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 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT01471665 | GSK2190915 Neutrophilic Asthma Study | PHASE2 | COMPLETED | 14 | — | — | Jun 1, 2011 | May 1, 2012 | Nov 22, 2016 | 1 | United Kingdom |
| NCT00812929 | A Clinical Trial to Test a Study Drug in Volunteers Who Develop Asthma Following Exercise | PHASE2 | COMPLETED | 47 | — | — | Dec 1, 2008 | Jul 15, 2009 | Sep 19, 2017 | 6 | United States |
| NCT00748306 | Study in Mild Asthmatic Patients | PHASE2 | COMPLETED | 19 | — | — | Dec 1, 2008 | Sep 1, 2009 | Oct 12, 2016 | 4 | Netherlands, United Kingdom |
| NCT00812773 | Study to Evaluate GSK2190915 in Subjects With Mild Asthma | PHASE2 | COMPLETED | 17 | — | — | Dec 1, 2008 | Jul 1, 2009 | Oct 12, 2016 | 3 | United Kingdom |
| NCT01411111 | A Repeat Dose Study to Investigate the Interaction of GSK2190915 on the Pharmacokinetics of Rosuvastatin | PHASE1 | COMPLETED | 28 | — | — | Jan 6, 2011 | Feb 23, 2011 | Jul 25, 2017 | 1 | United Kingdom |
| NCT00955383 | GSK2190915 Safety and Pharmacokinetic Study in Healthy Japanese Subjects | PHASE1 | COMPLETED | 12 | — | — | Aug 14, 2009 | Oct 12, 2009 | Jun 14, 2017 | 1 | Germany |
| NCT02224521 | GSK2190915A - Bioavailability Study | PHASE1 | COMPLETED | 67 | — | — | Apr 20, 2009 | Jun 8, 2010 | Jun 14, 2017 | 1 | United Kingdom |
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 ...