Heart Failure
Conditions
Keywords
GSK2798745, TRPV4 Channel Blocker, Pharmacodynamics, Adults, Congestive Heart Failure
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.
Interventions
DRUGGSK2798745
GSK2798745 will be supplied as granule filled capsule with unit dose strength of 2.4 mg to be administered orally with 240 mL water.
DRUGPlacebo
Placebo will be supplied as blend filled capsule to be administered orally with 240 mL water.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Diffusing Capacity of the Lung for Carbon Monoxide (DLco) on Pulmonary Gas Transfer (Site: Mayo) | Baseline, Day 4, Day 5 and Day 7 of each treatment period | 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) | Baseline, Day 4, Day 5 and Day 7 of each treatment period | 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
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in DLco Following Exercise and Following an Intravenous Saline Infusion (Site: Mayo) | Baseline, Day 5 and Day 7 of each treatment period | 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) | Baseline, Day 5 and Day 7 of each treatment period | 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 Heart Rate | Baseline and up to Day 7 of each treatment period | 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 | Baseline and up to Day 7 of each treatment period | 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 the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Baseline and Day 7 of each treatment period | 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 | Baseline, Day 4 and Day 7 of each treatment period | 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) | Baseline, Day 4 and Day 7 of each treatment period | 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 | Baseline, Day 4 and Day 7 of each treatment period | 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 | Baseline, Day 5 and Day 7 of each treatment period | 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) | Up to Day 7 of each treatment period | 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) | Baseline and up to Day 7 of each treatment period | 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 Temperature | Baseline and up to Day 7 of each treatment period | 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 | Baseline and up to Day 7 of each treatment period | 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 | Up to Day 7 in each treatment period | 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 | Baseline and up to Day 7 in each treatment period | 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 | Baseline and up to Day 7 of each treatment period | 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) | Baseline and up to Day 7 of each treatment period | 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 Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) | Baseline, Day 4, Day 5 and Day 7 of each treatment period | 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 Digoxin Level | Baseline and up to Day 7 in each treatment period | 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 | Baseline and up to Day 7 in each treatment period | 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 | Baseline and up to Day 7 in each treatment period | 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 | Baseline and up to Day 7 in each treatment period | 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 | Baseline and up to Day 7 in each treatment period | 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 | Baseline and up to Day 7 in each treatment period | 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 | Baseline and up to Day 7 in each treatment period | 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 | Baseline and up to Day 7 in each treatment period | 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 | Baseline and up to Day 7 in each treatment period | 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 | Baseline and up to Day 7 in each treatment period | 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) | Up to Day 46 | 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 | Baseline and Day 7 of each treatment period | 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 | 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) | 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 | 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) | 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 | 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) | 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 | 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) | 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. |
| Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Baseline and up to Day 7 of each treatment period | 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 Capillary Blood Volume (Vc) | Baseline, Day 4, Day 5 and Day 7 of each treatment period | 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. |
Countries
United States
Participant flow
Recruitment details
This was a randomized, double-blind, sponsor-unblinded, placebo-controlled, 2 by 2 crossover study in adults with heart failure. A total of 11 participants with Congestive Heart Failure were enrolled in the study. Study was conducted in the United States.
Participants by arm
| Arm | Count |
|---|---|
| All Treatment Combined Eligible participants were randomized to one of two treatment sequences AP and PA where A=GSK2798745 2.4 mg and P=Placebo. In sequence AP, participants received GSK2798745 2.4 milligrams (mg) once daily orally with 240 milliliter (mL) water in Period 1 and placebo in Period 2 for 7 days. In sequence PA, participants received placebo in Period 1 and GSK2798745 2.4mg once daily orally with 240 mL water in Period 2 for 7 days. In both sequence AP and PA, treatment periods were separated by a washout period of 14 days. Data represents all treatments combined. | 11 |
| Total | 11 |
Baseline characteristics
| Characteristic | All Treatment Combined |
|---|---|
| Age, Continuous | 67.7 Years STANDARD_DEVIATION 12.9 |
| Race/Ethnicity, Customized African American/African Heritage | 4 Participants |
| Race/Ethnicity, Customized White | 7 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 11 |
| other Total, other adverse events | 5 / 11 | 7 / 11 |
| serious Total, serious adverse events | 0 / 11 | 1 / 11 |
Outcome results
Primary
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.
Time frame: Baseline, Day 4, Day 5 and Day 7 of each treatment period
Population: Analysis Population comprised of participants in the 'All Subjects' population having Baseline and post-Baseline assessments of the endpoint of interest for both periods. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Diffusing Capacity of the Lung for Carbon Monoxide (DLco) on Pulmonary Gas Transfer (Site: Mayo) | Day 5,pre infusion,n =7,7 | -1.0 mL/mmHg/min | Standard Deviation 0.94 |
| Placebo | Change From Baseline in the Diffusing Capacity of the Lung for Carbon Monoxide (DLco) on Pulmonary Gas Transfer (Site: Mayo) | Day 5,post infusion,n =7,7 | -0.8 mL/mmHg/min | Standard Deviation 0.65 |
| Placebo | Change From Baseline in the Diffusing Capacity of the Lung for Carbon Monoxide (DLco) on Pulmonary Gas Transfer (Site: Mayo) | Day 7,pre exercise,n =7,7 | -0.6 mL/mmHg/min | Standard Deviation 1.63 |
| Placebo | Change From Baseline in the Diffusing Capacity of the Lung for Carbon Monoxide (DLco) on Pulmonary Gas Transfer (Site: Mayo) | Day 7,post exercise,n =7,7 | 0.4 mL/mmHg/min | Standard Deviation 1.38 |
| Placebo | Change From Baseline in the Diffusing Capacity of the Lung for Carbon Monoxide (DLco) on Pulmonary Gas Transfer (Site: Mayo) | Day -1, post exercise,n =7,7 | 0.6 mL/mmHg/min | Standard Deviation 0.98 |
| Placebo | Change From Baseline in the Diffusing Capacity of the Lung for Carbon Monoxide (DLco) on Pulmonary Gas Transfer (Site: Mayo) | Day 4, n =6,7 | -0.4 mL/mmHg/min | Standard Deviation 0.85 |
| GSK2798745 2.4 mg | Change From Baseline in the Diffusing Capacity of the Lung for Carbon Monoxide (DLco) on Pulmonary Gas Transfer (Site: Mayo) | Day -1, post exercise,n =7,7 | 1.4 mL/mmHg/min | Standard Deviation 1.47 |
| GSK2798745 2.4 mg | Change From Baseline in the Diffusing Capacity of the Lung for Carbon Monoxide (DLco) on Pulmonary Gas Transfer (Site: Mayo) | Day 5,pre infusion,n =7,7 | 0.4 mL/mmHg/min | Standard Deviation 1.31 |
| GSK2798745 2.4 mg | Change From Baseline in the Diffusing Capacity of the Lung for Carbon Monoxide (DLco) on Pulmonary Gas Transfer (Site: Mayo) | Day 7,post exercise,n =7,7 | 1.6 mL/mmHg/min | Standard Deviation 2.45 |
| GSK2798745 2.4 mg | Change From Baseline in the Diffusing Capacity of the Lung for Carbon Monoxide (DLco) on Pulmonary Gas Transfer (Site: Mayo) | Day 5,post infusion,n =7,7 | -0.7 mL/mmHg/min | Standard Deviation 0.81 |
| GSK2798745 2.4 mg | Change From Baseline in the Diffusing Capacity of the Lung for Carbon Monoxide (DLco) on Pulmonary Gas Transfer (Site: Mayo) | Day 4, n =6,7 | 0.6 mL/mmHg/min | Standard Deviation 1.16 |
| GSK2798745 2.4 mg | Change From Baseline in the Diffusing Capacity of the Lung for Carbon Monoxide (DLco) on Pulmonary Gas Transfer (Site: Mayo) | Day 7,pre exercise,n =7,7 | 0.7 mL/mmHg/min | Standard Deviation 1.91 |
95% CI: [-0.925, 2.512]
Primary
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
Time frame: Baseline, Day 4, Day 5 and Day 7 of each treatment period
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Diffusing Capacity of the Lung for DLco on Pulmonary Gas Transfer (Site: Hennepin) | Day 5,post infusion,n =4,4 | 0.7 mL/mmHg/min | Standard Deviation 1.47 |
| Placebo | Change From Baseline in the Diffusing Capacity of the Lung for DLco on Pulmonary Gas Transfer (Site: Hennepin) | Day 4, n =4, 3 | 1.5 mL/mmHg/min | Standard Deviation 1.11 |
| Placebo | Change From Baseline in the Diffusing Capacity of the Lung for DLco on Pulmonary Gas Transfer (Site: Hennepin) | Day 7,pre exercise, n =4,3 | 0.4 mL/mmHg/min | Standard Deviation 1.82 |
| Placebo | Change From Baseline in the Diffusing Capacity of the Lung for DLco on Pulmonary Gas Transfer (Site: Hennepin) | Day 5,pre infusion,n =4,3 | 0.2 mL/mmHg/min | Standard Deviation 0.53 |
| Placebo | Change From Baseline in the Diffusing Capacity of the Lung for DLco on Pulmonary Gas Transfer (Site: Hennepin) | Day 7,post exercise, n =4,3 | 1.2 mL/mmHg/min | Standard Deviation 1.01 |
| Placebo | Change From Baseline in the Diffusing Capacity of the Lung for DLco on Pulmonary Gas Transfer (Site: Hennepin) | Day -1, post exercise, n =4, 3 | 1.3 mL/mmHg/min | Standard Deviation 1.32 |
| GSK2798745 2.4 mg | Change From Baseline in the Diffusing Capacity of the Lung for DLco on Pulmonary Gas Transfer (Site: Hennepin) | Day 7,post exercise, n =4,3 | 0.4 mL/mmHg/min | Standard Deviation 1.12 |
| GSK2798745 2.4 mg | Change From Baseline in the Diffusing Capacity of the Lung for DLco on Pulmonary Gas Transfer (Site: Hennepin) | Day -1, post exercise, n =4, 3 | 1.0 mL/mmHg/min | Standard Deviation 0.47 |
| GSK2798745 2.4 mg | Change From Baseline in the Diffusing Capacity of the Lung for DLco on Pulmonary Gas Transfer (Site: Hennepin) | Day 5,pre infusion,n =4,3 | -0.3 mL/mmHg/min | Standard Deviation 0.24 |
| GSK2798745 2.4 mg | Change From Baseline in the Diffusing Capacity of the Lung for DLco on Pulmonary Gas Transfer (Site: Hennepin) | Day 5,post infusion,n =4,4 | 0.8 mL/mmHg/min | Standard Deviation 1.31 |
| GSK2798745 2.4 mg | Change From Baseline in the Diffusing Capacity of the Lung for DLco on Pulmonary Gas Transfer (Site: Hennepin) | Day 7,pre exercise, n =4,3 | -0.6 mL/mmHg/min | Standard Deviation 1.2 |
| GSK2798745 2.4 mg | Change From Baseline in the Diffusing Capacity of the Lung for DLco on Pulmonary Gas Transfer (Site: Hennepin) | Day 4, n =4, 3 | 0.1 mL/mmHg/min | Standard Deviation 1.05 |
Secondary
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
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)
Population: PK Parameter Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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-tau), Period 1, Day 1,n=6 | 128.3513 hour*nanogram per mL | Geometric Coefficient of Variation 70.4 |
| Placebo | 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-tau), Period 1, Day 7,n=5 | 202.2948 hour*nanogram per mL | Geometric Coefficient of Variation 132.1 |
| Placebo | 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-tau), Period 2, Day 1,n=5 | 137.7473 hour*nanogram per mL | Geometric Coefficient of Variation 38.4 |
| Placebo | 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-tau), Period 2, Day 7,n=5 | 274.0828 hour*nanogram per mL | Geometric Coefficient of Variation 70.9 |
| Placebo | 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 | AUCall, Period 1, Day 1,n=6 | 127.9049 hour*nanogram per mL | Geometric Coefficient of Variation 70.4 |
| Placebo | 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 | AUCall Period 1, Day 7,n=5 | 174.7273 hour*nanogram per mL | Geometric Coefficient of Variation 121.5 |
| Placebo | 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 | AUCall Period 2, Day 1,n=5 | 137.5038 hour*nanogram per mL | Geometric Coefficient of Variation 38.4 |
| Placebo | 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 | AUCall, Period 2, Day 7,n=5 | 269.0902 hour*nanogram per mL | Geometric Coefficient of Variation 70.5 |
| Placebo | 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), Period 1, Day 1,n=6 | 127.9049 hour*nanogram per mL | Geometric Coefficient of Variation 70.4 |
| Placebo | 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) Period 1, Day 7,n=5 | 174.7273 hour*nanogram per mL | Geometric Coefficient of Variation 121.5 |
| Placebo | 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) Period 2, Day 1,n=5 | 137.5038 hour*nanogram per mL | Geometric Coefficient of Variation 38.4 |
| Placebo | 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), Period 2, Day 7,n=5 | 269.0902 hour*nanogram per mL | Geometric Coefficient of Variation 70.5 |
Secondary
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.
Time frame: Baseline and up to Day 7 in each treatment period
Population: All Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | AST,Period 1, Day 7,n=5,5 | -3.2 International units per liter | Standard Deviation 3.56 |
| Placebo | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | Creatine kinase,Period 1, Day 7,n=5,6 | -64.0 International units per liter | Standard Deviation 105.02 |
| Placebo | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | GGT,Period 1, Day 4,n=5,6 | -6.0 International units per liter | Standard Deviation 6.86 |
| Placebo | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | Creatine kinase,Period 2, Day 4,n=5,4 | -18.0 International units per liter | Standard Deviation 25.03 |
| Placebo | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | ALT,Period 2, Day 7,n=6,5 | 5.3 International units per liter | Standard Deviation 6.5 |
| Placebo | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | Creatine kinase,Period 2, Day 7,n=6,5 | -15.8 International units per liter | Standard Deviation 22.05 |
| Placebo | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | GGT,Period 1, Day 7,n=5,6 | -9.8 International units per liter | Standard Deviation 11.82 |
| Placebo | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | ALT,Period 1, Day 4,n=5,6 | -1.8 International units per liter | Standard Deviation 1.92 |
| Placebo | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | ALT,Period 2, Day 4,n=5,5 | 2.8 International units per liter | Standard Deviation 5.59 |
| Placebo | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | AST,Period 2, Day 4,n=5,5 | 0.0 International units per liter | Standard Deviation 9.97 |
| Placebo | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | GGT,Period 2, Day 4,n=5,5 | 5.8 International units per liter | Standard Deviation 16.95 |
| Placebo | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | ALP,Period 1, Day 4,n=5,6 | 0.6 International units per liter | Standard Deviation 6.54 |
| Placebo | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | ALT,Period 1, Day 7,n=5,6 | -1.2 International units per liter | Standard Deviation 2.77 |
| Placebo | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | ALP,Period 1, Day 7,n=5,6 | -1.0 International units per liter | Standard Deviation 7 |
| Placebo | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | GGT,Period 2, Day 7,n=6,5 | 9.0 International units per liter | Standard Deviation 22.09 |
| Placebo | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | ALP,Period 2, Day 4,n=5,5 | 0.4 International units per liter | Standard Deviation 6.73 |
| Placebo | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | AST,Period 2, Day 7,n=6,5 | 4.2 International units per liter | Standard Deviation 7 |
| Placebo | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | ALP,Period 2, Day 7,n=6,5 | 8.0 International units per liter | Standard Deviation 21.46 |
| Placebo | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | Creatine kinase,Period 1, Day 4,n=5,6 | -57.4 International units per liter | Standard Deviation 90.68 |
| Placebo | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | AST,Period 1, Day 4,n=5,6 | -4.0 International units per liter | Standard Deviation 4.8 |
| GSK2798745 2.4 mg | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | Creatine kinase,Period 1, Day 4,n=5,6 | -27.7 International units per liter | Standard Deviation 36.14 |
| GSK2798745 2.4 mg | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | ALT,Period 1, Day 7,n=5,6 | -6.2 International units per liter | Standard Deviation 8.8 |
| GSK2798745 2.4 mg | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | AST,Period 1, Day 4,n=5,6 | -6.7 International units per liter | Standard Deviation 9.65 |
| GSK2798745 2.4 mg | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | AST,Period 1, Day 7,n=5,5 | -7.2 International units per liter | Standard Deviation 8.04 |
| GSK2798745 2.4 mg | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | AST,Period 2, Day 4,n=5,5 | -8.0 International units per liter | Standard Deviation 2.92 |
| GSK2798745 2.4 mg | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | AST,Period 2, Day 7,n=6,5 | -4.8 International units per liter | Standard Deviation 1.92 |
| GSK2798745 2.4 mg | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | GGT,Period 1, Day 4,n=5,6 | -12.5 International units per liter | Standard Deviation 20.71 |
| GSK2798745 2.4 mg | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | GGT,Period 1, Day 7,n=5,6 | -9.5 International units per liter | Standard Deviation 11.06 |
| GSK2798745 2.4 mg | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | GGT,Period 2, Day 4,n=5,5 | -4.8 International units per liter | Standard Deviation 7.73 |
| GSK2798745 2.4 mg | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | GGT,Period 2, Day 7,n=6,5 | -5.2 International units per liter | Standard Deviation 5.54 |
| GSK2798745 2.4 mg | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | ALT,Period 1, Day 4,n=5,6 | -5.5 International units per liter | Standard Deviation 10.41 |
| GSK2798745 2.4 mg | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | Creatine kinase,Period 1, Day 7,n=5,6 | -19.5 International units per liter | Standard Deviation 54.42 |
| GSK2798745 2.4 mg | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | Creatine kinase,Period 2, Day 4,n=5,4 | -59.0 International units per liter | Standard Deviation 68.33 |
| GSK2798745 2.4 mg | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | Creatine kinase,Period 2, Day 7,n=6,5 | -47.8 International units per liter | Standard Deviation 29.2 |
| GSK2798745 2.4 mg | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | ALT,Period 2, Day 4,n=5,5 | -3.6 International units per liter | Standard Deviation 2.88 |
| GSK2798745 2.4 mg | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | ALT,Period 2, Day 7,n=6,5 | -2.6 International units per liter | Standard Deviation 2.7 |
| GSK2798745 2.4 mg | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | ALP,Period 1, Day 4,n=5,6 | -17.8 International units per liter | Standard Deviation 35.65 |
| GSK2798745 2.4 mg | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | ALP,Period 1, Day 7,n=5,6 | -15.2 International units per liter | Standard Deviation 30.96 |
| GSK2798745 2.4 mg | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | ALP,Period 2, Day 4,n=5,5 | -0.8 International units per liter | Standard Deviation 2.39 |
| GSK2798745 2.4 mg | Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT) Values | ALP,Period 2, Day 7,n=6,5 | 1.2 International units per liter | Standard Deviation 6.3 |
Secondary
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.
