GSK1278863 Effects on Eccentric Exercise-Induced Muscle Damage

NCT02231190 | Completed Phase 1

• 1 other identifier: 200884
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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).

Conditions

Tendon Injuries

Keywords

muscle soreness; Muscle damage and recovery; muscle function; eccentric exercise

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (9)

• Change in MVC following eccentric exercise from pre-eccentric exercise in subjects treated with GSK1278863 or placebo

  Up to 72 hrs

• Percent change in MVC following eccentric exercise from pre-eccentric exercise in subjects treated with GSK1278863 or placebo

  Up to 72 hrs

• Number of subjects with adverse events(AE)

  Up to Day 15

• Vital signs assessment as a safety measure

  Up to Day 15

• Electrocardiogram (ECG) assessment as a safety measure

  Up to Day 15

Study Arms (2)

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

Drug: GSK1278863

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

Drug: Placebo

Interventions

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

GSK1278863

Placebo DRUG

GSK1278863 matching placebo will be supplied as oral tablets for administration with 240 mL of water after end of eccentric exercise

Placebo

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males between 18 and 35 years of age inclusive, at the time of signing the informed consent.

You may not qualify if:

• 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%).
• 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.
• Criteria Based Upon Medical History
• History of dizziness or vertigo.
• Uncontrolled hypertension \[diastolic blood pressure (BP) \>100 millimeter of mercury (mmHg) or systolic BP \>170mmHg\] at Screening.
• Taking anti-inflammatory, glucocorticoid or other pain medication more than 2 times per week over the previous month.
• Unwilling to 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:
• 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.
• History of drug abuse or dependence within 6 months of the study.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Baltimore, Maryland, 21225, United States

Location

Related Links

• Results for study 200884 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Tendon Injuries; Myalgia

Interventions

GSK1278863

Condition Hierarchy (Ancestors)

Wounds and Injuries; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Musculoskeletal Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2014
• First Posted: September 4, 2014
• Study Start: January 15, 2015
• Primary Completion: June 12, 2015
• Study Completion: June 12, 2015
• Last Updated: May 9, 2017

Record last verified: 2017-05

Locations

US (1)