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This study is the first administration of GSK2798745 in humans. This will be a sponsor un-blinded, placebo-controlled study to investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GSK2798745, given as single and repeat oral doses to healthy subjects and stable heart failure (HF) subjects. Approximately 28 healthy subjects will be enrolled in the study cohorts (Cohort 1-3) involving single and repeat dose escalations of GSK2798745, while up to 24 stable heart failure subjects will be enrolled in Cohort 4 involving single and repeat dose administration of GSK2798745, with the dose selected based on data from healthy subject cohorts. This would be followed by enrollment of up to 8 subjects with heart failure in Cohort 5 involving repeat dose administration of GSK2798745. The study duration, including screening and follow-up, is not expected to exceed 17 weeks for subjects in the study (in any cohort).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | Eight subjects will be randomized to 1 of 4 placebo-controlled dose sequences with 2 subjects in each sequence and each subject having four dose periods (3 active dose of GSK2798745 + 1 placebo dose). GSK2798745 will be administered in a liquid form (suspension or solution) in this cohort. In each treatment period, the subjects will be fasting from the prior midnight to four hours post-dose (Day 1). |
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| Cohort 2 | Experimental | Twelve subjects will receive GSK2798745 in three single-dose treatment periods in a fixed sequence. The actual dose-selected will be determined based on review of emerging safety and exposure data from Cohort 1. The dosing will be done in 3 study periods for investigating bioavailability and food effects. In Period 1, subjects will be fasting from midnight to four hours post-dose and will receive GSK2798745 in a liquid form (suspension or solution). In Period 2, subjects will be fasting from midnight to four hours post-dose and will receive a capsule formulation of GSK2798745. In Period 3, subjects will receive GSK2798745 capsule following a standard high fat/high calorie meal. |
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| Cohort 3 | Experimental | Sixteen subjects will be randomized to 2 repeat dose cohorts with 8 subjects in each cohort in a ratio of 6:2 (treatments: placebo). Food intake timing will be determined based on data from Cohorts 1 and 2 (if Cohort 2 is conducted before Cohort 3). Doses will be administered once daily from Day 1 through Day14. Based on data from Cohort 1, the second dose in the repeat-dose period may be skipped to estimate the time invariance in PK. Dosing may be altered to twice daily based on the results obtained in the initial study cohort. Subjects will be fasted from midnight to 4 hours after dosing on Day 1 and Day 14 that entail serial PK sampling. Meal timings on other days will be based on previous cohort data. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK2798745 solution | Drug | Clear, colourless GSK2798745 (0.1 to 0.4mg) solution in aqueous citrate buffer with 4% captisol |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Vital Sign Values of Potential Clinical Concern in Healthy Participants | Vital signs included seated supine systolic blood pressure (SBP) and diastolic blood pressure (DBP), heart rate (HR), and respiratory rate (RR). Vital signs criteria of potential clinical concern were SBP: <100 and >170 millimeters of mercury (mmHg); DBP: <50 and >110 mmHg and HR: <50 and >120 beats per minute (bpm). Only those parameters for which at least one value of potential clinical concern was reported are summarized. All Subjects Population includes any participant enrolled into the study who received at least one dose of study medication within a cohort | Up to 17 Weeks |
| Number of Participants With Vital Sign Values of Potential Clinical Concern in Stable Heart Failure Participants | Vital signs included seated supine systolic blood pressure (SBP) and diastolic blood pressure (DBP), heart rate (HR), and respiratory rate (RR). Vital signs criteria of potential clinical concern were SBP: <100 and >170 millimeters of mercury (mmHg); DBP: <50 and >110 mmHg and HR: <50 and >120 beats per minute (bpm). Only those parameters for which at least one value of potential clinical concern was reported are summarized. All Subjects Population includes any participant enrolled into the study who received at least one dose of study medication within a cohort | Up to 17 weeks |
| Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern in Healthy Participants | ECGs will be obtained in the semi-supine position after at least 5 minutes. The potential clinical concern range for ECG parameters are: QRS interval: >200 milliseconds (msec); time from ECG Q wave to the end of the T wave corresponding to electrical systole corrected for heart rate using Bazett's formula (QTcB):>500msec; time from ECG Q wave to the end of the T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula (QTcF interval): >500 msec; PR interval:>300msec. The number of participants with ECG values of potential clinical concern have been presented. | Up to 17 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (AUC[0-inf]) Following Single and Repeat Doses of GSK2798745 in Healthy Subjects | Blood samples for Pharmacokinetic (PK) analysis were obtained at Day 1 of each treatment period for analysis of AUC[0-inf]. Log untransformed values for AUC[0-inf] has been presented. The 'PK Population' includes 'All Subjects' population for whom a pharmacokinetic sample was obtained and analyzed. |
