Back to resultsA Study to Evaluate the Effect of the Transient Receptor Potential Vanilloid 4 (TRPV4) Channel Blocker, GSK2798745, on Pulmonary Gas Transfer and Respiration in Patients With Congestive Heart Failure
Primary Purpose
Heart Failure
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
GSK2798745
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure focused on measuring GSK2798745, TRPV4 Channel Blocker, Pharmacodynamics, Adults, Congestive Heart Failure
Eligibility Criteria
Inclusion Criteria:
- >=21 years of age at the time of signing the informed consent form.
- Diagnosis of heart failure (New York Heart Association Class II-IV) for a minimum of 3 months prior to screening.
- Clinically stable with no changes in optimized guidance-directed medications and no hospitalizations for heart failure for at least 1 month prior to Screening.
- N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) >1000 picogram per milliliter (pg/mL) measured within 6 months prior to OR at Screening.
- Average DLco measurements outside the normal range (percent [%] predicted DLco < 80%) during the Screening Period.
- Body mass index (BMI) >=18 and <=40 kilogram per meter square (kg/m^2).
- Male or female of non-childbearing potential-
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in the protocol.
Exclusion Criteria:
- History of acute coronary syndromes including unstable angina or myocardial infarction within 6 months of screening.
- Coronary revascularization including angioplasty and stenting within 6 months of Screening.
- History of stroke or seizure disorder within 5 years of Screening.
- Diagnosis of asthma.
- Diagnosis of chronic obstructive pulmonary disease (COPD) with FEV1 <50% of predicted measured within 4 weeks of Screening.
- History of a condition that required radiation therapy to the thorax.
- History of any type of malignancy within the past five years with the exception of successfully treated basal cell cancer of the skin.
- Active ulcer disease or gastrointestinal bleeding.
- Current or chronic history of liver disease, known hepatic impairment, or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Alanine transaminase (ALT) >2x Upper Limit of Normal (ULN) and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- QT interval corrected (QTc) > 450 millisecond (msec) or QTc > 480 msec in subjects with Bundle Branch Block.
- History or current evidence of any serious or clinically significant gastrointestinal, renal, endocrine, neurologic, hematologic or other condition that is uncontrolled on permitted therapies or that would, in the opinion of the investigator or the GlaxoSmithKline (GSK) medical monitor, make the subject unsuitable for inclusion in this study.
- Use of medications specified for the treatment of COPD including short- and long acting bronchodilators (beta-agonists and anticholinergics) and inhaled glucocorticoids as well as oxygen therapy.
- Use of a listed prohibited medication within the restricted timeframe relative to the first dose of study medication.
- Use of a strong inhibitors or inducers of cytochrome P450 (CYP) 3A or p-glycoprotein.
- Current smoker.
- History of drug/substance abuse within the past 2 years.
- History of alcohol abuse within 6 months of the study. Defined as an average weekly alcohol consumption of >14 drinks for men or >7 drinks for women. One drink is equivalent to 12 grams (g) of alcohol: approximately 12 ounces (360 milliliters [mL]) of beer, 5 ounces (150 mL) of wine, or 1.5 ounces of (45 mL) 80 proof distilled spirits.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
- Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months of screening. For potent immunosuppressive agents, subjects with presence of hepatitis B core antibody (HBcAb) should also be excluded.
- A positive pre-study drug/alcohol screen.
- Use of another investigational product in a clinical study within the following time period prior to the first administration of study medication 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 4 investigational medicinal products within 12 months prior to the first administration of study medication.
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
GSK2798745 and Placebo
Arm Description
Each subject will be randomized to receive GSK2798745 2.4 milligrams (mg) and Placebo once daily for 7 days, each in one of the two treatment periods. Two treatment periods will be separated by a 14-day washout period.
Outcomes
Primary Outcome Measures
Change From Baseline in the Diffusing Capacity of the Lung for Carbon Monoxide (DLco) on Pulmonary Gas Transfer (Site: Mayo)
DLco is a measure of the ability of a gas to transfer from alveoli across the alveolar epithelium and capillary endothelium to the red blood cells. Changes in DLco reflect the alveolar-capillary membrane conductance. Acute pulmonary congestion causes a reduction in DLco. In participants with heart failure, decrease in DLco serves as a predictor of disease progression. An impairment in the diffusing capacity of the lung may be related to symptoms and exercise intolerance associated with heart failure. DLco was measured just prior to and after the 3- minute step test on Days -1, and 7 and just prior to and after an intravenous saline infusion on Day 5. Day -1 was Baseline and change from Baseline was calculated from Day -1 pre-exercise of the respective period, except when calculating the post-infusion change from Baseline, where the pre-infusion value was used as Baseline. Data of DLco (milliliter per millimeter of mercury per minute [mL/mmHg/min]) for Mayo site is presented.
