As per non-clinical studies, prolyl hydroxylase inhibitor GSK1278863 can protect muscle from unaccustomed exercise induced muscle damage and enhance functional muscle repair. This study is designed to investigate arm function, pain and other pharmacodynamic (PD) markers after unaccustomed maximal eccentric exercise with concurrent administration of GSK1278863 or placebo. Primary objective of the study is to evaluate the protective effects of GSK1278863 on eccentric exercise induced muscle injury. Subjects will be randomized in a 1:1 ratio (1 subject on GSK1278863 for every 1 subject on placebo). Each subject will be given five oral doses of GSK1278863/placebo in total. The first dose will be administered immediately after completion of eccentric exercise and then 4, 8, 24, and 48 hours later. Subjects will be housed till day 4 in unit and will return for a follow-up visit 7-10 days after discharge. After enrolment of approximately 30 subjects, enrolment will be paused and planned interim analysis will be performed to decide whether to terminate enrolment/study, continue dosing or to reduce the dose to 5 milligrams (mg).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
26
GSK1278863 will be supplied as oral tablet of strength 100mg, 5mg(5mg if a low dose is elected for subjects enrolled after interim analysis) to be administered with 240 mL of water after end of eccentric exercise
GSK1278863 matching placebo will be supplied as oral tablets for administration with 240 mL of water after end of eccentric exercise
GSK Investigational Site
Baltimore, Maryland, United States
Maximal voluntary contraction (MVC) following eccentric exercise in subjects treated with GSK1278863 or placebo
Muscle strength is a measure of the amount of force produced during a maximal voluntary contraction of the elbow flexors. It will be assessed in the non-dominant arm by a maximal isometric (fixed length) contraction using Cybex ergometer in a seated position after completion of eccentric exercise
Time frame: Up to 72 hours (hrs)
Change in MVC following eccentric exercise from pre-eccentric exercise in subjects treated with GSK1278863 or placebo
Change in muscle strength from pre-eccentric exercise to completion of eccentric exercise will be assessed
Time frame: Up to 72 hrs
Percent change in MVC following eccentric exercise from pre-eccentric exercise in subjects treated with GSK1278863 or placebo
Percent change in muscle strength from pre-eccentric exercise to completion of eccentric exercise will be assessed
Time frame: Up to 72 hrs
Number of subjects with adverse events(AE)
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
Time frame: Up to Day 15
Vital signs assessment as a safety measure
Vital signs includes systolic and diastolic blood pressure, pulse rate and respiratory rate
Time frame: Up to Day 15
Electrocardiogram (ECG) assessment as a safety measure
Single 12-lead ECGs will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, Total cardiac output (QT), and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals
Time frame: Up to Day 15
Laboratory parameters assessment as a safety measure
Laboratory parameters include hematology, clinical chemistry, and urinalysis
Time frame: Up to Day 15
Change in subject pain assessment using a visual analog scale
Arm pain will be assessed for the exercised arm with a visual analog scale on a scale of 0-100 millimeter (mm) during two stimuli; during passive stretching and during MVC contraction, post-exercise and after completion of eccentric exercise
Time frame: Up to 72 hrs
Change in degree of motion and resting arm angle from post-exercise
Subjects will be asked to maximally flex their elbow and then maximally extend their elbow, joint angle will be measured using a manual goniometer at maximum flexion and maximum extension. Range of motion will be calculated by subtracting the flexion angle from the extension angle
Time frame: Up to 72 hrs
Composite of PK parameters
PK parameters include maximum observed concentration (Cmax), time of occurrence of Cmax (tmax), and Area under the concentration-time curve from zero (pre-dose) to 24h \[AUC(0-24)\]
Time frame: Up to Day 2
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.