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Inclusion Criteria:
For Healthy Subject Cohorts (1-3):
For Heart Failure Subjects (Cohorts 4 and 5):
Exclusion Criteria:
For Heart Failure Subjects (Cohort 4):
For Heart Failure Subjects (Cohort 5):
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Cambridge | CB2 2GG | United Kingdom | |||
| GSK Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30637626 | Derived | Goyal N, Skrdla P, Schroyer R, Kumar S, Fernando D, Oughton A, Norton N, Sprecher DL, Cheriyan J. Clinical Pharmacokinetics, Safety, and Tolerability of a Novel, First-in-Class TRPV4 Ion Channel Inhibitor, GSK2798745, in Healthy and Heart Failure Subjects. Am J Cardiovasc Drugs. 2019 Jun;19(3):335-342. doi: 10.1007/s40256-018-00320-6. |
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Sixty one par. entered this 5-cohort study where Cohorts 1-3 were healthy par. and Cohorts 4 and 5 were par. with stable heart failure. Of those,1 par. was withdrawn pre-dose due to issues with ECG values. In Cohort 1 and 2, par. were randomized to sequence and in Cohorts 3, 4 and 5 par. were randomized to drug or placebo
This study is a placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single dose (SD) and repeat, ascending doses (RD) of GSK2798745 in healthy participants (par.) and stable heart failure par. This study was conducted at two centers in the United Kingdom
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 | Healthy participants received single oral doses of GSK2798745 0.25 milligram (mg), 1 mg, 5 mg, 12.5 mg and one dose of GSK2798745 matching placebo in fasted state. Participants fasted from midnight to four hours post-dose. GSK2798745 was administered in a liquid form (suspension) in this single dose escalation cohort. |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Cohort 4 | Experimental | Eighteen stable HF subjects will be randomized in this cohort with a treatment:placebo ratio of 1:1. If required, an additional number of subjects (up to 24 total) will be randomized. An additional separate dose group of approximately 18 to 24 subjects may be randomized to GSK2798745 or placebo to gain additional safety, tolerability,pharmacokinetic and pharmacodynamic information, if needed. The subjects will receive GSK2798745 in a single dose (at least the first 6 subjects) followed by a 7 -days repeat dose. Based on data from the cohorts 1, 2 and 3, the dose will be 2.4 mg (initial) in the first group utilizing the capsule formulation administered with or without food. |
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| Cohort 5 | Experimental | Eight HF subjects will be randomized in this cohort with a treatment: placebo ratio of 3:1. This cohort will evaluate safety, pharmacokinetics, and lung permeability (DLco and DLno) in a boarder, more general population of patients with HF, NYHA Class II or III. Subjects will receive GSK2798745 or placebo (based on randomization) for 7 days. The dose will be 2.4 mg utilizing the capsule formulation administered with or without food. Subjects will remain in house from Day -1 until Day 4 and be fitted with a remote monitoring device; Day 5, 6 and 8 visits will be in home (on Days 5 and 6, they will receive study medication, collect samples for pharmacokinetic analysis, and assess vital signs); and subjects will return to the clinic for Day 7 visit. |
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| GSK2798745 suspension | Drug | Aqueous suspension of GSK2798745 (>=0.5 mg) |
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| GSK2798745 capsule | Drug | White Opaque granule filled capsules of GSK2798745 (>=0.5 mg) |
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| Placebo solution | Drug | Clear, colourless solution of aqueous citrate buffer with 4% captisol |
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| Placebo suspension | Drug | Visually matching aqueous suspension of hypromellose acetate succinate powder |
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| Placebo capsule | Drug | Matching white opaque placebo blend filled capsule |
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| Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern in Stable Heart Failure Participants |
ECGs will be obtained in the semi-supine position after at least 5 minutes. The potential clinical concern range for ECG parameters are: QRS interval: >200 milliseconds (msec); time from ECG Q wave to the end of the T wave corresponding to electrical systole corrected for heart rate using Bazett's formula (QTcB):>500msec; time from ECG Q wave to the end of the T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula (QTcF interval): >500 msec; PR interval:>300msec. The number of participants with ECG values of potential clinical concern have been presented. |
| Up to 17 weeks |