Time frame: Baseline and up to Day 7 of each treatment period
Population: All Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Albumin and Total Protein Values | Albumin,Period 1, Day 4,n=5,6 | -1.6 Grams per liter | Standard Deviation 1.52 |
| Placebo | Change From Baseline in Albumin and Total Protein Values | Albumin,Period 1, Day 7,n=5,6 | -0.6 Grams per liter | Standard Deviation 2.3 |
| Placebo | Change From Baseline in Albumin and Total Protein Values | Albumin,Period 2, Day 4,n=5,5 | -0.4 Grams per liter | Standard Deviation 0.55 |
| Placebo | Change From Baseline in Albumin and Total Protein Values | Albumin,Period 2, Day 7,n=6,5 | 0.2 Grams per liter | Standard Deviation 1.83 |
| Placebo | Change From Baseline in Albumin and Total Protein Values | Total protein,Period 1, Day 4,n=5,6 | -1.0 Grams per liter | Standard Deviation 5.15 |
| Placebo | Change From Baseline in Albumin and Total Protein Values | Total protein,Period 1, Day 7,n=5,6 | 0.8 Grams per liter | Standard Deviation 5.22 |
| Placebo | Change From Baseline in Albumin and Total Protein Values | Total protein,Period 2, Day 4,n=5,5 | -1.6 Grams per liter | Standard Deviation 2.07 |
| Placebo | Change From Baseline in Albumin and Total Protein Values | Total protein,Period 2, Day 7,n=6,5 | -0.8 Grams per liter | Standard Deviation 3.54 |
| GSK2798745 2.4 mg | Change From Baseline in Albumin and Total Protein Values | Total protein,Period 2, Day 7,n=6,5 | 2.8 Grams per liter | Standard Deviation 1.64 |
| GSK2798745 2.4 mg | Change From Baseline in Albumin and Total Protein Values | Albumin,Period 1, Day 4,n=5,6 | -0.5 Grams per liter | Standard Deviation 2.59 |
| GSK2798745 2.4 mg | Change From Baseline in Albumin and Total Protein Values | Total protein,Period 1, Day 4,n=5,6 | -1.5 Grams per liter | Standard Deviation 5.36 |
| GSK2798745 2.4 mg | Change From Baseline in Albumin and Total Protein Values | Albumin,Period 1, Day 7,n=5,6 | -0.3 Grams per liter | Standard Deviation 1.75 |
| GSK2798745 2.4 mg | Change From Baseline in Albumin and Total Protein Values | Total protein,Period 2, Day 4,n=5,5 | 0.4 Grams per liter | Standard Deviation 3.58 |
| GSK2798745 2.4 mg | Change From Baseline in Albumin and Total Protein Values | Albumin,Period 2, Day 4,n=5,5 | -0.2 Grams per liter | Standard Deviation 1.79 |
| GSK2798745 2.4 mg | Change From Baseline in Albumin and Total Protein Values | Total protein,Period 1, Day 7,n=5,6 | -1.2 Grams per liter | Standard Deviation 4.17 |
| GSK2798745 2.4 mg | Change From Baseline in Albumin and Total Protein Values | Albumin,Period 2, Day 7,n=6,5 | 0.8 Grams per liter | Standard Deviation 1.3 |
Secondary
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.
Time frame: Baseline, Day 4, Day 5 and Day 7 of each treatment period
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Capillary Blood Volume (Vc) | Day 5,post infusion, n =7, 7 | -4.9 mL | Standard Deviation 14.19 |
| Placebo | Change From Baseline in Capillary Blood Volume (Vc) | Day 5,pre infusion, n =7, 7 | -0.1 mL | Standard Deviation 11.6 |
| Placebo | Change From Baseline in Capillary Blood Volume (Vc) | Day 7,pre exercise, n =7, 7 | -4.7 mL | Standard Deviation 12.86 |
| Placebo | Change From Baseline in Capillary Blood Volume (Vc) | Day 4, n =6, 7 | -2.6 mL | Standard Deviation 8.64 |
| Placebo | Change From Baseline in Capillary Blood Volume (Vc) | Day 7, post exercise,n =7,7 | 0.3 mL | Standard Deviation 12.33 |
| Placebo | Change From Baseline in Capillary Blood Volume (Vc) | Day -1,post exercise, n =7, 7 | 1.6 mL | Standard Deviation 8.39 |
| GSK2798745 2.4 mg | Change From Baseline in Capillary Blood Volume (Vc) | Day 7, post exercise,n =7,7 | 3.3 mL | Standard Deviation 15.35 |
| GSK2798745 2.4 mg | Change From Baseline in Capillary Blood Volume (Vc) | Day -1,post exercise, n =7, 7 | 10.4 mL | Standard Deviation 14.77 |
| GSK2798745 2.4 mg | Change From Baseline in Capillary Blood Volume (Vc) | Day 5,pre infusion, n =7, 7 | 3.0 mL | Standard Deviation 12.99 |
| GSK2798745 2.4 mg | Change From Baseline in Capillary Blood Volume (Vc) | Day 5,post infusion, n =7, 7 | -2.3 mL | Standard Deviation 11.7 |
| GSK2798745 2.4 mg | Change From Baseline in Capillary Blood Volume (Vc) | Day 7,pre exercise, n =7, 7 | -2.6 mL | Standard Deviation 13.99 |
| GSK2798745 2.4 mg | Change From Baseline in Capillary Blood Volume (Vc) | Day 4, n =6, 7 | -0.2 mL | Standard Deviation 9.4 |
Secondary
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.
Time frame: Baseline and up to Day 7 of each treatment period
Population: All Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Chloride,Period 2, Day 4,n=5,5 | -0.8 Millimoles per liter | Standard Deviation 1.79 |
| Placebo | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Calcium,Period 1, Day 7,n=5,6 | 0.05988 Millimoles per liter | Standard Deviation 0.120434 |
| Placebo | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Calcium,Period 2, Day 4,n=5,5 | -0.05489 Millimoles per liter | Standard Deviation 0.020875 |
| Placebo | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Calcium,Period 2, Day 7,n=6,5 | -0.06238 Millimoles per liter | Standard Deviation 0.07188 |
| Placebo | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Chloride,Period 1, Day 4,n=5,6 | -1.8 Millimoles per liter | Standard Deviation 1.48 |
| Placebo | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Chloride,Period 1, Day 7,n=5,6 | -1.0 Millimoles per liter | Standard Deviation 1.87 |
| Placebo | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Calcium,Period 1, Day 4,n=5,6 | 0.01497 Millimoles per liter | Standard Deviation 0.080074 |
| Placebo | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Chloride,Period 2, Day 7,n=6,5 | -2.0 Millimoles per liter | Standard Deviation 4.82 |
| Placebo | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Glucose,Period 1, Day 4,n=5,6 | 3.63035 Millimoles per liter | Standard Deviation 4.132346 |
| Placebo | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Glucose,Period 1, Day 7,n=5,6 | 2.04277 Millimoles per liter | Standard Deviation 2.486018 |
| Placebo | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Glucose,Period 2, Day 4,n=5,5 | 1.68750 Millimoles per liter | Standard Deviation 2.144009 |
| Placebo | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Glucose,Period 2, Day 7,n=6,5 | 1.51727 Millimoles per liter | Standard Deviation 4.849639 |
| Placebo | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Potassium,Period 1, Day 4,n=5,6 | 0.22 Millimoles per liter | Standard Deviation 0.319 |
| Placebo | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Potassium,Period 1, Day 7,n=5,6 | 0.16 Millimoles per liter | Standard Deviation 0.27 |
| Placebo | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Potassium,Period 2, Day 4,n=5,5 | 0.04 Millimoles per liter | Standard Deviation 0.397 |
| Placebo | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Potassium,Period 2, Day 7,n=6,5 | -0.23 Millimoles per liter | Standard Deviation 0.592 |
| Placebo | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Sodium,Period 1, Day 4,n=5,6 | -1.0 Millimoles per liter | Standard Deviation 4 |
| Placebo | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Sodium,Period 1, Day 7,n=5,6 | -1.4 Millimoles per liter | Standard Deviation 3.36 |
| Placebo | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Sodium,Period 2, Day 4,n=5,5 | -1.0 Millimoles per liter | Standard Deviation 1.58 |
| Placebo | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Sodium,Period 2, Day 7,n=6,5 | -2.2 Millimoles per liter | Standard Deviation 2.32 |
| Placebo | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Urea/BUN,Period 1, Day 4,n=5,6 | -0.0714 Millimoles per liter | Standard Deviation 1.34528 |
| Placebo | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Urea/BUN,Period 1, Day 7,n=5,6 | -0.4284 Millimoles per liter | Standard Deviation 1.86188 |
| Placebo | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Urea/BUN,Period 2, Day 4,n=5,5 | -1.2852 Millimoles per liter | Standard Deviation 3.02504 |
| Placebo | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Urea/BUN,Period 2, Day 7,n=6,5 | -0.2975 Millimoles per liter | Standard Deviation 4.41537 |
| GSK2798745 2.4 mg | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Urea/BUN,Period 2, Day 4,n=5,5 | -0.5712 Millimoles per liter | Standard Deviation 2.53193 |
| GSK2798745 2.4 mg | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Calcium,Period 1, Day 4,n=5,6 | -0.06653 Millimoles per liter | Standard Deviation 0.187817 |
| GSK2798745 2.4 mg | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Potassium,Period 1, Day 4,n=5,6 | 0.33 Millimoles per liter | Standard Deviation 0.388 |
| GSK2798745 2.4 mg | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Calcium,Period 1, Day 7,n=5,6 | -0.05822 Millimoles per liter | Standard Deviation 0.185817 |
| GSK2798745 2.4 mg | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Sodium,Period 2, Day 4,n=5,5 | -0.8 Millimoles per liter | Standard Deviation 2.59 |
| GSK2798745 2.4 mg | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Calcium,Period 2, Day 4,n=5,5 | 0.00998 Millimoles per liter | Standard Deviation 0.041749 |
| GSK2798745 2.4 mg | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Potassium,Period 1, Day 7,n=5,6 | 0.35 Millimoles per liter | Standard Deviation 0.619 |
| GSK2798745 2.4 mg | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Calcium,Period 2, Day 7,n=6,5 | 0.02994 Millimoles per liter | Standard Deviation 0.044632 |
| GSK2798745 2.4 mg | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Urea/BUN,Period 1, Day 7,n=5,6 | -0.1785 Millimoles per liter | Standard Deviation 2.17448 |
| GSK2798745 2.4 mg | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Chloride,Period 1, Day 4,n=5,6 | -1.3 Millimoles per liter | Standard Deviation 1.97 |
| GSK2798745 2.4 mg | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Potassium,Period 2, Day 4,n=5,5 | 0.26 Millimoles per liter | Standard Deviation 0.27 |
| GSK2798745 2.4 mg | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Chloride,Period 1, Day 7,n=5,6 | 0.5 Millimoles per liter | Standard Deviation 1.76 |
| GSK2798745 2.4 mg | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Sodium,Period 2, Day 7,n=6,5 | -1.6 Millimoles per liter | Standard Deviation 1.67 |
| GSK2798745 2.4 mg | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Chloride,Period 2, Day 4,n=5,5 | -2.0 Millimoles per liter | Standard Deviation 2.35 |
| GSK2798745 2.4 mg | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Potassium,Period 2, Day 7,n=6,5 | 0.14 Millimoles per liter | Standard Deviation 0.378 |
| GSK2798745 2.4 mg | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Chloride,Period 2, Day 7,n=6,5 | -2.4 Millimoles per liter | Standard Deviation 1.82 |
| GSK2798745 2.4 mg | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Urea/BUN,Period 2, Day 7,n=6,5 | 0.0714 Millimoles per liter | Standard Deviation 2.8493 |
| GSK2798745 2.4 mg | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Glucose,Period 1, Day 4,n=5,6 | 2.04462 Millimoles per liter | Standard Deviation 3.557566 |
| GSK2798745 2.4 mg | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Sodium,Period 1, Day 4,n=5,6 | -2.0 Millimoles per liter | Standard Deviation 1.55 |
| GSK2798745 2.4 mg | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Glucose,Period 1, Day 7,n=5,6 | 0.61986 Millimoles per liter | Standard Deviation 5.924289 |
| GSK2798745 2.4 mg | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Urea/BUN,Period 1, Day 4,n=5,6 | 2.2610 Millimoles per liter | Standard Deviation 3.82285 |
| GSK2798745 2.4 mg | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Glucose,Period 2, Day 4,n=5,5 | 3.96341 Millimoles per liter | Standard Deviation 3.372569 |
| GSK2798745 2.4 mg | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Sodium,Period 1, Day 7,n=5,6 | -1.2 Millimoles per liter | Standard Deviation 2.48 |
| GSK2798745 2.4 mg | Change From Baseline in Chemistry: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN) | Glucose,Period 2, Day 7,n=6,5 | 1.23232 Millimoles per liter | Standard Deviation 2.196471 |
Secondary
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.
Time frame: Baseline and up to Day 7 in each treatment period
Population: All Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Chemistry: N-terminal Pro-Brain Natriuretic Peptide | Period 1 Day 7,n=5,6 | -279.0 Nanograms per liter | Standard Deviation 455.83 |
| Placebo | Change From Baseline in Chemistry: N-terminal Pro-Brain Natriuretic Peptide | Period 2 Day 7,n=6,5 | -347.7 Nanograms per liter | Standard Deviation 1134.08 |
| GSK2798745 2.4 mg | Change From Baseline in Chemistry: N-terminal Pro-Brain Natriuretic Peptide | Period 1 Day 7,n=5,6 | 214.2 Nanograms per liter | Standard Deviation 702.54 |
| GSK2798745 2.4 mg | Change From Baseline in Chemistry: N-terminal Pro-Brain Natriuretic Peptide | Period 2 Day 7,n=6,5 | -121.6 Nanograms per liter | Standard Deviation 340.7 |
Secondary
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.