Change From Baseline in the Diffusing Capacity of the Lung for DLco on Pulmonary Gas Transfer (Site: Hennepin)
DLco is a measure of the ability of a gas to transfer from the alveoli across the alveolar epithelium and the capillary endothelium to the red blood cells. Changes in DLco reflect the alveolar-capillary membrane conductance. Acute pulmonary congestion cause a reduction in DLco. In participants with heart failure, decrease in DLco serves as a predictor of disease progression. An impairment in the diffusing capacity of the lung may be related to the symptoms and exercise intolerance associated with heart failure. DLco was measured just prior to and after the 3- minute step test on Days -1, and 7 and just prior to and after an intravenous saline infusion on Day 5. Day -1 was Baseline and change from Baseline was calculated from Day -1 Pre-Exercise of the respective period, except when calculating the post-infusion change from Baseline, where the pre-infusion value was used as the Baseline. Statistical analysis was not performed as the sample size was too small
Secondary Outcome Measures
Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM)
DLno is a measure of the ability of a gas to transfer from the alveoli across the alveolar epithelium and the capillary endothelium to the red blood cells. Changes in DLco reflect the alveolar-capillary DM. Since nitric oxide has a greater affinity for hemoglobin, transfer of gas mainly limits the diffusion of nitric oxide across the alveolar capillary membrane. Day -1 was Baseline and change from Baseline was calculated from Day -1 pre-exercise of the respective period, except when calculating the post-infusion change from Baseline, where the pre-infusion value was used as Baseline. The data is presented only for participants from the Mayo Clinic as the data was not collected at Hennepin.
Change From Baseline in Capillary Blood Volume (Vc)
Vc is defined as volume of blood within the capillaries. Day -1 was Baseline and change from Baseline was calculated from Day -1 pre-exercise of the respective period, except when calculating the post-infusion change from Baseline, where the pre-infusion value was used as the Baseline. The data is presented only for participants from the Mayo Clinic as the data was not collected at Hennepin.
Change From Baseline in DLco Following Exercise and Following an Intravenous Saline Infusion (Site: Mayo)
DLco is a measure of the ability of a gas to transfer from the alveoli across the alveolar epithelium and the capillary endothelium to the red blood cells. Changes in DLco reflect the alveolar-capillary membrane conductance. Acute pulmonary congestion causes a reduction in DLco. In participants with heart failure, decrease in DLco serves as a predictor of disease progression. DLco was measured just prior to and after the 3- minute step test on Days -1, and 7 and just prior to and after an intravenous saline infusion on Day 5. Day -1 was Baseline and change from Baseline was calculated from Day -1 pre-exercise of the respective period, except when calculating the post-infusion change from Baseline, where the pre-infusion value was used as the Baseline. Data for DLco following exercise and following an intravenous saline infusion is presented for Mayo site.
Change From Baseline in DLco Following Exercise and Following an Intravenous Saline Infusion (Site: Hennepin)
DLco is a measure of the ability of a gas to transfer from the alveoli across the alveolar epithelium and the capillary endothelium to the red blood cells. Changes in DLco reflect the alveolar-capillary membrane conductance. Acute pulmonary congestion cause a reduction in DLco. In participants with heart failure, decrease in DLco serves as a predictor of disease progression. DLco was measured just prior to and after the 3- minute step test on Days -1, and 7 and just prior to and after an intravenous saline infusion on Day 5. Day -1 was Baseline and change from Baseline was calculated from Day -1 pre-Exercise of the respective period, except when calculating the post-infusion change from Baseline, where the pre-infusion value was used as the Baseline. Data for DLco following exercise and following an intravenous saline infusion is presented for Hennepin site is presented.
Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio
Participants were asked to participate in a submaximal exercise test that consisted of 3 parts: a 2-minute (min) resting Baseline, a 3-min step exercise and a 1-min recovery period. Throughout the test, breathing pattern, gas exchange, and heart rate were monitored using a simplified gas analysis system. Respiratory exchange ratio and the Borg Rating of Perceived Exertion measures were utilized to ensure participants perform progressive exercise while maintaining a submaximal level throughout the exercise period. Minute ventilation, breath frequency, tidal volume, oxygen consumption, carbon dioxide (CO2) production, Respiratory exchange ratio (RER) and end tidal CO2 were obtained from the breath-by-breath gas measurements. The VE/VCO2 slope and other variables were derived from this data. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point.
Change From Baseline in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Forced Expiratory Flows (FEF) 25-75, FEF50 and FEF75
FEV1 was defined as the volume of air that can be forced out in one second after taking a deep breath. FVC is the total amount of air exhaled during the lung function test. FEF is the the flow (or speed) of air coming out of the lung during the middle portion of a forced expiration. FEF 25-75, FEF50 and FEF75 is defined as a reduction in forced expiratory flow at 25 to 75 percent of the pulmonary volume. Results presented combines data across all sites. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point.
Change From Baseline in Functional Residual Capacity (FRC)
FRC is the volume of air present in the lungs at the end of passive expiration. FRC was planned to be measured by body plethysmography. Analysis was planned but not performed. FRC parameter was not collected because other measures which were collected served as reasonable surrogates.
Change From Baseline in End-expiratory Lung Volume (EELV) Measured by Body Plethysmograph
EELV corresponds to FRC in the presence of positive end expiration pressure (PEEP). Analysis was planned but not performed. EELV parameter was not collected because other measures which were collected served as reasonable surrogates.