| Number of Participants With Clinical Chemistry Laboratory Values of Potential Clinical Concern in Healthy Participants | Blood samples were collected from participants to evaluate clinical parameters of potential clinical concern. Clinical parameters included blood urea nitrogen, potassium, total and direct bilirubin, creatinine chloride, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase, alkaline phosphatase, uric acid, glucose, fasting troponin, albumin, sodium calcium total protein, and creatine phosphokinase. The number of participants with clinical chemistry values of potential clinical concern have been presented. | Up to 17 weeks |
| Number of Participants With Clinical Chemistry Laboratory Values of Potential Clinical Concern in Stable Heart Failure Participants | Blood samples were collected from participants to evaluate clinical parameters of potential clinical concern. Clinical parameters included blood urea nitrogen, potassium, total and direct bilirubin, creatinine chloride, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase, alkaline phosphatase, uric acid, glucose, fasting troponin, albumin, sodium calcium total protein, and creatine phosphokinase. The number of participants with clinical chemistry values of potential clinical concern have been presented. | Up to 17 weeks |
| Number of Participants With Hematology Parameter Laboratory Values of Potential Clinical Concern in Healthy Participants | Blood samples were collected from participants to evaluate hematology parameters of potential clinical concern. Hematology parameters included platelet count, red blood cells count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, neutrophils, white blood cells count, lymphocytes, reticulocyte count, monocytes, hemoglobin, eosinophil, hematocrit, and basophiles. The number of participants with hematology values of potential clinical concern have been presented. | Up to 17 weeks |
| Number of Participants With Hematology Parameter Laboratory Values of Potential Clinical Concern in Stable Heart Failure Participants | Blood samples were collected from participants to evaluate hematology parameters of potential clinical concern. Hematology parameters included platelet count, red blood cells count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, neutrophils, white blood cells count, lymphocytes, reticulocyte count, monocytes, hemoglobin, eosinophil, hematocrit, and basophiles. The number of participants with hematology values of potential clinical concern have been presented. | Up to 17 weeks |
| Number of Participants With Abnormal Routine Urinalysis in Healthy Participants | Urine samples were collected to analyze specific gravity, determining potential of hydrogen (pH), glucose, protein, blood, and ketones by dipstick method, and microscopic examination (if blood or protein is abnormal). The number of participants with abnormal urinalysis data have been presented. | Up to 17 weeks |
| Number of Participants With Abnormal Routine Urinalysis in Stable Heart Failure Participants | Urine samples were collected to analyze specific gravity, determining potential of hydrogen (pH), glucose, protein, blood, and ketones by dipstick method, and microscopic examination (if blood or protein is abnormal). The number of participants with abnormal urinalysis data have been presented. | Up to 17 weeks |
| Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) in Healthy Participants | An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, is a congenital anomaly or birth defect, any other situation according to medical or scientific judgment, or is associated with liver injury and impaired liver function will be categorized as SAE. | Up to 17 weeks |
| Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) in Stable Heart Failure Participants | An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, is a congenital anomaly or birth defect, any other situation according to medical or scientific judgment, or is associated with liver injury and impaired liver function will be categorized as SAE. | Up to 17 weeks |
| Day 1 |
| Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of GSK2798745 in Healthy Participants | Blood samples for PK analysis were obtained at Day 1 and Day 14 of each treatment period for analysis of Cmax. Log transformed values for Cmax has been presented. | Day 1 (Cohort 1,2,3) and Day 14 (Cohort 3) |
| Time to Occurrence of Cmax (Tmax) Following Single and Repeat Doses of GSK2798745 in Healthy Participants | Blood samples for PK analysis were obtained at Day 1 of each treatment period and Day 14 of Cohort 3 for analysis of tmax. Log untransformed values for tmax has been presented. | Day 1 (Cohort 1,2,3) and Day 14 (Cohort 3) |
| Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of GSK2798745 in Stable Heart Failure Participants | Blood samples for PK analysis were obtained at Day 1 and Day 7 of each treatment period for analysis of Cmax. Log untransformed values for Cmax has been presented. | Day 1 and Day 7 |
| Area Under the Concentration-time Curve From Pre-dose to 24 Hours Post-dose (AUC [0-24]) Following Single and Repeat Doses of GSK2798745 in Stable Heart Failure Participants | Blood samples for PK analysis were obtained at Day 1 and Day 7 of each treatment period for analysis of AUC (0-24). Log untransformed values for Cmax has been presented. | Day 1 and Day 7 |
| London |
| NW10 7EW |
| United Kingdom |
| Cohort 2 |
