Pharmacokinetic Study of Cabotegravir Long-acting in Healthy Adult Volunteers

Inclusion Criteria:

- Between 18 and 55 years of age inclusive, at the time of signing the informed consent.

- Healthy as determined by the investigator or medically qualified designee based on a
medical evaluation including medical history, physical examination, laboratory tests
and cardiac monitoring.

- A subject with a clinical abnormality or laboratory parameter(s) which is/are not
specifically listed in the inclusion or exclusion criteria, outside the reference
range for the population being studied may be included only if the investigator in
consultation with the medical monitor agree and document that the finding is unlikely
to introduce additional risk factors and will not interfere with the study procedures.
A single repeat of a procedure or lab parameter is allowed to determine eligibility.

- Body weight >= 40 kilogram (kg) and body mass index (BMI) within the range 18.5 to 35
kg /meter square (inclusive).

- Male or female

- A female subject is eligible to participate if she is pre-menopausal, has an intact
uterus and cervix, AND is not pregnant (as confirmed by a negative human chorionic
gonadotrophin [hCG] test), not lactating, and at least one of the following conditions
applies: a) Non-reproductive potential defined as: Pre-menopausal females with one of
the following: Documented tubal ligation, Documented hysteroscopic tubal occlusion
procedure with follow-up confirmation of bilateral tubal occlusion, Documented
Bilateral Oophorectomy. b)Reproductive potential and agrees to follow one of the
options listed below in the GlaxoSmithKline (GSK) Modified List of Highly Effective
Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) requirements
from 30 days prior to the first dose of study medication and until at least five
terminal half-lives OR until any continuing pharmacologic effect has ended, whichever
is longer (can be up to 66 weeks on study) after the last dose of study medication and
completion of the follow-up visit. Female subjects desiring pregnancy or foresee that
they might wish to become pregnant within 52 weeks of receiving a CAB LA injection
must be excluded. All subjects participating in the study must be counseled on safe
sexual practices including the use of effective barrier methods to minimize risk of
HIV transmission.

- Capable of giving signed informed consent, which includes compliance with the
requirements and restrictions listed in the consent form and in this protocol.

Exclusion Criteria:

- Liver Function: ALT or AST > upper limit of normal (ULN)

- Total bilirubin >ULN (isolated total bilirubin >ULN is acceptable if total bilirubin
is fractionated and direct bilirubin <35%)

- Current or chronic history of liver disease, or known hepatic or biliary abnormalities
(with the exception of Gilbert's syndrome or asymptomatic gallstones).

- Corrected QT (QTc) Interval: QTc > 450 milliseconds (msec):

NOTES: The QTc is the QT interval corrected for heart rate according to Bazette's formula
(QTcB), machine-read or manually over-read. QTcB will be used to determine eligibility for
an individual subject. Exclusion criteria for screening electrocardiogram (ECG) (a single
repeat is allowed for eligibility determination): Heart rate (<45 and >100 beats per minute
(bpm) for males and <50 and >100 bpm for females; QRS duration: >120 msec; QTc interval:
>450 msec for males and females

- The subject's systolic blood pressure is outside the range of 90-140 millimeter (mm)
mercury (Hg), or diastolic blood pressure is outside the range of 45-90 mmHg.

- History of clinically significant cardiovascular disease including:

Evidence of previous myocardial infarction (pathologic Q waves, S-T segment changes (except
early repolarization); 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; Any conduction
abnormality (including but not specific to left or right complete bundle branch block, AV
block (2nd degree [type II] or higher), Wolf Parkinson White [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 (>=3 consecutive ventricular ectopic beats) or sustained ventricular
tachycardia.

- History of ongoing or clinically relevant seizure disorder within the previous 2
years, including subjects who have required treatment for seizures within this time
period. A prior history of seizure, with a seizure free period of at least 2 years,
off anti-epileptics, 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

- Use of any concurrent prohibited medications as outlined in protocol

- History of regular alcohol consumption within 6 months of the study defined as: An
average weekly intake of >14 drinks for males or >7 drinks for females. One drink is
equivalent to 12 gram (g) of alcohol: 12 ounces (360 milliliter [mL]) of beer, 5
ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.

- Inability or unwillingness to comply with lifestyle and/or dietary restrictions
outlined in protocol.

- High-risk behavior for HIV infection which includes, but is not limited to, one of the
following risk factors within six months before entering the study (Day 1 of the oral
lead-in): Unprotected vaginal or anal sex with a known HIV infected person or a casual
partner, engaged in sex work for money or drugs, acquired a sexually transmitted
disease, high risk partner currently or in the previous six months or intravenous drug
use.

- 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 Medical
Monitor, contraindicates their participation.

- For subjects participating in magnetic resonance imaging (MRI) imaging:
Contraindication for MRI scanning (as assessed by local MRI safety questionnaire),
which includes but is not limited to: a) Intracranial aneurysm clips (except Sugita)
or other non-MRI compatible metallic objects; b) Intra- orbital metal fragments that
have not been removed by a medical professional; c) Pacemakers or other implanted
cardiac rhythm management devices and non-MRI compatible heart valves, d) Inner ear
implants, e) History of claustrophobia

- Positive hepatitis B surface antigen or positive hepatitis B core antibody with
negative hepatitis B surface antibody test result at screening or within 3 months
prior to first dose of study treatment.

- Positive hepatitis C antibody test result at screening or within 3 months prior to
first dose of study treatment

- A positive pre-study drug/alcohol screen. A positive drug screen is permitted if due
to a prescribed medication, provided that medication is not on the list of prohibited
medications and approved by the investigator and medical monitor.

- A positive test for HIV antibody.

- A positive pre-study screen for sexually transmitted diseases including Neisseria
gonorrhea or Chlamydia trachomatis, Trichomonas, syphilis, or an active Herpes simplex
virus (HSV) genital lesion.

- Presence of a tattoo or other dermatological condition overlying the buttocks which in
the opinion of the investigator may interfere with the interpretation of injection
site reactions.

- 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).

- Exposure to more than four new chemical entities within 12 months prior to the first
dosing day.

- Where participation in the study would result in donation of blood or blood products
in excess of 500 mL within a 56 day period.

- Unwillingness or inability to follow the procedures outlined in the protocol.

- Subject is mentally or legally incapacitated.

Additional Criteria for Female Subjects Only:

- Any current medical conditions that in the opinion of the investigator may compromise
the conduct or analysis of the genital tract sampling (e.g., active genital tract
infection or lesions).

- Inability to abstain from the use of intravaginal products (e.g. tampons, spermicides,
lubricants, vaginal hygiene products, diaphragms) for 72 hours prior to the genital
tract sample collection visits and for up to 72 hours after.

- Inability to abstain from any sexual activity (e.g., vaginal intercourse,
masturbation, and penetration of the vagina by penises, fingers, tampons, sex toys)
for 72 hours prior to the genital tract sample collection visits and for up to 72
hours after.

Additional Criteria for Male Subjects and Female Subjects who consent to rectal PK
sampling:

- Any current medical conditions that in the opinion of the investigator may compromise
the conduct or analysis of the rectal compartment sampling (e.g., active rectal
compartment infection, lesions or disease).

- Inability to abstain from the use of intrarectal products (e.g., suppositories,
lubricants) for 72 hours prior to the rectal compartment sample collection visits and
for up to 72 hours after.

- Inability to abstain from any receptive anal sexual activity (e.g., anal receptive
intercourse and penetration of the rectum by fingers, sex toys or other) for 72 hours
prior to the rectal compartment sample collection visit and for up to 72 hours after.