A Study to Investigate the Safety and Pharmacokinetics of a Single Dose of GSK2256294 in Healthy Young Males and Elderly Subjects
Status: | Completed |
---|---|
Conditions: | Chronic Obstructive Pulmonary Disease, Pulmonary, Pulmonary |
Therapuetic Areas: | Pulmonary / Respiratory Diseases |
Healthy: | No |
Age Range: | 18 - Any |
Updated: | 5/5/2014 |
Start Date: | January 2014 |
End Date: | April 2014 |
Contact: | US GSK Clinical Trials Call Center |
Email: | GSKClinicalSupportHD@gsk.com |
Phone: | 877-379-3718 |
A Study to Evaluate the Effect of Age, Food and Gender on Tolerability and Pharmacokinetics of GSK2256294 Following a Single Oral Administration in Healthy Fed and Fasted Elderly Subjects. This Study Will Also Evaluate the Biliary Metabolites in Healthy Young Males Following a Single Dose of GSK2256294
This study will investigate the safety and pharmacokinetics (PK) of a single dose of
GSK2256294 in healthy young and elderly subjects to explore the effects of food, gender and
age on drug exposure. The biliary metabolites in healthy young males will be investigated
using the Entero-test after a single oral dose of GSK2256294. This study will be conducted
in two cohorts (Cohort 1 and Cohort 2). Cohort 1 is open label in order to characterise the
PK profile of GSK2256294 in healthy young males and also to investigate the biliary
metabolites of GSK2256294. Cohort 2 uses a crossover design to allow comparison of the PK
parameters of GSK2256294 between in the fed and fasted state within subject and also to
compare the PK parameters of GSK2256294 between male and female subjects. A washout period
of a minimum of 2 weeks has been chosen to allow and adequate washout of GSK2256294.
GSK2256294 in healthy young and elderly subjects to explore the effects of food, gender and
age on drug exposure. The biliary metabolites in healthy young males will be investigated
using the Entero-test after a single oral dose of GSK2256294. This study will be conducted
in two cohorts (Cohort 1 and Cohort 2). Cohort 1 is open label in order to characterise the
PK profile of GSK2256294 in healthy young males and also to investigate the biliary
metabolites of GSK2256294. Cohort 2 uses a crossover design to allow comparison of the PK
parameters of GSK2256294 between in the fed and fasted state within subject and also to
compare the PK parameters of GSK2256294 between male and female subjects. A washout period
of a minimum of 2 weeks has been chosen to allow and adequate washout of GSK2256294.
Inclusion Criteria:
- Safety - All Cohorts
- 12 lead ECG without any clinically significant abnormality as judged by the
Investigator, and ECGs QT duration corrected for heart rate by Fridericia's formula
(QTcF) <450 milliseconds (msec) determined by the average of triplicate ECGs.
- Male subjects with female partners of child-bearing potential must agree to use one
of the contraception methods listed in the protocol. This criterion must be followed
from the time of the first dose of study medication until 2 weeks post-last dose.
- Body weight >=60 kilogram (kg) and body mass index (BMI) within the range 19 - 35 kg
per meter square (kg/m^2) (inclusive).
- Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <=1.5xUpper limit
of normal [ULN] (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 parameter
outside the reference range for the population being studies may be included only of
the Investigator agree that the finding is unlikely to introduce additional risk
factors and will not interfere with study procedures. Consultation with the GSK
Medical Monitor is required.
- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.
- Safety - Cohort 2 Only
- 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
[for this definition, "documented" refers to the outcome of the
investigator's/designee's review of the subject's medical history for study
eligibility, as obtained via a verbal interview with the subject or from the
subject's medical records]; or postmenopausal defined as 12 months of spontaneous
amenorrhea [in questionable cases a blood sample with simultaneous follicle
stimulating hormone (FSH) >40 milli international units per milliliter (mIU/mL) and
estradiol <40 picogram per milliliter (pg/mL) (<147 picomole per liter) is
confirmatory]. [Females on hormone replacement therapy (HRT) and whose menopausal
status is in doubt will be required to use one of the contraception methods listed in
the protocol if they wish to continue their HRT during the study. Otherwise, they
must discontinue HRT to allow confirmation of post-menopausal status prior to study
enrolment. For most forms of HRT, at least 2-4 weeks will elapse between the
cessation of therapy and the blood draw; this interval depends on the type and dosage
of HRT. Following confirmation of their post-menopausal status, they can resume use
of HRT during the study without use of a contraceptive method.]
- Other - Cohort 1 Only.
- Cohort 1 only: Male aged between 18 and 45 years of age inclusive, at the time of
signing the informed consent.
Cohort 1 only: BP <=130/80.
- Other - Cohort 2 Only
- Cohort 2 only: Male and females (of non-child bearing potential) aged >=60 years of
age, at the time of signing the informed consent.
- Cohort 2 only: BP <=160/100.
Exclusion Criteria:
- Where participation in the study would result in donation of blood or blood products
in excess of 500 mL within a 56 day period.
- Exposure to more than four new chemical entities within 12 months prior to the first
dosing day.
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 regular alcohol consumption within 6 months of the study defined as: an
average weekly intake of >14 drinks for males or >7 drinks for females. One drink is
equivalent to 12 grams 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.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening.
- A positive test for human immunodeficiency virus (HIV) antibody.
- A positive pre-study drug/alcohol screen.
- Subjects with a history of any type of malignancy with the exception of successfully
treated squamous cell cancer of the skin.
- History of sensitivity to the study medication, or components thereof or a history of
drug allergy that, in the opinion of the Investigator or GSK Medical Monitor,
contraindicated their participation.
- Urinary cotinine levels indicative of smoking or history or regular use of tobacco-
or nicotine-containing products within 6 months prior to screening.
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