A 12-week, randomized, double-blind, placebo-controlled study evaluating the effect of eszopiclone 2 mg on sleep/wake function in older adults with primary and comorbid insomnia.

BACKGROUND: Longer-term pharmacologic studies for insomnia in older individuals are sparse. OBJECTIVE: To evaluate the efficacy and safety of 12 weeks of nightly eszopiclone in elderly outpatients with insomnia. METHODS: Participants (65-85 years) met DSM-IV-TR criteria for insomnia with total sleep times (TST) < or = 6 h, and wake time after sleep onset (WASO) > or = 45 min. Participants were randomized to 12 weeks of eszopiclone 2 mg (n = 194) or placebo (n = 194), followed by a 2-week single-blind placebo run-out. Subject-reported measures of sleep (sTST, sleep latency [sSL], sWASO) and daytime function (alertness, concentration, wellbeing, ability to function) were assessed. AEs were monitored. RESULTS: Subjects treated with 2 mg eszopiclone slept longer at night on average and at every individual time point compared to baseline than placebo subjects, as measured by TST over the 12-week double-blind period (P < 0.0001). Mean sTST over the double-blind period for eszopiclone-treated subjects was 360.08 min compared to 297.86 min at baseline, a mean change of 63.24 min. Over the double-blind period, eszopiclone-treated subjects also experienced a significantly greater improvement in sSL compared to placebo, with a mean decrease of 24.62 min versus a mean decrease of 19.92 min, respectively (P = 0.0014). Eszopiclone subjects also experienced a significantly greater decrease in WASO (mean decrease of 36.4 min) compared to placebo subjects (decrease of 14.8 min) (P < 0.0001). Post-discontinuation, sleep parameters were statistically improved versus baseline for eszopiclone (P-values < or = 0.01), indicating no rebound. The most common AEs (> or = 5%) were headache (eszopiclone 13.9%, placebo 12.4%), unpleasant taste (12.4%, 1.5%), and nasopharyngitis (5.7%, 6.2%). CONCLUSION: In this Phase IV trial of older adults with insomnia, eszopiclone significantly improved patient-reported sleep and daytime function relative to placebo. Improvements occurred within the first week and were maintained for 3 months, with no evidence of rebound insomnia following discontinuation. The 12 weeks of treatment were well tolerated. CLINICAL TRIAL INFORMATION: A Long-Term Safety and Efficacy Study of Eszopiclone in Elderly Subjects With Primary Chronic Insomnia; Registration #NCT00386334; URL - http://www.clinicaltrials.gov/ct2/show/NCT00386334?term=eszopiclone&rank=24

Comparison of the efficacy and safety of arformoterol 15 microg twice daily and arformoterol 30 microg once daily in COPD: a single-dose, multicenter, randomized, modified-blind, two-way crossover study.

OBJECTIVE: The aim of this study was to compare the efficacy and safety of nebulized arformoterol 15 microg/2 mL twice daily (ARF15 BID) and 30 microg/4 mL once daily (ARF30 QD) in subjects with moderate to severe chronic obstructive pulmonary disease (COPD). METHODS: In this single-dose, multicenter, randomized, modified-blind, 2-way crossover study, subjects aged > or =45 years with moderate to severe COPD, a forced expiratory volume in 1 second (FEV(1)) > or =0.7 L, and < or =65% predicted FEV1, and a FEV(1):forced vital capacity ratio < or =70% were randomly assigned to receive single-day treatment with ARF15 BID or ARF30 QD in random order, separated by a 5 +/- 2-day washout period. The primary efficacy end point was time-normalized AUC of FEV(1) from baseline (hour 0) to 24 hours (FEV(1)AUC(0-24)). Secondary efficacy end points were time-normalized AUC of FEV(1) from baseline to 12 hours (FEV(1)AUC(0-12)) and from 12 to 24 hours (FEV(1)AUC(12-24)), and FEV(1) at 24 hours after administration of the morning dose (trough FEV(1)). Equivalence of the 2 therapies was assessed by comparing the 90% CI value for the difference of the least squares mean (LSM) to a study-specific predefined equivalence range for change in FEV(1)AUC(0-24) of -0.07 to 0.07 L. RESULTS: A total of 33 subjects were enrolled (20 men, 13 women; mean [SD] age, 64.5 [8.8] years; 15 subjects received ARF15 BID first; 18 received ARF30 QD first). ARF15 BID and ARF30 QD were associated with similar improvements from baseline in (FEV(1)AUC(0-24), LSM 0.15 and 0.16 L, respectively; Delta, 0.01 L; 90% CI, -0.02 to 0.04) and trough FEV(1) (LSM, 0.15 and 0.12 L, respectively; Delta, -0.03 L; 90% CI, -0.09 to 0.03). FEV(1)AUC(0-12) was improved more with ARF30 QD than ARF15 BID (Delta, 0.06 L; 90% CI, 0.04 to 0.09), and FEV(1)AUC(12-24) was improved more with ARF15 BID than ARF30 Qd (Delta, -0.04 L; 90% CI, -0.08 to 0.01). The 90% CI for FEV(1)AUC(0-24) for the treatment difference between ARF15 BID and ARF30 QD was within the prespecified range of -0.07 to 0.07 L, indicating that both treatments resulted in equivalent FEV(1)AUC(0-24) values. CONCLUSIONS: In these subjects with moderate to severe COPD, single-day administrations of ARF15 BID or ARF30 QD were associated with FEV(1) responses over a period of 24 hours that were considered equivalent per the protocol definition employed in the present study. FEV1 improvement over 12 hours was greater for ARF30 QD after the morning dose and for ARF15 BID after the evening dose. ClinicalTrials.gov Identifier: NCT00571428.