Change From Baseline in Dyspnea Score
Dyspnea was assessed using a standardized, validated 5-point Likert scale. Participants were asked to check the box next to the statement that most accurately described their current state of breathlessness or shortness of breath. Scale consisted of 5 points : 1- Not short of breath, 2- Mildly short of breath, 3- Moderately short of breath, 4- Severely short of breath and 5- Very severely short of breath. Participants rated their current state of breathlessness on this 5 point scale. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point .
Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only)
Continuous remote monitoring was performed during each 7-day study period utilizing the Preventice BodyGuardian Remote Monitoring System. Participants were instructed to wear the sensor throughout each study period. Respiratory monitoring data was collected in different body positions like standing, leaning, lying and unknown. Data is presented only for participants from Mayo clinic.
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP)
SBP and DBP were measured in a semi-supine position after 5 minutes rest at Baseline and up to 7 days of each treatment period. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from specified time point value.
Change From Baseline in Heart Rate
Heart rate was measured in a semi-supine position after 5 minutes rest at Baseline and up to 7 days of each treatment period. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point.
Change From Baseline in Respiration Rate
Respiration rate was measured in a semi-supine position after 5 minutes rest at Baseline and up to 7 days of each treatment period. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point.
Change From Baseline in Temperature
Body temperature was measured in a semi-supine position after 5 minutes rest at Baseline and up to 7 days of each treatment period. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point.
Change From Baseline in Percent Oxygen in Blood
Percent oxygen in blood was measured using pulse oximetry in a semi-supine position after 5 minutes rest at Baseline and up to 7 days of each treatment period. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Triplicate 12-lead ECG was obtained using an automated ECG machine at Baseline (Day-1) and single ECG measurements (M) were taken on Day 4 and Day 7. Data for number of participants with abnormal-clinically significant (CS) and abnormal-not clinically significant (NCS) ECG data is presented.
Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values
Blood samples were collected to analyze the chemistry parameters including ALT, ALP, AST, creatine kinase and GGT. Change from Baseline is presented for these parameters. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point.
Change From Baseline in Albumin and Total Protein Values
Blood samples were collected to analyze the chemistry parameters including albumin and total protein. Change from Baseline is presented for these parameters. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point.
Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN)
Blood samples were collected to analyze the chemistry parameters including Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN. Change from Baseline is presented for these parameters. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from specified time point value.
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid
Blood samples were collected to analyze the chemistry parameters including Creatinine, Direct Bilirubin, Total Bilirubin and Uric acid. Change from Baseline was presented for these parameters. Day -1 was Baseline and change from Baseline was calculated by subtracting the baseline value from specified time point value.
Change From Baseline in Digoxin Level
Blood samples were collected to analyze the digoxin levels. Change from Baseline is presented for these parameters. Day -1 was Baseline and change from Baseline was calculated by subtracting the baseline value from specified time point value. NA indicates data not available. Standard deviation could not be calculated as a single participant was analyzed.
Change From Baseline in Troponin I Levels and Type I Collagen Cross-linked C-telopeptide
Blood samples were collected to analyze the troponin I level and type I collagen cross-linked C-telopeptide (T1CCT). Change from Baseline was presented for these parameters. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point.
Change From Baseline in Chemistry: N-terminal Pro-Brain Natriuretic Peptide
Blood samples were collected to analyze the Chemistry parameter N-terminal pro-Brain Natriuretic Peptide. Change from Baseline is presented for these parameters. Day -1 was Baseline and change from Baseline is calculated by subtracting the baseline value from specified time point value.
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils
Blood samples were collected to analyze the Hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet count, White Blood Cell (WBC) count, Total Neutrophils. Change from Baseline is presented for these parameters. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from specified time point value.
Change From Baseline in Hematocrit
Blood samples were collected to analyze the Hematology parameter Hematocrit. Change from Baseline is presented for this parameter. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from specified time point value.
Change From Baseline in Hemoglobin
Blood samples were collected to analyze Hemoglobin. Change from Baseline is presented for this parameter. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from specified time point value.
Change From Baseline in Mean Corpuscle Volume
Blood samples were collected to analyze Mean Corpuscle Volume. Change from Baseline is presented for this parameter. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from specified time point value.
Change From Baseline in Red Blood Cell Count (RBC) and Reticulocytes
Blood samples were collected to analyze the Hematology parameters including RBC and Reticulocytes. Change from Baseline is presented for these parameters. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from specified time point value.
Change From Baseline in Mean Corpuscle Hemoglobin Concentration
Blood samples were collected to analyze Mean Corpuscle Hemoglobin concentration . Change from Baseline is presented for this parameter. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from specified time point value. NA indicates data was not available. Standard deviation could not be calculated as a single participant was analyzed at the specified time point
Change From Baseline in Mean Corpuscle Hemoglobin
Blood samples were collected to analyze Mean Corpuscle Hemoglobin. Change from Baseline was presented for this parameter. Day -1 was Baseline and change from Baseline was calculated by subtracting the baseline value from specified time point value. NA indicates data was not available. Standard deviation could not be calculated as a single participant was analyzed at the specified time point
Number of Participants With All Adverse Events (AE) and Serious Adverse Events (SAE)
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinemia were categorized as SAE. Number of participants with AE and SAE are reported.
Change From Baseline in Participant Reported Health Status (SF-36) Acute Score
The SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile. The vitality sub-score assesses energy and fatigue, and ranges from 0 (worst) - 100 (best). Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from specified time point value.