Healthy participants received three single oral doses of GSK2798745 5 mg in fasted state and following a standard meal. GSK2798745 was administered in a liquid suspension and capsule formulation to evaluate food effect and relative bioavailability. |
| FG002 | Cohort 3 | Healthy participants received repeat oral doses of GSK2798745 5 mg or matching placebo (ratio 3:1) in fasted state. Participants fasted from midnight to four hours post-dose. GSK2798745 was administered in a liquid formulation (suspension) |
| FG003 | Cohort 4 (GSK2798745 2.4 mg SD and RD) | Participants with heart failure received single oral and subsequent 7-days repeat-dose evaluation of GSK2798745 2.4 mg . GSK2798745 was administered in capsule formulation |
| FG004 | Cohort 4 (Placebo RD) | Participants with heart failure received placebo. Placebo was administered in capsule formulation |
| FG005 | Cohort 5 (GSK2798745 2.4 mg RD) | Participants with heart failure received repeat-doses of GSK2798745 2.4 mg. GSK2798745 was administered in capsule formulation |
| FG006 | Cohort 5 (Placebo RD) | Participants with heart failure received placebo. Placebo was administered in capsule formulation |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 | Healthy participants received single oral doses of GSK2798745 0.25 milligram (mg), 1 mg, 5 mg, 12.5 mg and one dose of GSK2798745 matching placebo in fasted state. Participants fasted from midnight to four hours post-dose. GSK2798745 was administered in a liquid form (suspension) in this single dose escalation cohort. |
| BG001 | Cohort 2 | Healthy participants received three single oral doses of GSK2798745 5 mg in fasted state and following a standard meal. GSK2798745 was administered in a liquid suspension and capsule formulation to evaluate food effect and relative bioavailability. |
| BG002 | Cohort 3 | Healthy participants received repeat oral doses of GSK2798745 5 mg or matching placebo (ratio 3:1) in fasted state. Participants fasted from midnight to four hours post-dose. GSK2798745 was administered in a liquid formulation (suspension) |
| BG003 | Cohort 4 (GSK2798745 2.4 mg SD and RD) | Participants with heart failure received single oral and subsequent 7-days repeat-dose evaluation of GSK2798745 2.4 mg . GSK2798745 was administered in capsule formulation |
| BG004 | Cohort 4 (Placebo RD) | Participants with heart failure received placebo. Placebo was administered in capsule formulation |
| BG005 | Cohort 5 (GSK2798745 2.4 mg RD) | Participants with heart failure received repeat-doses of GSK2798745 2.4 mg. GSK2798745 was administered in capsule formulation |
| BG006 | Cohort 5 (Placebo RD) | Participants with heart failure received placebo. Placebo was administered in capsule formulation |
| BG007 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | Count of Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
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| Primary | Number of Participants With Vital Sign Values of Potential Clinical Concern in Healthy Participants | Vital signs included seated supine systolic blood pressure (SBP) and diastolic blood pressure (DBP), heart rate (HR), and respiratory rate (RR). Vital signs criteria of potential clinical concern were SBP: <100 and >170 millimeters of mercury (mmHg); DBP: <50 and >110 mmHg and HR: <50 and >120 beats per minute (bpm). Only those parameters for which at least one value of potential clinical concern was reported are summarized. All Subjects Population includes any participant enrolled into the study who received at least one dose of study medication within a cohort | All Subjects Population | Posted | Number | Participants | Up to 17 Weeks |
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| Primary | Number of Participants With Vital Sign Values of Potential Clinical Concern in Stable Heart Failure Participants | Vital signs included seated supine systolic blood pressure (SBP) and diastolic blood pressure (DBP), heart rate (HR), and respiratory rate (RR). Vital signs criteria of potential clinical concern were SBP: <100 and >170 millimeters of mercury (mmHg); DBP: <50 and >110 mmHg and HR: <50 and >120 beats per minute (bpm). Only those parameters for which at least one value of potential clinical concern was reported are summarized. All Subjects Population includes any participant enrolled into the study who received at least one dose of study medication within a cohort | All Subjects Population | Posted | Number | Participants | Up to 17 weeks |
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| Primary | Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern in Healthy Participants | ECGs will be obtained in the semi-supine position after at least 5 minutes. The potential clinical concern range for ECG parameters are: QRS interval: >200 milliseconds (msec); time from ECG Q wave to the end of the T wave corresponding to electrical systole corrected for heart rate using Bazett's formula (QTcB):>500msec; time from ECG Q wave to the end of the T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula (QTcF interval): >500 msec; PR interval:>300msec. The number of participants with ECG values of potential clinical concern have been presented. | All Subjects Population | Posted | Number | Participants | Up to 17 weeks |