Time frame: Baseline and up to Day 7 of each treatment period
Population: All Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Creatinine,Period 1, Day 4,n=5,6 | -8.1328 Micromoles per liter | Standard Deviation 17.06601 |
| Placebo | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Creatinine,Period 1, Day 7,n=5,6 | -13.2600 Micromoles per liter | Standard Deviation 15.912 |
| Placebo | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Creatinine,Period 2, Day 4,n=5,5 | -6.0112 Micromoles per liter | Standard Deviation 12.84693 |
| Placebo | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Creatinine,Period 2, Day 7,n=6,5 | -4.8620 Micromoles per liter | Standard Deviation 26.95113 |
| Placebo | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Direct Bilirubin,Period 1, Day 4,n=5,6 | -0.684 Micromoles per liter | Standard Deviation 0.9366 |
| Placebo | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Direct Bilirubin,Period 1, Day 7,n=5,5 | -0.342 Micromoles per liter | Standard Deviation 0.7647 |
| Placebo | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Direct Bilirubin,Period 2, Day 4,n=5,5 | -0.340 Micromoles per liter | Standard Deviation 0.7659 |
| Placebo | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Direct Bilirubin,Period 2, Day 7,n=6,5 | -0.285 Micromoles per liter | Standard Deviation 0.6981 |
| Placebo | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Total Bilirubin,Period 1, Day 4,n=5,6 | 1.368 Micromoles per liter | Standard Deviation 2.8098 |
| Placebo | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Total Bilirubin,Period 1, Day 7,n=5,6 | 0.684 Micromoles per liter | Standard Deviation 1.9497 |
| Placebo | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Total Bilirubin,Period 2, Day 4,n=5,5 | -0.000 Micromoles per liter | Standard Deviation 3.1991 |
| Placebo | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Total Bilirubin,Period 2, Day 7,n=6,5 | -0.285 Micromoles per liter | Standard Deviation 1.9991 |
| Placebo | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Uric acid,Period 1, Day 4,n=5,6 | -17.8440 Micromoles per liter | Standard Deviation 35.4393 |
| Placebo | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Uric acid,Period 1, Day 7,n=5,6 | -42.8256 Micromoles per liter | Standard Deviation 40.20954 |
| Placebo | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Uric acid,Period 2, Day 4,n=5,5 | -17.8440 Micromoles per liter | Standard Deviation 29.4411 |
| Placebo | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Uric acid,Period 2, Day 7,n=6,5 | 25.7747 Micromoles per liter | Standard Deviation 111.31927 |
| GSK2798745 2.4 mg | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Uric acid,Period 2, Day 7,n=6,5 | 9.5168 Micromoles per liter | Standard Deviation 19.99448 |
| GSK2798745 2.4 mg | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Creatinine,Period 1, Day 4,n=5,6 | 11.4920 Micromoles per liter | Standard Deviation 29.13179 |
| GSK2798745 2.4 mg | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Total Bilirubin,Period 1, Day 4,n=5,6 | -1.425 Micromoles per liter | Standard Deviation 1.6813 |
| GSK2798745 2.4 mg | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Creatinine,Period 1, Day 7,n=5,6 | -9.4293 Micromoles per liter | Standard Deviation 12.58472 |
| GSK2798745 2.4 mg | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Uric acid,Period 1, Day 4,n=5,6 | 18.8353 Micromoles per liter | Standard Deviation 47.1983 |
| GSK2798745 2.4 mg | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Creatinine,Period 2, Day 4,n=5,5 | -2.6520 Micromoles per liter | Standard Deviation 14.83172 |
| GSK2798745 2.4 mg | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Total Bilirubin,Period 1, Day 7,n=5,6 | 0.002 Micromoles per liter | Standard Deviation 2.1646 |
| GSK2798745 2.4 mg | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Creatinine,Period 2, Day 7,n=6,5 | 3.7128 Micromoles per liter | Standard Deviation 11.43064 |
| GSK2798745 2.4 mg | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Uric acid,Period 2, Day 4,n=5,5 | -1.1896 Micromoles per liter | Standard Deviation 24.66807 |
| GSK2798745 2.4 mg | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Direct Bilirubin,Period 1, Day 4,n=5,6 | -0.572 Micromoles per liter | Standard Deviation 0.8856 |
| GSK2798745 2.4 mg | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Total Bilirubin,Period 2, Day 4,n=5,5 | -5.472 Micromoles per liter | Standard Deviation 9.2403 |
| GSK2798745 2.4 mg | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Direct Bilirubin,Period 1, Day 7,n=5,5 | -0.344 Micromoles per liter | Standard Deviation 1.4331 |
| GSK2798745 2.4 mg | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Uric acid,Period 1, Day 7,n=5,6 | -29.7400 Micromoles per liter | Standard Deviation 51.57983 |
| GSK2798745 2.4 mg | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Direct Bilirubin,Period 2, Day 4,n=5,5 | -1.026 Micromoles per liter | Standard Deviation 1.5295 |
| GSK2798745 2.4 mg | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Total Bilirubin,Period 2, Day 7,n=6,5 | -5.130 Micromoles per liter | Standard Deviation 10.1885 |
| GSK2798745 2.4 mg | Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, Uric Acid | Direct Bilirubin,Period 2, Day 7,n=6,5 | -0.684 Micromoles per liter | Standard Deviation 0.9366 |
Secondary
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.
Time frame: Baseline, Day 4, Day 5 and Day 7 of each treatment period
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) | DM,Day 7, post-exercise,n =7,7 | 0.7 mL/mmHg/min | Standard Deviation 2.44 |
| Placebo | Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) | DM,Day 7,pre-exercise, n =7, 7 | -0.9 mL/mmHg/min | Standard Deviation 2.81 |
| Placebo | Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) | DLno,Day -1,post-exercise, n =7, 7 | 2.1 mL/mmHg/min | Standard Deviation 1.87 |
| Placebo | Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) | DLno,Day 4, n =6, 7 | -2.3 mL/mmHg/min | Standard Deviation 4.01 |
| Placebo | Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) | DLno,Day 5,pre-infusion, n =7, 7 | -6.0 mL/mmHg/min | Standard Deviation 6.5 |
| Placebo | Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) | DLno,Day 5,post-infusion, n =7, 7 | -2.7 mL/mmHg/min | Standard Deviation 3.83 |
| Placebo | Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) | DLno,Day 7,pre-exercise, n =7, 7 | -1.9 mL/mmHg/min | Standard Deviation 6.19 |
| Placebo | Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) | DLno,Day 7, post-exercise,n =7,7 | 1.5 mL/mmHg/min | Standard Deviation 5.37 |
| Placebo | Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) | DM,Day -1,post-exercise, n =7, 7 | 1.0 mL/mmHg/min | Standard Deviation 0.85 |
| Placebo | Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) | DM,Day 4, n =6, 7 | -1.0 mL/mmHg/min | Standard Deviation 1.82 |
| Placebo | Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) | DM,Day 5,pre-infusion, n =7, 7 | -2.7 mL/mmHg/min | Standard Deviation 2.95 |
| Placebo | Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) | DM,Day 5,post-infusion, n =7, 7 | -1.2 mL/mmHg/min | Standard Deviation 1.74 |
| GSK2798745 2.4 mg | Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) | DM,Day 5,pre-infusion, n =7, 7 | 1.2 mL/mmHg/min | Standard Deviation 3.92 |
| GSK2798745 2.4 mg | Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) | DLno,Day 7, post-exercise,n =7,7 | 8.6 mL/mmHg/min | Standard Deviation 10.19 |
| GSK2798745 2.4 mg | Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) | DM,Day 7, post-exercise,n =7,7 | 4.1 mL/mmHg/min | Standard Deviation 4.74 |
| GSK2798745 2.4 mg | Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) | DLno,Day 4, n =6, 7 | 5.0 mL/mmHg/min | Standard Deviation 5.51 |
| GSK2798745 2.4 mg | Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) | DLno,Day -1,post-exercise, n =7, 7 | 3.5 mL/mmHg/min | Standard Deviation 3.66 |
| GSK2798745 2.4 mg | Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) | DM,Day -1,post-exercise, n =7, 7 | 1.7 mL/mmHg/min | Standard Deviation 1.53 |
| GSK2798745 2.4 mg | Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) | DM,Day 5,post-infusion, n =7, 7 | -1.5 mL/mmHg/min | Standard Deviation 1.49 |
| GSK2798745 2.4 mg | Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) | DLno,Day 5,pre-infusion, n =7, 7 | 2.4 mL/mmHg/min | Standard Deviation 8.56 |
| GSK2798745 2.4 mg | Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) | DM,Day 4, n =6, 7 | 2.4 mL/mmHg/min | Standard Deviation 2.61 |
| GSK2798745 2.4 mg | Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) | DLno,Day 5,post-infusion, n =7, 7 | -3.3 mL/mmHg/min | Standard Deviation 3.27 |
| GSK2798745 2.4 mg | Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) | DM,Day 7,pre-exercise, n =7, 7 | 2.8 mL/mmHg/min | Standard Deviation 4.55 |
| GSK2798745 2.4 mg | Change From Baseline in Diffusing Capacity of the Lung for Nitric Oxide (DLno) and Membrane Conductance (DM) | DLno,Day 7,pre-exercise, n =7, 7 | 6.0 mL/mmHg/min | Standard Deviation 9.96 |
Secondary
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.
Time frame: Baseline and up to Day 7 in each treatment period
Population: All Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Digoxin Level | Period 1 Day 1,n=3,1 | -0.17080 Nanomoles per liter | Standard Deviation 0.322378 |
| Placebo | Change From Baseline in Digoxin Level | Period 1 Day 2,n=3,1 | 0.17080 Nanomoles per liter | Standard Deviation 0.073959 |
| Placebo | Change From Baseline in Digoxin Level | Period 1 Day 3,n=3,1 | 0.12810 Nanomoles per liter | Standard Deviation 0.1281 |
| Placebo | Change From Baseline in Digoxin Level | Period 1 Day 4,n=3,1 | -0.10248 Nanomoles per liter | Standard Deviation 0.419417 |
| Placebo | Change From Baseline in Digoxin Level | Period 1 Day 5,n=3,1 | 0.25620 Nanomoles per liter | Standard Deviation 0.221876 |
| Placebo | Change From Baseline in Digoxin Level | Period 1 Day 6,n=3,1 | 0.17080 Nanomoles per liter | Standard Deviation 0.147917 |
| Placebo | Change From Baseline in Digoxin Level | Period 1 Day 7,n=3,1 | -0.00000 Nanomoles per liter | Standard Deviation 0.1281 |
| Placebo | Change From Baseline in Digoxin Level | Period 2 Day 1,n=1,3 | -0.25620 Nanomoles per liter | — |
| Placebo | Change From Baseline in Digoxin Level | Period 2 Day 2,n=1,3 | -0.25620 Nanomoles per liter | — |
| Placebo | Change From Baseline in Digoxin Level | Period 2 Day 3,n=1,3 | -0.25620 Nanomoles per liter | — |
| Placebo | Change From Baseline in Digoxin Level | Period 2 Day 4,n=1,3 | -0.38430 Nanomoles per liter | — |
| Placebo | Change From Baseline in Digoxin Level | Period 2 Day 5,n=1,3 | -0.25620 Nanomoles per liter | — |
| Placebo | Change From Baseline in Digoxin Level | Period 2 Day 6,n=1,3 | -0.12810 Nanomoles per liter | — |
| Placebo | Change From Baseline in Digoxin Level | Period 2 Day 7,n=1,3 | -0.25620 Nanomoles per liter | — |
| GSK2798745 2.4 mg | Change From Baseline in Digoxin Level | Period 2 Day 4,n=1,3 | 0.42700 Nanomoles per liter | Standard Deviation 0.195676 |
| GSK2798745 2.4 mg | Change From Baseline in Digoxin Level | Period 1 Day 1,n=3,1 | 0.38430 Nanomoles per liter | — |
| GSK2798745 2.4 mg | Change From Baseline in Digoxin Level | Period 2 Day 1,n=1,3 | 0.34160 Nanomoles per liter | Standard Deviation 0.266661 |
| GSK2798745 2.4 mg | Change From Baseline in Digoxin Level | Period 1 Day 2,n=3,1 | 0.25620 Nanomoles per liter | — |
| GSK2798745 2.4 mg | Change From Baseline in Digoxin Level | Period 2 Day 6,n=1,3 | 0.29890 Nanomoles per liter | Standard Deviation 0.391352 |
| GSK2798745 2.4 mg | Change From Baseline in Digoxin Level | Period 1 Day 3,n=3,1 | 0.25620 Nanomoles per liter | — |
| GSK2798745 2.4 mg | Change From Baseline in Digoxin Level | Period 2 Day 2,n=1,3 | 0.46970 Nanomoles per liter | Standard Deviation 0.295834 |
| GSK2798745 2.4 mg | Change From Baseline in Digoxin Level | Period 1 Day 4,n=3,1 | 0.12810 Nanomoles per liter | — |
| GSK2798745 2.4 mg | Change From Baseline in Digoxin Level | Period 2 Day 5,n=1,3 | 0.25620 Nanomoles per liter | Standard Deviation 0.1281 |
| GSK2798745 2.4 mg | Change From Baseline in Digoxin Level | Period 1 Day 5,n=3,1 | 0.38430 Nanomoles per liter | — |
| GSK2798745 2.4 mg | Change From Baseline in Digoxin Level | Period 2 Day 3,n=1,3 | 0.17080 Nanomoles per liter | Standard Deviation 0.195676 |
| GSK2798745 2.4 mg | Change From Baseline in Digoxin Level | Period 1 Day 6,n=3,1 | 0.00000 Nanomoles per liter | — |
| GSK2798745 2.4 mg | Change From Baseline in Digoxin Level | Period 2 Day 7,n=1,3 | 0.42700 Nanomoles per liter | Standard Deviation 0.369793 |
| GSK2798745 2.4 mg | Change From Baseline in Digoxin Level | Period 1 Day 7,n=3,1 | 0.00000 Nanomoles per liter | — |
Secondary
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.
Time frame: Baseline, Day 5 and Day 7 of each treatment period
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in DLco Following Exercise and Following an Intravenous Saline Infusion (Site: Hennepin) | Day -1,post exercise,n=4,3 | 1.3 mL/mmHg/min | Standard Deviation 1.32 |
| Placebo | Change From Baseline in DLco Following Exercise and Following an Intravenous Saline Infusion (Site: Hennepin) | Day 5,post infusion,n=4,4 | 0.7 mL/mmHg/min | Standard Deviation 1.47 |
| Placebo | Change From Baseline in DLco Following Exercise and Following an Intravenous Saline Infusion (Site: Hennepin) | Day 7, post exercise,n=4,3 | 1.2 mL/mmHg/min | Standard Deviation 1.01 |
| GSK2798745 2.4 mg | Change From Baseline in DLco Following Exercise and Following an Intravenous Saline Infusion (Site: Hennepin) | Day -1,post exercise,n=4,3 | 1.0 mL/mmHg/min | Standard Deviation 0.47 |
| GSK2798745 2.4 mg | Change From Baseline in DLco Following Exercise and Following an Intravenous Saline Infusion (Site: Hennepin) | Day 5,post infusion,n=4,4 | 0.8 mL/mmHg/min | Standard Deviation 1.31 |
| GSK2798745 2.4 mg | Change From Baseline in DLco Following Exercise and Following an Intravenous Saline Infusion (Site: Hennepin) | Day 7, post exercise,n=4,3 | 0.4 mL/mmHg/min | Standard Deviation 1.12 |
Secondary
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.
