Clinical trial NCT02040480: Bioavailability and Food Effect Study of Gelatin Formulation and Immediate Release Tablet Formulation of Afuresertib
Official title: A Single Center, Randomized, Open-Label, Sequential, Single Dose, 3-Period Crossover Study to Evaluate the Bioavailability and Food Effect of a Gelatin Formulation and Immediate Release Tablet Formulation of Afuresertib, an AKT Inhibitor, in Normal Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: bioavailability
food effect
formulation
GSK2110183
afuresertib
AKT inhibitor
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2014-01-20
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study is being conducted to measure the relative bioavailability of the original gelatin capsule formulation and a new formulation, immediate release (IR) tablet of Afuresertib (GSK2110183). The study will be composed of Screening, Treatment, and Follow-up Periods. A subject's total time involved in the study will be approximately 9 weeks. The study will enroll approximately 18 healthy volunteers.


Eligibility criteria: Inclusion Criteria:

* Provided signed written informed consent
* Healthy Male or female between 18 and 40 years of age inclusive, at the time the informed consent is obtained.
* Body weight \>=50 kilograms (kg) and body mass index (BMI) of \>=18 and \<= 32 kg/meter square (m\^2).
* 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 contraception methods.
* Alanine aminotransferase, alkaline phosphatase and bilirubin \<=1.5xupper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
* Based on single or averaged QT interval corrected (QTc) values of triplicate ECGs obtained over a brief recording period: QTcB \<450 millisecond (msec); or QTcB \<480 msec in subjects with Bundle Branch Block.
* Able to swallow and retain orally administered study treatment and does not have any clinically significant gastrointestinal (GI) abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach and/or bowels.

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, dyspepsia, peptic ulcer disease, 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 10 grams (g) of alcohol: 270 mL of full strength beer (4.8%), 375 mL of mid strength beer (3.5%), 470 mL of light beer (2.7%), 250 mL pre-mix full strength spirit (5%), 100mL of wine (13.5%) and 30 mL of spirit (40%).

* 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
* A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of Screening.
* Smoking or history or regular 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 immuno 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.
* Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures.
* Any prohibited medications or recent consumption of citrus products.

Primary outcomes:
measure: Composite of pharmacokinetic (PK) parameters to determine relative bioavailability of afuresertib after administering it as a single dose in an original gelatin capsule in the fasted state and in a newly formulated IR tablet in the fed and fasted state.
timeFrame: PK Samples will be collected Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 120, and 168 hours post-dose
Secondary outcomes:
measure: Number of subjects with adverse events (AEs).
timeFrame: Up to 9 weeks
measure: Clinical laboratory parameter assessment as a measure of safety and tolerability
timeFrame: Up to 9 weeks
measure: Concomitant medications review as a measure of safety and tolerability
timeFrame: Up to 9 weeks
measure: Electrocardiogram (ECGs) measurement as a measure of safety and tolerability
timeFrame: Up to 9 weeks
measure: Vital sign measurement as a measure of safety and tolerability
timeFrame: Up to 9 weeks
measure: Composite of PK parameter following single dose administration of IR tablet in fasted state
timeFrame: PK Samples will be collected Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 120, and 168 hours post-dose
Other outcomes:
Locations:
city: Randwick
country: Australia
facility: GSK Investigational Site
state: New South Wales
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: