A Safety, Tolerability, Acceptability, and Pharmacokinetic (PK) Study of Cabotegravir (CAB) in Healthy Human Immunodeficiency Virus (HIV)-Uninfected Chinese Men
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: Oral CAB; CAB LA
Intervention description: CAB tablet will be formulated as white to almost white, oval shaped, film coated 30 mg tablets, administered orally once daily. The CAB tablets will be packaged in bottles containing 30 tablets each.; CAB LA is a sterile white to slightly colored suspension containing 200 mg/mL of CAB as free acid for administration by IM injection in gluteus medius.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Eligible subjects will receive oral doses of CAB for 4 weeks followed by IM dosing with CAB LA at Week 5, Week 9, Week 17, Week 25 and Week 33.
Masking: None (Open Label)
Masking description: This will be an open-label study; hence, there will be no masking.
Enrollment: 48.0
Sex: Male
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: GSK1265744; Pre-Exposure Prophylaxis; Human immunodeficiency virus; Cabotegravir; Pharmacokinetics

Summary:

      The pre-exposure prophylaxis (PrEP) is an important component in the overall strategy for
      prevention of HIV infection. Cabotegravir (CAB) is an integrase strand transfer inhibitor
      currently in development for treatment and prevention of HIV infection. CAB possesses
      attributes that allow formulation and delivery as a LA parenteral product. CAB is being
      developed as both oral and long acting (LA) injectable formulations. This study is designed
      to evaluate the PK, safety, tolerability, and acceptability of CAB LA in adult HIV uninfected
      Chinese male subjects at low risk for HIV acquisition. Eligible subjects will receive oral
      CAB during oral phase of the study followed by CAB LA intramuscular (IM) injection during
      injection phase of the study. Approximately 60 subjects will be screened, of which,
      approximately 48 subjects will enter the oral phase and 40 subjects will enter the injection
      phase of the study. The maximum study duration will be approximately 89 weeks including oral
      phase, injection phase and follow-up phase.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects must be 18 to 65 years of age inclusive, at the time of signing the informed
             consent.

          -  Subjects are male at birth.

          -  Subjects who have non-reactive point of care (POC) HIV test and undetectable HIV-1
             ribose nucleic acid (RNA) at screening.

          -  At risk of acquiring HIV, defined as having at least one casual male or female sex
             partner in the past 24 months.

          -  Healthy as determined by a responsible and experienced physician, based on a medical
             evaluation including medical history, physical examination, laboratory tests and
             cardiac monitoring at the time of screening.

          -  Capable of giving written informed consent.

          -  Agree to appropriate use of contraceptive measures during heterosexual intercourse.
             All subjects should be counseled on safer sexual practices including the use and
             benefit/risk of effective barrier methods (example given (e.g.), male condom) to
             reduce the risk of sexually transmitted infections.

          -  Willing to undergo all required study procedures.

        Exclusion Criteria:

          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities
             (with the exception of Gilbert's syndrome or asymptomatic gallstones).

          -  History of the following cardiac diseases: myocardial infarction, congestive heart
             failure, documented hypertrophic cardiomyopathy, sustained ventricular tachycardia.

          -  Active skin disease or disorder (that is [i.e.], infection, inflammation, dermatitis,
             eczema, drug rash, psoriasis, urticaria). Mild cases of localized acne or folliculitis
             or other mild skin condition may not be exclusionary at the discretion of the
             Investigator of Record or Medical Monitor.

          -  Subjects determined by the Investigator to have a high risk of seizures, including
             subjects with an unstable or poorly controlled seizure disorder. A subject with a
             prior history of seizure may be considered for enrolment if the Investigator believes
             the risk of seizure recurrence is low. All cases of prior seizure history should be
             discussed with the Medical Monitor prior to enrolment.

          -  Any medical condition, including psychiatric conditions that in the judgment of the
             investigator would interfere with the subject's ability to complete study procedures.

          -  Subjects who, in the investigator's judgment, poses a significant suicide risk.

          -  Use of antiretroviral (ARV) therapy (e.g., for Post exposure prophylaxis [PEP] or
             PrEP) in the past 30 days.

          -  Use of high dose aspirin or any other anticoagulant or antiplatelet medication that
             would interfere with the ability to receive IM injections.

          -  Assessed by the Investigator of Record or designee as being at "high risk" for HIV
             infection. This may include one or more of the following: the negative partner in an
             HIV serodiscordant couple where the HIV infected partner is not suppressed; men who
             exchange sex for goods or money; men who have engaged in any condomless anal
             intercourse within the past 6 months; men who have had greater than 5 male or female
             sexual partners within the past 6 months; men who have had a sexually transmitted
             disease within the past 6 months; any other behavior assessed by the investigator as
             "high risk".

          -  History of drug or alcohol consumption that in the opinion of the Principal
             Investigator will interfere with study participation.

          -  Ongoing intravenous drug use - episodic use or any use in the past 90 days is
             exclusionary (as assessed by the study investigator).

          -  One or more reactive HIV test results at screening or enrolment, even if HIV infection
             is not confirmed. Negative HIV RNA must also be documented at screening.

          -  Co-enrolment in any other HIV interventional research study (provided by self-report
             or other available documentation) or prior enrolment and receipt of the active arm
             (i.e., NOT a placebo) of a HIV vaccine trial (provided by available documentation).

          -  Any of the following laboratory values during the screening period: positive hepatitis
             C antibody result; positive Hepatitis B surface antigen (HBsAg); hemoglobin <11 grams
             per deciliter (g/dL); absolute neutrophil count <750 cells/ cubic millimeter (mm^3);
             platelet count <=100,000 cells/mm^3; presence of a coagulopathy as defined by an
             international normalized ratio(INR)>1.5 or a partial thromboplastin time (PTT) >45
             seconds; calculated creatinine clearance <60 milliliter/minute (mL/minute) using the
             Cockcroft-Gault equation; a single repeat test is allowed during the screening period
             to verify a result, with the exception of HIV tests.

          -  Subjects with an ALT, alkaline phosphatase or bilirubin >=1.5x Upper limit of normal
             (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and
             direct bilirubin <35 percent).

          -  The subject has a tattoo or other dermatological condition overlying the gluteus
             region which may interfere with interpretation of injection site reactions.