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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/NCT01827644




Registration number
NCT01827644
Ethics application status
Date submitted
5/04/2013
Date registered
9/04/2013
Date last updated
13/11/2017

Titles & IDs
Public title
Bioavailability and Food Effect of the Original Gelatin Formulation and Two New Formulations of Afuresertib in Normal Healthy Volunteers
Scientific title
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
Secondary ID [1] 0 0
117313
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 - Afuresertib GC - Fasted State
Treatment: Drugs - Afuresertib HPMC capsule - Fasted State
Treatment: Drugs - Afuresertib ECT - Fasted State
Treatment: Drugs - Afuresertib GC - Fed State
Treatment: Drugs - Afuresertib HPMC capsule - Fed State
Treatment: Drugs - Afuresertib ECT - Fed State

Experimental: Sequence 1 - Subjects will receive single doses of AFU HPMC capsule administered in a fasted state, AFU ECT administered in a fasted state, AFU HPMC capsule administered in a fed state and AFU GC administered in a fasted state (sequentially), on Day 1 of Dosing Period 1, 2, 3 and 4 (one treatment per period) respectively, with a minimum 10 Day washout between the doses in each Dosing Period

Experimental: Sequence 2 - Subjects will receive single doses of AFU ECT administered in a fasted state, AFU ECT administered in a fed state, AFU GC administered in a fasted state and AFU GC administered in a fed state (sequentially), on Day 1 of Dosing Period 1, 2, 3 and 4 (one treatment per period) respectively, with a minimum 10 Day washout between the doses in each Dosing Period.

Experimental: Sequence 3 - Subjects will receive single doses of AFU GC administered in a fasted state, AFU GC administered in a fed state, AFU ECT administered in a fed state and AFU HPMC capsule administered in a fasted state (sequentially), on Day 1 of Dosing Period 1, 2, 3 and 4 (one treatment per period) respectively, with a minimum 10 Day washout between the doses in each Dosing Period.

Experimental: Sequence 4 - Subjects will receive single doses of AFU GC administered in a fed state, AFU HPMC capsule administered in a fed state, AFU HPMC capsule administered in a fasted state and AFU ECT administered in a fasted state (sequentially), on Day 1 of Dosing Period 1, 2, 3 and 4 (one treatment per period) respectively, with a minimum 10 Day washout between the doses in each Dosing Period

Experimental: Sequence 5 - Subjects will receive single doses of AFU ECT administered in a fed state, AFU HPMC capsule administered in a fasted state, AFU GC administered in a fed state and AFU HPMC capsule administered in a fed state (sequentially), on Day 1 of Dosing Period 1, 2, 3 and 4 (one treatment per period) respectively, with a minimum 10 Day washout between the doses in each Dosing Period

Experimental: Sequence 6 - Subjects will receive single doses of AFU HPMC capsule administered in a fed state, AFU GC administered in a fasted state, AFU ECT administered in a fasted state and AFU ECT administered in a fed state (sequentially), on Day 1 of Dosing Period 1, 2, 3 and 4 (one treatment per period) respectively, with a minimum 10 Day washout between the doses in each Dosing Period


Treatment: Drugs: Afuresertib GC - Fasted State
White opaque hard gelatin capsule containing afuresertib 25 mg. Subjects will receive single oral dose of afuresertib GC administered in fasted state

Treatment: Drugs: Afuresertib HPMC capsule - Fasted State
White opaque HPMC capsule containing afuresertib 25 mg. Subjects will receive single oral dose of afuresertib HPMC capsule administered in fasted state

Treatment: Drugs: Afuresertib ECT - Fasted State
White to off white, round, biconvex coated tablet containing afuresertib 25 mg. Subjects will receive single oral dose of afuresertib ECT administered in fasted state

Treatment: Drugs: Afuresertib GC - Fed State
White opaque hard gelatin capsule containing afuresertib 25 mg. Subjects will receive single oral dose of afuresertib GC administered in fed state

Treatment: Drugs: Afuresertib HPMC capsule - Fed State
White opaque HPMC capsule containing afuresertib 25 mg. Subjects will receive single oral dose of afuresertib HPMC capsule administered in fed state

Treatment: Drugs: Afuresertib ECT - Fed State
White to off white, round, biconvex coated tablet containing afuresertib 25 mg. Subjects will receive single oral dose of afuresertib ECT administered in fed state
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Composite of plasma pharmacokinetics (PK) parameters of afuresertib, following administration with and without food
Timepoint [1] 0 0
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
Secondary outcome [1] 0 0
Safety and tolerability of afuresertib as assessed by number of subjects with adverse events (AEs)
Timepoint [1] 0 0
Up to 9 weeks
Secondary outcome [2] 0 0
Safety and tolerability of afuresertib as assessed by clinical laboratory tests
Timepoint [2] 0 0
Up to 9 weeks
Secondary outcome [3] 0 0
Safety and tolerability of afuresertib as assessed by concomitant medications review
Timepoint [3] 0 0
Up to 9 weeks
Secondary outcome [4] 0 0
Safety and tolerability of afuresertib as assessed by electrocardiograms (ECG) measurements
Timepoint [4] 0 0
Up to 9 weeks
Secondary outcome [5] 0 0
Safety and tolerability of afuresertib as assessed by vital signs measurement
Timepoint [5] 0 0
Up to 9 weeks
Secondary outcome [6] 0 0
Change in phosphoAKT (pAKT) levels in peripheral blood samples following administration of a gelatin capsule, HPMC capsule and ECT
Timepoint [6] 0 0
Pre-dose and 2, 12, and 24 hours post-dose in each dosing period.

Eligibility
Key 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
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 (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

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
24/04/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
12/07/2013
Sample size
Target
Accrual to date
Final
36
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne

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

Ethics approval
Ethics application status

Summary
Brief summary
This will be a randomized, open-label, sequential, single dose, 4-period crossover study.
This study is being conducted to measure the relative bioavailability of the original gelatin
capsule (GC) formulation and two new formulations (hydroxypropyl-methylcellulose [HPMC]
capsule and enteric coated tablet [ECT]) of afuresertib (AFU), in the fed and fasted state.
The study will be composed of Screening, Treatment, and Follow-up Periods. Screening
assessments to determine subject eligibility will be performed within 3 weeks prior to the
first dose of study drug in the Treatment Period. Eligible subjects will be randomized to
receive 4 of the 6 possible study treatments (A: AFU GC administered in a fasted state, B:
AFU GC administered in a fed state, C: AFU HPMC capsule administered in a fasted state, D:
AFU HPMC capsule administered in a fed state, E: AFU ECT administered in a fasted state, F:
AFU ECT administered in a fed state) in 4 treatment periods (one per treatment period).
Subjects will receive a single dose of one of the six study treatments (A, B, C, D, E, F) on
Day 1 of each Dosing Period, according to one of the 6 treatment sequences (CEDA, EFAB, ABFC,
BDCE, FCBD, DAEF). There will be a minimum of 10 Day washout period between the doses
administered in each Treatment Period. A Follow-up visit will be conducted within 10-14 days
after the last dose. A subject's total time involved in the study will be approximately 9
weeks. At least 36 subjects will be enrolled in the study, to ensure that at least 6 subjects
will be randomized to receive each treatment sequence.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01827644
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/NCT01827644