A Randomized, Open-label, 3-period Crossover Study in Healthy Subjects to Determine the Effect of Particle Size on the Pharmacokinetics of Single Oral 100mg Doses of GSK1278863A

GlaxoSmithKline1 site in 1 country30 target enrollmentFebruary 25, 2011

ConditionsAnaemia

InterventionsGSK1278863A

DrugsGSK1278863A

Overview

Phase: Phase 1
Intervention: GSK1278863A
Conditions: Anaemia
Sponsor: GlaxoSmithKline
Enrollment: 30
Locations: 1
Primary Endpoint: Area under plasma concentration-time curve (AUC (0-inf)) and maximum plasma concentration (Cmax) of GSK1278863A.
Status: Completed
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

A randomized, open-label, 3-period crossover study.

Detailed Description

A randomized, open label, 3-period crossover study in healthy subjects. The primary objective of this study is to determine the relative bioavailability of GSK1278863A after single oral doses of 100mg GSK1278863A tablets with particle sizes of 13, 29, or 41 micrometers (um) in healthy subjects.

Registry

clinicaltrials.gov

Start Date

February 25, 2011

End Date

April 18, 2011

Last Updated

8 years ago

Study Type

Interventional

Study Design

Crossover

Sex

All

Investigators

Sponsor

GlaxoSmithKline

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•AST, ALT, alkaline phosphatase and bilirubin \<= 1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
•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.
•Male or female between 18 and 55 years of age inclusive, at the time of signing the informed consent.
•A 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.
•Male subjects with female partners of child-bearing potential must agree to use contraception methods
•Body weight \>=50kg and BMI within the range 19 to 29.9kg/m2 (inclusive).
•Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
•QTcB or QTcF \< 450 msec; or QTc \< 480 msec in subjects with Bundle Branch Block.
•Subjects must have a normal resting blood pressure, after having rested quietly in a supine position for at least 15 minutes, defined as: \>=100mm Hg systolic/60mm Hg diastolic and \<=140mm Hg systolic/90mm Hg diastolic.

Exclusion Criteria

•Any clinically relevant abnormality identified on the screening medical assessment, laboratory examination, or ECG (12 lead) judged by the Investigator and /or medical monitor to potentially introduce additional risk factors and/or interfere with the study procedures.
•Significant cardiac, pulmonary, metabolic, renal, hepatic, neurological, psychiatric, or gastrointestinal conditions that in the opinion of the investigator and/or GSK medical monitor, places the subject at an unacceptable risk as participant in this trial.
•A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 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.
•CPK above the normal range.
•Calculated creatinine clearance: \<80mL/min.
•Subjects with a pre-exisisting condition interfering with normal gastrointestinal anatomy or motility, and/or hepatic function-that could interfere with the absorption, metabolism, and/or excretion of the study drugs.
•History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of \>21 drinks for males or \>14 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 ml) of beer, 5 ounces (150 ml) of wine or 1.5 ounces (45 ml) of 80 proof distilled spirits.

Arms & Interventions

GSK1278863A 100mg (X90=13um)

single dose

Intervention: GSK1278863A

GSK1278863A 100mg (x90=29Um)

single dose

Intervention: GSK1278863A

GSK1278863 100mg (X90=41um)

single dose

Intervention: GSK1278863A

Outcomes

Primary Outcomes

Area under plasma concentration-time curve (AUC (0-inf)) and maximum plasma concentration (Cmax) of GSK1278863A.

Time Frame: pre-dose to 24 hours post-dose

To determine the relative bioavailability of GSK1278863A after single oral doses of 100 mg GSK1278863A tablets with particle sizes of 13, 29 and 41um in healthy subjects.

Secondary Outcomes

Safety and tolerability of investigational product as assessed by clinical monitoring of vital signs (blood pressure, pulse rate), ECGs, and laboratory data, as well as reporting of adverse events.(Duration of subject study participation)
Cmax, AUC (0-t), AUC(0-infinite), tmax, and t1/2 (as data permit) of GSK1278863A metabolites.(pre-dose to 24 hours post-dose)