Area Under the Concentration Time Curve (AUC) Time Zero to the Last Time of the Last Quantifiable Concentration (AUC(0-t)), AUC Over the Dosing Interval After First and Last Dose (AUC(0-tau)) and AUCall for GSK2798745
AUC(0-t), AUC(0-tau) and AUCall for GSK2798745 were determined based on intensive Pharmacokinetic (PK) sampling at the following time points: Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8 and 12 hours on Day 1, pre-dose and at 12 hours post dose on Day 2, pre-dose on Days 3 to 6, Pre-dose, 0.5, 1, 1.5, 2, 3, 5 and 10 hours on Day 7 and at 24 and 48 hours. PK parameter population included all participants in the PK Concentration Population for whom valid and evaluable pharmacokinetic parameters were derived
Maximum Drug Concentration (Cmax) for GSK2798745
Blood samples for PK analysis were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8 and 12 hours on Day 1, pre-dose and at 12 hours post dose on Day 2, pre-dose on Days 3 to 6, Pre-dose, 0.5, 1, 1.5, 2, 3, 5 and 10 hours on Day 7 and at 24 and 48 hours on Days 8 and 9. Cmax was defined as maximum observed plasma concentration of drug.
Time to Maximum Observed Plasma Concentration (Tmax) for GSK2798745
Blood samples for PK analysis were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8 and 12 hours on Day 1, pre-dose and at 12 hours post dose on Day 2, pre-dose on Days 3 to 6, Pre-dose, 0.5, 1, 1.5, 2, 3, 5 and 10 hours on Day 7 and at 24 and 48 hours on Days 8 and 9. Tmax was defined as time to maximum observed plasma concentration of drug.
Elimination Half Life (T½) for GSK2798745
Blood samples for PK analysis were planned to be collected at pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8 and 12 hours on Day 1, pre-dose and at 12 hours post dose on Day 2, pre-dose on Days 3 to 6, Pre-dose, 0.5, 1, 1.5, 2, 3, 5 and 10 hours on Day 7 and at 24 and 48 hours on Days 8 and 9. T½ was defined as Elimination half life of drug. Data is not available for t1/2. The analysis was planned but not performed. PK sampling scheme was not adequate enough to reliably estimate the t1/2 of GSK2798745.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02497937
Brief Title
A Study to Evaluate the Effect of the Transient Receptor Potential Vanilloid 4 (TRPV4) Channel Blocker, GSK2798745, on Pulmonary Gas Transfer and Respiration in Patients With Congestive Heart Failure
Official Title
A Randomized, Double-blind, Sponsor Un-blinded, Placebo-controlled, Phase 2a Crossover Study to Evaluate the Effect of the TRPV4 Channel Blocker, GSK2798745, on Pulmonary Gas Transfer and Respiration in Patients With Congestive Heart Failure
Study Type
Interventional
2. Study Status
Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
April 13, 2016 (Actual)
Primary Completion Date
August 21, 2017 (Actual)
Study Completion Date
August 21, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study is a single centre, randomised, double-blind, sponsor-unblinded, placebo-controlled, 2 by 2 crossover study in adults with heart failure. In blocking the TRPV4 ion channel and reducing pulmonary interstitial fluid, GSK2798745 may improve pulmonary function, respiration, and gas exchange as well as sleep-disordered breathing in patients with heart failure. Therefore, the current study is designed to investigate the effect of repeat administration of GSK2798745 on pulmonary gas exchange and pulmonary function.
A sufficient number of subjects with heart failure will be enrolled so that 12 subjects complete the two study periods and critical assessments. Subjects will be randomised to receive either GSK2798745 or placebo once daily for a period of 7 days in one treatment period and alternate study medication in the second treatment period. Both the treatment periods will be separated by a washout period of at least 14-days.
This study will consist of a Screening visit within 14 days of the start of Period I and two treatment periods wherein eligible subjects will be randomised to one of the two treatment sequences, a follow-up visit approximately 2 weeks after the completion of second study period. The total duration of the study is approximately 8 weeks from screening to follow-up visit.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure
Keywords
GSK2798745, TRPV4 Channel Blocker, Pharmacodynamics, Adults, Congestive Heart Failure
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GSK2798745 and Placebo
Arm Type
Experimental
Arm Description
Each subject will be randomized to receive GSK2798745 2.4 milligrams (mg) and Placebo once daily for 7 days, each in one of the two treatment periods. Two treatment periods will be separated by a 14-day washout period.
Intervention Type
Drug
Intervention Name(s)
GSK2798745
Intervention Description
GSK2798745 will be supplied as granule filled capsule with unit dose strength of 2.4 mg to be administered orally with 240 mL water.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo will be supplied as blend filled capsule to be administered orally with 240 mL water.