Time frame: Baseline, Day 5 and Day 7 of each treatment period
Population: Analysis Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in DLco Following Exercise and Following an Intravenous Saline Infusion (Site: Mayo) | Day -1,post exercise | 0.6 mL/mmHg/min | Standard Deviation 0.98 |
| Placebo | Change From Baseline in DLco Following Exercise and Following an Intravenous Saline Infusion (Site: Mayo) | Day 5,post infusion | -0.8 mL/mmHg/min | Standard Deviation 0.65 |
| Placebo | Change From Baseline in DLco Following Exercise and Following an Intravenous Saline Infusion (Site: Mayo) | Day 7, post exercise | 0.4 mL/mmHg/min | Standard Deviation 1.38 |
| GSK2798745 2.4 mg | Change From Baseline in DLco Following Exercise and Following an Intravenous Saline Infusion (Site: Mayo) | Day -1,post exercise | 1.4 mL/mmHg/min | Standard Deviation 1.47 |
| GSK2798745 2.4 mg | Change From Baseline in DLco Following Exercise and Following an Intravenous Saline Infusion (Site: Mayo) | Day 5,post infusion | -0.7 mL/mmHg/min | Standard Deviation 0.81 |
| GSK2798745 2.4 mg | Change From Baseline in DLco Following Exercise and Following an Intravenous Saline Infusion (Site: Mayo) | Day 7, post exercise | 1.6 mL/mmHg/min | Standard Deviation 2.45 |
Secondary
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 .
Time frame: Baseline, Day 5 and Day 7 of each treatment period
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Dyspnea Score | Period 1 Day5,pre infusion,n=5,6 | 0.2 Scores on a scale | Standard Deviation 0.45 |
| Placebo | Change From Baseline in Dyspnea Score | Period 1 Day-1,post exercise,n=4,2 | 0.5 Scores on a scale | Standard Deviation 0.58 |
| Placebo | Change From Baseline in Dyspnea Score | Period 1 Day5,pre infusion-Orthopnea,n=5,6 | 0.2 Scores on a scale | Standard Deviation 0.45 |
| Placebo | Change From Baseline in Dyspnea Score | Period 1 Day7,pre exercise,n=5,6 | 0.0 Scores on a scale | Standard Deviation 0 |
| Placebo | Change From Baseline in Dyspnea Score | Period 1 Day7,post exercise,n=3,2 | 1.3 Scores on a scale | Standard Deviation 2.31 |
| Placebo | Change From Baseline in Dyspnea Score | Period 2 Day -1,post exercise,n=2,3 | 2.0 Scores on a scale | Standard Deviation 2.83 |
| Placebo | Change From Baseline in Dyspnea Score | Period 2 Day5,pre infusion,n=6,5 | -0.3 Scores on a scale | Standard Deviation 1.03 |
| Placebo | Change From Baseline in Dyspnea Score | Period 2 Day5,pre infusion-Orthopnea,n=6,5 | -0.3 Scores on a scale | Standard Deviation 1.03 |
| Placebo | Change From Baseline in Dyspnea Score | Period 2 Day7,pre exercise,n=6,5 | -0.5 Scores on a scale | Standard Deviation 0.84 |
| Placebo | Change From Baseline in Dyspnea Score | Period 2 Day7,post exercise,n=3,4 | -1.0 Scores on a scale | Standard Deviation 1 |
| GSK2798745 2.4 mg | Change From Baseline in Dyspnea Score | Period 2 Day5,pre infusion-Orthopnea,n=6,5 | -0.4 Scores on a scale | Standard Deviation 0.89 |
| GSK2798745 2.4 mg | Change From Baseline in Dyspnea Score | Period 2 Day -1,post exercise,n=2,3 | 1.3 Scores on a scale | Standard Deviation 1.15 |
| GSK2798745 2.4 mg | Change From Baseline in Dyspnea Score | Period 1 Day-1,post exercise,n=4,2 | 0.5 Scores on a scale | Standard Deviation 0.71 |
| GSK2798745 2.4 mg | Change From Baseline in Dyspnea Score | Period 1 Day5,pre infusion,n=5,6 | -0.2 Scores on a scale | Standard Deviation 0.41 |
| GSK2798745 2.4 mg | Change From Baseline in Dyspnea Score | Period 2 Day7,post exercise,n=3,4 | 0.3 Scores on a scale | Standard Deviation 1.71 |
| GSK2798745 2.4 mg | Change From Baseline in Dyspnea Score | Period 1 Day5,pre infusion-Orthopnea,n=5,6 | -0.2 Scores on a scale | Standard Deviation 0.41 |
| GSK2798745 2.4 mg | Change From Baseline in Dyspnea Score | Period 2 Day5,pre infusion,n=6,5 | -0.2 Scores on a scale | Standard Deviation 1.1 |
| GSK2798745 2.4 mg | Change From Baseline in Dyspnea Score | Period 1 Day7,pre exercise,n=5,6 | 0.0 Scores on a scale | Standard Deviation 0.63 |
| GSK2798745 2.4 mg | Change From Baseline in Dyspnea Score | Period 2 Day7,pre exercise,n=6,5 | -0.4 Scores on a scale | Standard Deviation 0.89 |
| GSK2798745 2.4 mg | Change From Baseline in Dyspnea Score | Period 1 Day7,post exercise,n=3,2 | 0.5 Scores on a scale | Standard Deviation 0.71 |
Secondary
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.
Time frame: Baseline, Day 4 and Day 7 of each treatment period
Population: Analysis Population. Analysis was planned but not performed. EELV parameter was not collected because other measures which were collected served as reasonable surrogates.
Secondary
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.
Time frame: Baseline, Day 4 and Day 7 of each treatment period
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Forced Expiratory Flows (FEF) 25-75, FEF50 and FEF75 | FVC,Day 4,n=10,11 | -0.0 Liters | Standard Deviation 0.11 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Forced Expiratory Flows (FEF) 25-75, FEF50 and FEF75 | FVC,Day 7,n=11,11 | -0.0 Liters | Standard Deviation 0.1 |
| Placebo | 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,Day 4,n=10,11 | -0.1 Liters | Standard Deviation 0.09 |
| Placebo | 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,Day 7,n=11,11 | -0.1 Liters | Standard Deviation 0.08 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Forced Expiratory Flows (FEF) 25-75, FEF50 and FEF75 | FEF 25-75,Day 4,n=10,11 | -0.2 Liters | Standard Deviation 0.26 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Forced Expiratory Flows (FEF) 25-75, FEF50 and FEF75 | FEF 25-75,Day 7,n=11,11 | -0.1 Liters | Standard Deviation 0.16 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Forced Expiratory Flows (FEF) 25-75, FEF50 and FEF75 | FEF50,Day 4,n=10,11 | -0.3 Liters | Standard Deviation 0.36 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Forced Expiratory Flows (FEF) 25-75, FEF50 and FEF75 | FEF50,Day 7,n=11,11 | -0.2 Liters | Standard Deviation 0.3 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Forced Expiratory Flows (FEF) 25-75, FEF50 and FEF75 | FEF75,Day 4,n=10,11 | -0.0 Liters | Standard Deviation 0.08 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Forced Expiratory Flows (FEF) 25-75, FEF50 and FEF75 | FEF75,Day 7,n=11,11 | -0.0 Liters | Standard Deviation 0.06 |
| GSK2798745 2.4 mg | Change From Baseline in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Forced Expiratory Flows (FEF) 25-75, FEF50 and FEF75 | FEF50,Day 7,n=11,11 | -0.0 Liters | Standard Deviation 0.32 |
| GSK2798745 2.4 mg | Change From Baseline in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Forced Expiratory Flows (FEF) 25-75, FEF50 and FEF75 | FVC,Day 4,n=10,11 | -0.1 Liters | Standard Deviation 0.1 |
| GSK2798745 2.4 mg | Change From Baseline in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Forced Expiratory Flows (FEF) 25-75, FEF50 and FEF75 | FEF 25-75,Day 7,n=11,11 | -0.1 Liters | Standard Deviation 0.25 |
| GSK2798745 2.4 mg | Change From Baseline in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Forced Expiratory Flows (FEF) 25-75, FEF50 and FEF75 | FVC,Day 7,n=11,11 | -0.0 Liters | Standard Deviation 0.19 |
| GSK2798745 2.4 mg | Change From Baseline in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Forced Expiratory Flows (FEF) 25-75, FEF50 and FEF75 | FEF75,Day 7,n=11,11 | -0.0 Liters | Standard Deviation 0.1 |
| GSK2798745 2.4 mg | 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,Day 4,n=10,11 | -0.0 Liters | Standard Deviation 0.09 |
| GSK2798745 2.4 mg | Change From Baseline in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Forced Expiratory Flows (FEF) 25-75, FEF50 and FEF75 | FEF50,Day 4,n=10,11 | 0.0 Liters | Standard Deviation 0.43 |
| GSK2798745 2.4 mg | 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,Day 7,n=11,11 | -0.0 Liters | Standard Deviation 0.12 |
| GSK2798745 2.4 mg | Change From Baseline in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Forced Expiratory Flows (FEF) 25-75, FEF50 and FEF75 | FEF75,Day 4,n=10,11 | 0.0 Liters | Standard Deviation 0.14 |
| GSK2798745 2.4 mg | Change From Baseline in Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Forced Expiratory Flows (FEF) 25-75, FEF50 and FEF75 | FEF 25-75,Day 4,n=10,11 | 0.1 Liters | Standard Deviation 0.34 |
Secondary
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.
Time frame: Baseline, Day 4 and Day 7 of each treatment period
Population: Analysis Population. Analysis was planned but not performed. FRC parameter was not collected because other measures which were collected served as reasonable surrogates.
Secondary
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.
Time frame: Baseline and up to Day 7 of each treatment period
Population: All Subjects population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Heart Rate | Period 1, Day 1,n=5,6 | -7.0 beats per minute | Standard Deviation 7.42 |
| Placebo | Change From Baseline in Heart Rate | Period 1, Day 2,n=5,6 | -5.8 beats per minute | Standard Deviation 5.36 |
| Placebo | Change From Baseline in Heart Rate | Period 1, Day 3,n=5,6 | -2.4 beats per minute | Standard Deviation 9.21 |
| Placebo | Change From Baseline in Heart Rate | Period 1,Day 4,n=5,6 | -4.6 beats per minute | Standard Deviation 10.16 |
| Placebo | Change From Baseline in Heart Rate | Period 1, Day 5,n=5,6 | -4.8 beats per minute | Standard Deviation 7.79 |
| Placebo | Change From Baseline in Heart Rate | Period 1, Day 6,n=5,6 | -6.2 beats per minute | Standard Deviation 5.81 |
| Placebo | Change From Baseline in Heart Rate | Period 1, Day 7,n=5,6 | -3.2 beats per minute | Standard Deviation 7.95 |
| Placebo | Change From Baseline in Heart Rate | Period 2, Day 1,n=6,5 | -7.3 beats per minute | Standard Deviation 9.46 |
| Placebo | Change From Baseline in Heart Rate | Period 2, Day 2,n=6,5 | -8.0 beats per minute | Standard Deviation 15.8 |
| Placebo | Change From Baseline in Heart Rate | Period 2, Day 3,n=6,5 | -7.5 beats per minute | Standard Deviation 16.34 |
| Placebo | Change From Baseline in Heart Rate | Period 2, Day 4,n=6,5 | -9.0 beats per minute | Standard Deviation 13.52 |
| Placebo | Change From Baseline in Heart Rate | Period 2, Day 5,n=6,5 | -11.0 beats per minute | Standard Deviation 15.67 |
| Placebo | Change From Baseline in Heart Rate | Period 2, Day 6,n=6,5 | -11.0 beats per minute | Standard Deviation 16.46 |
| Placebo | Change From Baseline in Heart Rate | Period 2, Day 7,n=6,5 | -11.2 beats per minute | Standard Deviation 14.46 |
| GSK2798745 2.4 mg | Change From Baseline in Heart Rate | Period 2, Day 4,n=6,5 | 0.6 beats per minute | Standard Deviation 5.86 |
| GSK2798745 2.4 mg | Change From Baseline in Heart Rate | Period 1, Day 1,n=5,6 | 5.2 beats per minute | Standard Deviation 11.46 |
| GSK2798745 2.4 mg | Change From Baseline in Heart Rate | Period 2, Day 1,n=6,5 | 7.0 beats per minute | Standard Deviation 9.08 |
| GSK2798745 2.4 mg | Change From Baseline in Heart Rate | Period 1, Day 2,n=5,6 | -2.8 beats per minute | Standard Deviation 15.72 |
| GSK2798745 2.4 mg | Change From Baseline in Heart Rate | Period 2, Day 6,n=6,5 | 2.2 beats per minute | Standard Deviation 9.04 |
| GSK2798745 2.4 mg | Change From Baseline in Heart Rate | Period 1, Day 3,n=5,6 | -0.8 beats per minute | Standard Deviation 17.6 |
| GSK2798745 2.4 mg | Change From Baseline in Heart Rate | Period 2, Day 2,n=6,5 | -1.0 beats per minute | Standard Deviation 2.35 |
| GSK2798745 2.4 mg | Change From Baseline in Heart Rate | Period 1,Day 4,n=5,6 | -4.0 beats per minute | Standard Deviation 16.84 |
| GSK2798745 2.4 mg | Change From Baseline in Heart Rate | Period 2, Day 5,n=6,5 | 0.2 beats per minute | Standard Deviation 4.15 |
| GSK2798745 2.4 mg | Change From Baseline in Heart Rate | Period 1, Day 5,n=5,6 | 2.2 beats per minute | Standard Deviation 6.31 |
| GSK2798745 2.4 mg | Change From Baseline in Heart Rate | Period 2, Day 3,n=6,5 | -4.0 beats per minute | Standard Deviation 4.8 |
| GSK2798745 2.4 mg | Change From Baseline in Heart Rate | Period 1, Day 6,n=5,6 | 0.8 beats per minute | Standard Deviation 4.12 |
| GSK2798745 2.4 mg | Change From Baseline in Heart Rate | Period 2, Day 7,n=6,5 | -1.2 beats per minute | Standard Deviation 10.52 |
| GSK2798745 2.4 mg | Change From Baseline in Heart Rate | Period 1, Day 7,n=5,6 | 5.2 beats per minute | Standard Deviation 5.08 |
Secondary
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.
Time frame: Baseline and up to Day 7 in each treatment period
Population: All Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Hematocrit | Period 1, Day 4,n=5,6 | -0.0084 Proportion of red blood cells in blood | Standard Deviation 0.0191 |
| Placebo | Change From Baseline in Hematocrit | Period 1, Day 7,n=5,6 | -0.0086 Proportion of red blood cells in blood | Standard Deviation 0.02329 |
| Placebo | Change From Baseline in Hematocrit | Period 2, Day 4,n=5,5 | 0.0046 Proportion of red blood cells in blood | Standard Deviation 0.00513 |
| Placebo | Change From Baseline in Hematocrit | Period 2, Day 7,n=6,5 | -0.0120 Proportion of red blood cells in blood | Standard Deviation 0.01381 |
| GSK2798745 2.4 mg | Change From Baseline in Hematocrit | Period 2, Day 7,n=6,5 | -0.0164 Proportion of red blood cells in blood | Standard Deviation 0.02519 |
| GSK2798745 2.4 mg | Change From Baseline in Hematocrit | Period 1, Day 4,n=5,6 | -0.0092 Proportion of red blood cells in blood | Standard Deviation 0.01641 |
| GSK2798745 2.4 mg | Change From Baseline in Hematocrit | Period 2, Day 4,n=5,5 | -0.0138 Proportion of red blood cells in blood | Standard Deviation 0.02905 |
| GSK2798745 2.4 mg | Change From Baseline in Hematocrit | Period 1, Day 7,n=5,6 | -0.0045 Proportion of red blood cells in blood | Standard Deviation 0.02336 |
Secondary
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.
