Overview

Effect of Rifampin (RIF) on the Pharmacokinetics (PK) of Oral Cabotegravir (CAB) in Healthy Subjects

Status:
Completed
Trial end date:
2015-09-01
Target enrollment:
0
Participant gender:
All
Summary
CAB is an integrase inhibitor that is currently in Phase 2 clinical trials for the treatment and prevention of human immunodeficiency virus-1 (HIV-1) infection. RIF, a rifamycin used for treatment of tuberculosis (common co-infection in HIV-infected subjects), is a known inducer of uridine diphosphate (UDP)-glucuronosyltransferases (UGTs) and Cytochrome P450 3A4 (CYP3A4). CAB is primarily metabolized via UGT1A1 and UGT1A9, thus a drug interaction between CAB and RIF is possible. This study will be a phase I, single-center, open label, fixed-sequence cross-over study to compare the single dose PK of CAB oral 30 milligrams (mg) when co-administered with RIF 600 mg once daily at steady-state to those of CAB oral 30 mg administered alone. Fifteen subjects are planned to be enrolled to obtain 12 evaluable subjects for this study.
Phase:
Phase 1
Accepts Healthy Volunteers?
Accepts Healthy Volunteers
Details
Lead Sponsor:
ViiV Healthcare
Collaborator:
GlaxoSmithKline
Treatments:
Rifampin
Criteria
Inclusion Criteria:

- 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
cardiac monitoring.

- 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 - A 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 per
mililiter (MIU/mL) and estradiol <40 picogram/milliliter (pg/mL) (<147 picomoles/liter
[pmol/L]) is confirmatory]; c) Reproductive potential and agrees to follow one of the
options listed 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.

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

- Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <=1x upper limit of
normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated
and direct bilirubin <35%).

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 clinically significant cardiovascular disease including: a) Exclusion
criteria for screening ECG (a single repeat is allowed for eligibility determination):
Heart rate <45 and >100 beats per minute for male subjects and <50 and >100 beats per
minute for female subjects, QRS duration >120 millisecond (msec), and QT interval
corrected by Fridericia's formula (QTcF) >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 (AV)
block [2nd degree (type II) or higher], Wolf Parkinson White [WPW] syndrome) which in
the opinion of the principal Investigator and GSK Medical Monitor, will interfere with
the safety for the individual subject; 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.

- Subjects must abstain from taking prescription or non-prescription drugs (including
vitamins and dietary or herbal 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 until completion of the follow-up visit, unless in the
opinion of the Investigator and sponsor the medication will not interfere with the
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 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.

- A history of regular use of tobacco, or nicotine-containing products within 30 days
prior to screening.

- 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 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 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.