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| Primary | Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern in Stable Heart Failure Participants | ECGs will be obtained in the semi-supine position after at least 5 minutes. The potential clinical concern range for ECG parameters are: QRS interval: >200 milliseconds (msec); time from ECG Q wave to the end of the T wave corresponding to electrical systole corrected for heart rate using Bazett's formula (QTcB):>500msec; time from ECG Q wave to the end of the T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula (QTcF interval): >500 msec; PR interval:>300msec. The number of participants with ECG values of potential clinical concern have been presented. | All Subjects Population | Posted | Number | Participants | Up to 17 weeks |
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| Primary | Number of Participants With Clinical Chemistry Laboratory Values of Potential Clinical Concern in Healthy Participants | Blood samples were collected from participants to evaluate clinical parameters of potential clinical concern. Clinical parameters included blood urea nitrogen, potassium, total and direct bilirubin, creatinine chloride, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase, alkaline phosphatase, uric acid, glucose, fasting troponin, albumin, sodium calcium total protein, and creatine phosphokinase. The number of participants with clinical chemistry values of potential clinical concern have been presented. | All Subjects Population | Posted | Number | Participants | Up to 17 weeks |
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| Primary | Number of Participants With Clinical Chemistry Laboratory Values of Potential Clinical Concern in Stable Heart Failure Participants | Blood samples were collected from participants to evaluate clinical parameters of potential clinical concern. Clinical parameters included blood urea nitrogen, potassium, total and direct bilirubin, creatinine chloride, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase, alkaline phosphatase, uric acid, glucose, fasting troponin, albumin, sodium calcium total protein, and creatine phosphokinase. The number of participants with clinical chemistry values of potential clinical concern have been presented. | All Subjects Population | Posted | Number | Participants | Up to 17 weeks |
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| Primary | Number of Participants With Hematology Parameter Laboratory Values of Potential Clinical Concern in Healthy Participants | Blood samples were collected from participants to evaluate hematology parameters of potential clinical concern. Hematology parameters included platelet count, red blood cells count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, neutrophils, white blood cells count, lymphocytes, reticulocyte count, monocytes, hemoglobin, eosinophil, hematocrit, and basophiles. The number of participants with hematology values of potential clinical concern have been presented. | All subjects population | Posted | Number | Participants | Up to 17 weeks |
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| Primary | Number of Participants With Hematology Parameter Laboratory Values of Potential Clinical Concern in Stable Heart Failure Participants | Blood samples were collected from participants to evaluate hematology parameters of potential clinical concern. Hematology parameters included platelet count, red blood cells count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, neutrophils, white blood cells count, lymphocytes, reticulocyte count, monocytes, hemoglobin, eosinophil, hematocrit, and basophiles. The number of participants with hematology values of potential clinical concern have been presented. | All Subjects Population | Posted | Number | Participants | Up to 17 weeks |
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| Primary | Number of Participants With Abnormal Routine Urinalysis in Healthy Participants | Urine samples were collected to analyze specific gravity, determining potential of hydrogen (pH), glucose, protein, blood, and ketones by dipstick method, and microscopic examination (if blood or protein is abnormal). The number of participants with abnormal urinalysis data have been presented. | All Subjects Population | Posted | Number | Participants | Up to 17 weeks |
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| Primary | Number of Participants With Abnormal Routine Urinalysis in Stable Heart Failure Participants | Urine samples were collected to analyze specific gravity, determining potential of hydrogen (pH), glucose, protein, blood, and ketones by dipstick method, and microscopic examination (if blood or protein is abnormal). The number of participants with abnormal urinalysis data have been presented. | All Subjects Population | Posted | Number | Participants | Up to 17 weeks |
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| Primary | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) in Healthy Participants | An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, is a congenital anomaly or birth defect, any other situation according to medical or scientific judgment, or is associated with liver injury and impaired liver function will be categorized as SAE. | All Subjects Population | Posted | Number | Participants | Up to 17 weeks |
