- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01673555
Effects of GSK1278863A on Pulmonary Artery Pressure in Healthy Volunteers
June 7, 2017 updated by: GlaxoSmithKline
A Randomized, Placebo-controlled, Study to Evaluate the Effects of GSK1278863A on Pulmonary Artery Pressure in Healthy Volunteers
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.
Study Overview
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].
Study Type
Interventional
Enrollment (Actual)
49
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Maryland
-
Baltimore, Maryland, United States, 21225
- GSK Investigational Site
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 55 years (ADULT)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
Male
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: BASIC_SCIENCE
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: SINGLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
PLACEBO_COMPARATOR: Placebo
|
Placebo
|
EXPERIMENTAL: GSK1278863 5mg
|
GSK1278863
|
EXPERIMENTAL: GSK1278863 100mg
|
GSK1278863
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Placebo-adjusted change from baseline in PASP (estimated by transthoracic echocardiography) under normoxic conditions following 5 days of GSK1278863
Time Frame: Day 5
|
Day 5
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
8 hours
|
Day 1
|
Placebo-adjusted change from baseline in PASP under normoxic and hypoxic conditions following 1 day of therapy
Time Frame: Day 1
|
Day 1
|
|
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
|
8 hours
|
Day 5
|
Placebo-adjusted change from baseline in PASP under hypoxic conditions following 5 days of GSK1278863
Time Frame: Day 5
|
Day 5
|
|
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
|
Through-out the study
|
Day 5
|
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
|
Through-out the study
|
Day 5
|
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
|
Exploratory outcomes; through-out the study
|
Day 5
|
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
|
Exploratory outcomes; through-out the study
|
Day 5
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
May 15, 2012
Primary Completion (ACTUAL)
November 19, 2012
Study Completion (ACTUAL)
November 19, 2012
Study Registration Dates
First Submitted
July 12, 2012
First Submitted That Met QC Criteria
August 23, 2012
First Posted (ESTIMATE)
August 28, 2012
Study Record Updates
Last Update Posted (ACTUAL)
June 9, 2017
Last Update Submitted That Met QC Criteria
June 7, 2017
Last Verified
June 1, 2017
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- 116008
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Study Data/Documents
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Statistical Analysis Plan
Information identifier: 116008Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Dataset Specification
Information identifier: 116008Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Clinical Study Report
Information identifier: 116008Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Study Protocol
Information identifier: 116008Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Annotated Case Report Form
Information identifier: 116008Information comments: For additional information about this study please refer to the GSK Clinical Study Register
-
Individual Participant Data Set
Information identifier: 116008Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Informed Consent Form
Information identifier: 116008Information comments: For additional information about this study please refer to the GSK Clinical Study Register
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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