Tulin Shekar

Efficacy and safety characteristics of mometasone furoate/formoterol fumarate fixed-dose combination in subjects with moderate to very severe COPD: findings from pooled analysis of two randomized, 52-week placebo-controlled trials

Background The clinical efficacy and safety of a mometasone furoate/formoterol fumarate (MF/F) fixed-dose combination formulation administered via a metered-dose inhaler was investigated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). Methods Two 52-week, multicenter, double-blind, placebo-controlled trials with identical study designs were conducted in current or ex-smokers (aged ≥40 years), and pooled study results are presented herein. Subjects (n = 2251) were randomized to 26 weeks of twice-daily treatment with MF/F 400/10 μg, MF/F 200/10 μg, MF 400 μg, F 10 μg, or placebo. After the 26-week treatment period, placebo subjects completed the trial and 75% of subjects on active treatment entered a 26-week safety extension. Coprimary efficacy variables were mean changes in forced expiratory volume in one second (FEV1), area under the curve from 0 to 12 hours postdose (AUC0–12 h), and morning predose/trough FEV1 from baseline to the week 13 endpoint. Key secondary efficacy variables were St George’s Respiratory Questionnaire scores, symptom-free nights, time-to-first exacerbation, and partly stable COPD at the week 26 endpoint. Results In the 26-week treatment period, significantly greater increases in FEV1 AUC0–12 h occurred with MF/F 400/10 versus MF 400 and placebo at the week 13 and week 26 endpoints (P ≤ 0.032). These increases were over three-fold greater with MF/F 400/10 than with MF 400. Also, significantly greater increases in morning predose/trough FEV1 occurred with MF/F 400/10 versus F 10 and placebo at the week 13 endpoint (P < 0.05). The increase was four-fold greater with MF/F 400/10 than with F 10. All active treatment groups achieved minimum clinically important differences from baseline (>4 units) in St George’s Respiratory Questionnaire scores at week 26. Symptom-free nights increased by ≥14% in the MF/F 400/10, MF 400, and F 10 groups (P ≤ 0.033 versus placebo). The incidence of exacerbations was lower in the MF/F groups (≤33.3%) than it was in the MF, formoterol, and placebo groups (≥33.8%) over the 26-week treatment period. The incidence of adverse events was similar in the active-treated and placebo-treated subjects across 26 weeks of treatment. Over the 1-year study period, there were no notable differences in the incidence or types of adverse events between the MF/F 400/10 and MF/F 200/10 groups compared with the MF or formoterol groups. Differences in rates of individual treatment-emergent adverse events were <3% between treatment groups. Rates of pneumonia were low (≤2%) across all treatment groups. Conclusion Patients treated with MF/F demonstrated significant improvements in lung function, health status, and exacerbation rates. Although significant improvements were seen with both doses, a trend showing a dose-response effect was observed in the lung function measurements.

Mometasone furoate nasal spray reduces the ocular symptoms of seasonal allergic rhinitis

BACKGROUND Mometasone furoate nasal spray (MFNS), a potent intranasal corticosteroid with proved efficacy in relieving nasal allergic rhinitis symptoms, has demonstrated effectiveness in improving ocular symptoms associated with seasonal allergic rhinitis (SAR) in retrospective analyses. OBJECTIVE We sought to evaluate prospectively the efficacy of MFNS in reducing total ocular symptom scores (TOSSs) and individual ocular symptoms in subjects with SAR. METHODS Subjects 12 years or older (n = 429) with moderate-to-severe baseline symptoms were randomized to MFNS, 200 microg once daily, or placebo in this 15-day, double-blind, parallel-group study. Subjects evaluated morning instantaneous TOSSs and daily reflective TOSSs, total nasal symptom scores (TNSSs; both instantaneous TNSSs and reflective TNSSs, respectively), and individual ocular and nasal symptoms. Mean changes from baseline averaged over days 2 to 15 (instantaneous) and days 1 to 15 (reflective) were calculated. Quality of life was assessed by using the Rhinoconjunctivitis Quality of Life Questionnaire. RESULTS MFNS treatment yielded significant reductions from baseline versus placebo in instantaneous TOSSs (-0.34, P = .026, coprimary end point), instantaneous TNSSs (-0.88, P < .001, coprimary end point), reflective TOSSs (-0.44, P = .005), and reflective TNSSs (-1.06, P < .001). Significant decreases in all individual reflective ocular symptoms and instantaneous eye itching/burning and eye watering/tearing were observed for MFNS versus placebo (P < .05). Numeric improvements in instantaneous eye redness were seen but did not reach statistical significance. Improvements in Rhinoconjunctivitis Quality of Life Questionnaire total scores and individual symptom domains were achieved with MFNS treatment versus placebo (P < .001). MFNS was well tolerated. CONCLUSION This prospective study demonstrates that MFNS significantly reduces ocular symptoms in subjects with SAR.

