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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GSK1278863 | Experimental | Subjects will be given five oral doses of GSK1278863 100 mg (5mg if a low dose is elected for subjects enrolled after interim analysis). The first dose will be administered immediately after completion of eccentric exercise, and then at 4, 8, 24, and 48 hours |
|
| Placebo | Placebo Comparator | Subjects will be given five oral doses of Placebo. The first dose will be administered immediately after completion of eccentric exercise, and then at 4, 8, 24, and 48 hours |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK1278863 | Drug | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Up to 72 hours (hrs) |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Up to 72 hrs |
| Percent change in MVC following eccentric exercise from pre-eccentric exercise in subjects treated with GSK1278863 or placebo |
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Inclusion Criteria:
Exclusion Criteria:
Criteria Based Upon Medical History
An average weekly intake of >14 drinks for males. One drink is equivalent to 12 grams(g) of alcohol: 12 ounces [360 milliliter (mL)] of beer, 5 ounces (150mL) of wine or 1.5 ounces (45mL) of 80 proof distilled spirits.
Criteria Based Upon Diagnostic Assessments
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Baltimore | Maryland | 21225 | United States |
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| Label | URL |
|---|---|
| Results for study 200884 can be found on the GSK Clinical Study Register. | View source |
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| ID | Term |
|---|---|
| D013708 | Tendon Injuries |
| D063806 | Myalgia |
| ID | Term |
|---|---|
| D014947 | Wounds and Injuries |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D009468 | Neuromuscular Diseases |
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| ID | Term |
|---|---|
| C000599718 | GSK1278863 |
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| Placebo | Drug | GSK1278863 matching placebo will be supplied as oral tablets for administration with 240 mL of water after end of eccentric exercise |
|
Percent change in muscle strength from pre-eccentric exercise to completion of eccentric exercise will be assessed |
| 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 | Up to Day 15 |
| Vital signs assessment as a safety measure | Vital signs includes systolic and diastolic blood pressure, pulse rate and respiratory rate | 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 | Up to Day 15 |
| Laboratory parameters assessment as a safety measure | Laboratory parameters include hematology, clinical chemistry, and urinalysis | 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 | 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 | 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)] | Up to Day 2 |
| D009422 |
| Nervous System Diseases |
| D059352 | Musculoskeletal Pain |
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |