Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
GSK2190915 · 7 trials · 1 indication
Pharmacodynamics
FEV1 was recorded in triplicate, with participant encouraged to inhale fully despite any presence of chest tightness. For FEV1, a pre-challenge Baseline was defined for each challenge time point as maximum of triplicate measurements performed prior to challenge. The maximal percentage change within 60 minutes following exercise challenge was derived by taking minimum (i.e., most negative) percentage change in FEV1 over 5, 10, 15, 30, 45 and 60 minutes post challenge. Percent change FEV1 = 100\*(FEV1 - Pre-challenge FEV1)/ Pre-challenge FEV1. If the exercise challenge was not completed successfully (i.e. heart rate maintained at \>=80% of the predicted value for 6 minutes), FEV1 maximal percent change (0-60)was set to be missing. Analysis was performed using a mixed effects model, including period, treatment and covariates for predose FEV1. Estimates and 95% confidence intervals for treatment difference between each active dose and placebo for each challenge time point were calculated.
PK parameters including area under the plasma concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC \[0-∞\]), Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a subject across all treatments (AUC\[0-t\]), concentrations at 24h post dose (C24), maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), terminal half-life (t1/2) and oral clearance (CL/F) for Cohort 1, 2, 3 will be measured.
PK parameters including area under the plasma concentration-time curve over the dosing interval (AUC \[0-tau\]), trough C24, Cmax, Tmax, and accumulation for Cohort 4 will be measured.
PK parameters including AUC (0-∞), AUC (0-t), C24, Cmax, Tmax, t1/2 and CL/F for Cohort 5 and 6 will be measured.
| Arm | Type | Description |
|---|---|---|
| GSK2190915 100mg | EXPERIMENTAL | This is a crossover study so patients will receive 100mg of GSK2190915 once daily for up to 16 days followed by a wash out period of at least 14 days before they cross over onto the placebo arm of the study. |
| Placebo | PLACEBO_COMPARATOR | This is a crossover study so patients will receive placebo once daily for up to 16 days followed by a wash out period of at least 14 days before they cross over onto the GSK2190915 100mg arm of the study. |
| GSK2190915 10 mg | EXPERIMENTAL | - |
| GSK2190915 50 mg | EXPERIMENTAL | - |
| GSK2190915 100 mg | EXPERIMENTAL | - |
| GSK2190915 200 mg | EXPERIMENTAL | - |
| GSK2190915 | EXPERIMENTAL | Intervention |
| 3 day repeat dose | EXPERIMENTAL | - |
| Rosuvastatin foll by GSK2190915 30mg + rosuvastatin | ACTIVE_COMPARATOR | Subjects will be orally administered rosuvastatin 10 mg/day for 7 days in treatment period 1. The subjects will then receive rosuvastatin 10 mg/day in combination with GSK2190915 30 mg/day for 7 days in treatment period 2A. |
| Rosuvastatin foll by GSK2190915 100mg + rosuvastatin | ACTIVE_COMPARATOR | Subjects will be orally administered rosuvastatin 10 mg/day for 7 days in treatment period 1. The subjects will then receive rosuvastatin 10 mg/day in combination with GSK2190915 100 mg/day for 7 days in treatment period 2B. |
| Cohort 1 | EXPERIMENTAL | Subjects will be assigned to any of the 4 dosage regimen (A, B, C, D) in four periods. A= GSK2190915 Solution, 50mg single dose, fasted; B = GSK2190915 Capsule Formulation A, 50mg single dose (1 x 50mg capsule), fasted; C= GSK2190915 Capsule Formulation B, 50mg single dose (1 x 50mg capsule), fasted; D= GSK2190915 Capsule Formulation C, 50mg single dose (1 x 50mg capsule), fasted. |
| Cohort 2 | EXPERIMENTAL | The selected formulation will be dosed with GSK2190915 capsule formulation at 20mg (fasted), 100mg (fasted), 100mg (fed) and 200mg (fasted). |