Mometasone furoate nasal spray plus oxymetazoline nasal spray: short-term efficacy and safety in seasonal allergic rhinitis.

Background Allergic rhinitis (AR) and associated congestion adversely affect patients’ lives. The intranasal corticosteroid mometasone furoate nasal spray (MFNS) is effective for AR symptoms including nasal congestion, and the intranasal decongestant oxymetazoline (OXY) is effective against nasal congestion, but the combination has not been fully studied. This study was designed to assess the efficacy of the combination of MFNS and OXY for the relief of seasonal allergic rhinitis (SAR) symptoms. Methods This phase 2 controlled clinical trial randomized adolescent and adult subjects (≥12 years; 2-year SAR) to MFNS q.d. (200 μg) + 3 sprays/nostril of OXY 0.05% (MFNS + OXY3); MFNS q.d. + 1 spray/nostril of OXY (MFNS + OXY1); MFNS q.d.; OXY b.i.d.; or placebo for 15 days, with 1-week follow-up. Coprimary end points were change from baseline in morning/evening (A.M./P.M.) instantaneous (NOW) total nasal symptom score (TNSS) over days 1–15 and AUC (AUC[0–4 hr]) change from baseline in day 1 congestion. Results In 705 subjects, both combinations reduced A.M./P.M. NOW TNSS over days 1–15 significantly more than OXY b.i.d. or placebo (p ≤ 0.002). Mean standardized AUC(0–4 hr) day 1 congestion change from baseline was significantly greater in combination and OXY b.i.d. groups (MFNS + OXY3, −0.92; MFNS + OXY1, −0.80; OXY b.i.d., −1.06) versus placebo (–0.57) and MFNS q.d. (–0.63). Combinations and MFNS q.d. were significantly effective for A.M./P.M. NOW TNSS over each weekly period; OXY b.i.d. was superior to placebo in week 1. Adverse events (AEs) were few and similar across treatments; one MFNS q.d. and one placebo subject experienced a serious AE, with neither considered treatment related. Conclusion Combining MFNS with OXY relieves SAR symptoms, including congestion, with faster onset of action than MFNS q.d. and better sustained efficacy than OXY b.i.d.

Efficacy and safety of a fixed-dose combination of mometasone furoate and formoterol fumarate in subjects with moderate to very severe COPD: results from a 52-week Phase III trial.

Background A clinical trial of mometasone furoate/formoterol fumarate (MF/F) administered via a metered-dose inhaler in subjects with moderate to very severe chronic obstructive pulmonary disease (COPD) investigated the efficacy and safety of a fixed-dose combination of MF/F. Methods This multicenter, double-blind, placebo-controlled trial had a 26-week treatment period and a 26-week safety extension. Subjects (n = 1055; ≥40 years) were current or ex- smokers randomized to twice-daily treatment with inhaled MF/F 400/10 μg, MF/F 200/10 μg, MF 400 μg, F 10 μg, or placebo. The coprimary endpoints of the trial were mean changes from baseline in forced expiratory volume in 1 second (FEV1) over 0–12 hours (AUC0–12 FEV1) with MF/F versus MF, and in morning predose FEV1 with MF/F versus F. Key secondary endpoints were quality of life (Saint George’s Respiratory Questionnaire [SGRQ]), symptom-free nights, and partly stable COPD at 26 weeks, as well as time to first COPD exacerbation. Results Significant improvements in FEV1 AUC0–12 occurred at endpoint with MF/F 400/10 and MF/F 200/10 versus MF 400 (P ≤ 0.007). Significant bronchodilation occurred in 5 minutes with MF/F, and serial spirometry demonstrated sustained FEV1 improvements with MF/F over the treatment period. Significant improvements in morning predose FEV1 occurred with both MF/F doses, and these effects were further investigated by excluding results for subjects whose morning FEV1 data were collected >2 days after the last dose of study treatment. Improvements in SGRQ total scores surpassed the minimum clinically important difference of at least 4 units with MF/F 400/10. MF/F 400/10 significantly reduced the time-to-first COPD exacerbation. Similar proportions of subjects in all five treatment groups reported treatment-emergent adverse events. Rates of pneumonia were low (≤1.0%) across treatment groups. Conclusion MF/F 400/10 μg twice daily was shown to be an effective therapy for patients with moderate to very severe COPD, and both MF/F 400/10 μg twice daily and MF/F 200/10 μg twice daily were well tolerated.