Primary Outcome Measure Information:
Title
Change From Baseline in the Diffusing Capacity of the Lung for Carbon Monoxide (DLco) on Pulmonary Gas Transfer (Site: Mayo)
Description
DLco is a measure of the ability of a gas to transfer from alveoli across the alveolar epithelium and capillary endothelium to the red blood cells. Changes in DLco reflect the alveolar-capillary membrane conductance. Acute pulmonary congestion causes a reduction in DLco. In participants with heart failure, decrease in DLco serves as a predictor of disease progression. An impairment in the diffusing capacity of the lung may be related to symptoms and exercise intolerance associated with heart failure. DLco was measured just prior to and after the 3- minute step test on Days -1, and 7 and just prior to and after an intravenous saline infusion on Day 5. Day -1 was Baseline and change from Baseline was calculated from Day -1 pre-exercise of the respective period, except when calculating the post-infusion change from Baseline, where the pre-infusion value was used as Baseline. Data of DLco (milliliter per millimeter of mercury per minute [mL/mmHg/min]) for Mayo site is presented.
Time Frame
Baseline, Day 4, Day 5 and Day 7 of each treatment period
Title
Change From Baseline in the Diffusing Capacity of the Lung for DLco on Pulmonary Gas Transfer (Site: Hennepin)
Description
DLco is a measure of the ability of a gas to transfer from the alveoli across the alveolar epithelium and the capillary endothelium to the red blood cells. Changes in DLco reflect the alveolar-capillary membrane conductance. Acute pulmonary congestion cause a reduction in DLco. In participants with heart failure, decrease in DLco serves as a predictor of disease progression. An impairment in the diffusing capacity of the lung may be related to the symptoms and exercise intolerance associated with heart failure. DLco was measured just prior to and after the 3- minute step test on Days -1, and 7 and just prior to and after an intravenous saline infusion on Day 5. Day -1 was Baseline and change from Baseline was calculated from Day -1 Pre-Exercise of the respective period, except when calculating the post-infusion change from Baseline, where the pre-infusion value was used as the Baseline. Statistical analysis was not performed as the sample size was too small
Time Frame
Baseline, Day 4, Day 5 and Day 7 of each treatment period
Secondary Outcome Measure Information:
Title
Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM)
Description
DLno is a measure of the ability of a gas to transfer from the alveoli across the alveolar epithelium and the capillary endothelium to the red blood cells. Changes in DLco reflect the alveolar-capillary DM. Since nitric oxide has a greater affinity for hemoglobin, transfer of gas mainly limits the diffusion of nitric oxide across the alveolar capillary membrane. Day -1 was Baseline and change from Baseline was calculated from Day -1 pre-exercise of the respective period, except when calculating the post-infusion change from Baseline, where the pre-infusion value was used as Baseline. The data is presented only for participants from the Mayo Clinic as the data was not collected at Hennepin.
Time Frame
Baseline, Day 4, Day 5 and Day 7 of each treatment period
Title
Change From Baseline in Capillary Blood Volume (Vc)
Description
Vc is defined as volume of blood within the capillaries. Day -1 was Baseline and change from Baseline was calculated from Day -1 pre-exercise of the respective period, except when calculating the post-infusion change from Baseline, where the pre-infusion value was used as the Baseline. The data is presented only for participants from the Mayo Clinic as the data was not collected at Hennepin.
Time Frame
Baseline, Day 4, Day 5 and Day 7 of each treatment period
Title
Change From Baseline in DLco Following Exercise and Following an Intravenous Saline Infusion (Site: Mayo)
Description
DLco is a measure of the ability of a gas to transfer from the alveoli across the alveolar epithelium and the capillary endothelium to the red blood cells. Changes in DLco reflect the alveolar-capillary membrane conductance. Acute pulmonary congestion causes a reduction in DLco. In participants with heart failure, decrease in DLco serves as a predictor of disease progression. DLco was measured just prior to and after the 3- minute step test on Days -1, and 7 and just prior to and after an intravenous saline infusion on Day 5. Day -1 was Baseline and change from Baseline was calculated from Day -1 pre-exercise of the respective period, except when calculating the post-infusion change from Baseline, where the pre-infusion value was used as the Baseline. Data for DLco following exercise and following an intravenous saline infusion is presented for Mayo site.
Time Frame
Baseline, Day 5 and Day 7 of each treatment period
Title
Change From Baseline in DLco Following Exercise and Following an Intravenous Saline Infusion (Site: Hennepin)
Description
DLco is a measure of the ability of a gas to transfer from the alveoli across the alveolar epithelium and the capillary endothelium to the red blood cells. Changes in DLco reflect the alveolar-capillary membrane conductance. Acute pulmonary congestion cause a reduction in DLco. In participants with heart failure, decrease in DLco serves as a predictor of disease progression. DLco was measured just prior to and after the 3- minute step test on Days -1, and 7 and just prior to and after an intravenous saline infusion on Day 5. Day -1 was Baseline and change from Baseline was calculated from Day -1 pre-Exercise of the respective period, except when calculating the post-infusion change from Baseline, where the pre-infusion value was used as the Baseline. Data for DLco following exercise and following an intravenous saline infusion is presented for Hennepin site is presented.