| Cohort 3 | EXPERIMENTAL | Cohort 3 will be a 4-way complete crossover study with single doses of 20mg and 200mg of up to two capsule formulations taken forward from cohort 2 in 10 healthy adult subjects in the fasted state. |
| Cohort 4 | EXPERIMENTAL | The regimen for Cohort 4 will be either the highest dose (200mg) of the capsule formulation (A, B or C) taken forward from the previous cohorts or the solution formulation (200mg). |
| Cohort 5 | EXPERIMENTAL | Subjects will take milled and micronised tablet formulations of GSK2190915 in the fasted state in periods 1 and 2, and will take milled and micronised tablet formulations of GS2190915 in the fed state in periods 3 and 4. |
| Cohort 6 | EXPERIMENTAL | Tablet formulations (milled and micronised, different to the Cohort 5 formulations) of GSK2190915 will be dosed in the fasted and fed (after a light breakfast) states. |
| Name | Type | Description |
|---|---|---|
| GSK2190915 100mg | DRUG | GSK2190915 is a high affinity 5-lipoxygenase-activating protein (FLAP) inhibitor. Dosing will occur once daily for up to 16 days. |
| Placebo | DRUG | Placebo will be administered once daily for up to 16 days. |
| GSK2190915 | DRUG | This study will assess FEV1 at various intervals following exercise challenge in subjects who have been administered a single dose of 10 mg, 50 mg, 100 mg, or 200 mg GSK2190915, compared to a placebo control. |
| GSK2190915 - 100mcg | DRUG | GSK2190915 is a high affinity 5-lipoxygenase-activating protein (FLAP) inhibitor |
| Rosuvastatin 10 mg | DRUG | days 1-14 |
| GSK2190915 30mg | DRUG | 1x30mg tablet, days 8-14 |
| GSK2190915 Solution. | DRUG | Aqueous Solution, 10mg/mL. |
| GSK2190915 Granule Capsule (A) | DRUG | GSK2190915A granule filled in to Gelatin capsules |
| GSK2190915 Semi-solid Lipid Capsule (B) | DRUG | GSK2190915A dispersed in a lipid vehicle and filled in to HPMC capsules |
| GSK2190915 Liquid Lipid Capsule (C) | DRUG | GSK2190915A dissolved in lipid vehicle milled and filled in to Gelatin capsules |
| GSK2190915 Milled Tablet | DRUG | GSK2190915A granule is blended, compressed into tablets and aqueous film coated |
| GSK2190915 Micronised Tablet | DRUG | GSK2190915A granule is blended, compressed into tablets and aqueous film coated |
Inclusion Criteria: * Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) \< 2xUpper limit of normal (ULN); alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). * Males and females ages 18 ...
GSK2190915 is an investigational small molecule being developed for the treatment of asthma. It is currently in Phase 2 clinical development and has been studied in multiple trials, including a Phase 2 study in patients with neutrophilic asthma. The drug is not yet approved and remains under clinical investigation.
GSK2190915 is being developed by GSK plc, a global biopharmaceutical company listed on the stock exchange under the ticker GSK. The company has conducted multiple clinical trials to evaluate the safety, pharmacokinetics, and efficacy of this investigational drug for asthma.
GSK2190915 is in Phase 2 clinical development for asthma. It has completed a total of seven trials, including Phase 1 and Phase 2 studies. No active trials are currently ongoing, and the drug remains investigational, meaning it has not been approved by regulatory authorities.
GSK2190915 has been studied in several clinical trials, including NCT00955383, a Phase 1 safety and pharmacokinetic study in healthy Japanese subjects; NCT01411111, a drug interaction study with rosuvastatin; NCT01471665, a Phase 2 study in patients with neutrophilic asthma; and NCT02224521, a bioavailability study. All trials have been completed.
GSK2190915 and GSK2190915A refer to the same investigational drug. The compound has been studied under both names in clinical trials, with GSK2190915A appearing in a bioavailability study (NCT02224521). Both names denote the same small molecule being developed for asthma.