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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02040480




Registration number
NCT02040480
Ethics application status
Date submitted
16/01/2014
Date registered
20/01/2014
Date last updated
13/11/2017

Titles & IDs
Public title
Bioavailability and Food Effect Study of Gelatin Formulation and Immediate Release Tablet Formulation of Afuresertib
Scientific 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
Secondary ID [1] 0 0
201039
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK2110183 Gelatin Capsule
Treatment: Drugs - GSK2110183 IR Tablet

Experimental: Sequence 1 - Participants will receive treatment in following sequence in each of the three study periods (one treatment per period): ABC

Experimental: Sequence 2 - Participants will receive treatment in following sequence in each of the three study periods (one treatment per period): ACB

Experimental: Sequence 3 - Participants will receive treatment in following sequence in each of the three study periods (one treatment per period): BAC

Experimental: Sequence 4 - Participants will receive treatment in following sequence in each of the three study periods (one treatment per period): BCA

Experimental: Sequence 5 - Participants will receive treatment in following sequence in each of the three study periods (one treatment per period): CAB

Experimental: Sequence 6 - Participants will receive treatment in following sequence in each of the three study periods (one treatment per period): CBA


Treatment: Drugs: GSK2110183 Gelatin Capsule
White opaque hard gelatin capsule with a unit dose strength of 25 milligrams (mg) for oral administration

Treatment: Drugs: GSK2110183 IR Tablet
White round biconvex film coated IR tablet with a unit dose strength of 25 mg for oral administration
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
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 outcome [1] 0 0
Number of subjects with adverse events (AEs).
Timepoint [1] 0 0
Up to 9 weeks
Secondary outcome [2] 0 0
Clinical laboratory parameter assessment as a measure of safety and tolerability
Timepoint [2] 0 0
Up to 9 weeks
Secondary outcome [3] 0 0
Concomitant medications review as a measure of safety and tolerability
Timepoint [3] 0 0
Up to 9 weeks
Secondary outcome [4] 0 0
Electrocardiogram (ECGs) measurement as a measure of safety and tolerability
Timepoint [4] 0 0
Up to 9 weeks
Secondary outcome [5] 0 0
Vital sign measurement as a measure of safety and tolerability
Timepoint [5] 0 0
Up to 9 weeks
Secondary outcome [6] 0 0
Composite of PK parameter following single dose administration of IR tablet in fasted state
Timepoint [6] 0 0
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

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
40 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/02/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
4/04/2014
Sample size
Target
Accrual to date
Final
18
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
GSK Investigational Site - Randwick
Recruitment postcode(s) [1] 0 0
2031 - Randwick

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02040480
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02040480