Time frame: Baseline and up to Day 7 in each treatment period
Population: All Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Monocytes,Period 2, Day 4,n=5,5 | -0.064 Giga cells per liter | Standard Deviation 0.1236 |
| Placebo | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Eosinophils,Period 1, Day 4,n=5,6 | 0.042 Giga cells per liter | Standard Deviation 0.0239 |
| Placebo | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Monocytes,Period 2, Day 7,n=6,5 | -0.015 Giga cells per liter | Standard Deviation 0.128 |
| Placebo | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Lymphocytes,Period 1, Day 4,n=5,6 | 0.128 Giga cells per liter | Standard Deviation 0.2876 |
| Placebo | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Platelet count,Period 1, Day 4,n=5,6 | -1.0 Giga cells per liter | Standard Deviation 9.87 |
| Placebo | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Basophils,Period 1, Day 7,n=5,6 | 0.000 Giga cells per liter | Standard Deviation 0.01 |
| Placebo | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Platelet count,Period 1, Day 7,n=5,6 | -0.8 Giga cells per liter | Standard Deviation 17.46 |
| Placebo | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Lymphocytes,Period 1, Day 7,n=5,6 | 0.054 Giga cells per liter | Standard Deviation 0.1014 |
| Placebo | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Platelet count,Period 2, Day 4,n=5,5 | -12.8 Giga cells per liter | Standard Deviation 9.36 |
| Placebo | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Eosinophils,Period 1, Day 7,n=5,6 | 0.058 Giga cells per liter | Standard Deviation 0.0512 |
| Placebo | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Platelet count,Period 2, Day 7,n=6,5 | -6.7 Giga cells per liter | Standard Deviation 21.5 |
| Placebo | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Lymphocytes,Period 2, Day 4,n=5,5 | -0.024 Giga cells per liter | Standard Deviation 0.1636 |
| Placebo | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | WBC,Period 1, Day 4,n=5,6 | 0.614 Giga cells per liter | Standard Deviation 1.2143 |
| Placebo | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Basophils,Period 2, Day 7,n=6,5 | 0.002 Giga cells per liter | Standard Deviation 0.0098 |
| Placebo | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | WBC,Period 1, Day 7,n=5,6 | 0.034 Giga cells per liter | Standard Deviation 0.6344 |
| Placebo | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Lymphocytes,Period 2, Day 7,n=6,5 | 0.025 Giga cells per liter | Standard Deviation 0.1512 |
| Placebo | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | WBC,Period 2, Day 4,n=5,5 | 0.156 Giga cells per liter | Standard Deviation 0.6105 |
| Placebo | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Eosinophils,Period 2, Day 4,n=5,5 | -0.012 Giga cells per liter | Standard Deviation 0.0482 |
| Placebo | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | WBC,Period 2, Day 7,n=6,5 | -0.252 Giga cells per liter | Standard Deviation 0.6902 |
| Placebo | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Monocytes,Period 1, Day 4,n=5,6 | -0.044 Giga cells per liter | Standard Deviation 0.0611 |
| Placebo | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Total Neutrophils,Period 1, Day 4,n=5,6 | 0.472 Giga cells per liter | Standard Deviation 1.0817 |
| Placebo | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Basophils,Period 2, Day 4,n=5,5 | -0.002 Giga cells per liter | Standard Deviation 0.011 |
| Placebo | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Total Neutrophils,Period 1, Day 7,n=5,6 | -0.064 Giga cells per liter | Standard Deviation 0.6789 |
| Placebo | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Monocytes,Period 1, Day 7,n=5,6 | 0.006 Giga cells per liter | Standard Deviation 0.0853 |
| Placebo | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Total Neutrophils,Period 2, Day 4,n=5,5 | 0.252 Giga cells per liter | Standard Deviation 0.6034 |
| Placebo | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Eosinophils,Period 2, Day 7,n=6,5 | -0.007 Giga cells per liter | Standard Deviation 0.0301 |
| Placebo | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Total Neutrophils,Period 2, Day 7,n=6,5 | -0.267 Giga cells per liter | Standard Deviation 0.6555 |
| Placebo | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Basophils,Period 1, Day 4,n=5,6 | 0.004 Giga cells per liter | Standard Deviation 0.0089 |
| GSK2798745 2.4 mg | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Total Neutrophils,Period 2, Day 7,n=6,5 | -0.080 Giga cells per liter | Standard Deviation 0.5928 |
| GSK2798745 2.4 mg | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Basophils,Period 1, Day 4,n=5,6 | 0.007 Giga cells per liter | Standard Deviation 0.032 |
| GSK2798745 2.4 mg | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Basophils,Period 1, Day 7,n=5,6 | 0.010 Giga cells per liter | Standard Deviation 0.0358 |
| GSK2798745 2.4 mg | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Basophils,Period 2, Day 4,n=5,5 | 0.002 Giga cells per liter | Standard Deviation 0.013 |
| GSK2798745 2.4 mg | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Basophils,Period 2, Day 7,n=6,5 | -0.004 Giga cells per liter | Standard Deviation 0.0089 |
| GSK2798745 2.4 mg | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Eosinophils,Period 1, Day 4,n=5,6 | 0.033 Giga cells per liter | Standard Deviation 0.0859 |
| GSK2798745 2.4 mg | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Eosinophils,Period 1, Day 7,n=5,6 | 0.038 Giga cells per liter | Standard Deviation 0.0412 |
| GSK2798745 2.4 mg | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Eosinophils,Period 2, Day 4,n=5,5 | -0.022 Giga cells per liter | Standard Deviation 0.092 |
| GSK2798745 2.4 mg | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Eosinophils,Period 2, Day 7,n=6,5 | -0.018 Giga cells per liter | Standard Deviation 0.1154 |
| GSK2798745 2.4 mg | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Lymphocytes,Period 1, Day 4,n=5,6 | -0.110 Giga cells per liter | Standard Deviation 0.4315 |
| GSK2798745 2.4 mg | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Lymphocytes,Period 1, Day 7,n=5,6 | -0.122 Giga cells per liter | Standard Deviation 0.4964 |
| GSK2798745 2.4 mg | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Lymphocytes,Period 2, Day 4,n=5,5 | 0.098 Giga cells per liter | Standard Deviation 0.3725 |
| GSK2798745 2.4 mg | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Lymphocytes,Period 2, Day 7,n=6,5 | 0.126 Giga cells per liter | Standard Deviation 0.2508 |
| GSK2798745 2.4 mg | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Monocytes,Period 1, Day 4,n=5,6 | -0.082 Giga cells per liter | Standard Deviation 0.1628 |
| GSK2798745 2.4 mg | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Monocytes,Period 1, Day 7,n=5,6 | 0.012 Giga cells per liter | Standard Deviation 0.17 |
| GSK2798745 2.4 mg | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Monocytes,Period 2, Day 4,n=5,5 | -0.014 Giga cells per liter | Standard Deviation 0.115 |
| GSK2798745 2.4 mg | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Monocytes,Period 2, Day 7,n=6,5 | 0.008 Giga cells per liter | Standard Deviation 0.1087 |
| GSK2798745 2.4 mg | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Platelet count,Period 1, Day 4,n=5,6 | -3.2 Giga cells per liter | Standard Deviation 27.26 |
| GSK2798745 2.4 mg | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Platelet count,Period 1, Day 7,n=5,6 | -2.7 Giga cells per liter | Standard Deviation 25.23 |
| GSK2798745 2.4 mg | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Platelet count,Period 2, Day 4,n=5,5 | 1.0 Giga cells per liter | Standard Deviation 12.79 |
| GSK2798745 2.4 mg | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Platelet count,Period 2, Day 7,n=6,5 | 9.0 Giga cells per liter | Standard Deviation 18.4 |
| GSK2798745 2.4 mg | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | WBC,Period 1, Day 4,n=5,6 | -0.100 Giga cells per liter | Standard Deviation 1.313 |
| GSK2798745 2.4 mg | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | WBC,Period 1, Day 7,n=5,6 | 0.250 Giga cells per liter | Standard Deviation 0.8118 |
| GSK2798745 2.4 mg | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | WBC,Period 2, Day 4,n=5,5 | 0.252 Giga cells per liter | Standard Deviation 1.0176 |
| GSK2798745 2.4 mg | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | WBC,Period 2, Day 7,n=6,5 | 0.064 Giga cells per liter | Standard Deviation 0.3369 |
| GSK2798745 2.4 mg | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Total Neutrophils,Period 1, Day 4,n=5,6 | 0.043 Giga cells per liter | Standard Deviation 0.8491 |
| GSK2798745 2.4 mg | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Total Neutrophils,Period 1, Day 7,n=5,6 | 0.345 Giga cells per liter | Standard Deviation 0.4476 |
| GSK2798745 2.4 mg | Change From Baseline in Hematology: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, White Blood Cell (WBC) Count, Total Neutrophils | Total Neutrophils,Period 2, Day 4,n=5,5 | 0.162 Giga cells per liter | Standard Deviation 0.8436 |
Secondary
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.
Time frame: Baseline and up to Day 7 in each treatment period
Population: All Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Hemoglobin | Period 1, Day 4,n=5,6 | -1.0 Gram per liter | Standard Deviation 6.67 |
| Placebo | Change From Baseline in Hemoglobin | Period 2, Day 4,n=5,5 | 1.6 Gram per liter | Standard Deviation 2.41 |
| Placebo | Change From Baseline in Hemoglobin | Period 1, Day 7,n=5,6 | 0.8 Gram per liter | Standard Deviation 10.87 |
| Placebo | Change From Baseline in Hemoglobin | Period 2, Day 7,n=6,5 | -3.5 Gram per liter | Standard Deviation 4.93 |
| GSK2798745 2.4 mg | Change From Baseline in Hemoglobin | Period 1, Day 7,n=5,6 | -2.2 Gram per liter | Standard Deviation 6.55 |
| GSK2798745 2.4 mg | Change From Baseline in Hemoglobin | Period 1, Day 4,n=5,6 | -4.3 Gram per liter | Standard Deviation 7.42 |
| GSK2798745 2.4 mg | Change From Baseline in Hemoglobin | Period 2, Day 7,n=6,5 | -3.4 Gram per liter | Standard Deviation 7.89 |
| GSK2798745 2.4 mg | Change From Baseline in Hemoglobin | Period 2, Day 4,n=5,5 | -3.8 Gram per liter | Standard Deviation 7.85 |
Secondary
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
Time frame: Baseline and up to Day 7 in each treatment period
Population: All Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean Corpuscle Hemoglobin | Period 2, Day 4,n=1,3 | 0.00 Picograms | — |
| Placebo | Change From Baseline in Mean Corpuscle Hemoglobin | Period 1, Day 4,n=3,1 | 0.70 Picograms | Standard Deviation 0.656 |
| Placebo | Change From Baseline in Mean Corpuscle Hemoglobin | Period 2, Day 7,n=1,3 | 0.40 Picograms | — |
| Placebo | Change From Baseline in Mean Corpuscle Hemoglobin | Period 1, Day 7,n=3,1 | 0.70 Picograms | Standard Deviation 1.044 |
| GSK2798745 2.4 mg | Change From Baseline in Mean Corpuscle Hemoglobin | Period 2, Day 7,n=1,3 | 0.33 Picograms | Standard Deviation 0.503 |
| GSK2798745 2.4 mg | Change From Baseline in Mean Corpuscle Hemoglobin | Period 1, Day 4,n=3,1 | 0.20 Picograms | — |
| GSK2798745 2.4 mg | Change From Baseline in Mean Corpuscle Hemoglobin | Period 2, Day 4,n=1,3 | 0.27 Picograms | Standard Deviation 0.231 |
| GSK2798745 2.4 mg | Change From Baseline in Mean Corpuscle Hemoglobin | Period 1, Day 7,n=3,1 | -0.20 Picograms | — |
Secondary
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
Time frame: Baseline and up to Day 7 in each treatment period
Population: All Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean Corpuscle Hemoglobin Concentration | Period 1, Day 4,n=3,1 | 8.0 grams per liter | Standard Deviation 7.94 |
| Placebo | Change From Baseline in Mean Corpuscle Hemoglobin Concentration | Period 1, Day 7,n=3,1 | 13.7 grams per liter | Standard Deviation 12.22 |
| Placebo | Change From Baseline in Mean Corpuscle Hemoglobin Concentration | Period 2, Day 4,n=1,3 | -1.0 grams per liter | — |
| Placebo | Change From Baseline in Mean Corpuscle Hemoglobin Concentration | Period 2, Day 7,n=1,3 | -2.0 grams per liter | — |
| GSK2798745 2.4 mg | Change From Baseline in Mean Corpuscle Hemoglobin Concentration | Period 2, Day 7,n=1,3 | 6.0 grams per liter | Standard Deviation 8.66 |
| GSK2798745 2.4 mg | Change From Baseline in Mean Corpuscle Hemoglobin Concentration | Period 1, Day 4,n=3,1 | -3.0 grams per liter | — |
| GSK2798745 2.4 mg | Change From Baseline in Mean Corpuscle Hemoglobin Concentration | Period 2, Day 4,n=1,3 | 2.7 grams per liter | Standard Deviation 6.66 |
| GSK2798745 2.4 mg | Change From Baseline in Mean Corpuscle Hemoglobin Concentration | Period 1, Day 7,n=3,1 | -8.0 grams per liter | — |
Secondary
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.
Time frame: Baseline and up to Day 7 in each treatment period
Population: All Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean Corpuscle Volume | Period 1, Day 4,n=5,6 | 0.20 Femtoliters | Standard Deviation 1.402 |
| Placebo | Change From Baseline in Mean Corpuscle Volume | Period 1, Day 7,n=5,6 | -0.92 Femtoliters | Standard Deviation 1.152 |
| Placebo | Change From Baseline in Mean Corpuscle Volume | Period 2, Day 4,n=5,5 | 0.04 Femtoliters | Standard Deviation 0.493 |
| Placebo | Change From Baseline in Mean Corpuscle Volume | Period 2, Day 7,n=6,5 | 0.23 Femtoliters | Standard Deviation 1.003 |
| GSK2798745 2.4 mg | Change From Baseline in Mean Corpuscle Volume | Period 2, Day 7,n=6,5 | -0.50 Femtoliters | Standard Deviation 1.086 |
| GSK2798745 2.4 mg | Change From Baseline in Mean Corpuscle Volume | Period 1, Day 4,n=5,6 | 0.97 Femtoliters | Standard Deviation 1.218 |
| GSK2798745 2.4 mg | Change From Baseline in Mean Corpuscle Volume | Period 2, Day 4,n=5,5 | 0.08 Femtoliters | Standard Deviation 0.926 |
| GSK2798745 2.4 mg | Change From Baseline in Mean Corpuscle Volume | Period 1, Day 7,n=5,6 | 0.55 Femtoliters | Standard Deviation 0.946 |
Secondary
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.
