             investigational product.

          -  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 medications refer to GSK1265744 or placebo.

          -  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).

          -  Where participation in the study would result in donation of blood or blood products
             in excess of 500 mL within a 56 day period.

          -  History of clinically relevant pancreatitis or hepatitis within the previous 6 months.

          -  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.

          -  Exclusion Criteria for Screening ECG (A single repeat is allowed for eligibility
             determination):

        Exclusion Criteria for Screening ECG:

        Males Females Heart rate <45 and >100 bpm <50 and >100 bpm QRS duration >120 msec >120 msec
        QTc interval (Bazett) > 450 msec > 450 msec Non-sustained (≥ 3 consecutive beats) or
        sustained ventricular tachycardia. Sinus Pauses >3 seconds. 2nd degree (Type II) or higher
        AV block. Evidence of previous myocardial infarction (pathologic Q waves, S-T segment
        changes (except early repolarization)).