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| Primary | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) in Stable Heart Failure Participants | An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, is a congenital anomaly or birth defect, any other situation according to medical or scientific judgment, or is associated with liver injury and impaired liver function will be categorized as SAE. | All Subjects Population | Posted | Number | Participants | Up to 17 weeks |
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| Secondary | Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (AUC[0-inf]) Following Single and Repeat Doses of GSK2798745 in Healthy Subjects | Blood samples for Pharmacokinetic (PK) analysis were obtained at Day 1 of each treatment period for analysis of AUC[0-inf]. Log untransformed values for AUC[0-inf] has been presented. The 'PK Population' includes 'All Subjects' population for whom a pharmacokinetic sample was obtained and analyzed. | Pharmacokinetic Population | Posted | Mean | Standard Deviation | hour*nanogram per milliliter (h*ng/mL) | Day 1 |
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| Secondary | Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of GSK2798745 in Healthy Participants | Blood samples for PK analysis were obtained at Day 1 and Day 14 of each treatment period for analysis of Cmax. Log transformed values for Cmax has been presented. | Pharmacokinetic Population | Posted | Mean | Standard Deviation | ng/mL | Day 1 (Cohort 1,2,3) and Day 14 (Cohort 3) |
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| Secondary | Time to Occurrence of Cmax (Tmax) Following Single and Repeat Doses of GSK2798745 in Healthy Participants | Blood samples for PK analysis were obtained at Day 1 of each treatment period and Day 14 of Cohort 3 for analysis of tmax. Log untransformed values for tmax has been presented. | Pharmacokinetic Population | Posted | Median | Full Range | hours | Day 1 (Cohort 1,2,3) and Day 14 (Cohort 3) |
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| Secondary | Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of GSK2798745 in Stable Heart Failure Participants | Blood samples for PK analysis were obtained at Day 1 and Day 7 of each treatment period for analysis of Cmax. Log untransformed values for Cmax has been presented. | Pharmacokinetic Population | Posted | Mean | Standard Deviation | ng/mL | Day 1 and Day 7 |
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| Secondary | Area Under the Concentration-time Curve From Pre-dose to 24 Hours Post-dose (AUC [0-24]) Following Single and Repeat Doses of GSK2798745 in Stable Heart Failure Participants | Blood samples for PK analysis were obtained at Day 1 and Day 7 of each treatment period for analysis of AUC (0-24). Log untransformed values for Cmax has been presented. | Pharmacokinetic Population | Posted | Mean | Standard Deviation | hour*ng/mL | Day 1 and Day 7 |
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On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the Follow up (Up to 17 weeks)
AEs and SAEs were collected in All Subjects Population which comprised all the participants enrolled into the study and received at least one dose of study medication within a cohort
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1 | Healthy participants received single oral doses of GSK2798745 0.25 milligram (mg), 1 mg, 5 mg, 12.5 mg and one dose of GSK2798745 matching placebo in fasted state. Participants fasted from midnight to four hours post-dose. GSK2798745 was administered in a liquid form (suspension) in this single dose escalation cohort. | 0 | 9 | 0 | 9 | 5 | 9 |
| EG001 | Cohort 2 | Healthy participants received three single oral doses of GSK2798745 5 mg in fasted state and following a standard meal. GSK2798745 was administered in a liquid suspension and capsule formulation to evaluate food effect and relative bioavailability. | 0 | 12 | 0 | 12 | 7 | 12 |
| EG002 | Cohort 3 | Healthy participants received repeat oral doses of GSK2798745 5 mg or matching placebo (ratio 3:1) in fasted state. Participants fasted from midnight to four hours post-dose. GSK2798745 was administered in a liquid formulation (suspension) | 0 | 8 | 0 | 8 | 6 | 8 |
| EG003 | Cohort 4 | Participants with heart failure received single oral and subsequent 7-days repeat-dose evaluation of GSK2798745 2.4 mg or placebo in capsule formulation | 0 | 23 | 0 | 23 | 22 | 23 |
| EG004 | Cohort 5 | Participants with heart failure received repeat-doses of GSK2798745 2.4 mg or placebo in capsule formulation | 0 | 8 | 0 | 8 | 8 | 8 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | 19.1 | Systematic Assessment |
| |
| Migraine with aura | Nervous system disorders | 19.1 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | 19.1 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | 19.1 | Systematic Assessment |
| |
| Seasonal allergy | Immune system disorders | 19.1 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | 19.1 | Systematic Assessment |
| |
| Scab | Skin and subcutaneous tissue disorders | 19.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | 19.1 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | 19.1 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | 19.1 | Systematic Assessment |
