Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT02119260 | A First Time in Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GSK2798745 in Healthy Subjects and Stable Heart Failure Patients | PHASE2 | COMPLETED | 61 | — | — | Jun 9, 2014 | Dec 25, 2016 | Sep 27, 2018 | 2 | United Kingdom |
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
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
| Arm | Type | Description |
|---|---|---|
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| Name | Type | Description |
|---|---|---|
| GSK2798745 solution | DRUG | Clear, colourless GSK2798745 (0.1 to 0.4mg) solution in aqueous citrate buffer with 4% captisol |
| GSK2798745 suspension | DRUG | Aqueous suspension of GSK2798745 (\>=0.5 mg) |
| GSK2798745 capsule | DRUG | White Opaque granule filled capsules of GSK2798745 (\>=0.5 mg) |
| Placebo solution | DRUG | Clear, colourless solution of aqueous citrate buffer with 4% captisol |
| Placebo suspension | DRUG | Visually matching aqueous suspension of hypromellose acetate succinate powder |
| Placebo capsule | DRUG | Matching white opaque placebo blend filled capsule |
Inclusion Criteria: For Healthy Subject Cohorts (1-3): * Male or female 18-75 years of age inclusive, at the time of signing the informed consent. * Healthy as determined by a responsible and experienced physician, based on an evaluation including medical history, physical examination, laboratory ...