Time frame: Baseline and Day 7 of each treatment period
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Role-Physical, Period 1, Day 7,n=4,6 | -0.5 Score on a scale | Standard Deviation 3.11 |
| Placebo | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Social Functioning, Period 1, Day 7,n=5,6 | -0.6 Score on a scale | Standard Deviation 0.55 |
| Placebo | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Bodily Pain, Period 2, Day 7,n=5,5 | -0.2 Score on a scale | Standard Deviation 1.1 |
| Placebo | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Social Functioning, Period 2, Day 7,n=5,5 | 0.6 Score on a scale | Standard Deviation 0.89 |
| Placebo | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Physical Functioning, Period 2, Day 7,n=5,5 | 1.0 Score on a scale | Standard Deviation 1.22 |
| Placebo | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Role- Emotional, Period 1, Day 7,n=4,6 | 1.3 Score on a scale | Standard Deviation 2.5 |
| Placebo | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | General Health,Period 1, Day 7,n=5,6 | 1.8 Score on a scale | Standard Deviation 2.49 |
| Placebo | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Role- Emotional, Period 2, Day 7,n=5,5 | -0.2 Score on a scale | Standard Deviation 3.19 |
| Placebo | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Role-Physical, Period 2, Day 7,n=5,5 | 2.0 Score on a scale | Standard Deviation 3.67 |
| Placebo | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Mental Health, Period 1, Day 7,n=5,6 | 0.6 Score on a scale | Standard Deviation 0.55 |
| Placebo | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | General Health,Period 2, Day 7,n=5,5 | 0.0 Score on a scale | Standard Deviation 0.71 |
| Placebo | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Mental Health, Period 2, Day 7,n=5,5 | 0.2 Score on a scale | Standard Deviation 1.79 |
| Placebo | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Physical Functioning, Period 1, Day 7,n=5,6 | 3.0 Score on a scale | Standard Deviation 4 |
| Placebo | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Vitality, Period 1, Day 7,n=5,6 | 1.2 Score on a scale | Standard Deviation 1.79 |
| Placebo | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Physical Health Score,Period 2, Day 7,n=5,5 | 2.8 Score on a scale | Standard Deviation 3.03 |
| Placebo | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Bodily Pain, Period 1, Day 7,n=5,5 | -1.0 Score on a scale | Standard Deviation 1.41 |
| Placebo | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Mental Health Score, Period 1, Day 7,n=5,6 | 5.2 Score on a scale | Standard Deviation 6.53 |
| Placebo | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Vitality, Period 2, Day 7,n=5,5 | -0.4 Score on a scale | Standard Deviation 1.14 |
| Placebo | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Mental Health Score, Period 2, Day 7,n=5,5 | 0.2 Score on a scale | Standard Deviation 4.09 |
| Placebo | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Physical Health Score,Period 1, Day 7,n=5,6 | 5.8 Score on a scale | Standard Deviation 8.23 |
| GSK2798745 2.4 mg | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Mental Health Score, Period 2, Day 7,n=5,5 | 1.4 Score on a scale | Standard Deviation 3.85 |
| GSK2798745 2.4 mg | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Physical Functioning, Period 1, Day 7,n=5,6 | 1.2 Score on a scale | Standard Deviation 0.75 |
| GSK2798745 2.4 mg | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Physical Functioning, Period 2, Day 7,n=5,5 | -0.4 Score on a scale | Standard Deviation 2.19 |
| GSK2798745 2.4 mg | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Role-Physical, Period 1, Day 7,n=4,6 | 3.7 Score on a scale | Standard Deviation 3.93 |
| GSK2798745 2.4 mg | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Role-Physical, Period 2, Day 7,n=5,5 | 0.4 Score on a scale | Standard Deviation 2.7 |
| GSK2798745 2.4 mg | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Bodily Pain, Period 1, Day 7,n=5,5 | -1.2 Score on a scale | Standard Deviation 1.1 |
| GSK2798745 2.4 mg | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Bodily Pain, Period 2, Day 7,n=5,5 | 0.4 Score on a scale | Standard Deviation 1.14 |
| GSK2798745 2.4 mg | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | General Health,Period 1, Day 7,n=5,6 | -1.5 Score on a scale | Standard Deviation 5.79 |
| GSK2798745 2.4 mg | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | General Health,Period 2, Day 7,n=5,5 | -1.4 Score on a scale | Standard Deviation 2.97 |
| GSK2798745 2.4 mg | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Vitality, Period 1, Day 7,n=5,6 | -1.2 Score on a scale | Standard Deviation 1.17 |
| GSK2798745 2.4 mg | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Vitality, Period 2, Day 7,n=5,5 | -0.8 Score on a scale | Standard Deviation 2.17 |
| GSK2798745 2.4 mg | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Social Functioning, Period 1, Day 7,n=5,6 | 0.5 Score on a scale | Standard Deviation 1.22 |
| GSK2798745 2.4 mg | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Social Functioning, Period 2, Day 7,n=5,5 | -0.2 Score on a scale | Standard Deviation 1.1 |
| GSK2798745 2.4 mg | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Role- Emotional, Period 1, Day 7,n=4,6 | 1.0 Score on a scale | Standard Deviation 1.55 |
| GSK2798745 2.4 mg | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Role- Emotional, Period 2, Day 7,n=5,5 | 1.2 Score on a scale | Standard Deviation 4.09 |
| GSK2798745 2.4 mg | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Mental Health, Period 1, Day 7,n=5,6 | 0.3 Score on a scale | Standard Deviation 0.52 |
| GSK2798745 2.4 mg | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Mental Health, Period 2, Day 7,n=5,5 | 1.2 Score on a scale | Standard Deviation 1.79 |
| GSK2798745 2.4 mg | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Physical Health Score,Period 1, Day 7,n=5,6 | 1.7 Score on a scale | Standard Deviation 3.83 |
| GSK2798745 2.4 mg | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Physical Health Score,Period 2, Day 7,n=5,5 | -1.0 Score on a scale | Standard Deviation 5.61 |
| GSK2798745 2.4 mg | Change From Baseline in Participant Reported Health Status (SF-36) Acute Score | Mental Health Score, Period 1, Day 7,n=5,6 | 0.7 Score on a scale | Standard Deviation 1.97 |
Secondary
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.
Time frame: Baseline and up to Day 7 of each treatment period
Population: All Subjects population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Percent Oxygen in Blood | Period 1, Day 1,n=4,6 | 0.0 Percentage of oxygen | Standard Deviation 0.82 |
| Placebo | Change From Baseline in Percent Oxygen in Blood | Period 1, Day 2,n=4,5 | 1.3 Percentage of oxygen | Standard Deviation 0.96 |
| Placebo | Change From Baseline in Percent Oxygen in Blood | Period 1, Day 3,n=3,6 | 0.7 Percentage of oxygen | Standard Deviation 1.53 |
| Placebo | Change From Baseline in Percent Oxygen in Blood | Period 1,Day 4,n=4,6 | 0.3 Percentage of oxygen | Standard Deviation 0.96 |
| Placebo | Change From Baseline in Percent Oxygen in Blood | Period 1, Day 5,n=4,6 | 1.0 Percentage of oxygen | Standard Deviation 1.63 |
| Placebo | Change From Baseline in Percent Oxygen in Blood | Period 1, Day 6,n=4,6 | 0.3 Percentage of oxygen | Standard Deviation 0.96 |
| Placebo | Change From Baseline in Percent Oxygen in Blood | Period 1, Day 7,n=4,6 | -0.3 Percentage of oxygen | Standard Deviation 1.71 |
| Placebo | Change From Baseline in Percent Oxygen in Blood | Period 2, Day 1,n=6,5 | -1.0 Percentage of oxygen | Standard Deviation 2.83 |
| Placebo | Change From Baseline in Percent Oxygen in Blood | Period 2, Day 2,n=6,5 | 0.2 Percentage of oxygen | Standard Deviation 2.99 |
| Placebo | Change From Baseline in Percent Oxygen in Blood | Period 2, Day 3,n=6,4 | -0.8 Percentage of oxygen | Standard Deviation 2.64 |
| Placebo | Change From Baseline in Percent Oxygen in Blood | Period 2, Day 4,n=6,5 | -1.0 Percentage of oxygen | Standard Deviation 2.61 |
| Placebo | Change From Baseline in Percent Oxygen in Blood | Period 2, Day 5,n=6,5 | -0.2 Percentage of oxygen | Standard Deviation 1.33 |
| Placebo | Change From Baseline in Percent Oxygen in Blood | Period 2, Day 6,n=6,5 | -0.5 Percentage of oxygen | Standard Deviation 2.17 |
| Placebo | Change From Baseline in Percent Oxygen in Blood | Period 2, Day 7,n=6,5 | 0.2 Percentage of oxygen | Standard Deviation 2.04 |
| GSK2798745 2.4 mg | Change From Baseline in Percent Oxygen in Blood | Period 2, Day 4,n=6,5 | 1.4 Percentage of oxygen | Standard Deviation 1.82 |
| GSK2798745 2.4 mg | Change From Baseline in Percent Oxygen in Blood | Period 1, Day 1,n=4,6 | -0.3 Percentage of oxygen | Standard Deviation 1.37 |
| GSK2798745 2.4 mg | Change From Baseline in Percent Oxygen in Blood | Period 2, Day 1,n=6,5 | -0.6 Percentage of oxygen | Standard Deviation 1.82 |
| GSK2798745 2.4 mg | Change From Baseline in Percent Oxygen in Blood | Period 1, Day 2,n=4,5 | -1.2 Percentage of oxygen | Standard Deviation 0.84 |
| GSK2798745 2.4 mg | Change From Baseline in Percent Oxygen in Blood | Period 2, Day 6,n=6,5 | 0.2 Percentage of oxygen | Standard Deviation 1.79 |
| GSK2798745 2.4 mg | Change From Baseline in Percent Oxygen in Blood | Period 1, Day 3,n=3,6 | -0.7 Percentage of oxygen | Standard Deviation 1.75 |
| GSK2798745 2.4 mg | Change From Baseline in Percent Oxygen in Blood | Period 2, Day 2,n=6,5 | 0.0 Percentage of oxygen | Standard Deviation 1.22 |
| GSK2798745 2.4 mg | Change From Baseline in Percent Oxygen in Blood | Period 1,Day 4,n=4,6 | 0.0 Percentage of oxygen | Standard Deviation 1.1 |
| GSK2798745 2.4 mg | Change From Baseline in Percent Oxygen in Blood | Period 2, Day 5,n=6,5 | 0.2 Percentage of oxygen | Standard Deviation 1.3 |
| GSK2798745 2.4 mg | Change From Baseline in Percent Oxygen in Blood | Period 1, Day 5,n=4,6 | 0.5 Percentage of oxygen | Standard Deviation 2.66 |
| GSK2798745 2.4 mg | Change From Baseline in Percent Oxygen in Blood | Period 2, Day 3,n=6,4 | -0.3 Percentage of oxygen | Standard Deviation 2.36 |
| GSK2798745 2.4 mg | Change From Baseline in Percent Oxygen in Blood | Period 1, Day 6,n=4,6 | -0.2 Percentage of oxygen | Standard Deviation 1.72 |
| GSK2798745 2.4 mg | Change From Baseline in Percent Oxygen in Blood | Period 2, Day 7,n=6,5 | 0.0 Percentage of oxygen | Standard Deviation 1.87 |
| GSK2798745 2.4 mg | Change From Baseline in Percent Oxygen in Blood | Period 1, Day 7,n=4,6 | -0.3 Percentage of oxygen | Standard Deviation 1.51 |
Secondary
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.
Time frame: Baseline and up to Day 7 in each treatment period
Population: All Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Red Blood Cell Count (RBC) and Reticulocytes | RBC,Period 1, Day 4,n=5,6 | -0.100 Trillion cells per liter | Standard Deviation 0.1943 |
| Placebo | Change From Baseline in Red Blood Cell Count (RBC) and Reticulocytes | RBC,Period 1, Day 7,n=5,6 | -0.056 Trillion cells per liter | Standard Deviation 0.2637 |
| Placebo | Change From Baseline in Red Blood Cell Count (RBC) and Reticulocytes | RBC,Period 2, Day 4,n=5,5 | 0.014 Trillion cells per liter | Standard Deviation 0.0937 |
| Placebo | Change From Baseline in Red Blood Cell Count (RBC) and Reticulocytes | RBC,Period 2, Day 7,n=6,5 | -0.188 Trillion cells per liter | Standard Deviation 0.236 |
| Placebo | Change From Baseline in Red Blood Cell Count (RBC) and Reticulocytes | Reticulocytes,Period 1, Day 4,n=5,6 | -0.00148 Trillion cells per liter | Standard Deviation 0.002167 |
| Placebo | Change From Baseline in Red Blood Cell Count (RBC) and Reticulocytes | Reticulocytes,Period 1, Day 7,n=5,6 | 0.00049 Trillion cells per liter | Standard Deviation 0.004412 |
| Placebo | Change From Baseline in Red Blood Cell Count (RBC) and Reticulocytes | Reticulocytes,Period 2, Day 4,n=5,5 | 0.00367 Trillion cells per liter | Standard Deviation 0.032819 |
| Placebo | Change From Baseline in Red Blood Cell Count (RBC) and Reticulocytes | Reticulocytes,Period 2, Day 7,n=6,5 | 0.00868 Trillion cells per liter | Standard Deviation 0.019263 |
| GSK2798745 2.4 mg | Change From Baseline in Red Blood Cell Count (RBC) and Reticulocytes | Reticulocytes,Period 2, Day 7,n=6,5 | 0.00086 Trillion cells per liter | Standard Deviation 0.001831 |
| GSK2798745 2.4 mg | Change From Baseline in Red Blood Cell Count (RBC) and Reticulocytes | RBC,Period 1, Day 4,n=5,6 | -0.160 Trillion cells per liter | Standard Deviation 0.2555 |
| GSK2798745 2.4 mg | Change From Baseline in Red Blood Cell Count (RBC) and Reticulocytes | Reticulocytes,Period 1, Day 4,n=5,6 | -0.00388 Trillion cells per liter | Standard Deviation 0.012096 |
| GSK2798745 2.4 mg | Change From Baseline in Red Blood Cell Count (RBC) and Reticulocytes | RBC,Period 1, Day 7,n=5,6 | -0.083 Trillion cells per liter | Standard Deviation 0.27 |
| GSK2798745 2.4 mg | Change From Baseline in Red Blood Cell Count (RBC) and Reticulocytes | Reticulocytes,Period 2, Day 4,n=5,5 | 0.00051 Trillion cells per liter | Standard Deviation 0.007178 |
| GSK2798745 2.4 mg | Change From Baseline in Red Blood Cell Count (RBC) and Reticulocytes | RBC,Period 2, Day 4,n=5,5 | -0.146 Trillion cells per liter | Standard Deviation 0.2708 |
| GSK2798745 2.4 mg | Change From Baseline in Red Blood Cell Count (RBC) and Reticulocytes | Reticulocytes,Period 1, Day 7,n=5,6 | 0.00021 Trillion cells per liter | Standard Deviation 0.010985 |
| GSK2798745 2.4 mg | Change From Baseline in Red Blood Cell Count (RBC) and Reticulocytes | RBC,Period 2, Day 7,n=6,5 | -0.150 Trillion cells per liter | Standard Deviation 0.227 |
Secondary
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.
Time frame: Baseline and up to Day 7 of each treatment period
Population: All Subjects population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Respiration Rate | Period 1, Day 3,n=5,6 | 0.2 breaths per minute | Standard Deviation 1.79 |
| Placebo | Change From Baseline in Respiration Rate | Period 1, Day 7,n=5,6 | 1.2 breaths per minute | Standard Deviation 4.38 |
| Placebo | Change From Baseline in Respiration Rate | Period 2, Day 5,n=6,5 | 2.3 breaths per minute | Standard Deviation 3.44 |
| Placebo | Change From Baseline in Respiration Rate | Period 2, Day 1,n=6,5 | 2.3 breaths per minute | Standard Deviation 3.67 |
| Placebo | Change From Baseline in Respiration Rate | Period 1,Day 4,n=5,6 | 0.6 breaths per minute | Standard Deviation 1.67 |
| Placebo | Change From Baseline in Respiration Rate | Period 2, Day 2,n=6,5 | 2.7 breaths per minute | Standard Deviation 2.73 |
| Placebo | Change From Baseline in Respiration Rate | Period 1, Day 2,n=5,6 | -0.2 breaths per minute | Standard Deviation 2.86 |
| Placebo | Change From Baseline in Respiration Rate | Period 2, Day 3,n=6,5 | 1.7 breaths per minute | Standard Deviation 3.88 |
| Placebo | Change From Baseline in Respiration Rate | Period 1, Day 5,n=5,6 | 1.2 breaths per minute | Standard Deviation 2.59 |
| Placebo | Change From Baseline in Respiration Rate | Period 1, Day 1,n=5,6 | 0.6 breaths per minute | Standard Deviation 0.89 |
| Placebo | Change From Baseline in Respiration Rate | Period 2, Day 6,n=6,5 | 2.7 breaths per minute | Standard Deviation 1.03 |
| Placebo | Change From Baseline in Respiration Rate | Period 1, Day 6,n=5,6 | -0.2 breaths per minute | Standard Deviation 3.63 |
| Placebo | Change From Baseline in Respiration Rate | Period 2, Day 7,n=6,5 | 1.0 breaths per minute | Standard Deviation 2.45 |
| Placebo | Change From Baseline in Respiration Rate | Period 2, Day 4,n=6,5 | 1.7 breaths per minute | Standard Deviation 3.67 |
| GSK2798745 2.4 mg | Change From Baseline in Respiration Rate | Period 2, Day 7,n=6,5 | -1.0 breaths per minute | Standard Deviation 1.73 |
| GSK2798745 2.4 mg | Change From Baseline in Respiration Rate | Period 2, Day 4,n=6,5 | 4.6 breaths per minute | Standard Deviation 3.58 |
| GSK2798745 2.4 mg | Change From Baseline in Respiration Rate | Period 1, Day 1,n=5,6 | 1.0 breaths per minute | Standard Deviation 3.95 |
| GSK2798745 2.4 mg | Change From Baseline in Respiration Rate | Period 1, Day 2,n=5,6 | 0.7 breaths per minute | Standard Deviation 3.01 |
| GSK2798745 2.4 mg | Change From Baseline in Respiration Rate | Period 1, Day 3,n=5,6 | 2.0 breaths per minute | Standard Deviation 3.46 |
| GSK2798745 2.4 mg | Change From Baseline in Respiration Rate | Period 1,Day 4,n=5,6 | 0.8 breaths per minute | Standard Deviation 1.79 |
| GSK2798745 2.4 mg | Change From Baseline in Respiration Rate | Period 1, Day 5,n=5,6 | 1.8 breaths per minute | Standard Deviation 4.58 |
| GSK2798745 2.4 mg | Change From Baseline in Respiration Rate | Period 1, Day 6,n=5,6 | 2.0 breaths per minute | Standard Deviation 3.1 |
| GSK2798745 2.4 mg | Change From Baseline in Respiration Rate | Period 1, Day 7,n=5,6 | 1.7 breaths per minute | Standard Deviation 3.44 |
| GSK2798745 2.4 mg | Change From Baseline in Respiration Rate | Period 2, Day 1,n=6,5 | 1.0 breaths per minute | Standard Deviation 3.74 |
| GSK2798745 2.4 mg | Change From Baseline in Respiration Rate | Period 2, Day 2,n=6,5 | 3.2 breaths per minute | Standard Deviation 2.39 |
| GSK2798745 2.4 mg | Change From Baseline in Respiration Rate | Period 2, Day 3,n=6,5 | 3.0 breaths per minute | Standard Deviation 2 |
| GSK2798745 2.4 mg | Change From Baseline in Respiration Rate | Period 2, Day 5,n=6,5 | 1.0 breaths per minute | Standard Deviation 3 |
| GSK2798745 2.4 mg | Change From Baseline in Respiration Rate | Period 2, Day 6,n=6,5 | 2.6 breaths per minute | Standard Deviation 2.41 |
Secondary
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.
