Eli O. Meltzer

The objective of this pooled analysis was to demonstrate the clinically meaningful effect of GSP301, a nasal spray combination of olopatadine hydrochloride (OLO) and mometasone furoate (MF), in treating both nasal and ocular symptoms of seasonal allergic rhinitis (SAR). Results were pooled from 3 double-blind, randomized, placebo-controlled 14-days studies. Patients (12-65 years, n=2,971) with SAR were equally randomized to twice-daily GSP301 (OLO 665 μg/MF 25 μg), OLO (665 μg), MF (25 μg), or placebo. Reflective total of 7 symptom scores (rT7SS, 4 rhinitis + 3 ocular symptoms) were determined. Mean %change from baseline was analyzed using a mixed-effect model repeated measures, 50% responder rates by chi-square tests and time to response by survival analysis. GSP301 effectively reduced rT7SS over the 14 days treatment with relative improvements of 104% and 84% compared to MF (p<0.001) and OLO (p<0.001), respectively. Percent change from baseline in rT7SS was significantly improved with GSP301 (33.58%) compared to placebo (23.28%, p<0.001), OLO (28.90%, p<0.001) and MF (28.20%, p<0.001). Significantly more patients achieved 50% reduction in rT7SS with GSP301 over 14 days with relative improvements of 172% and 116% compared to MF (p<0.001) and OLO (p=0.003). Time to response was significantly faster with GSP301 (30% percentile 4 days) than placebo (10 day, p<0.001), OLO (7 days, p=0.035) and MF (7 days, p=0.017). GSP301 provides a clinically meaningful and statistically significant improvement in total nasal and ocular symptoms compared to individual monotherapies.

The primary lung function endpoint in clinical trials in adolescent and adult patients with asthma is usually forced expiratory volume in one second (FEV1). The objective of our analysis was to assess whether peak expiratory flow (PEF) is a suitable alternative primary lung function endpoint. For this assessment, we calculated post hoc the correlation between pre-dose FEV1 and pre-dose PEF measured under supervision in the clinic and, for both lung function parameters, the correlations between supervised clinic and unsupervised home measurements, using the results from the 8 Phase III parallel-group trials of the global clinical development programme with tiotropium Respimat® in patients with asthma aged 12 to 75 years. Across all 8 trials included in this analysis, changes in lung function from baseline correlated well between pre-dose FEV1 and pre-dose PEF when both were measured under supervision in the clinic. Correlation between supervised in-clinic and unsupervised home measurements was stronger for pre-dose PEF than for pre-dose FEV1. Pre-dose PEF measured at home could be an alternative primary lung function endpoint for trials in adolescent and adult patients with asthma. Using home-measured PEF could facilitate trial conduct and improve the convenience for patients by relocating scheduled assessments from the clinic to the patient’s home. Adolescents aged 12 to 17 years: RubaTinA-asthma® ( NCT01257230 ), PensieTinA-asthma® ( NCT01277523 ). Adults aged 18 to 75 years: GraziaTinA-asthma® ( NCT01316380 ), MezzoTinA-asthma® ( NCT01172808 / NCT01172821 ), CadenTinA-asthma® ( NCT01340209 ), PrimoTinA-asthma® ( NCT00772538 / NCT00776984 ). All from Clinicaltrials.gov ( https://clinicaltrials.gov/ ).

Background: Despite current guidelines, many patients with asthma remain symptomatic, particularly those intolerant of, unresponsive to, or uncontrolled by long-acting beta 2‐agonists (LABAs). Tiotropium bromide, delivered through the Respimat soft-mist inhaler in 2 puffs of 1.25 micrograms each, is approved for the long-term, maintenance treatment of asthma in patients aged ≥6 years. Objective: An overview of the use of once-daily tiotropium Respimat 2.5 micrograms in adults and adolescents with varying degrees of asthma severity. The role of the parasympathetic nervous system in the pathophysiology of asthma, the development of tiotropium for respiratory disease, and the value of the Respimat inhaler are also discussed. Methods: A literature search of all phase II and phase III trials of once-daily tiotropium Respimat 2.5 micrograms. Results: Once-daily tiotropium Respimat 2.5 micrograms was studied in five phase III studies: three studies in adults and two in adolescents aged 12‐17 years. Tiotropium Respimat 2.5 micrograms demonstrated efficacy in adults and adolescents with mild, moderate, or severe asthma, showing significant improvements in lung function and asthma control in patients with uncontrolled asthma despite inhaled corticosteroids (ICS) or ICS plus LABA use. The adverse event profile of tiotropium was very acceptable, with safety similar to placebo. Conclusion: Once-daily tiotropium Respimat 2.5 micrograms has positive attributes that include efficacy, a safety profile similar to placebo, once-daily dosing, administration by inhalation, and delivery in the easy-to-use and consistent-dosing Respimat device. However, more data are needed on the effects of tiotropium on clinical outcomes, patients' day-to-day lives, and real-world effectiveness.