Phase I Study to Evaluate Safety, Pharmacokinetics and Pharmacodynamics of GSK2256098 in Healthy Volunteers (FTIH)

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00996671
First received: October 15, 2009
Last updated: June 10, 2010
Last verified: June 2010
  Purpose

The purpose of this study is to test the safety of a new drug and to look at how the drug is handled by your body. This is the first time the drug will be given to people, the drug has been safely given to animals over many days at higher doses than will be given in the study. The study will be done in healthy men and woman to determine what effects, good or bad, it has on thier health. This study will find out:

If the drug has any side effects after one dose of the drug is given? How much of the drug gets into the bloodstream, and how long does the body take to get rid of it? If the drug causes any changes to a substance that is in skin, hair or blood.


Condition Intervention Phase
Cancer
Drug: Placebo
Drug: GSK2256098
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • To characterize the safety of single doses of GSK2256098 in adult healthy subjects [ Time Frame: within 10-14 days following administration of study drug ] [ Designated as safety issue: Yes ]
  • To characterize the single dose pharmacokinetics of GSK2256098 in blood and urine in adult healthy subjects [ Time Frame: 14 days after administration of study drug ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To examine the dose proportionality of GSK2256098 pharmacokinetic parameters following single dose administration in healthy subjects [ Time Frame: 14 days ]
  • To explore dose- and concentration-effect relationships for various safety parameters, if appropriate [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
  • To estimate the effect of high fat/calorie meal on the pharmacokinetics, safety, and tolerability of a single dose of GSK2256098. [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
  • To explore and potentially identify small molecules or cytokines in plasma which may serve as biomarkers for future studies [ Time Frame: 14 days ] [ Designated as safety issue: No ]

Enrollment: 38
Study Start Date: November 2009
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Escalation Cohorts
single dose administration escalating doses starting at 20 mg and continue escalation; the highest dose in this study will not exceed the mean Day 1 exposure in male dogs at the NOAEL dose (6 mg/kg/day).
Drug: Placebo
Placebo to be used as comparator for GSK2256098
Drug: GSK2256098
focal adhesion kinase inhibitor given as a single dose
Experimental: Food effect Cohort
Dose to be selected based on emerging safety and PK data; subjects will be given FDA standard high fat meal followed by single dose of study drug.
Drug: GSK2256098
focal adhesion kinase inhibitor given as a single dose

Detailed Description:

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 appropriate.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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 screening.
  • 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00996671

Locations
Australia, Victoria
GSK Investigational Site
Melbourne, Victoria, Australia, 3004
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Study Director, GSK
ClinicalTrials.gov Identifier: NCT00996671     History of Changes
Other Study ID Numbers: 113581
Study First Received: October 15, 2009
Last Updated: June 10, 2010
Health Authority: Australia: Human Research Ethics Committee

Keywords provided by GlaxoSmithKline:
first time in human
focal adhesion kinase inhibitor
healthy volunteers

ClinicalTrials.gov processed this record on April 20, 2014