Effects of GSK1278863A on Pulmonary Artery Pressure in Healthy Volunteers

NCT01673555 | Completed Phase 1

• 1 other identifier: 116008
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

This protocol is designed to explore whether short-term therapy with GSK1278863 affects PASP under normoxic and hypoxic conditions in healthy volunteers. Healthy subjects will be evaluated using echocardiography to estimate PASP based on the velocity of the tricuspid regurgitant jet. Resting PASP will be assessed under normoxic (room air) conditions, as well as after 30 minutes' exposure to 15% O2 before, during, and after short-term treatment with GSK1278863.

Conditions

Anaemia

Keywords

GSK1278863; Pulmonary artery pressure

Outcome Measures

Primary Outcomes (1)

• Placebo-adjusted change from baseline in PASP (estimated by transthoracic echocardiography) under normoxic conditions following 5 days of GSK1278863

  Day 5

Secondary Outcomes (8)

• Placebo-adjusted change from baseline in PASP under normoxic and hypoxic conditions 8 hours after the first dose of study treatment

  Day 1

• Placebo-adjusted change from baseline in PASP under normoxic and hypoxic conditions following 1 day of therapy

  Day 1

• Placebo-adjusted change from baseline in PASP under normoxic and hypoxic conditions 8 hours after the fifth dose of study treatment

  Day 5

• Placebo-adjusted change from baseline in PASP under hypoxic conditions following 5 days of GSK1278863

  Day 5

• Clinical safety and tolerability data including AE reporting, ECGs, vital signs, physical exam findings and clinical laboratory values, including hematologic parameters

  Day 5

Study Arms (3)

GSK1278863 5mg

EXPERIMENTAL

GSK1278863 5mg

Drug: GSK1278863

GSK1278863 100mg

EXPERIMENTAL

GSK1278863 100mg

Drug: GSK1278863

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

GSK1278863 DRUG

GSK1278863

GSK1278863 100mg; GSK1278863 5mg

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• AST, ALT, alkaline phosphatase and bilirubin less than and equal to 1.5xULN (isolated bilirubin greater than 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%).
• Healthy as determined by a responsible and experienced physician, based on a medical evaluation including \[medical history, physical examination and laboratory tests\]. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk and will not interfere with the study procedures.
• A hemoglobin value at screening between 13.5- 16 g/dL.
• Male subjects between 18 and 55 years of age inclusive, at the time of signing the informed consent.
• Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until the follow-up visit.
• BMII less than and equal to 32 kg/m2
• Single QTcB or QTcF less than 450 msec
• 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 under normoxic conditions.

You may not qualify if:

• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result.
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• A positive pre-study drug/alcohol screen.
• Any history of IV drug abuse.
• A positive test for HIV antibody.
• History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of greater than 14 drinks for males or greater than 7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 ml) of beer, 5 ounces (150 ml) of wine or 1.5 ounces (45 ml) of 80 proof distilled spirits.
• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) 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, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
• Strong family history of malignancy.
• Subjects with sickle cell trait.
• History of pulmonary hypertension

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Baltimore, Maryland, 21225, United States

Location

Related Publications (1)

• Olson E, Demopoulos L, Haws TF, Hu E, Fang Z, Mahar KM, Qin P, Lepore J, Bauer TA, Hiatt WR. Short-term treatment with a novel HIF-prolyl hydroxylase inhibitor (GSK1278863) failed to improve measures of performance in subjects with claudication-limited peripheral artery disease. Vasc Med. 2014 Dec;19(6):473-82. doi: 10.1177/1358863X14557151. Epub 2014 Nov 6.

  PMID: 25377872 DERIVED

Related Links

• Results for study 116008 can be found on the GSK Clinical Study Register.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Anemia

Interventions

GSK1278863

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2012
• First Posted: August 28, 2012
• Study Start: May 15, 2012
• Primary Completion: November 19, 2012
• Study Completion: November 19, 2012
• Last Updated: June 9, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will share

Locations

US (1)