Time frame: Baseline and up to Day 7 of each treatment period
Population: All Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | DBP,Period 1, Day 1,n=5,6 | -3.4 Millimeters of mercury | Standard Deviation 10.14 |
| Placebo | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | SBP,Period 2, Day 1,n=6,5 | -14.0 Millimeters of mercury | Standard Deviation 22.45 |
| Placebo | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | DBP,Period 1, Day 2,n=5,6 | -7.6 Millimeters of mercury | Standard Deviation 8.02 |
| Placebo | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | SBP,Period 1, Day 5,n=5,6 | -10.4 Millimeters of mercury | Standard Deviation 11.78 |
| Placebo | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | DBP,Period 1, Day 3,n=5,6 | -14.6 Millimeters of mercury | Standard Deviation 4.83 |
| Placebo | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | SBP,Period 2, Day 2,n=6,5 | -12.7 Millimeters of mercury | Standard Deviation 31.65 |
| Placebo | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | DBP,Period 1,Day 4,n=5,6 | -5.0 Millimeters of mercury | Standard Deviation 9.62 |
| Placebo | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | SBP,Period 1, Day 4,n=5,6 | -9.2 Millimeters of mercury | Standard Deviation 9.71 |
| Placebo | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | DBP,Period 1, Day 5,n=5,6 | -8.0 Millimeters of mercury | Standard Deviation 8.03 |
| Placebo | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | SBP,Period 2, Day 3,n=6,5 | -14.5 Millimeters of mercury | Standard Deviation 34.88 |
| Placebo | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | DBP,Period 1, Day 6,n=5,6 | -9.8 Millimeters of mercury | Standard Deviation 5.67 |
| Placebo | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | SBP,Period 1, Day 2,n=5,6 | -7.8 Millimeters of mercury | Standard Deviation 13.86 |
| Placebo | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | DBP,Period 1, Day 7,n=5,6 | 0.2 Millimeters of mercury | Standard Deviation 13.01 |
| Placebo | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | SBP,Period 2, Day 4,n=6,5 | -13.5 Millimeters of mercury | Standard Deviation 25.62 |
| Placebo | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | DBP,Period 2, Day 1,n=6,5 | -9.2 Millimeters of mercury | Standard Deviation 13.91 |
| Placebo | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | SBP,Period 1, Day 6,n=5,6 | -12.8 Millimeters of mercury | Standard Deviation 7.05 |
| Placebo | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | DBP,Period 2, Day 2,n=6,5 | -9.7 Millimeters of mercury | Standard Deviation 18.41 |
| Placebo | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | SBP,Period 2, Day 5,n=6,5 | -19.0 Millimeters of mercury | Standard Deviation 23.1 |
| Placebo | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | DBP,Period 2, Day 3,n=6,5 | -7.2 Millimeters of mercury | Standard Deviation 20.47 |
| Placebo | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | SBP,Period 1, Day 1,n=5,6 | -6.8 Millimeters of mercury | Standard Deviation 7.12 |
| Placebo | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | DBP,Period 2, Day 4,n=6,5 | -9.8 Millimeters of mercury | Standard Deviation 12.27 |
| Placebo | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | SBP,Period 2, Day 6,n=6,5 | -12.5 Millimeters of mercury | Standard Deviation 16.38 |
| Placebo | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | DBP,Period 2, Day 5,n=6,5 | -10.7 Millimeters of mercury | Standard Deviation 15.38 |
| Placebo | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | SBP,Period 1, Day 7,n=5,6 | -3.2 Millimeters of mercury | Standard Deviation 18.74 |
| Placebo | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | DBP,Period 2, Day 6,n=6,5 | -8.2 Millimeters of mercury | Standard Deviation 11.62 |
| Placebo | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | SBP,Period 2, Day 7,n=6,5 | -11.5 Millimeters of mercury | Standard Deviation 27.57 |
| Placebo | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | DBP,Period 2, Day 7,n=6,5 | -9.3 Millimeters of mercury | Standard Deviation 13.95 |
| Placebo | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | SBP,Period 1, Day 3,n=5,6 | -8.8 Millimeters of mercury | Standard Deviation 12.52 |
| GSK2798745 2.4 mg | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | DBP,Period 2, Day 7,n=6,5 | 1.2 Millimeters of mercury | Standard Deviation 11.03 |
| GSK2798745 2.4 mg | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | SBP,Period 1, Day 1,n=5,6 | 2.5 Millimeters of mercury | Standard Deviation 19.56 |
| GSK2798745 2.4 mg | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | SBP,Period 1, Day 2,n=5,6 | -2.5 Millimeters of mercury | Standard Deviation 12.49 |
| GSK2798745 2.4 mg | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | SBP,Period 1, Day 3,n=5,6 | 0.0 Millimeters of mercury | Standard Deviation 10.41 |
| GSK2798745 2.4 mg | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | SBP,Period 1, Day 5,n=5,6 | 0.3 Millimeters of mercury | Standard Deviation 24.91 |
| GSK2798745 2.4 mg | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | SBP,Period 1, Day 6,n=5,6 | 0.0 Millimeters of mercury | Standard Deviation 14.85 |
| GSK2798745 2.4 mg | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | SBP,Period 1, Day 7,n=5,6 | 9.0 Millimeters of mercury | Standard Deviation 25.17 |
| GSK2798745 2.4 mg | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | SBP,Period 2, Day 1,n=6,5 | -9.2 Millimeters of mercury | Standard Deviation 17.33 |
| GSK2798745 2.4 mg | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | SBP,Period 2, Day 2,n=6,5 | -6.4 Millimeters of mercury | Standard Deviation 15.92 |
| GSK2798745 2.4 mg | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | SBP,Period 2, Day 3,n=6,5 | -8.0 Millimeters of mercury | Standard Deviation 11.75 |
| GSK2798745 2.4 mg | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | SBP,Period 2, Day 4,n=6,5 | -4.4 Millimeters of mercury | Standard Deviation 14.05 |
| GSK2798745 2.4 mg | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | SBP,Period 2, Day 5,n=6,5 | -10.8 Millimeters of mercury | Standard Deviation 14.57 |
| GSK2798745 2.4 mg | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | SBP,Period 2, Day 6,n=6,5 | -7.4 Millimeters of mercury | Standard Deviation 10.57 |
| GSK2798745 2.4 mg | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | SBP,Period 2, Day 7,n=6,5 | -2.2 Millimeters of mercury | Standard Deviation 14.36 |
| GSK2798745 2.4 mg | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | DBP,Period 1, Day 1,n=5,6 | 0.3 Millimeters of mercury | Standard Deviation 12.06 |
| GSK2798745 2.4 mg | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | DBP,Period 1, Day 2,n=5,6 | -4.0 Millimeters of mercury | Standard Deviation 14.03 |
| GSK2798745 2.4 mg | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | DBP,Period 1, Day 3,n=5,6 | -0.3 Millimeters of mercury | Standard Deviation 9.99 |
| GSK2798745 2.4 mg | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | DBP,Period 1,Day 4,n=5,6 | -4.3 Millimeters of mercury | Standard Deviation 12.21 |
| GSK2798745 2.4 mg | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | DBP,Period 1, Day 5,n=5,6 | -5.8 Millimeters of mercury | Standard Deviation 11.2 |
| GSK2798745 2.4 mg | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | DBP,Period 1, Day 6,n=5,6 | 0.2 Millimeters of mercury | Standard Deviation 8.23 |
| GSK2798745 2.4 mg | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | DBP,Period 1, Day 7,n=5,6 | 6.5 Millimeters of mercury | Standard Deviation 12 |
| GSK2798745 2.4 mg | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | DBP,Period 2, Day 1,n=6,5 | 0.4 Millimeters of mercury | Standard Deviation 9.5 |
| GSK2798745 2.4 mg | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | DBP,Period 2, Day 2,n=6,5 | -8.0 Millimeters of mercury | Standard Deviation 8.43 |
| GSK2798745 2.4 mg | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | DBP,Period 2, Day 3,n=6,5 | -2.0 Millimeters of mercury | Standard Deviation 6.82 |
| GSK2798745 2.4 mg | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | DBP,Period 2, Day 4,n=6,5 | 1.2 Millimeters of mercury | Standard Deviation 12.79 |
| GSK2798745 2.4 mg | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | DBP,Period 2, Day 5,n=6,5 | -3.6 Millimeters of mercury | Standard Deviation 8.41 |
| GSK2798745 2.4 mg | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | DBP,Period 2, Day 6,n=6,5 | 5.2 Millimeters of mercury | Standard Deviation 9.26 |
| GSK2798745 2.4 mg | Change From Baseline in Systolic Blood Pressure(SBP) and Diastolic Blood Pressure (DBP) | SBP,Period 1, Day 4,n=5,6 | 0.8 Millimeters of mercury | Standard Deviation 14.66 |
Secondary
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.
Time frame: Baseline and up to Day 7 of each treatment period
Population: All Subjects population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Temperature | Period 1, Day 1,n=5,6 | -0.2 Celsius | Standard Deviation 0.55 |
| Placebo | Change From Baseline in Temperature | Period 1, Day 2,n=5,6 | -0.1 Celsius | Standard Deviation 0.16 |
| Placebo | Change From Baseline in Temperature | Period 1, Day 3,n=5,6 | 0.0 Celsius | Standard Deviation 0.15 |
| Placebo | Change From Baseline in Temperature | Period 1,Day 4,n=5,6 | 0.2 Celsius | Standard Deviation 0.34 |
| Placebo | Change From Baseline in Temperature | Period 1, Day 5,n=5,6 | -0.1 Celsius | Standard Deviation 0.11 |
| Placebo | Change From Baseline in Temperature | Period 1, Day 6,n=5,6 | 0.0 Celsius | Standard Deviation 0.3 |
| Placebo | Change From Baseline in Temperature | Period 1, Day 7,n=5,6 | -0.0 Celsius | Standard Deviation 0.16 |
| Placebo | Change From Baseline in Temperature | Period 2, Day 1,n=6,5 | 0.2 Celsius | Standard Deviation 0.55 |
| Placebo | Change From Baseline in Temperature | Period 2, Day 2,n=6,5 | 0.2 Celsius | Standard Deviation 0.44 |
| Placebo | Change From Baseline in Temperature | Period 2, Day 3,n=6,5 | 0.0 Celsius | Standard Deviation 0.49 |
| Placebo | Change From Baseline in Temperature | Period 2, Day 4,n=6,5 | 0.1 Celsius | Standard Deviation 0.46 |
| Placebo | Change From Baseline in Temperature | Period 2, Day 5,n=6,5 | -0.2 Celsius | Standard Deviation 0.26 |
| Placebo | Change From Baseline in Temperature | Period 2, Day 6,n=6,5 | 0.1 Celsius | Standard Deviation 0.42 |
| Placebo | Change From Baseline in Temperature | Period 2, Day 7,n=6,5 | 0.1 Celsius | Standard Deviation 0.39 |
| GSK2798745 2.4 mg | Change From Baseline in Temperature | Period 2, Day 4,n=6,5 | -0.2 Celsius | Standard Deviation 0.21 |
| GSK2798745 2.4 mg | Change From Baseline in Temperature | Period 1, Day 1,n=5,6 | -0.0 Celsius | Standard Deviation 0.1 |
| GSK2798745 2.4 mg | Change From Baseline in Temperature | Period 2, Day 1,n=6,5 | 0.1 Celsius | Standard Deviation 0.13 |
| GSK2798745 2.4 mg | Change From Baseline in Temperature | Period 1, Day 2,n=5,6 | -0.0 Celsius | Standard Deviation 0.24 |
| GSK2798745 2.4 mg | Change From Baseline in Temperature | Period 2, Day 6,n=6,5 | -0.1 Celsius | Standard Deviation 0.24 |
| GSK2798745 2.4 mg | Change From Baseline in Temperature | Period 1, Day 3,n=5,6 | -0.0 Celsius | Standard Deviation 0.33 |
| GSK2798745 2.4 mg | Change From Baseline in Temperature | Period 2, Day 2,n=6,5 | -0.0 Celsius | Standard Deviation 0.28 |
| GSK2798745 2.4 mg | Change From Baseline in Temperature | Period 1,Day 4,n=5,6 | -0.2 Celsius | Standard Deviation 0.12 |
| GSK2798745 2.4 mg | Change From Baseline in Temperature | Period 2, Day 5,n=6,5 | -0.1 Celsius | Standard Deviation 0.19 |
| GSK2798745 2.4 mg | Change From Baseline in Temperature | Period 1, Day 5,n=5,6 | -0.1 Celsius | Standard Deviation 0.19 |
| GSK2798745 2.4 mg | Change From Baseline in Temperature | Period 2, Day 3,n=6,5 | -0.1 Celsius | Standard Deviation 0.21 |
| GSK2798745 2.4 mg | Change From Baseline in Temperature | Period 1, Day 6,n=5,6 | -0.1 Celsius | Standard Deviation 0.32 |
| GSK2798745 2.4 mg | Change From Baseline in Temperature | Period 2, Day 7,n=6,5 | 0.1 Celsius | Standard Deviation 0.21 |
| GSK2798745 2.4 mg | Change From Baseline in Temperature | Period 1, Day 7,n=5,6 | -0.2 Celsius | Standard Deviation 0.29 |
Secondary
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.