| |
| Abdominal pain lower | Gastrointestinal disorders | 19.1 | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | 19.1 | Systematic Assessment |
| |
| Lip blister | Gastrointestinal disorders | 19.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | 19.1 | Systematic Assessment |
| |
| Catheter site bruise | General disorders | 19.1 | Systematic Assessment |
| |
| Fatigue | General disorders | 19.1 | Systematic Assessment |
| |
| Pain | General disorders | 19.1 | Systematic Assessment |
| |
| Arthropod bite | Injury, poisoning and procedural complications | 19.1 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | 19.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | 19.1 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | 19.1 | Systematic Assessment |
| |
| Oropharyngeal | Respiratory, thoracic and mediastinal disorders | 19.1 | Systematic Assessment |
| |
| Ear disorder | Ear and labyrinth disorders | 19.1 | Systematic Assessment |
| |
| Blepharospasm | Eye disorders | 19.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | 19.1 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | 19.1 | Systematic Assessment |
| |
| Dermatitis contact | Skin and subcutaneous tissue disorders | 19.1 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | 19.1 | Systematic Assessment |
| |
| Hearing impaired | Ear and labyrinth disorders | 19.1 | Systematic Assessment |
| |
| Feeling abnormal | General disorders | 19.1 | Systematic Assessment |
| |
| Agitation | Psychiatric disorders | 19.1 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | 19.1 | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | 19.1 | Systematic Assessment |
| |
| Ventricular tachycardia | Cardiac disorders | 19.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | 19.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | 19.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | 19.1 | Systematic Assessment |
| |
| Feeling hot | General disorders | 19.1 | Systematic Assessment |
| |
| Audiogram abnormal | Investigations | 19.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 19.1 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 19.1 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | 19.1 | Systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | 19.1 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | 19.1 | Systematic Assessment |
| |
| Joint swelling | Musculoskeletal and connective tissue disorders | 19.1 | Systematic Assessment |
| |
| Musculoskeletal discomfort | Musculoskeletal and connective tissue disorders | 19.1 | Systematic Assessment |
| |
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | 19.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 19.1 | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | 19.1 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | 19.1 | Systematic Assessment |
| |
| Laceration | Injury, poisoning and procedural complications | 19.1 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | 19.1 | Systematic Assessment |
| |
| Skin burning sensation | Skin and subcutaneous tissue disorders | 19.1 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | 19.1 | Systematic Assessment |
| |
| Gastrointestinal sounds abnormal | Gastrointestinal disorders | 19.1 | Systematic Assessment |
| |
| Hyperaemia | Vascular disorders | 19.1 | Systematic Assessment |
|
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
| ID | Term |
|---|---|
| D011654 | Pulmonary Edema |
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000656065 | GSK2798745 |
Not provided
Not provided
Not provided
| Male |
|
| White-White/Caucasian/European Heritage |
|
| African American/African Heritage & White |
|
| Asian & White |
|
| Title | Measurements |
|---|---|
|
| HR |
|
| OG003 | Cohort 5 (Placebo RD) | Participants with heart failure received placebo. Placebo was administered in capsule formulation |
|
|
| OG002 | Cohort 3 | Healthy participants received repeat oral doses of GSK2798745 5 mg or matching placebo (ratio 3:1) in fasted state. Participants fasted from midnight to four hours post-dose. GSK2798745 was administered in a liquid formulation (suspension) |
|
|
| Participants |
|
|
| OG002 |
| Cohort 3 |
Healthy participants received repeat oral doses of GSK2798745 5 mg or matching placebo (ratio 3:1) in fasted state. Participants fasted from midnight to four hours post-dose. GSK2798745 was administered in a liquid formulation (suspension) |
|
|
|
|
| Cohort 3 |
Healthy participants received repeat oral doses of GSK2798745 5 mg or matching placebo (ratio 3:1) in fasted state. Participants fasted from midnight to four hours post-dose. GSK2798745 was administered in a liquid formulation (suspension) |
|
|
|
|
|
|
| OG002 | Cohort 3 | Healthy participants received repeat oral doses of GSK2798745 5 mg or matching placebo (ratio 3:1) in fasted state. Participants fasted from midnight to four hours post-dose. GSK2798745 was administered in a liquid formulation (suspension) |
|
|
| Participants |
|
|
Healthy participants received single oral doses of GSK2798745 5 mg and one dose of GSK2798745 matching placebo in fasted state. Participants fasted from midnight to four hours post-dose. GSK2798745 was administered in a liquid form (suspension) in this single dose escalation cohort.
