Tendon Injuries
Conditions
Keywords
muscle soreness, Muscle damage and recovery, muscle function, eccentric exercise
Brief summary
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).
Interventions
DRUGGSK1278863
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
DRUGPlacebo
GSK1278863 matching placebo will be supplied as oral tablets for administration with 240 mL of water after end of eccentric exercise
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* A subject will be eligible for inclusion in this study only if all of the following criteria apply: * Males between 18 and 35 years of age inclusive, at the time of signing the informed consent. * 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(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 GSK Medical Monitor agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Subjects with hemoglobin values outside the normal range should always be excluded from enrolment. * Body weight \>= 70 kilogram (kg) and Body mass index (BMI) within the range 22.0 to 34.0 (inclusive). * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. * Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin \<= 1.5x Upper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). * Corrected QT interval (QTc) \< 450 milliseconds (msec) based on single or average QTc value of triplicate values obtained over a brief recording period. The QT correction formula (Fridericia's) used to determine inclusion and discontinuation should be the same throughout the study. * At least a 1year history of no regular (2-3 times per week) exercise and no heavy exertion within past week, and in the examining physician's opinion the study participant's physical condition/physique is consistent with a history of no regular physical activity for the past year. * No strenuous exercise involving the arms during the last 10 weeks (e.g., resistance training, rock climbing, rowing, chopping wood, digging, shovelling, sawing). * The subject is mentally and legally able to comply with the requirements and restrictions of the protocol and has provided signed informed consent prior to participation in any protocol-specific procedures, including Screening procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximal voluntary contraction (MVC) following eccentric exercise in subjects treated with GSK1278863 or placebo | Up to 72 hours (hrs) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent change in MVC following eccentric exercise from pre-eccentric exercise in subjects treated with GSK1278863 or placebo | Up to 72 hrs | Percent change in muscle strength from pre-eccentric exercise to completion of eccentric exercise will be assessed |
| Number of subjects with adverse events(AE) | Up to Day 15 | 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 |
| Vital signs assessment as a safety measure | Up to Day 15 | Vital signs includes systolic and diastolic blood pressure, pulse rate and respiratory rate |
| Electrocardiogram (ECG) assessment as a safety measure | Up to Day 15 | 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 |
| Change in MVC following eccentric exercise from pre-eccentric exercise in subjects treated with GSK1278863 or placebo | Up to 72 hrs | Change in muscle strength from pre-eccentric exercise to completion of eccentric exercise will be assessed |
| Change in subject pain assessment using a visual analog scale | Up to 72 hrs | 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 |
| Change in degree of motion and resting arm angle from post-exercise | Up to 72 hrs | 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 |
| Composite of PK parameters | Up to Day 2 | 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 \[AUC(0-24)\] |
| Laboratory parameters assessment as a safety measure | Up to Day 15 | Laboratory parameters include hematology, clinical chemistry, and urinalysis |
Countries
United States
Outcome results
None listed