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 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT02262689 | To Evaluate Effects of GSK2256294 on Pulmonary Artery Pressure in Healthy Volunteers Under Normoxic and Hypoxic Conditions | PHASE1 | COMPLETED | 30 | — | — | Jan 8, 2015 | Apr 24, 2015 | May 9, 2017 | 1 | United States |
| NCT02006537 | A Study to Investigate the Safety and Pharmacokinetics of a Single Dose of GSK2256294 in Healthy Young Males and Elderly Subjects | PHASE1 | COMPLETED | 28 | — | — | Jan 31, 2014 | May 27, 2014 | May 9, 2017 | 1 | United States |
| NCT01762774 | A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Doses of GSK2256294 in Healthy Volunteers, and Single and Repeat Doses of GSK2256294 in Adult Male Moderately Obese Smokers | PHASE1 | COMPLETED | 56 | — | — | Jan 16, 2013 | May 1, 2014 | May 9, 2017 | 1 | United Kingdom |
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 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. |
| Placebo | PLACEBO_COMPARATOR | Randomised subjects will be instructed to take three capsules of matching placebo, 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 supplied as gelatin capsule to be administered orally with the unit dose 5 mg / dose level 15 mg |
| Placebo | DRUG | Matched Placebo will be supplied as gelatin capsule to be administered orally |
Inclusion Criteria: * AGE: Between 18 and 65 years of age inclusive, at the time of signing the informed consent * Screening echocardiogram of at least good quality, without clinically significant abnormalities, and with mild-moderate tricuspid regurgitation sufficient for the reliable estimation o...