A Single Center, Randomized, Open-Label, Sequential, Single Dose, 4-Period Crossover Study to Evaluate the Bioavailability and Food Effect of a Gelatin Formulation and Two Prototype Formulations of Afuresertib, an AKT Inhibitor, in Normal Healthy Volunteers
Inclusion Criteria:
- Healthy as determined by a responsible and experienced physician, based on a medical
evaluation including medical history, physical examination, laboratory tests and
cardiac monitoring.
- Male or female between 18 and 40 years of age inclusive, at the time of signing the
informed consent
- Body weight >=50 kilograms (kg) and body mass index (BMI) <=32 kg/m^2 (square meter)
- A female subject is eligible to participate if she is of: (A) Non-childbearing
potential defined as pre-menopausal females with a documented tubal ligation or
hysterectomy or postmenopausal defined as 12 months of spontaneous amenorrhea (B)
Child-bearing potential with negative pregnancy test as determined by serum human
chorionic gonadotropin (hCG) test at Screening and prior to dosing, AND: agrees to
use one of the acceptable contraception methods
- Male subjects with female partners of child-bearing potential must agree to use one
of the acceptable contraception methods.
- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form
- Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <=1.5 x Upper
Limit of Normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is
fractionated and direct bilirubin <35%).
- Based on single or averaged corrected QT interval (QTc) values of triplicate
electrocardiograms (ECGs) obtained over a brief recording period: QTc <450
milliseconds (msec) or QTc <480 msec in subjects with Bundle Branch Block
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 gastroesophageal reflux disease (GERD), dyspepsia, gastrointestinal (GI)
bleeding, GI surgery that could affect motility
- History of atrial arrhythmias
- History of regular alcohol consumption within 6 months of the study defined as: an
average weekly intake of >21 units for males or >14 units for females. One unit is
equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 mL) of beer, 1
glass (125 mL) of wine or 1 (25 mL) measure of spirits.
- History of sensitivity to heparin or heparin-induced thrombocytopenia
- 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
- Use of prescription or non-prescription medications, vitamins, and dietary or herbal
supplements (including St John's Wort) within 7 days (or 14 days if the
drug/supplement is a potential enzyme inducer) or 5 half-lives (whichever is longer)
prior to the first dose of study drug until completion of the Follow-up Period,
unless in the opinion of the Investigator and GSK Medical Monitor the medication will
not interfere with the study
- Unable to abstain from smoking tobacco or the use of nicotine-containing products
while admitted to the clinic
- Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or
pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior
to the first dose of Study Drug on Day 1 of Dosing Period 1, until completion of the
Follow-up Period
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of Screening
- History of heavy use of tobacco- or nicotine-containing products within 6 months
prior to Screening.
- A positive drug/alcohol screen at Screening or upon check-in to the clinic on Day -1
of each Dosing Period
- A positive test for Human Immunodeficiency Virus (HIV) antibody
- Pregnant females as determined by positive serum hCG test at Screening or prior to
dosing.
- Where participation in the study would result in donation of blood or blood products
in excess of 500 mL within a 56 day period
- Lactating females
- 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