A novel simple, specific, sensitive, accurate and precise reversed phase high performance liquid chromatographic method (RP-HPLC/UV) was developed and validated for the simultaneous estimation of Glycopyrronium bromide (GLY), Indacaterol acetate (IND) and Mometasone furoate (MOF) in pure form, in laboratory prepared mixtures and in pharmaceutical dosage form. Experimental design methodology was applied by using Plackett-Burman and face-centered composite designs to achieve the best resolution with minimum experimental trials. The designed model was statistically analyzed, graphically presented by surface plots and the relationships between coefficients of the derived polynomial equations were interpreted. Chromatographic separation was achieved on Inertsil ODS C18 column (250 ×4.6 mm, 5 µm) at ambient temperature using a mobile phase composed of methanol: 0.1% glacial acetic acid (pH4) in a gradient elution at a flow rate 1 mL /min. UV detection was carried out at 233 nm. Response was found to be linear in the concentration range of 20-120 µg /mL with regression coefficient (r2 = 0.999) for GLY, 50-300 µg /mL with regression coefficient (r2 = 0.9995) for IND and 50-300 µg /mL with regression coefficient (r2 = 0.9998) for MOF. The method was validated as per ICH guidelines and satisfactory results were achieved. The method was successfully applied for the analysis of the cited drugs in their fixed dose combination (FDC) pharmaceutical formulation. Statistical comparison between the results obtained by the proposed method and the reference methods for GLY, IND and MOF showed no significant difference. The developed method could be implemented in quality control aspects of the cited drugs. Four green metrics were used to evaluate the new RP-HPLC/UV method\'s greenness and compare it to other published techniques.

BACKGROUND: Baseline characteristics could potentially guide asthma treatments. We evaluated whether baseline eosinophil levels affect the efficacy of mometasone/indacaterol/glycopyrronium (MF/IND/GLY) in patients with inadequately controlled asthma.
METHODS: In this post hoc analysis of IRIDIUM study, efficacy of high-dose MF/IND/GLY (160/150/50 μg, once-daily [o.d.]) versus high-dose MF/IND (320/150 μg o.d.) and high-dose fluticasone/salmeterol (FLU/SAL [500/50 μg, twice-daily [b.i.d.]); and efficacy of pooled MF/IND/GLY (160/150/50 μg and 80/150/50 μg) versus pooled MF/IND (320/150 μg and 160/150 μg) was evaluated in patient subgroups with baseline blood eosinophil count of <300 cells/μL or ≥300 cells/μL.
RESULTS: Overall, 3065 patients were included. At Week 26, high-dose MF/IND/GLY showed improved trough FEV1 versus high-dose MF/IND (Δ78mL [<300 cells/μL]; Δ54mL [≥300 cells/μL]) and FLU/SAL (Δ112mL [<300 cells/μL]; Δ98mL [≥300 cells/μL]). Similarly, pooled MF/IND/GLY also showed improved trough FEV1 versus pooled MF/IND (Δ75mL [<300 cells/μL]; Δ68mL [≥300 cells/μL]). Over 52 weeks, high-dose MF/IND/GLY reduced the annualized rate of moderate or severe asthma exacerbations by 23% and 10%, severe exacerbations by 31% and 15%, and all exacerbation by 33% and 10% versus high-dose MF/IND for subgroups with <300 cells/μL and ≥300 cells/μL, respectively; and by 33% and 41%, 45% and 42%, 42% and 39% versus FLU/SAL, respectively. Similarly, pooled MF/IND/GLY reduced exacerbations by 22% and 8%, 21% and 7%, 27% and 8%, versus pooled MF/IND, for the respective subgroups.
CONCLUSIONS: MF/IND/GLY showed improvement in lung function and reduction in asthma exacerbations over MF/IND and FLU/SAL independent of baseline eosinophil levels, indicating that eosinophil levels did not affect the efficacy of MF/IND/GLY in patients with inadequately controlled asthma.
BACKGROUND: ClinicalTrials.gov, NCT02571777 (IRIDIUM).

UNASSIGNED: We evaluated the cost-effectiveness of high-dose indacaterol acetate (IND)/glycopyrronium bromide (GLY)/mometasone furoate (MF) (150/50/160 μg, once daily) compared with high-dose salmeterol/fluticasone (SAL/FLU; 50/500 µg, twice daily)+tiotropium (TIO; 5 µg, once daily) (SAL/FLU+TIO) and with high-dose SAL/FLU (50/500 µg, twice daily) for the treatment of inadequately controlled moderate-to-severe asthma.
UNASSIGNED: A Markov model estimated the incremental cost-effectiveness ratio of treatment with high-dose IND/GLY/MF compared with SAL/FLU+TIO and high-dose IND/GLY/MF compared with SAL/FLU. The model included three health states (day-to-day symptoms without exacerbations, day-to-day symptoms with exacerbations, and death) with a 4-week cycle length. A lifetime time horizon was used. Exacerbation rates and utility values were derived from ARGON and IRIDIUM clinical trials. Canadian dollars (CAD$, 2020) were applied.
UNASSIGNED: IND/GLY/MF was the less costly and more effective treatment strategy compared with SAL/FLU+TIO and SAL/FLU in the base-case analyses. IND/GLY/MF had lower costs (CAD $33,501 versus CAD $50,907) and higher quality-adjusted life-years (QALYs) (18.37 versus 18.06 QALYs) compared with SAL/FLU+TIO. Compared with SAL/FLU, IND/GLY/MF had lower costs (CAD $33,408 versus CAD $36,577) and higher QALYs (19.33 versus 19.04 QALYs). IND/GLY/MF was the most cost-effective option in all scenarios tested.
UNASSIGNED: IND/GLY/MF was cost-effective at a willingness-to-pay threshold of CAD $50,000/QALY in patients with uncontrolled, moderate-to-severe asthma versus SAL/FLU+TIO and SAL/FLU in the base case and all scenarios tested.