Randomized controlled trial of desloratadine for persistent allergic rhinitis: correlations between symptom improvement and quality of life

Allergic rhinitis (AR) symptoms can impart emotional, quality of life (QOL), and work productivity burdens, especially in persistent AR (PER). Desloratadine, an H1-receptor antagonist, has been shown to be effective against nasal and nonnasal AR symptoms and to improve QOL. Exploratory analyses were conducted to evaluate whether desloratadine-mediated symptom improvement correlated with improvements in QOL and productivity. The Aerius Control: Clinical and Evaluative Profile of Treatment 2 (NCT00405964) study was a 12-week, multinational, randomized, placebo-controlled prospective study of once-daily desloratadine at 5 mg in subjects with moderate-to-severe PER. Assessments included twice-daily symptom severity ratings (0 = none to 3 = severe; total and individual symptoms), sleep interference (morning [A.M.]), interference with activities of daily living (ADL; evening [P.M.]), the Rhinoconjunctivitis Quality of Life Questionnaire-Standardized version (baseline and days 29 and 85), and the Work Productivity and Activity Impairment-Allergy-Specific questionnaire (baseline and weekly). Pearson product-moment correlation statistics (r) were determined to assess correlations between symptom score improvements and QOL factors. All desloratadine-treated patients (n = 360) were included in this exploratory analysis. In the desloratadine-treated patients, all correlations tested were positive (all p < 0.0001). The highest coefficients were seen for the correlations between A.M./P.M. PRIOR total five-symptom score and interference with ADL (r = 0.72) and between A.M. NOW congestion and ADL interference (r = 0.69). Continuous daily treatment of moderate-to-severe PER with desloratadine at 5 mg/day significantly improved symptoms, which correlated positively, albeit moderately, with QOL benefits and reversal of functional impairments caused by PER.

Mometasone furoate nasal spray for moderate-to-severe nasal congestion in subjects with seasonal allergic rhinitis.

Nasal congestion is a frequent, bothersome symptom of seasonal allergic rhinitis (SAR). Mometasone furoate nasal spray (MFNS) has established efficacy in treating nasal allergy symptoms, but no study has been conducted with the primary purpose of evaluating MFNS for relief of congestion. This study assessed MFNS for congestion and other nasal symptoms in SAR. Two double-blind, placebo-controlled studies randomized symptomatic SAR patients to 15 days of MFNS, 200 micrograms, or placebo q.d. each morning. Participants scored individual components of total nasal symptom score (TNSS; congestion, rhinorrhea, sneezing, and itching) on a 4-point scale in the morning (A.M.) and evening (P.M.). Symptoms were scored for the time of assessment (NOW) and for the previous 12 hours (PRIOR). The pooled population comprised 684 patients randomized to MFNS (n = 344) or placebo (n = 340). Change from baseline in A.M./P.M. PRIOR nasal congestion score averaged over days 1-15, the primary end point, was significantly (p < 0.001) greater with MFNS than with placebo (0.68-point [25.2%] reduction versus 0.45-point [16.0%] reduction, respectively). Reduction in A.M./P.M. PRIOR TNSS averaged over days 1-15, a key secondary end point, was also superior with MFNS (2.83 points [28.5%] versus 1.79 points [17.6%]; p < 0.001). Predose A.M. NOW congestion, other nasal symptoms, and TNSS improved significantly more with MFNS, indicating 24-hour efficacy. Adverse events were infrequent and localized; the most common (epistaxis and pharyngolaryngeal pain) occurred in 1.0% of MFNS patients. MFNS q.d. provides sustained relief for nasal congestion and other SAR symptoms.

The cost-effectiveness of treatment with desloratadine in patients with persistent allergic rhinitis

Abstract Objectives: A new classification of persistent allergic rhinitis (PER) has been developed by the ARIA working group. Although the burden of AR is significant, treatment itself is also costly. It is unclear if treatment based on the new definition of PER is cost-effective. Methods: The current study simulated the cost-effectiveness of desloratadine compared to placebo in the treatment of PER from the French societal perspective. Decision analysis was used to model the costs, effectiveness and cost-effectiveness over 12 months. Costs included medical expenditures (physician visits and prescription drugs) attributable to PER and related comorbidities and lost productivity due to absenteeism and presenteeism. Prices, tariffs and national wages were estimated from French national sources. Measures of effectiveness included: symptom-based visual analogue scale (VAS), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Total 5 Symptoms Score (T5SS), categorical improvement in therapeutic response, interference with activities of daily living (ADL) and sleep outcomes. Mild or symptom-free days and ‘responders’ were also captured as outcomes. Univariate and second-order multivariate probabilistic sensitivity analyses were conducted. Results: Treatment with desloratadine dominated placebo (cost less and resulted in greater effectiveness) for all measures of effectiveness. Of the individuals taking desloratadine 46.8% were classified as ‘responders’ vs. 34.8% for placebo (p = 0.0012). Individuals taking desloratadine experienced mild/no symptoms for 57.6% of study days vs. 36.5% for placebo (p = 0.002). The expected annual cost of treatment with desloratadine (€1819) was less than placebo (€2618). Lost productivity was the most significant contributor to total cost. Results of the 10,000 Monte Carlo simulations showed that treatment was cost-saving in 99.6% of simulations. Conclusions: Treatment of PER with desloratadine resulted in improved effectiveness and significant savings. While the cost of drug treatment is greater than that of no treatment, the downstream costs associated with not treating PER significantly outweigh the cost of treatment. Key limitations include the comparison of desloratadine to placebo and the sources of cost and effectiveness measures. Future studies should examine the cost-effectiveness of all available treatments for PER. In addition, many utilization, productivity and effectiveness measures were taken from clinical trials and may not accurately reflect ‘real world’ treatment patterns and outcomes.

