Addition of a 5-lipoxygenase-activating protein inhibitor to an inhaled corticosteroid (ICS) or an ICS/long-acting beta-2-agonist combination in subjects with asthma

Abstract

Objective:

To investigate the clinical benefits of ‘add-on’ therapy with GSK2190915 in combination with the inhaled corticosteroid (ICS) fluticasone propionate (FP) and the ICS/long-acting beta 2 agonist (LABA) combination FP/salmeterol in asthmatic subjects.

Methods:

Both studies were cross-over, randomized, double-blind, double-dummy and placebo-controlled in subjects with a forced expiratory volume in 1 second (FEV₁) best of >50 and ≤80% of predicted. Add-on to ICS: Subjects (n = 162) aged ≥12 years received FP 100 µg twice daily (BID) plus GSK2190915 100 mg once daily (QD); GSK2190915 300 mg QD; montelukast 10 mg QD; salmeterol 50 µg BID or placebo. Add-on to ICS/LABA: Female subjects (n = 145) aged ≥18 years received FP/salmeterol 250/50 µg BID plus GSK2190915 300 mg QD, montelukast 10 mg QD or placebo. In both studies, the primary endpoint was trough FEV₁ at the end of the treatment period. Secondary endpoints included a range of objective and patient-reported measures of efficacy.

Results:

Add-on to ICS: There was no statistically significant difference in the primary endpoint between either dose of GSK2190915 (add-on to FP) and placebo. Nominally statistically significant increases were demonstrated for GSK2190915 300 mg add-on relative to placebo for mean morning peak expiratory flow (p = 0.049), percentage of symptom-free days (p = 0.035) and percentage of symptom-free 24 h periods (p = 0.030). Add-on to ICS/LABA: There were no statistically significant differences on the primary endpoint between treatment regimens. Nominally statistically significant decreases were demonstrated in daytime (p = 0.023), night-time (p = 0.041) and 24 h (p = 0.019) short-acting beta 2 agonist usage with FP/salmeterol + GSK2190915 300 mg vs. FP/salmeterol + placebo.

Conclusion:

There was no clinically significant improvement in the primary endpoint following GSK2190915 add-on treatment; however, improvements in a range of secondary endpoints and biomarker data provided evidence of pharmacological activity. Improvements in response to background treatment may have been a limitation in both studies.

Trial registration:

Clinicaltrials.gov identifiers: NCT01156792 and NCT01248975.

Keywords::

• Asthma
• FLAP
• GSK2190915
• ICS
• LABA

Transparency

Declaration of funding

These studies were funded by GlaxoSmithKline.

Declaration of financial/other relationships

R.M.A.F. and S.-Y.H. are GlaxoSmithKline employees. D.C. and N.G.S. were employed by GlaxoSmithKline at the time the studies were conducted.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

We thank Todd Hankinson (add-on to ICS study) and Anne Briggs (add-on to ICS/LABA study) for the managing of the studies, and Stephanie Vick (add-on to ICS study) and Michelle Fry (add-on to ICS/LABA study) for data management of the studies. Dr Gareth Cuttle and Dr Justin Cook from Niche Science and Technology provided writing and editorial support to the development of this manuscript and were paid for these services by GlaxoSmithKline.