Time Frame
Baseline, Day 5 and Day 7 of each treatment period
Title
Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio
Description
Participants were asked to participate in a submaximal exercise test that consisted of 3 parts: a 2-minute (min) resting Baseline, a 3-min step exercise and a 1-min recovery period. Throughout the test, breathing pattern, gas exchange, and heart rate were monitored using a simplified gas analysis system. Respiratory exchange ratio and the Borg Rating of Perceived Exertion measures were utilized to ensure participants perform progressive exercise while maintaining a submaximal level throughout the exercise period. Minute ventilation, breath frequency, tidal volume, oxygen consumption, carbon dioxide (CO2) production, Respiratory exchange ratio (RER) and end tidal CO2 were obtained from the breath-by-breath gas measurements. The VE/VCO2 slope and other variables were derived from this data. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point.
Time Frame
Baseline and Day 7 of each treatment period
Title
Change From Baseline in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Forced Expiratory Flows (FEF) 25-75, FEF50 and FEF75
Description
FEV1 was defined as the volume of air that can be forced out in one second after taking a deep breath. FVC is the total amount of air exhaled during the lung function test. FEF is the the flow (or speed) of air coming out of the lung during the middle portion of a forced expiration. FEF 25-75, FEF50 and FEF75 is defined as a reduction in forced expiratory flow at 25 to 75 percent of the pulmonary volume. Results presented combines data across all sites. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point.
Time Frame
Baseline, Day 4 and Day 7 of each treatment period
Title
Change From Baseline in Functional Residual Capacity (FRC)
Description
FRC is the volume of air present in the lungs at the end of passive expiration. FRC was planned to be measured by body plethysmography. Analysis was planned but not performed. FRC parameter was not collected because other measures which were collected served as reasonable surrogates.
Time Frame
Baseline, Day 4 and Day 7 of each treatment period
Title
Change From Baseline in End-expiratory Lung Volume (EELV) Measured by Body Plethysmograph
Description
EELV corresponds to FRC in the presence of positive end expiration pressure (PEEP). Analysis was planned but not performed. EELV parameter was not collected because other measures which were collected served as reasonable surrogates.
Time Frame
Baseline, Day 4 and Day 7 of each treatment period
Title
Change From Baseline in Dyspnea Score
Description
Dyspnea was assessed using a standardized, validated 5-point Likert scale. Participants were asked to check the box next to the statement that most accurately described their current state of breathlessness or shortness of breath. Scale consisted of 5 points : 1- Not short of breath, 2- Mildly short of breath, 3- Moderately short of breath, 4- Severely short of breath and 5- Very severely short of breath. Participants rated their current state of breathlessness on this 5 point scale. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point .
Time Frame
Baseline, Day 5 and Day 7 of each treatment period
Title
Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only)
Description
Continuous remote monitoring was performed during each 7-day study period utilizing the Preventice BodyGuardian Remote Monitoring System. Participants were instructed to wear the sensor throughout each study period. Respiratory monitoring data was collected in different body positions like standing, leaning, lying and unknown. Data is presented only for participants from Mayo clinic.
Time Frame
Up to Day 7 of each treatment period
Title
Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP)
Description
SBP and DBP were measured in a semi-supine position after 5 minutes rest at Baseline and up to 7 days of each treatment period. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from specified time point value.
Time Frame
Baseline and up to Day 7 of each treatment period
Title
Change From Baseline in Heart Rate
Description
Heart rate was measured in a semi-supine position after 5 minutes rest at Baseline and up to 7 days of each treatment period. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point.
Time Frame
Baseline and up to Day 7 of each treatment period
Title
Change From Baseline in Respiration Rate
Description
Respiration rate was measured in a semi-supine position after 5 minutes rest at Baseline and up to 7 days of each treatment period. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point.
Time Frame
Baseline and up to Day 7 of each treatment period
Title
Change From Baseline in Temperature
Description
Body temperature was measured in a semi-supine position after 5 minutes rest at Baseline and up to 7 days of each treatment period. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point.
Time Frame
Baseline and up to Day 7 of each treatment period
Title
Change From Baseline in Percent Oxygen in Blood
Description
Percent oxygen in blood was measured using pulse oximetry in a semi-supine position after 5 minutes rest at Baseline and up to 7 days of each treatment period. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point.
Time Frame
Baseline and up to Day 7 of each treatment period
Title
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Description
Triplicate 12-lead ECG was obtained using an automated ECG machine at Baseline (Day-1) and single ECG measurements (M) were taken on Day 4 and Day 7. Data for number of participants with abnormal-clinically significant (CS) and abnormal-not clinically significant (NCS) ECG data is presented.
Time Frame
Up to Day 7 in each treatment period
Title
Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values
Description
Blood samples were collected to analyze the chemistry parameters including ALT, ALP, AST, creatine kinase and GGT. Change from Baseline is presented for these parameters. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point.
Time Frame
Baseline and up to Day 7 in each treatment period
Title
Change From Baseline in Albumin and Total Protein Values
Description
Blood samples were collected to analyze the chemistry parameters including albumin and total protein. Change from Baseline is presented for these parameters. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point.
Time Frame
Baseline and up to Day 7 of each treatment period
Title
Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN)
Description
Blood samples were collected to analyze the chemistry parameters including Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN. Change from Baseline is presented for these parameters. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from specified time point value.
Time Frame
Baseline and up to Day 7 of each treatment period
Title
Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid
Description
Blood samples were collected to analyze the chemistry parameters including Creatinine, Direct Bilirubin, Total Bilirubin and Uric acid. Change from Baseline was presented for these parameters. Day -1 was Baseline and change from Baseline was calculated by subtracting the baseline value from specified time point value.