Safety and immunogenicity of a single dose 23-valent pneumococcal polysaccharide vaccine in Russian subjects

ABSTRACT Pneumococcal infection is a major cause of pneumonia, bacteremia, and meningitis. Incidence of pneumococcal disease (PD) varies worldwide. The 23-valent pneumococcal polysaccharide vaccine (PPV23) displays an acceptable safety profile and has been demonstrated cost-effective in reducing burden of PD. Methods: Approximately 100 subjects from the Russian Federation who were either 2 to 49 y of age with increased risk for PD or ≥50 years of age were enrolled into the study (NCT01734239) to receive a single dose of PPV23 administered intramuscularly. Each subject was followed for local and systemic adverse events (AEs) for 5 and 14 days, respectively. Serious AEs were collected for 28 d postvaccination. Blood samples were collected immediately prior to vaccination and 28 d postvaccination for the measurement of IgG to serotypes 1, 6B, 14, 19F, and 23F. Results: High proportion of subjects had ≥2 -fold increase in IgG following receipt of PPV23. Rates were 92.0%, 83.0%, 89.0%, 81%, 84% for serotypes 1, 6B, 14, 19F, and 23F, respectively. Similar rates of responders and increases in the magnitude of immune responses were observed in both age groups (2–49, ≥50 ). PPV23 was generally safe and well tolerated. Injection site and systemic AEs were reported by 14.7% and 18.6% of study subjects, respectively. Conclusions: PPV23 is generally safe, well tolerated, and highly immunogenic when given as a single dose to Russian individuals 50 y of age and older, as well as Russian individuals 2 to 49 y of age who are at high risk for PD.

Mometasone furoate (MF) improves lung function in pediatric asthma: A double-blind, randomized controlled dose-ranging trial of MF metered-dose inhaler

Mometasone furoate (MF), delivered via dry‐powder inhaler (DPI) QD in the evening (PM), is a treatment option for pediatric patients with asthma. We evaluated MF delivered via a metered‐dose inhaler (MDI), in children ages 5–11 years with persistent asthma.

S100 – Mometasone Furoate Reduces Ocular Symptoms of Seasonal AR

Objectives To demonstrate clinical efficacy in reducing the ocular symptoms of SAR using mometasone furoate nasal spray (MFNS). Methods A phase III, double-blind, randomized, placebo-controlled, multi-center study compared the efficacy of MFNS 200 mcg QD, dosed in the morning (AM), for treatment of ocular symptoms associated with SAR. Subjects were at least 12 years old with at least a 2-year history of SAR. In daily diaries, subjects evaluated AM ocular symptom severity on a scale of 0 (none) to 3 (severe) on treatment Days 1 to 15. Co-primary endpoints included change from baseline in average instantaneous (AM) total nasal symptom score (sum of individual nasal symptom scores for congestion, rhinorrhea, sneezing, and itching) and instantaneous (AM) total ocular symptom score (iTOSS) (sum of individual eye symptom scores for itching/burning, tearing/watering, redness), Days 2 to 15. Results Subjects (429) with similar baseline characteristics and moderate-to-severe ocular symptoms received MFNS 200 mcg QD or placebo. MFNS 200 mcg QD demonstrated superiority over placebo in least squares mean changes from baseline in subject-rated, average AM iTOSS from Day 2 to 15 (−1.71 [−25.1%] and −1.37 [−20.1%], respectively; P equal to 0.026). MFNS was well tolerated. Conclusions MFNS 200 mcg QD demonstrated statistically significant improvements in AM iTOSS associated with SAR. These are the first prospective results demonstrating that MFNS significantly reduces ocular symptoms in subjects with SAR.