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A Phase I, Randomized, Single-Blind, Placebo-Controlled Dose-Escalation Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Food Effect Following Single Oral Doses of the Focal Adhesion Kinase Inhibitor, GSK2256098, in Healthy Subjects

Phase 1
18 Years
65 Years
Not Enrolling

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Trial Information

A Phase I, Randomized, Single-Blind, Placebo-Controlled Dose-Escalation Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Food Effect Following Single Oral Doses of the Focal Adhesion Kinase Inhibitor, GSK2256098, in Healthy Subjects

This study represents the first administration of the focal adhesion kinase (FAK) inhibitor
GSK2256098 to humans to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD),
and preliminary food effect following single oral doses in adult healthy subjects before
proceeding to studies in subjects with cancer that will be given at higher doses over an
extended period of time. FAK is a protein in the body that is important in cancer
development. Objectives of the study will be to characterize the safety of single doses of
GSK2256098; to characterize the single dose PK of GSK2256098 in the presence and absence of
food; to examine the dose proportionality of GSK2256098 PK parameters following single dose
administration; and to characterize the effect of single doses of GSK2256098 on phospho-FAK
(pFAK) tyrosine 397 (Y397) levels in skin and hair follicles. Dose- and
concentration-effect relationships for various safety parameters will be explored as

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. A subject with a clinical abnormality or laboratory parameters
outside the reference range for the population being studied may be included only if
the Investigator and the GSK Medical Monitor agree that the finding is unlikely to
introduce additional risk factors and will not interfere with the study procedures.

- AST, ALT, alkaline phosphatase and bilirubin less than or equal to 1.5 X ULN
(isolated bilirubin >1.5 X ULN is acceptable if bilirubin is fractionated and direct
bilirubin < 35%).

- Urine microalbumin: creatinine ratio < 300 mg/g.

- Male or female between 18 and 65 years of age inclusive, at the time of signing the
informed consent.

- female subject is eligible to participate if she is of: Non-childbearing potential
defined as pre-menopausal females with a documented tubal ligation or hysterectomy;
or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable
cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml
and estradiol < 40 pg/ml (<140 pmol/L) is confirmatory].

- Male subjects must agree to use one of the contraception methods listed in Section
8.1. This criterion must be followed from the time of the first dose of study
medication until the end of the follow-up period.

- Body weight greater than or equal to 50 kg and body mass index (BMI) within the range
18.5 to 30.0 kg/m2 (inclusive).

- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.

- Average QTcF < 450 msec (based on averaged results of three ECGs).

Exclusion Criteria:

- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within three months of screening.

- Current or chronic history of liver disease, or known hepatic or biliary
abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

- A positive pre-study drug/alcohol screen.

- A positive test for HIV antibody.

- History of alcohol consumption within six 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 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml) of wine or 1
(25 ml) measure of spirits.

- 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, five 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 or investigational products within
12 months prior to the first dosing day.

- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary
supplements (including St John's Wort) within seven days (or 14 days if the drug is a
potential enzyme inducer) or five half-lives (whichever is longer) prior to the first
dose of study medication, unless in the opinion of the Investigator and GSK Medical
Monitor the medication will not interfere with the study procedures or compromise
subject safety.

- 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.

- Where participation in the study would result in donation of blood or blood products
in excess of 500 mL within a 56 day period.

- Pregnant females as determined by positive serum hCG test at screening or positive
urine hCG test prior to dosing.

- Lactating females.

- Unwillingness or inability to follow the procedures outlined in the protocol.

- Subject is mentally or legally incapacitated.

- History of sensitivity to heparin or heparin-induced thrombocytopenia.

- Subjects who have asthma or a history of asthma or reactive airway disease.

- History of regular tobacco use or nicotine containing products within three months
prior to screening or a positive urine cotinine test result indicative of smoking at

- Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or
kumquats, pummelos, exotic citrus fruit (i.e., star fruit, bitter melon), grapefruit
hybrids or fruit juices from seven days prior to the first dose of study medication.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Outcome Measure:

To characterize the safety of single doses of GSK2256098 in adult healthy subjects

Outcome Time Frame:

within 10-14 days following administration of study drug

Safety Issue:


Principal Investigator

GSK Clinical Trials

Investigator Role:

Study Director

Investigator Affiliation:



Australia: Human Research Ethics Committee

Study ID:




Start Date:

November 2009

Completion Date:

March 2010

Related Keywords:

  • Cancer
  • first time in human
  • focal adhesion kinase inhibitor
  • healthy volunteers