| OG003 | Co 1 (GSK2798745 12.5 mg) | Healthy participants received single oral doses of GSK2798745 12.5 mg and one dose of GSK2798745 matching placebo in fasted state. Participants fasted from midnight to four hours post-dose. GSK2798745 was administered in a liquid form (suspension) in this single dose escalation cohort. |
| OG004 | Co 2 (GSK2798745 Fasted Suspension) | Healthy participants received three single oral doses of GSK2798745 5 mg in fasted state. GSK2798745 was administered in a liquid suspension to evaluate food effect and relative bioavailability. |
| OG005 | Co 2 (GSK2798745 Fasted Capsule) | Healthy participants received three single oral doses of GSK2798745 5 mg in fasted state. GSK2798745 was administered in a capsule formulation to evaluate food effect and relative bioavailability. |
| OG006 | Co 2 (GSK2798745 Fed Capsule) | Healthy participants received three single oral doses of GSK2798745 5 mg following a standard meal. GSK2798745 was administered in a capsule formulation to evaluate food effect and relative bioavailability. |
| OG007 | Co 3 (GSK2798745 Day 1-5mg) | Healthy participants received oral doses of GSK2798745 5 mg or matching placebo (ratio 3:1) in fasted state. Participants fasted from midnight to four hours post-dose. GSK2798745 was administered in a liquid formulation (suspension) |
| OG008 | Co 3 (GSK2798745 Day 14-5mg) | Healthy participants received repeat oral doses of GSK2798745 5 mg or matching placebo (ratio 3:1) in fasted state. Participants fasted from midnight to four hours post-dose. GSK2798745 was administered in a liquid formulation (suspension) |
|
|
| OG003 | Co 1 (GSK2798745 12.5 mg) | Healthy participants received single oral doses of GSK2798745 12.5 mg and one dose of GSK2798745 matching placebo in fasted state. Participants fasted from midnight to four hours post-dose. GSK2798745 was administered in a liquid form (suspension) in this single dose escalation cohort. |
| OG004 | Co 2 (GSK2798745 Fasted Suspension) | Healthy participants received three single oral doses of GSK2798745 5 mg in fasted state. GSK2798745 was administered in a liquid suspension to evaluate food effect and relative bioavailability. |
| OG005 | Co 2 (GSK2798745 Fasted Capsule) | Healthy participants received three single oral doses of GSK2798745 5 mg in fasted state. GSK2798745 was administered in a capsule formulation to evaluate food effect and relative bioavailability. |
| OG006 | Co 2 (GSK2798745 Fed Capsule) | Healthy participants received three single oral doses of GSK2798745 5 mg following a standard meal. GSK2798745 was administered in a capsule formulation to evaluate food effect and relative bioavailability. |
| OG007 | Co 3 (GSK2798745 Day 1-5mg) | Healthy participants received oral doses of GSK2798745 5 mg or matching placebo (ratio 3:1) in fasted state. Participants fasted from midnight to four hours post-dose. GSK2798745 was administered in a liquid formulation (suspension) |
| OG008 | Co 3 (GSK2798745 Day 14-5mg) | Healthy participants received repeat oral doses of GSK2798745 5 mg or matching placebo (ratio 3:1) in fasted state. Participants fasted from midnight to four hours post-dose. GSK2798745 was administered in a liquid formulation (suspension) |
|
|
| OG003 | Co 1 (GSK2798745 12.5 mg) | Healthy participants received single oral doses of GSK2798745 12.5 mg and one dose of GSK2798745 matching placebo in fasted state. Participants fasted from midnight to four hours post-dose. GSK2798745 was administered in a liquid form (suspension) in this single dose escalation cohort. |
| OG004 | Co 2 (GSK2798745 Fasted Suspension) | Healthy participants received three single oral doses of GSK2798745 5 mg in fasted state. GSK2798745 was administered in a liquid suspension to evaluate food effect and relative bioavailability. |
| OG005 | Co 2 (GSK2798745 Fasted Capsule) | Healthy participants received three single oral doses of GSK2798745 5 mg in fasted state. GSK2798745 was administered in a capsule formulation to evaluate food effect and relative bioavailability. |
| OG006 | Co 2 (GSK2798745 Fed Capsule) | Healthy participants received three single oral doses of GSK2798745 5 mg following a standard meal. GSK2798745 was administered in a capsule formulation to evaluate food effect and relative bioavailability. |
| OG007 | Co 3 (GSK2798745 Day 1-5mg) | Healthy participants received oral doses of GSK2798745 5 mg or matching placebo (ratio 3:1) in fasted state. Participants fasted from midnight to four hours post-dose. GSK2798745 was administered in a liquid formulation (suspension) |
| OG008 | Co 3 (GSK2798745 Day 14-5mg) | Healthy participants received repeat oral doses of GSK2798745 5 mg or matching placebo (ratio 3:1) in fasted state. Participants fasted from midnight to four hours post-dose. GSK2798745 was administered in a liquid formulation (suspension) |
|
|
|
|