Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
GSK2256294, normoxic, hypoxic, Pulmonary artery systolic pressure (PASP)
Brief summary
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.
Interventions
DRUGGSK2256294
GSK2256294 will be supplied as gelatin capsule to be administered orally with the unit dose 5 mg / dose level 15 mg
DRUGPlacebo
Matched Placebo will be supplied as gelatin capsule to be administered orally
Sponsors
Parexel
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline of PASP under hypoxic conditions | Day 1 and Day 7 | PASP is an indicator of cardiac hemodynamic status and is non-invasively estimated by echocardiography. Change from baseline in PASP under hypoxic conditions following 7 days of GSK2256294 15 milligrams (mg) once daily. Change from baseline was calculated as the Day 7 value minus the Day1 value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects with Adverse events (AEs) | Up to Day 32 | An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. |
| Assessment of 12-lead electrocardiogram (ECG) | Up to Day 32 | Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals |
| Change from baseline of PASP under normoxic conditions | Day 1 and Day 7 | The PASP is an indicator of cardiac hemodynamic status and is non-invasively estimated by echocardiography. Change from baseline in PASP under normoxic conditions following 7 days of GSK2256294 15 mg once daily. Change from baseline was calculated as the Day 7 value minus Day 1 value. |
| Assessment of physical examination findings | Up to Day 32 | A complete physical examination will include, at a minimum, assessment of the Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. Height and weight will also be measured and recorded. A brief physical examination will include, at a minimum assessments of the lungs, cardiovascular system, and abdomen (liver and spleen). |
| Assessment of clinical laboratory parameters | Up to Day 32 | Clinical laboratory parameters includes haematology, clinical chemistry and urinalysis |
| Assessment of vital sign measurements | Up to Day 32 | Vital sign assessments includes temperature, blood pressure (systolic and diastolic) and pulse rate. measurements |
Countries
United States
Outcome results
None listed