To Evaluate Effects of GSK2256294 on Pulmonary Artery Pressure in Healthy Volunteers Under Normoxic and Hypoxic Conditions
Status: | Completed |
---|---|
Conditions: | Chronic Obstructive Pulmonary Disease, Pulmonary |
Therapuetic Areas: | Pulmonary / Respiratory Diseases |
Healthy: | No |
Age Range: | 18 - 65 |
Updated: | 3/16/2015 |
Start Date: | January 2015 |
End Date: | April 2015 |
Contact: | US GSK Clinical Trials Call Center |
Email: | GSKClinicalSupportHD@gsk.com |
Phone: | 877-379-3718 |
A Randomised Placebo-controlled Study to Evaluate the Effects of GSK2256294 Following Repeat Dosing on Pulmonary Artery Pressure in Healthy Volunteers Under Normoxic and Hypoxic Conditions
The study evaluates the effect of GSK2256294 exposure at steady state on pulmonary artery
systolic pressure (PASP) in healthy volunteers, under hypoxic conditions, after 7 days of
dosing. It is single centre, double blind, randomized, placebo-controlled study to be
conducted in approximately 30 healthy volunteers. Subjects will be screened no more than 30
days. Subject will be admitted in clinical unit on Day -1. Subject will be dosed for 7 days
in unit in morning on all days except for dosing on Days 3 -6. Dosing on Days 3 -6 will
occur at home. Subjects will return to the unit on the evening of Day 6 and remain there
until Day 8. Subjects will undergo echocardiography under normoxic and hypoxic on Day 1
pre-dose and on Day 7 post-dose. Subject will be followed up for 28- 32 days after
discharge. The maximum estimated time that a subject will be enrolled in the study is 62
days from the screening visit to follow up.
systolic pressure (PASP) in healthy volunteers, under hypoxic conditions, after 7 days of
dosing. It is single centre, double blind, randomized, placebo-controlled study to be
conducted in approximately 30 healthy volunteers. Subjects will be screened no more than 30
days. Subject will be admitted in clinical unit on Day -1. Subject will be dosed for 7 days
in unit in morning on all days except for dosing on Days 3 -6. Dosing on Days 3 -6 will
occur at home. Subjects will return to the unit on the evening of Day 6 and remain there
until Day 8. Subjects will undergo echocardiography under normoxic and hypoxic on Day 1
pre-dose and on Day 7 post-dose. Subject will be followed up for 28- 32 days after
discharge. The maximum estimated time that a subject will be enrolled in the study is 62
days from the screening visit to follow up.
Inclusion Criteria:
- AGE: Between 18 and 65 years of age inclusive, at the time of signing the informed
consent
- Screening echocardiogram of at least good quality, without clinically significant
abnormalities, and with mild-moderate tricuspid regurgitation sufficient for the
reliable estimation of PASP, as determined by the echocardiography core laboratory or
responsible cardiologist.
- Screening PASP within the normal range according to site standards
- Healthy as determined by the investigator or medically qualified designee based on a
medical evaluation including medical history, physical examination, laboratory tests
and cardiac monitoring.
- A subject with a clinical abnormality or laboratory parameter(s) which is/are not
specifically listed in the inclusion or exclusion criteria, outside the reference
range for the population being studied may be included only if the investigator [in
consultation with the Medical Monitor if required] agree and document that the
finding is unlikely to introduce additional risk factors and will not interfere with
the study procedures.
- Body weight >= 60 kilogram and body mass index within the range 19 - 35 kilogram per
square meter (inclusive)
- Female subject is eligible to participate if she is of non-reproductive potential
defined as: Pre-menopausal females with one of the following: documented tubal
ligation, documented hysteroscopic tubal occlusion procedure with follow-up
confirmation of bilateral tubal occlusion, hysterectomy, and documented bilateral
oophorectomy. Postmenopausal criteria is defined as 12 months of spontaneous
amenorrhea [in questionable cases a blood sample with simultaneous follicle
stimulating hormone (FSH) and estradiol levels consistent with menopause (refer to
laboratory reference ranges for confirmatory levels)]; females on hormone replacement
therapy (HRT) must discontinue their HRT before the start of the study; for those
whose menopausal status is in doubt, they will be required to use one of the highly
effective contraception methods and may need to have a blood sample taken to check
FSH/estradiol levels.
- Male subjects with female partners of child bearing potential must comply with the
following contraception requirements from the time of first dose of study medication
until two weeks after the last dose of study medication; vasectomy with documentation
of azoospermia; male condom plus partner use of one of the contraceptive options
below: Contraceptive subdermal implant that meets the Standard Operating Procedure
(SOP)effectiveness criteria including a <1% rate of failure per year, as stated in
the product label, Intrauterine device or intrauterine system that meets SOP
effectiveness criteria including a <1% rate of failure per year, as stated in the
product label, Oral Contraceptive, either combined or progestogen alone, Injectable
progestogen, Contraceptive vaginal ring; percutaneous contraceptive patches. These
allowed methods of contraception are only effective when used consistently, correctly
and in accordance with the product label. The investigator is responsible for
ensuring that subjects understand how to properly use these methods of contraception.
- Capable of giving signed informed consent as described in protocol, which includes
compliance with the requirements and restrictions listed in the consent form and in
protocol
Exclusion Criteria:
- Subjects with sickle cell trait.
- History of pulmonary hypertension.
- Alanine aminotransferase (ALT) and bilirubin >1.5x Upper limit of normal (ULN)
(isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct
bilirubin <35%).
- Current or chronic history of liver disease, or known hepatic or biliary
abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- QTcF > 450 milliseconds (msec) NOTE: The QTc is the QT interval corrected for heart
rate according to Fridericia's formula (QTcF). The specific formula that will be used
to determine eligibility and discontinuation for an individual subject should be
determined prior to initiation of the study. In other words, several different
formulae cannot be used to calculate the QTc for an individual subject and then the
lowest QTc value used to include or discontinue the subject from the trial. For
purposes of data analysis, QTcF will be used as specified in the Reporting and
Analysis Plan (RAP).
- Permitted Medications and Non-Drug Therapies: Acetaminophen, at doses of =< 2
grams/day is permitted for use any time during the study. Other concomitant
medication may be considered on a case by case basis by the investigator in
consultation with the GSK Medical Monitor. All concomitant medications taken during
the study will be recorded in the case report form. The minimum requirement is that
drug name, dose administered and the dates of administration be recorded.
- Prohibited Medications and Non-Drug Therapies: Subjects must abstain from taking
prescription or non-prescription drugs (including vitamins and dietary or herbal
supplements), within 7 days (or 14 days if the drug is a potential enzyme inducer) or
5 half-lives (whichever is longer) prior to the first dose of study medication until
completion of the follow-up visit, unless in the opinion of the Investigator and
sponsor the medication will not interfere with the study. - History of regular
alcohol consumption within 6 months of the study defined as: For US sites: 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 milliliter [ml]) of beer, 5 ounces
(150 ml) of wine or 1.5 ounces (45 ml) of 80 proof distilled spirits.
- Urinary cotinine levels indicative of smoking or history or regular use of tobacco-
or nicotine-containing products within 6 months prior to screening
- 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 Medical
Monitor, contraindicates their participation
- Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test
result at screening or within 3 months prior to first dose of study treatment. For
potent immunosuppressive agents, subjects with presence of hepatitis B core antibody
(HBcAb) should also be excluded.
- A positive pre-study drug/alcohol screen.
- A positive test for Human Immunodeficiency Virus (HIV) antibody.
- Where participation in the study would result in donation of blood or blood products
in excess of 500 mL within 56 days.
- 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
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