Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
GSK2256294 · 4 trials · 5 indications
Summary tables and listings will be provided for all reported adverse events, defined as adverse events that start on or after the first administration of study drug. The reported adverse event term will be assigned a standardized preferred term. Adverse events will be summarized based on the number and percentage of patients experiencing the event. In the event a patient experiences repeat episodes of the same adverse event, then the event with the highest severity grade and strongest causal relationship to study treatment will be used for purposes of incidence tabulations. All deaths will be reported in a patient listing, which will include the primary cause of death and the number of days between the date of the last dose of study drug and death.
PASP is an indicator of cardiac hemodynamic status and is non-invasively estimated by echocardiography. Change from baseline in PASP under hypoxic conditions following 7 days of GSK2256294 15 milligrams (mg) once daily. Change from baseline was calculated as the Day 7 value minus the Day1 value.
PK parameters including area under the concentration-time curve (AUC) and maximum blood concentrations (Cmax), half life (T1/2), time to Cmax (Tmax) following a single oral dose of GSK2256294 administered under fed and fasted conditions in healthy elderly male and female subjects will be estimated
Twelve-lead ECGs will be obtained as a measure of safety and tolerability
Vital sign measurements will include systolic and diastolic blood pressure (BP) and pulse rate
Clinical laboratory assessments will include haematology, clinical chemistry, urinalysis and other screening tests
Vital signs include systolic blood pressure, diastolic blood pressure, and pulse rate. Vital signs will be collected with the subject semi-supine and after they have been resting for 5 minutes.
Vital signs include systolic blood pressure, diastolic blood pressure, and pulse rate. Vital signs will be collected with the subject semi-supine and after they have been resting for 5 minutes.
12-lead electrocardiograms (ECGs) will be obtained at each time point during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTcF intervals. ECGs will be obtained in the semi-supine position after the subject has been resting for at least 5 minutes.
12-lead electrocardiograms (ECGs) will be obtained at each time point during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTcF intervals. ECGs will be obtained in the semi-supine position after the subject has been resting for at least 5 minutes.
Vital signs include systolic blood pressure, diastolic blood pressure, and pulse rate. Vital signs will be collected with the subject semi-supine and after they have been resting for 5 minutes.
12-lead ECGs will be obtained at each time point during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTcF intervals. ECGs will be obtained in the semi-supine position after the subject has been resting for at least 5 minutes.
Safety data will include assessments of clinical laboratory tests (hematology, clinical chemistry and urinalysis).
Safety data will include assessments of clinical laboratory tests (hematology, clinical chemistry and urinalysis).
Safety data will include assessments of clinical laboratory tests (hematology, clinical chemistry and urinalysis).
Adverse events (AEs) will be recorded from the start of Study Treatment until the follow-up contact.
AEs will be recorded from the start of Study Treatment until the follow-up contact.
AEs will be recorded from the start of Study Treatment until the follow-up contact.
| Arm | Type | Description |
|---|---|---|
| GSK2256294 | ACTIVE_COMPARATOR | 10mg capsules of GSK2256294 will be administered in a single dose once daily enterally for a duration of 10 days. |
| Placebo | PLACEBO_COMPARATOR | 10mg matched placebo capsules will be administered in a single dose once daily enterally for a duration of 10 days. |
| GSK2256294 15 mg | EXPERIMENTAL | Randomised subjects will be instructed to take three capsules of GSK2256294 15 mg, each morning for 7 days. Subjects will undergo echocardiography under normoxic and hypoxic conditions on Day 1 pre-dose and on Day 7 post-dose. |
| Cohort 1 | EXPERIMENTAL | Cohort 1 will enrol 8 healthy male volunteers, who will receive a single 10 mg dose of GSK225694 in the fasted state. |
| Cohort 2 | EXPERIMENTAL | Cohort 2 will enrol 20 healthy elderly male and female volunteers (10 males and 10 females), who will receive a single 10 mg dose of GSK225694 in the fasted or fed state according to the randomization schedule. |
| Cohort 3 | EXPERIMENTAL | Obese adult male smoker subjects in Cohort 3 will receive single or twice daily dose of GSK2256294 or placebo for 14 days. Dose selection for Cohort 3 will be based on the safety, PK profile and enzyme inhibition obtained in cohorts 1 and 2. |
| Cohort 4 | EXPERIMENTAL | Obese adult male smoker subjects in Cohort 4 will receive single or twice daily dose of GSK2256294 or placebo for 14 days. Dose selection for Cohort 4 will be based on the safety, PK profile and enzyme inhibition obtained in cohorts 1 and 2 as well as safety and PK profile obtained in cohort 3. |
| Name | Type | Description |
|---|---|---|
| GSK2256294 | DRUG | GSK2256294 will be administered in a single dose once daily enteral for a duration of 10 days. |
| Placebo | DRUG | Placebo will be administered in a single dose once daily enteral for a duration of 10 days. |
Inclusion Criteria: 1. Age \> 18 2. Head CT evidence of subarachnoid hemorrhage 3. Digital subtraction cerebral angiography or CT angiogram documenting the presence of a cerebral aneurysm. Exclusion Criteria: 1. Symptom onset compatible with SAH of \> 3 days prior to admission to OHSU 2. Absence ...
GSK2256294 is an investigational small molecule developed by GSK plc. It has been studied in Phase 1 clinical trials for chronic obstructive pulmonary disease and aneurysmal subarachnoid hemorrhage. It is an inhibitor of the enzyme EPHX2, also known as soluble epoxide hydrolase, and has not been approved for any indication.
GSK2256294 has been studied in clinical trials for chronic obstructive pulmonary disease and for aneurysmal subarachnoid hemorrhage, including related complications such as delayed cerebral ischemia and cerebral vasospasm. It remains an investigational agent and is not approved for any use.
GSK2256294 targets EPHX2, also known as soluble epoxide hydrolase. It acts as an inhibitor of this enzyme. EPHX2 inhibition is the mechanism explored in its clinical development for respiratory and cerebrovascular conditions.
GSK2256294 is developed by GSK plc, which trades under the ticker GSK. The company sponsored the Phase 1 trials of the compound in the United States and the United Kingdom.
GSK2256294 is in Phase 1 development. All three of its recorded clinical trials are Phase 1 studies, and all have been completed. The drug is investigational and has not been approved by the FDA or any other regulator for commercial use.
GSK2256294 has been evaluated in completed Phase 1 trials including NCT03318783 in aneurysmal subarachnoid hemorrhage, NCT02262689 on pulmonary artery pressure in healthy volunteers, NCT02006537 on safety and pharmacokinetics in healthy young and elderly subjects, and NCT01762774 in healthy volunteers and moderately obese smokers.