Time frame: Baseline and Day 7 of each treatment period
Population: Analysis Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 2 Day -1,post 3 min | -4.7 Ratio | Standard Deviation 6.65 |
| Placebo | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 2 Day -1,post 1 min | -3.6 Ratio | Standard Deviation 4.1 |
| Placebo | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 1 Day 7,at rest | 2.4 Ratio | Standard Deviation 10.1 |
| Placebo | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 2 Day -1,post 2 min | -3.7 Ratio | Standard Deviation 4.68 |
| Placebo | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 1 Day -1,at rest,post 2 min | 1.6 Ratio | Standard Deviation 6.4 |
| Placebo | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 1 Day 7,post 1 min | 0.7 Ratio | Standard Deviation 10.1 |
| Placebo | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 2 Day -1,Recovery | -9.3 Ratio | Standard Deviation 3.04 |
| Placebo | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 1 Day -1,post 3 min | 0.7 Ratio | Standard Deviation 9.15 |
| Placebo | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 2 Day 7 at rest | -2.5 Ratio | Standard Deviation 6.3 |
| Placebo | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 1 Day 7,post 2 min | -1.2 Ratio | Standard Deviation 11.99 |
| Placebo | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 2 Day 7,post 1 min | -4.0 Ratio | Standard Deviation 4.4 |
| Placebo | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 1 Day -1,post 1 min | 1.3 Ratio | Standard Deviation 3.1 |
| Placebo | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 2 Day 7,post 2 min | -2.6 Ratio | Standard Deviation 4.16 |
| Placebo | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 1 Day 7,post 3 min | 1.6 Ratio | Standard Deviation 13.29 |
| Placebo | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 2 Day 7,post 3 min | -0.7 Ratio | Standard Deviation 10.21 |
| Placebo | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 1 Day -1,recovery | -5.1 Ratio | Standard Deviation 4.17 |
| Placebo | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 2 Day 7,Recovery | -2.1 Ratio | Standard Deviation 22.58 |
| Placebo | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 1 Day 7,recovery | -8.0 Ratio | Standard Deviation 5.68 |
| GSK2798745 2.4 mg | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 2 Day 7,Recovery | -7.6 Ratio | Standard Deviation 5.17 |
| GSK2798745 2.4 mg | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 1 Day -1,post 1 min | 0.3 Ratio | Standard Deviation 5 |
| GSK2798745 2.4 mg | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 1 Day -1,post 3 min | -4.5 Ratio | Standard Deviation 6.68 |
| GSK2798745 2.4 mg | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 1 Day -1,recovery | -5.7 Ratio | Standard Deviation 4.31 |
| GSK2798745 2.4 mg | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 1 Day 7,at rest | 0.6 Ratio | Standard Deviation 2.1 |
| GSK2798745 2.4 mg | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 1 Day 7,post 1 min | 0.0 Ratio | Standard Deviation 3.8 |
| GSK2798745 2.4 mg | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 1 Day 7,post 2 min | 1.6 Ratio | Standard Deviation 10.37 |
| GSK2798745 2.4 mg | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 1 Day 7,post 3 min | -1.2 Ratio | Standard Deviation 3.97 |
| GSK2798745 2.4 mg | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 1 Day 7,recovery | -5.4 Ratio | Standard Deviation 3.26 |
| GSK2798745 2.4 mg | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 2 Day -1,post 1 min | -2.1 Ratio | Standard Deviation 4.5 |
| GSK2798745 2.4 mg | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 2 Day -1,post 2 min | -2.8 Ratio | Standard Deviation 5.74 |
| GSK2798745 2.4 mg | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 2 Day -1,post 3 min | -4.2 Ratio | Standard Deviation 5.86 |
| GSK2798745 2.4 mg | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 2 Day -1,Recovery | -7.6 Ratio | Standard Deviation 6.13 |
| GSK2798745 2.4 mg | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 2 Day 7 at rest | -0.9 Ratio | Standard Deviation 4.2 |
| GSK2798745 2.4 mg | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 2 Day 7,post 1 min | -2.5 Ratio | Standard Deviation 3.7 |
| GSK2798745 2.4 mg | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 2 Day 7,post 2 min | -3.9 Ratio | Standard Deviation 4.98 |
| GSK2798745 2.4 mg | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 2 Day 7,post 3 min | -6.4 Ratio | Standard Deviation 3.65 |
| GSK2798745 2.4 mg | Change From Baseline in the Ventilation/Volume of Carbon Dioxide Production (VE/VCO2) Ratio | Period 1 Day -1,at rest,post 2 min | 1.8 Ratio | Standard Deviation 11.93 |
Secondary
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.
Time frame: Baseline and up to Day 7 in each treatment period
Population: All Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Troponin I Levels and Type I Collagen Cross-linked C-telopeptide | Troponin I,Period 1, Day 2,n=5,6 | -0.0044 Microgram per liter | Standard Deviation 0.00658 |
| Placebo | Change From Baseline in Troponin I Levels and Type I Collagen Cross-linked C-telopeptide | Troponin I,Period 1, Day 4,n=5,6 | -0.0118 Microgram per liter | Standard Deviation 0.01117 |
| Placebo | Change From Baseline in Troponin I Levels and Type I Collagen Cross-linked C-telopeptide | Troponin I,Period 1, Day 7,n=5,5 | -0.0112 Microgram per liter | Standard Deviation 0.01314 |
| Placebo | Change From Baseline in Troponin I Levels and Type I Collagen Cross-linked C-telopeptide | Troponin I,Period 2, Day 2,n=6,5 | 0.0023 Microgram per liter | Standard Deviation 0.00898 |
| Placebo | Change From Baseline in Troponin I Levels and Type I Collagen Cross-linked C-telopeptide | Troponin I,Period 2, Day 4,n=5,5 | -0.0036 Microgram per liter | Standard Deviation 0.00498 |
| Placebo | Change From Baseline in Troponin I Levels and Type I Collagen Cross-linked C-telopeptide | Troponin I,Period 2, Day 7,n=6,4 | -0.0012 Microgram per liter | Standard Deviation 0.01132 |
| Placebo | Change From Baseline in Troponin I Levels and Type I Collagen Cross-linked C-telopeptide | T1CCT,Period 1 Day 7,n=3,3 | -0.0133 Microgram per liter | Standard Deviation 0.03774 |
| Placebo | Change From Baseline in Troponin I Levels and Type I Collagen Cross-linked C-telopeptide | T1CCT,Period 2 Day 7,n=3,3 | -0.0343 Microgram per liter | Standard Deviation 0.12948 |
| GSK2798745 2.4 mg | Change From Baseline in Troponin I Levels and Type I Collagen Cross-linked C-telopeptide | T1CCT,Period 2 Day 7,n=3,3 | -0.0447 Microgram per liter | Standard Deviation 0.11186 |
| GSK2798745 2.4 mg | Change From Baseline in Troponin I Levels and Type I Collagen Cross-linked C-telopeptide | Troponin I,Period 1, Day 2,n=5,6 | -0.0007 Microgram per liter | Standard Deviation 0.00516 |
| GSK2798745 2.4 mg | Change From Baseline in Troponin I Levels and Type I Collagen Cross-linked C-telopeptide | Troponin I,Period 2, Day 4,n=5,5 | -0.0000 Microgram per liter | Standard Deviation 0.01225 |
| GSK2798745 2.4 mg | Change From Baseline in Troponin I Levels and Type I Collagen Cross-linked C-telopeptide | Troponin I,Period 1, Day 4,n=5,6 | -0.0008 Microgram per liter | Standard Deviation 0.00492 |
| GSK2798745 2.4 mg | Change From Baseline in Troponin I Levels and Type I Collagen Cross-linked C-telopeptide | T1CCT,Period 1 Day 7,n=3,3 | -0.1250 Microgram per liter | Standard Deviation 0.16975 |
| GSK2798745 2.4 mg | Change From Baseline in Troponin I Levels and Type I Collagen Cross-linked C-telopeptide | Troponin I,Period 1, Day 7,n=5,5 | -0.0056 Microgram per liter | Standard Deviation 0.00876 |
| GSK2798745 2.4 mg | Change From Baseline in Troponin I Levels and Type I Collagen Cross-linked C-telopeptide | Troponin I,Period 2, Day 7,n=6,4 | 0.0043 Microgram per liter | Standard Deviation 0.01902 |
| GSK2798745 2.4 mg | Change From Baseline in Troponin I Levels and Type I Collagen Cross-linked C-telopeptide | Troponin I,Period 2, Day 2,n=6,5 | 0.0002 Microgram per liter | Standard Deviation 0.00672 |
Secondary
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.
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)
Population: PK Parameter Population. 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.
Secondary
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 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)
Population: PK Parameter. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Drug Concentration (Cmax) for GSK2798745 | Period 1, Day 1,n=6 | 10.214 Nanograms per milliliter | Geometric Coefficient of Variation 36.3 |
| Placebo | Maximum Drug Concentration (Cmax) for GSK2798745 | Period 1, Day 7,n=5 | 15.687 Nanograms per milliliter | Geometric Coefficient of Variation 73.6 |
| Placebo | Maximum Drug Concentration (Cmax) for GSK2798745 | Period 2, Day 1,n=5 | 10.017 Nanograms per milliliter | Geometric Coefficient of Variation 48.3 |
| Placebo | Maximum Drug Concentration (Cmax) for GSK2798745 | Period 2, Day 7,n=5 | 15.428 Nanograms per milliliter | Geometric Coefficient of Variation 68.1 |
Secondary
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.
Time frame: Up to Day 7 in each treatment period
Population: All Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 1, Day 7, CS,n=5,6 | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 1, Day -1, M3, NCS,n=5,6 | 5 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 2, Day -1, M1, NCS,n=6,5 | 6 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 1, Day -1, M1, NCS,n=5,6 | 5 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 2 Day -1, M1, CS,n=6,5 | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 1, Day -1, M3, CS,n=5,6 | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 2, Day -1, M2, NCS,n=6,5 | 6 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 1, Day -1, M2, NCS,n=5,6 | 5 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 2, Day -1, M2, CS,n=6,5 | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 1, Day 4, NCS,n=5,6 | 5 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 2, Day -1, M3, NCS,n=6,5 | 6 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 2, Day 7, CS,n=6,5 | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 2, Day -1, M3, CS,n=6,5 | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 1, Day 4, CS,n=5,6 | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 2, Day 4, NCS,n=6,5 | 6 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 1, Day -1, M2, CS,n=5,6 | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 2, Day 4, CS,n=6,5 | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 1, Day 7, NCS,n=5,6 | 5 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 2, Day 7, NCS,n=6,5 | 6 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 1, Day -1, M1, CS,n=5,6 | 0 Participants |
| GSK2798745 2.4 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 2, Day 7, CS,n=6,5 | 0 Participants |
| GSK2798745 2.4 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 1, Day -1, M1, NCS,n=5,6 | 6 Participants |
| GSK2798745 2.4 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 1, Day -1, M1, CS,n=5,6 | 0 Participants |
| GSK2798745 2.4 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 1, Day -1, M2, NCS,n=5,6 | 6 Participants |
| GSK2798745 2.4 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 1, Day -1, M2, CS,n=5,6 | 0 Participants |
| GSK2798745 2.4 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 1, Day -1, M3, NCS,n=5,6 | 6 Participants |
| GSK2798745 2.4 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 1, Day -1, M3, CS,n=5,6 | 0 Participants |
| GSK2798745 2.4 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 1, Day 4, NCS,n=5,6 | 6 Participants |
| GSK2798745 2.4 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 1, Day 4, CS,n=5,6 | 0 Participants |
| GSK2798745 2.4 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 1, Day 7, NCS,n=5,6 | 6 Participants |
| GSK2798745 2.4 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 1, Day 7, CS,n=5,6 | 0 Participants |
| GSK2798745 2.4 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 2, Day -1, M1, NCS,n=6,5 | 5 Participants |
| GSK2798745 2.4 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 2 Day -1, M1, CS,n=6,5 | 0 Participants |
| GSK2798745 2.4 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 2, Day -1, M2, NCS,n=6,5 | 5 Participants |
| GSK2798745 2.4 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 2, Day -1, M2, CS,n=6,5 | 0 Participants |
| GSK2798745 2.4 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 2, Day -1, M3, NCS,n=6,5 | 5 Participants |
| GSK2798745 2.4 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 2, Day -1, M3, CS,n=6,5 | 0 Participants |
| GSK2798745 2.4 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 2, Day 4, NCS,n=6,5 | 5 Participants |
| GSK2798745 2.4 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 2, Day 4, CS,n=6,5 | 0 Participants |
| GSK2798745 2.4 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Period 2, Day 7, NCS,n=6,5 | 5 Participants |
Secondary
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.
Time frame: Up to Day 46
Population: All Subjects Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With All Adverse Events (AE) and Serious Adverse Events (SAE) | Any AE | 5 Participants |
| Placebo | Number of Participants With All Adverse Events (AE) and Serious Adverse Events (SAE) | Any SAE | 0 Participants |
| GSK2798745 2.4 mg | Number of Participants With All Adverse Events (AE) and Serious Adverse Events (SAE) | Any AE | 7 Participants |
| GSK2798745 2.4 mg | Number of Participants With All Adverse Events (AE) and Serious Adverse Events (SAE) | Any SAE | 1 Participants |
Secondary
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.
Time frame: Up to Day 7 of each treatment period
Population: All Subjects population comprised of all randomized participants who received at least one dose of study medication. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) | Day -1,Not set,n=4,3 | 22.9 breaths per minute | Standard Deviation 5.14 |
| Placebo | Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) | Day -1,Standing,n=4,4 | 15.3 breaths per minute | Standard Deviation 2.79 |
| Placebo | Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) | Day -1,Leaning,n=5,4 | 15.4 breaths per minute | Standard Deviation 3.06 |
| Placebo | Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) | Day -1,Lying,n=4,4 | 17 breaths per minute | Standard Deviation 3.08 |
| Placebo | Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) | Day 4,Not set,n=6,3 | 14.9 breaths per minute | Standard Deviation 3.64 |
| Placebo | Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) | Day 4,Standing,n=6,6 | 15.9 breaths per minute | Standard Deviation 3.39 |
| Placebo | Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) | Day 4,Leaning,n=6,6 | 18.6 breaths per minute | Standard Deviation 4.19 |
| Placebo | Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) | Day 4,Lying,n=6,5 | 16.8 breaths per minute | Standard Deviation 3.6 |
| Placebo | Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) | Day 4,Unknown,n=2,3 | 15.5 breaths per minute | Standard Deviation 2.18 |
| Placebo | Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) | Day 7,Not set,n=3,4 | 15.7 breaths per minute | Standard Deviation 3.88 |
| Placebo | Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) | Day 7,Standing,n=7,4 | 15.9 breaths per minute | Standard Deviation 3.54 |
| Placebo | Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) | Day 7,Leaning,n=6,4 | 15.7 breaths per minute | Standard Deviation 3.89 |
| Placebo | Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) | Day 7,Lying,n=7,4 | 16.8 breaths per minute | Standard Deviation 3.88 |
| GSK2798745 2.4 mg | Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) | Day 7,Not set,n=3,4 | 15.1 breaths per minute | Standard Deviation 2.76 |
| GSK2798745 2.4 mg | Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) | Day 4,Leaning,n=6,6 | 17.9 breaths per minute | Standard Deviation 3.94 |
| GSK2798745 2.4 mg | Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) | Day -1,Not set,n=4,3 | 13.3 breaths per minute | Standard Deviation 1.58 |
| GSK2798745 2.4 mg | Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) | Day 7,Leaning,n=6,4 | 17.5 breaths per minute | Standard Deviation 3.68 |
| GSK2798745 2.4 mg | Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) | Day -1,Standing,n=4,4 | 16.8 breaths per minute | Standard Deviation 3.43 |
| GSK2798745 2.4 mg | Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) | Day 4,Lying,n=6,5 | 16.5 breaths per minute | Standard Deviation 3.41 |
| GSK2798745 2.4 mg | Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) | Day -1,Leaning,n=5,4 | 17.7 breaths per minute | Standard Deviation 3.56 |
| GSK2798745 2.4 mg | Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) | Day 7,Standing,n=7,4 | 15.5 breaths per minute | Standard Deviation 3.53 |
| GSK2798745 2.4 mg | Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) | Day -1,Lying,n=4,4 | 15.6 breaths per minute | Standard Deviation 2.26 |
| GSK2798745 2.4 mg | Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) | Day -1,Unknown,n=0,2 | 17.5 breaths per minute | Standard Deviation 3.75 |
| GSK2798745 2.4 mg | Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) | Day 4,Unknown,n=2,3 | 13.2 breaths per minute | Standard Deviation 3.54 |
| GSK2798745 2.4 mg | Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) | Day 4,Not set,n=6,3 | 13.8 breaths per minute | Standard Deviation 1.09 |
| GSK2798745 2.4 mg | Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) | Day 7,Lying,n=7,4 | 16 breaths per minute | Standard Deviation 3.6 |
| GSK2798745 2.4 mg | Respiratory Rate Over Time Continuously Measured by Body Sensor (Site: Mayo Only) | Day 4,Standing,n=6,6 | 15.5 breaths per minute | Standard Deviation 3.1 |
Secondary
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.
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)
Population: PK Parameter population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Time to Maximum Observed Plasma Concentration (Tmax) for GSK2798745 | Period 1, Day 1,n=6 | 3.0 Hour |
| Placebo | Time to Maximum Observed Plasma Concentration (Tmax) for GSK2798745 | Period 1, Day 7,n=5 | 3.0 Hour |
| Placebo | Time to Maximum Observed Plasma Concentration (Tmax) for GSK2798745 | Period 2, Day 1,n=5 | 3.0 Hour |
| Placebo | Time to Maximum Observed Plasma Concentration (Tmax) for GSK2798745 | Period 2, Day 7,n=5 | 2.0 Hour |