Bioavailability and Food Effect of the Original Gelatin Formulation and Two New Formulations of Afuresertib in Normal Healthy Volunteers

NCT ID: NCT01827644

Last Updated: 2017-11-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-04-24

Study Completion Date

2013-07-12

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Cancer

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

AKT inhibitor formulation food effect bioavailability GSK2110183

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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

Group Type EXPERIMENTAL

Afuresertib GC - Fasted State

Intervention Type DRUG

White opaque hard gelatin capsule containing afuresertib 25 mg. Subjects will receive single oral dose of afuresertib GC administered in fasted state

Afuresertib HPMC capsule - Fasted State

Intervention Type DRUG

White opaque HPMC capsule containing afuresertib 25 mg. Subjects will receive single oral dose of afuresertib HPMC capsule administered in fasted state

Afuresertib ECT - Fasted State

Intervention Type DRUG

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

Afuresertib HPMC capsule - Fed State

Intervention Type DRUG

White opaque HPMC capsule containing afuresertib 25 mg. Subjects will receive single oral dose of afuresertib HPMC capsule administered in fed state

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.

Group Type EXPERIMENTAL

Afuresertib GC - Fasted State

Intervention Type DRUG

White opaque hard gelatin capsule containing afuresertib 25 mg. Subjects will receive single oral dose of afuresertib GC administered in fasted state

Afuresertib ECT - Fasted State

Intervention Type DRUG

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

Afuresertib GC - Fed State

Intervention Type DRUG

White opaque hard gelatin capsule containing afuresertib 25 mg. Subjects will receive single oral dose of afuresertib GC administered in fed state

Afuresertib ECT - Fed State

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

Afuresertib GC - Fasted State

Intervention Type DRUG

White opaque hard gelatin capsule containing afuresertib 25 mg. Subjects will receive single oral dose of afuresertib GC administered in fasted state

Afuresertib HPMC capsule - Fasted State

Intervention Type DRUG

White opaque HPMC capsule containing afuresertib 25 mg. Subjects will receive single oral dose of afuresertib HPMC capsule administered in fasted state

Afuresertib GC - Fed State

Intervention Type DRUG

White opaque hard gelatin capsule containing afuresertib 25 mg. Subjects will receive single oral dose of afuresertib GC administered in fed state

Afuresertib ECT - Fed State

Intervention Type DRUG

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

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

Group Type EXPERIMENTAL

Afuresertib HPMC capsule - Fasted State

Intervention Type DRUG

White opaque HPMC capsule containing afuresertib 25 mg. Subjects will receive single oral dose of afuresertib HPMC capsule administered in fasted state

Afuresertib ECT - Fasted State

Intervention Type DRUG

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

Afuresertib GC - Fed State

Intervention Type DRUG

White opaque hard gelatin capsule containing afuresertib 25 mg. Subjects will receive single oral dose of afuresertib GC administered in fed state

Afuresertib HPMC capsule - Fed State

Intervention Type DRUG

White opaque HPMC capsule containing afuresertib 25 mg. Subjects will receive single oral dose of afuresertib HPMC capsule administered in fed state

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

Group Type EXPERIMENTAL

Afuresertib HPMC capsule - Fasted State

Intervention Type DRUG

White opaque HPMC capsule containing afuresertib 25 mg. Subjects will receive single oral dose of afuresertib HPMC capsule administered in fasted state

Afuresertib GC - Fed State

Intervention Type DRUG

White opaque hard gelatin capsule containing afuresertib 25 mg. Subjects will receive single oral dose of afuresertib GC administered in fed state

Afuresertib HPMC capsule - Fed State

Intervention Type DRUG

White opaque HPMC capsule containing afuresertib 25 mg. Subjects will receive single oral dose of afuresertib HPMC capsule administered in fed state

Afuresertib ECT - Fed State

Intervention Type DRUG

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

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

Group Type EXPERIMENTAL

Afuresertib GC - Fasted State

Intervention Type DRUG

White opaque hard gelatin capsule containing afuresertib 25 mg. Subjects will receive single oral dose of afuresertib GC administered in fasted state

Afuresertib ECT - Fasted State

Intervention Type DRUG

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

Afuresertib HPMC capsule - Fed State

Intervention Type DRUG

White opaque HPMC capsule containing afuresertib 25 mg. Subjects will receive single oral dose of afuresertib HPMC capsule administered in fed state

Afuresertib ECT - Fed State

Intervention Type DRUG

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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 Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

GlaxoSmithKline

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

GSK Investigational Site

Melbourne, Victoria, Australia

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Australia

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

117313

Identifier Type: -

Identifier Source: org_study_id