This study is a single-center, randomized, open-label, two cohorts, 3-way cross-over design
in 36 subjects to assess the oral bioavailability of four new cabotegravir (CAB) sodium salt
tablet formulations relative to the current CAB sodium salt formulation being used in the
phase IIb studies under fasting conditions. All treatments will be administered as single
30 mg doses of CAB. Safety evaluations and serial PK samples will be collected during each
treatment period. A follow-up visit will occur 10 - 14 days after the last dose of study
drug. Treatment period doses will be separated by a 14 day washout. Participation in this
study will be approximately 12 weeks.
- Males and females between 18 and 65 years of age inclusive, at the time of signing
the informed consent.
- Healthy as determined by a responsible and experienced physician, based on a medical
evaluation including medical history, physical examination, laboratory tests and
- Body weight >=50 kilogram (kg) and body mass index (BMI) within the range 18.5 -31.0
kg/ meter square (m^2) (inclusive).
- Male or Female
- Female subject is eligible to participate if she is not pregnant (as confirmed by a
negative serum 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 [for this definition, "documented"
refers to the outcome of the investigator's/designee's review of the subject's
medical history for study eligibility, as obtained via a verbal interview with the
subject or from the subject's medical records]: Documented tubal ligation; Documented
hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral
tubal occlusion; Hysterectomy; Documented Bilateral Oophorectomy. b) Postmenopausal
defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample
with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent
with menopause >40 milli-International Units (MIU)/ milliliter (mL) and estradiol <40
picogram (pg)/mL (<147 picomole [pmol]/ liter [L]) is confirmatory]. c) 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 after the last dose of study medication and completion of
the follow-up visit. GSK Modified List of Highly Effective Methods for Avoiding
Pregnancy in FRP are as follows. This list does not apply to FRP with same sex
partners, when this is their preferred and usual lifestyle or for subjects who are
and will continue to be abstinent from penile-vaginal intercourse on a long term and
persistent basis. a) Intrauterine device or intrauterine system that meets the
standard operating procedure (SOP) effectiveness criteria including a <1% rate of
failure per year, as stated in the product label. b) Male partner sterilization with
documentation of azoospermia prior to the female subject's entry into the study, and
this male is the sole partner for that subject. c) Male condom combined with a
vaginal spermicide (foam, gel, film, cream, or suppository) only for the following 3
situations when there is a very low risk for developmental toxicity: Vaccines;
Monoclonal antibodies when there is no target biology concern; Compounds that have a
complete reproductive toxicology package and have not shown any signal for
developmental toxicity. These allowed methods of contraception are only effective
when used consistently, correctly and in accordance with the product label. The
investigator is responsible for ensuring that subjects understand how to properly use
these methods of contraception. Sexual inactivity by abstinence must be consistent
with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g.
calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not
acceptable methods of contraception.
- Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the consent form and in this protocol.
- Alanine transaminase (ALT), alkaline phosphatase and bilirubin <=1.5x Upper limit of
normal (ULN) (isolated bilirubin >1.5xULN is acceptable if 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).
- History of clinically significant cardiovascular disease including: a) Exclusion
criteria for screening Electrocardiogram (ECG) (a single repeat is allowed for
eligibility determination) Heart rate: Males: <45 and >100 beats per minute,
Females: <50 and >100 beats per minute; QRS duration: >120 millisecond (msec), QTc
interval (B): >450 msec; b) Evidence of previous myocardial infarction (pathologic Q
waves, S-T segment changes (except early repolarization). c) 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. d) Any conduction abnormality (including but not
specific to left or right complete bundle branch block, atrioventricular block (AV)
block [2nd degree (type II) or higher], Wolf Parkinson White [WPW] syndrome). e)
Sinus pauses >3 seconds. f) Any significant arrhythmia which, in the opinion of the
principal Investigator and GSK Medical Monitor, will interfere with the safety for
the individual subject. g) Non-sustained (>=3 consecutive ventricular ectopic beats)
or sustained ventricular tachycardia. NOTES: The QTc is the QT interval corrected for
heart rate according to Bazett's formula (QTcB), Fridericia's formula (QTcF), and/or
another method, machine-read or manually over-read. The specific formula that will be
used to determine eligibility and discontinuation for an individual subject should be
determined prior to initiation of the study. In other words, several different
formulae cannot be used to calculate the QTc for an individual subject and then the
lowest QTc value used to include or discontinue the subject from the trial. For
purposes of data analysis, QTcB, QTcF, another QT correction formula, or a composite
of available values of QTc will be used as specified in the Reporting and Analysis
- Concomitant medications that are prohibited for this study.
- 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 grams (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.
- 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.
- Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test
result at screening or within 3 months prior to first dose of study treatment.
Hepatitis B core antibody (HBcAb) with negative hepatitis b surface antibody should
also be excluded.
- A positive pre-study drug/alcohol screen.
- A positive test for Human Immunodeficiency Virus (HIV) antibody.
- Where participation in the study would result in donation of blood or blood products
in excess of 500 mL within a 56 day period.
- The subject's systolic blood pressure is outside the range of 90-140 millimeters of
mercury (mmHg), or diastolic blood pressure is outside the range of 45-90 mmHg.
- 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