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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

Phase 1
18 Years
40 Years
Not Enrolling

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Trial Information

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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Composite of plasma pharmacokinetics (PK) parameters of afuresertib, following administration with and without food

Outcome Description:

Relative bioavailability of afuresertib after single dose of a GC, HPMC capsule and ECT, with and without high fat/calorie meal, will be determined by the following PK parameters: Area under the plasma concentration time curve- from time zero (pre-dose) to infinite time [AUC(0-inf)] and from time zero (pre-dose) to last time of quantifiable concentration [AUC(0-t)], maximum observed plasma concentration (Cmax), time to Cmax (tmax), observed plasma concentration at 24 hours (C24), and minimal observed plasma concentration (Ct)

Outcome Time Frame:

PK samples will be collected at Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, and 72 hours post-dose in each dosing period

Safety Issue:


Principal Investigator

GSK Clinical Trials

Investigator Role:

Study Director

Investigator Affiliation:



Australia: Therapeutic Goods Administration

Study ID:




Start Date:

April 2013

Completion Date:

June 2013

Related Keywords:

  • Cancer
  • AKT inhibitor
  • formulation
  • food effect
  • bioavailability
  • GSK2110183