Effects of GSK1278863A on Pulmonary Artery Pressure in Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01673555
First received: July 12, 2012
Last updated: November 14, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Anaemia
Drug: GSK1278863
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science
Official Title: A Randomized, Placebo-controlled, Study to Evaluate the Effects of GSK1278863A on Pulmonary Artery Pressure in Healthy Volunteers

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Placebo-adjusted change from baseline in PASP (estimated by transthoracic echocardiography) under normoxic conditions following 5 days of GSK1278863 [ Time Frame: Day 5 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Placebo-adjusted change from baseline in PASP under normoxic and hypoxic conditions 8 hours after the first dose of study treatment [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    8 hours

  • Placebo-adjusted change from baseline in PASP under normoxic and hypoxic conditions following 1 day of therapy [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Placebo-adjusted change from baseline in PASP under normoxic and hypoxic conditions 8 hours after the fifth dose of study treatment [ Time Frame: Day 5 ] [ Designated as safety issue: No ]
    8 hours

  • Placebo-adjusted change from baseline in PASP under hypoxic conditions following 5 days of GSK1278863 [ Time Frame: Day 5 ] [ Designated as safety issue: No ]
  • Clinical safety and tolerability data including AE reporting, ECGs, vital signs, physical exam findings and clinical laboratory values, including hematologic parameters [ Time Frame: Day 5 ] [ Designated as safety issue: No ]
    Through-out the study

  • Plasma pharmacokinetics (AUC, Cmax, Tmax, T1/2, etc.) of GSK1278863 and its circulating metabolites (M2, M3, M4, M5, M6 and M13) [ Time Frame: Day 5 ] [ Designated as safety issue: No ]
    Through-out the study

  • RV size, RV ejection fraction, severity of tricuspid regurgitation, right ventricular outflow tract acceleration time at all time points at which echocardiograms are obtained (as data permit) [ Time Frame: Day 5 ] [ Designated as safety issue: No ]
    Exploratory outcomes; through-out the study

  • Biomarker/PD endpoints may include EPO, endothelin-1 and hepcidin or other markers of PHD or HIF activity, as data permit [ Time Frame: Day 5 ] [ Designated as safety issue: No ]
    Exploratory outcomes; through-out the study


Enrollment: 49
Study Start Date: May 2012
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK1278863 5mg
GSK1278863 5mg
Drug: GSK1278863
GSK1278863
Experimental: GSK1278863 100mg
GSK1278863 100mg
Drug: GSK1278863
GSK1278863
Placebo Comparator: Placebo
Placebo
Drug: Placebo
Placebo

Detailed Description:

This is a single-center, randomized, placebo-controlled, single-blinded (subjects and investigators will be blinded, GSK internal personnel will not be blinded) study designed to test whether short-term administration (5 days) of GSK1278863 affects PASP under normoxic and hypoxic conditions in healthy volunteers. Approximately 45 healthy subjects with mild-moderate baseline tricuspid regurgitation (sufficient to allow reliable assessment of PASP) will be enrolled into this study and will provide ~15 evaluable subjects in each arm [Placebo, 5 mg, and 100 mg GSK 1278863].

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01673555

Locations
United States, Maryland
GSK Investigational Site
Baltimore, Maryland, United States, 21225
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01673555     History of Changes
Other Study ID Numbers: 116008
Study First Received: July 12, 2012
Last Updated: November 14, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
GSK1278863
Pulmonary artery pressure

ClinicalTrials.gov processed this record on October 20, 2014