Comparison of levalbuterol and racemic albuterol in hospitalized patients with acute asthma or COPD: a 2-week, multicenter, randomized, open-label study.

BACKGROUND: The National Heart, Lung, and Blood Institute guideline recommends that dosing racemic albuterol be administered every 1 to 4 hours for treating patients with asthma or chronic obstructive pulmonary disease (COPD) in the hospital. Previously published preliminary and retrospective studies suggested that levalbuterol can be administered every 8 hours for the treatment of bronchoconstriction in hospitalized patients. However, it is unclear how the different dosing regimens affect the total number of nebulizations (scheduled plus as-needed treatments) and the costs of treatment of bronchoconstriction in a hospital setting. Moreover, it is not clear how the different dosing regimens affect symptom outcomes and health status in hospitalized patients with asthma or COPD. OBJECTIVE: The aim of this study was to evaluate these issues in hospitalized patients with acute asthma or COPD. METHODS: In this prospective, multicenter, randomized, open-label study, hospitalized patients aged > or = 18 years were randomly assigned to receive 14-day treatment with levalbuterol 1.25 mg q6-8h or racemic albuterol 2.5 mg q1-4h, administered per routine hospital practice at each institution. The primary efficacy end point was total number of nebulizations during hospitalization. Pulmonary function, symptom evaluation (subject general well-being score [SGWB], disease symptom assessment [DSA], and beta-mediated adverse effect scores), hospital costs (excluding medication costs) and hospital length of stay (LOS) were also evaluated. RESULTS: In the intent-to-treat population (n = 479; levalbuterol, 241;racemic albuterol, 238), the mean (SE) age was 55.3 (16.9) years, the majority of patients were white (57.8%), and the mean (SE) weight was 80.9 (24.5) kg. Demographic characteristics were similar between the 2 treatment groups, except that there were more females with COPD in the levalbuterol treatment group (63.88%) compared with the racemic albuterol treatment group (45.5%) (P = 0.005). Patients treated with levalbuterol required significantly fewer median total nebulizations (10 vs 12; P = 0.031) and scheduled nebulizations (9 vs 11; P = 0.009) compared with those in the racemic albuterol group. The 2 treatment groups required 0 rescue nebulizations. Mean (SD) forced expiratory volume in 1 second improved from baseline with both levalbuterol and racemic albuterol (0.06 [0.43] and 0.10 [0.37] L, respectively); these improvements were maintained throughout the hospital stay (0.11 [0.48] and 0.16 [0.52] L). DSA and SGWB scores improved significantly from baseline in both treatment groups, and beta-mediated adverse effects mean scores were significantly greater with levalbuterol versus racemic albuterol (P < 0.001). In the levalbuterol and racemic albuterol treatment groups, hospital LOS (70.6 and 65.7 hours, respectively), time to discharge (66.0 and 62.8 hours), and total hospital costs (least squares mean [SE], US $4869.30 [$343.58] and $4899.41 [$343.20]) were similar. CONCLUSIONS: In these hospitalized patients with acute asthma or COPD treated with levalbuterol every 6 to 8 hours or racemic albuterol every 1 to 4 hours, significantly fewer total nebulizations were required with levalbuterol, without an increased need for rescue nebulizations during 14 days of hospitalization. Both treatments were associated with improvements from baseline in symptoms and health status. The costs of treating bronchoconstriction in hospitalized patients were similar between the levalbuterol and racemic albuterol groups.

A comparison of levalbuterol with racemic albuterol in the treatment of acute severe asthma exacerbations in adults.