Time Frame
Baseline and up to Day 7 of each treatment period
Title
Change From Baseline in Digoxin Level
Description
Blood samples were collected to analyze the digoxin levels. Change from Baseline is presented for these parameters. Day -1 was Baseline and change from Baseline was calculated by subtracting the baseline value from specified time point value. NA indicates data not available. Standard deviation could not be calculated as a single participant was analyzed.
Time Frame
Baseline and up to Day 7 in each treatment period
Title
Change From Baseline in Troponin I Levels and Type I Collagen Cross-linked C-telopeptide
Description
Blood samples were collected to analyze the troponin I level and type I collagen cross-linked C-telopeptide (T1CCT). Change from Baseline was presented for these parameters. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from value at specified time point.
Time Frame
Baseline and up to Day 7 in each treatment period
Title
Change From Baseline in Chemistry: N-terminal Pro-Brain Natriuretic Peptide
Description
Blood samples were collected to analyze the Chemistry parameter N-terminal pro-Brain Natriuretic Peptide. Change from Baseline is presented for these parameters. Day -1 was Baseline and change from Baseline is calculated by subtracting the baseline value from specified time point value.
Time Frame
Baseline and up to Day 7 in each treatment period
Title
Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils
Description
Blood samples were collected to analyze the Hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet count, White Blood Cell (WBC) count, Total Neutrophils. Change from Baseline is presented for these parameters. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from specified time point value.
Time Frame
Baseline and up to Day 7 in each treatment period
Title
Change From Baseline in Hematocrit
Description
Blood samples were collected to analyze the Hematology parameter Hematocrit. Change from Baseline is presented for this parameter. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from specified time point value.
Time Frame
Baseline and up to Day 7 in each treatment period
Title
Change From Baseline in Hemoglobin
Description
Blood samples were collected to analyze Hemoglobin. Change from Baseline is presented for this parameter. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from specified time point value.
Time Frame
Baseline and up to Day 7 in each treatment period
Title
Change From Baseline in Mean Corpuscle Volume
Description
Blood samples were collected to analyze Mean Corpuscle Volume. Change from Baseline is presented for this parameter. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from specified time point value.
Time Frame
Baseline and up to Day 7 in each treatment period
Title
Change From Baseline in Red Blood Cell Count (RBC) and Reticulocytes
Description
Blood samples were collected to analyze the Hematology parameters including RBC and Reticulocytes. Change from Baseline is presented for these parameters. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from specified time point value.
Time Frame
Baseline and up to Day 7 in each treatment period
Title
Change From Baseline in Mean Corpuscle Hemoglobin Concentration
Description
Blood samples were collected to analyze Mean Corpuscle Hemoglobin concentration . Change from Baseline is presented for this parameter. Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from specified time point value. NA indicates data was not available. Standard deviation could not be calculated as a single participant was analyzed at the specified time point
Time Frame
Baseline and up to Day 7 in each treatment period
Title
Change From Baseline in Mean Corpuscle Hemoglobin
Description
Blood samples were collected to analyze Mean Corpuscle Hemoglobin. Change from Baseline was presented for this parameter. Day -1 was Baseline and change from Baseline was calculated by subtracting the baseline value from specified time point value. NA indicates data was not available. Standard deviation could not be calculated as a single participant was analyzed at the specified time point
Time Frame
Baseline and up to Day 7 in each treatment period
Title
Number of Participants With All Adverse Events (AE) and Serious Adverse Events (SAE)
Description
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinemia were categorized as SAE. Number of participants with AE and SAE are reported.
Time Frame
Up to Day 46
Title
Change From Baseline in Participant Reported Health Status (SF-36) Acute Score
Description
The SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile. The vitality sub-score assesses energy and fatigue, and ranges from 0 (worst) - 100 (best). Day -1 was Baseline and change from Baseline was calculated by subtracting the Baseline value from specified time point value.
Time Frame
Baseline and Day 7 of each treatment period
Title
Area Under the Concentration Time Curve (AUC) Time Zero to the Last Time of the Last Quantifiable Concentration (AUC(0-t)), AUC Over the Dosing Interval After First and Last Dose (AUC(0-tau)) and AUCall for GSK2798745
Description
AUC(0-t), AUC(0-tau) and AUCall for GSK2798745 were determined based on intensive Pharmacokinetic (PK) sampling at the following time points: Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8 and 12 hours on Day 1, pre-dose and at 12 hours post dose on Day 2, pre-dose on Days 3 to 6, Pre-dose, 0.5, 1, 1.5, 2, 3, 5 and 10 hours on Day 7 and at 24 and 48 hours. PK parameter population included all participants in the PK Concentration Population for whom valid and evaluable pharmacokinetic parameters were derived
Time Frame
Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8 and 12 hours post-dose), Day 2 (pre-dose, 12 hours post-dose), Days 3 to 6 (pre-dose), Day 7 (Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 10, 24 and 48 hours post-dose)
Title
Maximum Drug Concentration (Cmax) for GSK2798745
Description
Blood samples for PK analysis were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8 and 12 hours on Day 1, pre-dose and at 12 hours post dose on Day 2, pre-dose on Days 3 to 6, Pre-dose, 0.5, 1, 1.5, 2, 3, 5 and 10 hours on Day 7 and at 24 and 48 hours on Days 8 and 9. Cmax was defined as maximum observed plasma concentration of drug.
