GSK2190915A - Bioavailability Study

Asthma Clinical Trial

Official title: An Open-label, Randomised, Single-dose, Multi-cohort, Crossover Bioavailability Study of a Solution Formulation and Three Capsule Formulations of GSK2190915 in Healthy Adult Subjects Followed by a Repeat-dose, Randomized, Parallel Group, Double-blinded Study of One Selected Capsule Formulation and Matched Placebo in Elderly Healthy Subjects

Status Completed

Clinical Trial Summary

GSK2190915 is a high affinity 5-lipoxygenase-activating protein (FLAP) inhibitor that reduces inflammation in cells.

This study will evaluate three capsule and two tablet formulations to select the optimal formulation for further development. Safety will be assessed through clinical laboratory testing, 12-lead electrocardiogram (ECG), vital signs and Adverse Event/ Serious Adverse Event (AE/ SAE) recording.

Clinical Trial Description

GSK2190915 is a high affinity 5-lipoxygenase-activating protein (FLAP) inhibitor that attenuates the production of leukotrienes, through the blockage of the first committed step in the leukotriene pathway, 5 lipoxygenase (5-LO) activation. Leukotrienes are potent inflammatory molecules produced mainly by mast cells, eosinophils, monocytes/macrophage and neutrophils in response to allergic or inflammatory stimuli.

Clinical studies conducted to date with GSK2190915 have utilised an aqueous formulation of the compound. However, to progress the compound further in clinical development, a solid dose formulation is necessary. This study will evaluate the optimal capsule formulation from a selection of three available capsule formulations, and a dose, that can be taken forward for future clinical development. Since it is expected that the compound will be developed for Chronic Obstructive Pulmonary Disease (COPD), the study will also include a repeat-dose cohort with elderly subjects (smokers and non-smokers over 65 years of age) in order to evaluate the repeat-dose derived pharmacokinetic parameters of the selected capsule formulation in this population.

This is a multi-cohort study and upto 6 cohorts will be performed.

In cohort 1, the bioavailability of single doses of 50 milligrammes (50 mg) of three capsule formulations (capsule formulations A, B and C) in the fasted state will be assessed. Depending on the bioavailability data obtained from cohort 1, one, two or three capsule formulations may be taken forward into cohort 2.

If only one formulation is deemed to be suitable for progression, cohort 2 will be a single-dose, 4-way complete crossover study to investigate both food-effect and dose proportionality in 10 healthy adult subjects. The decision to progress this formulation to the final (repeat-dose) cohort (cohort 4) will be made based on favourable food interaction and proportionality in bioavailability between high and low doses in cohort 2.

If more than one capsule formulation fulfils the bioavailability criteria following cohort 1, cohort 2 will be a food-effect study with a 100mg single dose of two or three selected capsule formulations in healthy adult subjects. Progression to Cohort 3 will be dependent on the formulation/s meeting predetermined pharmacokinetic (PK) criteria. Cohort 3 will be a complete crossover study with single doses of 20mg and 200mg of each of upto two capsule formulations taken forward from cohort 2 in 10 healthy adult subjects in the fasted state. The aim of performing this cohort is to explore the dose proportionality between low and high doses of the two selected capsule formulations.

Cohort 4 is a 12-day repeat-dose, double-blinded, placebo-controlled study in 12 healthy elderly subjects (>65 years) in the fed or fasted state with once-daily dosing of the highest dose (200mg) of the capsule formulation (A, B or C) taken forward from the previous cohorts. The aim of this cohort is to investigate the accumulation of the selected formulation during repeat dosing.

Cohort 5 will be a 4-way complete crossover study with single doses of 100mg of two tablet formulations (milled and micronised) administered to healthy volunteers in the fed and fasted states. The aim of performing this cohort is to explore the single-dose pharmacokinetics of the two tablet formulations with a view to assessing their suitability for use in subsequent late- phase studies.

Cohort 6 will be a 4-way complete crossover study with single doses of 100mg of two modified tablet formulations (different from Cohort 5 formulations) administered to healthy volunteers in the fed and fasted states. The aim of performing this cohort is to explore the single-dose pharmacokinetics of the two modified tablet formulations with a view to assessing their suitability for use in subsequent late- phase studies. ;

Related Conditions & MeSH terms

• Asthma

• NCT number: NCT02224521
• Study type: Interventional
• Source: GlaxoSmithKline
• Status: Completed
• Phase: Phase 1
• Start date: April 20, 2009
• Completion date: June 8, 2010