UNLABELLED: This multicenter, randomized, double-blind trial compared nebulized levalbuterol (Lev) and racemic albuterol (Rac) in the treatment of acute asthma. METHODS: Adults with acute asthma exacerbations (FEV(1) 20%-55% predicted) received prednisone and either Lev (1.25 mg, n = 315) or Rac (2.5 mg, n = 312). Nebulized treatments were administered every 20 minutes in the first hour, then every 40 minutes for 3 additional doses, then as necessary for up to 24 hours. The primary end point was time to meet discharge criteria. Secondary end points included changes in lung function and hospitalization rates. A subset of 160 patients had plasma (S)-albuterol concentrations determined at study entry. RESULTS: Time to meet discharge criteria did not differ between the 2 treatments. FEV(1) improvement was greater following Lev compared with Rac, both after dose 1 and cumulatively over the entire treatment period (dose 1 in intent to treat [ITT] group: Lev 0.50 +/- 0.43 L, Rac 0.43 +/- 0.37 L; P = .02), particularly among the 60% of patients not on recent steroid therapy (dose 1: Lev 0.58 +/- 0.47 L, Rac 0.44 +/- 0.37 L; P < .01), and patients whose entry (S)-albuterol concentrations were in the highest quartile of those measured. A small and similar proportion of Lev-treated (7.0%) and Rac-treated (9.3%) patients required hospitalization (P = .28). Among patients not on steroids, fewer Lev- than Rac-treated patients required admission (3.8% vs 9.3%, P = .03), as was also the case for patients with high plasma (S)-albuterol concentrations. Asthma relapses (5% in 30 days) were lower than in previous reports and did not differ between groups. CONCLUSIONS: This study suggests that early, regular nebulized beta(2)-agonist and systemic corticosteroid therapy may reduce hospitalization and relapse rates in patients with acute severe asthma. Lev was well tolerated and compared favorably with Rac in improving airway function, particularly in those who were not on inhaled or oral corticosteroids and in those who had high plasma (S)-albuterol concentrations at presentation.

Evaluation of the efficacy and safety of levalbuterol in subjects with COPD.

The efficacy and safety of nebulized levalbuterol in adults with chronic obstructive pulmonary disease (COPD) was evaluated in this multicenter, randomized, double-blind, parallel design study. Randomized subjects (n = 209) received levalbuterol (LEV) 0.63 mg or 1.25 mg, racemic albuterol (RAC) 2.5 mg, or placebo (PBO) TID for 6 weeks. Serial spirometry was completed in-clinic after study drug alone (weeks 0, 2, and 6) or in combination with ipratropium bromide 0.5 mg (week 4). The primary endpoint was the averaged FEV1 AUC(0-8 hrs) over weeks 0, 2 and 6 compared with placebo. Other endpoints included rescue medication use, safety parameters, COPD exacerbations, and global evaluations. All active treatments demonstrated improvements in the percent change in FEV1 AUC(0-8 hrs) over the double-blind period and at each visit vs PBO (p < 0.05). Rescue medication use vs. baseline (doses/day) changed over time: PBO +0.38 +/- 3.3; LEV 0.63 mg +0.07 +/- 3.3; LEV 1.25 mg -0.84 +/- 3.8 (p = 0.02 vs. RAC); RAC +0.97 +/- 2.5. The overall rate of adverse events was PBO 56.4%, LEV 0.63 mg 56.6%, LEV 1.25 mg 67.3%, and RAC 65.4%. Protocol-defined COPD exacerbations occurred in all groups (PBO 12.7%, LEV 0.63 mg 11.3%; LEV 1.25 mg 18.4%; RAC 21.2%). Withdrawals due to COPD exacerbations were significantly higher in the RAC group compared with PBO (PBO 0%; LEV 0.63 mg 1.9%; LEV 1.25 mg 4.1%; RAC 9.6% p = 0.01 vs. PBO). In this study, levalbuterol treatment in subjects with COPD was generally well tolerated, produced significant bronchodilation compared with PBO, and improved clinical control of COPD as evidenced by reductions in rescue medication use compared with PBO and/or RAC.

Pairwise comparison of levalbuterol versus racemic albuterol in the treatment of moderate-to-severe asthma.

The object of this study is a post hoc pairwise comparison of levalbuterol versus racemic albuterol for asthma in a multicenter, double-blind, randomized, placebo-controlled clinical trial. The participants are patients > or =12 years of age (n = 362) with FEV1 45-70% of predicted. The patients received nebulized levalbuterol (0.63 or 1.25 mg), racemic albuterol (1.25 or 2.5 mg), or placebo t.i.d. for 4 weeks. The primary endpoints, published in Nelson HS, Bensch G, Pleskow WW, et al. Improved bronchodilation with levalbuterol compared with racemic albuterol in patients with asthma. J Allergy Clin Immunol 102:943-952, 1998, included comparisons of active treatments with placebo and of the combined levalbuterol with the combined racemic albuterol groups for pulmonary function and rescue medication use. After the first dose, levalbuterol 1.25 mg produced a significantly greater increase in the mean peak change in FEV1 compared with both doses of racemic albuterol (p < 0.03) in all patients and in those with more severe asthma. Levalbuterol 1.25 mg also produced a significantly greater (p < 0.05) mean area under the curve (AUC) of the FEV1 versus time plot (AUC FEV1) compared with all other treatments after the first dose in all patients and in the subset with more severe disease, illustrating better overall improvement in FEV1. Active treatment groups demonstrated significant improvements compared with the placebo group (p < 0.05), except for AUC FEV1 in the racemic albuterol 1.25-mg group at week 4. Levalbuterol in the absence of the (S)-isomer provided greater bronchodilation than the same quantity of (R)-albuterol delivered as the racemate. These data suggest that (S)-albuterol may compromise the efficacy of (R)-albuterol.