Time Frame
Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8 and 12 hours post-dose), Day 2 (pre-dose, 12 hours post-dose), Days 3 to 6 (pre-dose), Day 7 (Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 10, 24 and 48 hours post-dose)
Title
Time to Maximum Observed Plasma Concentration (Tmax) for GSK2798745
Description
Blood samples for PK analysis were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8 and 12 hours on Day 1, pre-dose and at 12 hours post dose on Day 2, pre-dose on Days 3 to 6, Pre-dose, 0.5, 1, 1.5, 2, 3, 5 and 10 hours on Day 7 and at 24 and 48 hours on Days 8 and 9. Tmax was defined as time to maximum observed plasma concentration of drug.
Time Frame
Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8 and 12 hours post-dose), Day 2 (pre-dose, 12 hours post-dose), Days 3 to 6 (pre-dose), Day 7 (Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 10, 24 and 48 hours post-dose)
Title
Elimination Half Life (T½) for GSK2798745
Description
Blood samples for PK analysis were planned to be collected at pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8 and 12 hours on Day 1, pre-dose and at 12 hours post dose on Day 2, pre-dose on Days 3 to 6, Pre-dose, 0.5, 1, 1.5, 2, 3, 5 and 10 hours on Day 7 and at 24 and 48 hours on Days 8 and 9. T½ was defined as Elimination half life of drug. Data is not available for t1/2. The analysis was planned but not performed. PK sampling scheme was not adequate enough to reliably estimate the t1/2 of GSK2798745.
Time Frame
Day 1 (Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8 and 12 hours post-dose), Day 2 (pre-dose, 12 hours post-dose), Days 3 to 6 (pre-dose), Day 7 (Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 10, 24 and 48 hours post-dose)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
>=21 years of age at the time of signing the informed consent form.
Diagnosis of heart failure (New York Heart Association Class II-IV) for a minimum of 3 months prior to screening.
Clinically stable with no changes in optimized guidance-directed medications and no hospitalizations for heart failure for at least 1 month prior to Screening.
N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) >1000 picogram per milliliter (pg/mL) measured within 6 months prior to OR at Screening.
Average DLco measurements outside the normal range (percent [%] predicted DLco < 80%) during the Screening Period.
Body mass index (BMI) >=18 and <=40 kilogram per meter square (kg/m^2).
Male or female of non-childbearing potential-
Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in the protocol.
Exclusion Criteria:
History of acute coronary syndromes including unstable angina or myocardial infarction within 6 months of screening.
Coronary revascularization including angioplasty and stenting within 6 months of Screening.
History of stroke or seizure disorder within 5 years of Screening.
Diagnosis of asthma.
Diagnosis of chronic obstructive pulmonary disease (COPD) with FEV1 <50% of predicted measured within 4 weeks of Screening.
History of a condition that required radiation therapy to the thorax.
History of any type of malignancy within the past five years with the exception of successfully treated basal cell cancer of the skin.
Active ulcer disease or gastrointestinal bleeding.
Current or chronic history of liver disease, known hepatic impairment, or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
Alanine transaminase (ALT) >2x Upper Limit of Normal (ULN) and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
QT interval corrected (QTc) > 450 millisecond (msec) or QTc > 480 msec in subjects with Bundle Branch Block.
History or current evidence of any serious or clinically significant gastrointestinal, renal, endocrine, neurologic, hematologic or other condition that is uncontrolled on permitted therapies or that would, in the opinion of the investigator or the GlaxoSmithKline (GSK) medical monitor, make the subject unsuitable for inclusion in this study.
Use of medications specified for the treatment of COPD including short- and long acting bronchodilators (beta-agonists and anticholinergics) and inhaled glucocorticoids as well as oxygen therapy.
Use of a listed prohibited medication within the restricted timeframe relative to the first dose of study medication.
Use of a strong inhibitors or inducers of cytochrome P450 (CYP) 3A or p-glycoprotein.
Current smoker.
History of drug/substance abuse within the past 2 years.
History of alcohol abuse within 6 months of the study. Defined as an average weekly alcohol consumption of >14 drinks for men or >7 drinks for women. One drink is equivalent to 12 grams (g) of alcohol: approximately 12 ounces (360 milliliters [mL]) of beer, 5 ounces (150 mL) of wine, or 1.5 ounces of (45 mL) 80 proof distilled spirits.
History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months of screening. For potent immunosuppressive agents, subjects with presence of hepatitis B core antibody (HBcAb) should also be excluded.
A positive pre-study drug/alcohol screen.
Use of another investigational product in a clinical study within the following time period prior to the first administration of study medication 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 4 investigational medicinal products within 12 months prior to the first administration of study medication.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55415
Country
United States
Facility Name
GSK Investigational Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Study to Evaluate the Effect of the Transient Receptor Potential Vanilloid 4 (TRPV4) Channel Blocker, GSK2798745, on Pulmonary Gas Transfer and Respiration in Patients With Congestive Heart Failure
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