Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
GSK356278 · 3 trials · 2 indications
The primary pharmacokinetic endpoints following oral administration are: peak plasma concentration (Cmax), time of peak plasma concentration (tmax), area under the plasma concentration-time curve over the dose interval , and area under the plasma concentration-time curve from time-zero extrapolated to infinite time, accumulation ratio (Ro), terminal half-life (t½ ), apparent oral clearance (CL/F) and trough concentration.
hematology, chemistry, liver function enzymes, troponin, B-type natriuretic peptide, inflammatory markers (Haptoglobin, fibrinogen, CRP, IL-6) and urinalysis
Inflammatory markers (Haptoglobin, fibrinogen, CRP, IL-6)
Brain regions of interest and associated radionuclitide-activity
serial sampling: GSK356278 concentration expressed as mass per unit of volume
| Arm | Type | Description |
|---|---|---|
| Cohort 1 | EXPERIMENTAL | A dose of 2mg per day for 10 days |
| Cohort 2 | EXPERIMENTAL | A dose of Xmg for 14 days. the dose will be determined from Cohort 1 not to exceed 14 mg |
| Cohort 3 | EXPERIMENTAL | a single dose of Ymg with a wash out of 7 days followed by 28 days of repeat dosing. The dose (Ymg) will be determined from cohort 1 and 2 not to exceed 14 mg. |
| GSK356278 | EXPERIMENTAL | Investigational drug |
| Cohort 1, Session 1 | EXPERIMENTAL | In Dosing Session 1, the subjects will be administered 0.5 mg GSK356278 and placebo in a fasted state. |
| Cohort 1, Session 2 | EXPERIMENTAL | In Dosing Session 2, the subjects will be administered GSK356278 (0.5 mg and 1.5 mg) and placebo in a fasted state. |
| Cohort 1, Session 3 | EXPERIMENTAL | In Dosing Session 3, the subjects will be administered GSK356278 (1.5 mg and 4 mg) and placebo in a fasted state. |
| Cohort 1, Session 4 | EXPERIMENTAL | In Dosing Session 4, the subjects will be administered GSK356278 (4 mg and 8 mg) and placebo in a fasted state. |
| Cohort 1, Session 5 | EXPERIMENTAL | In Dosing Session 5, the subjects will be administered GSK356278 8 mg and placebo in a fasted state. |
| Cohort 2, Session 1 | EXPERIMENTAL | In Dosing Session 1, the subjects will be administered 8 mg GSK356278 and placebo in a fasted state. |
| Cohort 2, Session 2 | EXPERIMENTAL | In Dosing Session 2, the subjects will be administered GSK356278 (8 mg and 16 mg) and placebo in a fasted state. |
| Cohort 2, Session 3 | EXPERIMENTAL | In Dosing Session 3, the subjects will be administered GSK356278 (16 mg and 30 mg) and placebo in a fasted state. |
| Cohort 2, Session 4 | EXPERIMENTAL | In Dosing Session 4, the subjects will be administered GSK356278 (30 mg and 50 mg) and placebo in a fasted state. |
| Cohort 2, Session 5 | EXPERIMENTAL | In Dosing Session 5, the subjects will be administered GSK356278 50 mg and placebo in a fasted state. The subjects will undergo food assessment session in Session 5 incase they experience nausea. In food assessment session, the subjects will receive a dose of GSK356278 after a standard breakfast. |
| Name | Type | Description |
|---|---|---|
| GSK356278 | DRUG | Cohort 1: A dose of 2mg per day for 10 days; Cohort 2: A dose of Xmg for 14 days. the dose will be determined from Cohort 1 not to exceed 14 mg; Cohort 3: a single dose of Ymg with a wash out of 7 days followed by 28 days of repeat dosing. The dose (Ymg) will be determined from cohort 1 and 2 not to exceed 14 mg. |
| Placebo | DRUG | Cohort 1, a placebo per day for 10 days Cohort 2, a placebo per day for 14 days Cohort 3, a single placebo with a wash out of 7 days followed by 28 days of repeat dosing of a placebo per day. |
| Rolipram | DRUG | Challenge Agent |
Inclusion Criteria: * AST, ALT, alkaline phosphatase and bilirubin less than and equal to 1.5xULN (isolated bilirubin greater than 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%). * Healthy as determined by a responsible and experienced physician, based on a m...
GSK356278 is an investigational small molecule being studied for Huntington Disease, Depressive Disorder and Anxiety Disorders. It is in Phase 1 clinical development and is not yet approved by regulatory authorities. All completed trials enrolled healthy volunteers, with some studies focused on conditions such as depression, anxiety, and Huntington Disease.
GSK356278 is a phosphodiesterase 4 (PDE4) inhibitor, as indicated by a positron emission tomography (PET) brain occupancy study. It is being investigated for its effects on the central nervous system in conditions like Huntington Disease, depressive disorder, and anxiety disorders.
GSK356278 is developed by GSK plc, a global biopharmaceutical company listed on the stock exchange under the ticker GSK. The company is conducting Phase 1 clinical trials to evaluate the safety, tolerability, and pharmacokinetics of this investigational drug.
GSK356278 is in Phase 1 clinical development. All associated trials have been completed, with no active or ongoing studies currently listed. The drug remains investigational and has not received approval from the U.S. Food and Drug Administration or other regulatory bodies for any indication.
GSK356278 has been studied in three completed Phase 1 trials: NCT01031186, a first-time-in-human study in healthy volunteers with depressive and anxiety disorders; NCT01573819, a repeat dose study in healthy volunteers for Huntington Disease; and NCT01602900, a PET brain occupancy study in healthy volunteers for Huntington Disease.
Yes, GSK356278 is a phosphodiesterase 4 (PDE4) inhibitor. This mechanism was evaluated in a healthy volunteer PET brain occupancy study (NCT01602900) to assess how the drug binds to PDE4 in the brain, which is relevant to its potential use in Huntington Disease and psychiatric conditions.