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Asthma exacerbations 17% 11% 14% *
p<0.001 versus albuterol and placebo. †
p<0.05 versus albuterol. ‡
p<0.001 versus placebo. Safe usage with maintenance of efficacy for periods up to 1 year has been documented. Effects in Patients With Asthma on Concomitant Inhaled Corticosteroids: Text Continues Below
In 4 clinical trials in adult and adolescent patients with asthma (N = 1,922), the effect of adding salmeterol to inhaled corticosteroid therapy was evaluated. The studies utilized the inhalation aerosol formulation of salmeterol xinafoate for a treatment period of 6 months. They compared the addition of salmeterol therapy to an increase (at least doubling) of the inhaled corticosteroid dose. Two randomized, double-blind, parallel-group clinical trials (N = 997) enrolled patients (ages 18 to 82 years) with persistent asthma who were
previously maintained but not adequately controlled on inhaled corticosteroid therapy. During the 2-week run-in period, all patients were switched to beclomethasone dipropionate 168 mcg twice daily. Patients still not adequately controlled were randomized to either the addition of SEREVENT Inhalation Aerosol 42 mcg twice daily or an increase of beclomethasone dipropionate to 336 mcg twice daily. As compared to the doubled dose of beclomethasone dipropionate, the addition of salmeterol resulted in statistically significantly greater improvements in pulmonary function and asthma symptoms, and statistically significantly greater reduction in supplemental albuterol use. The percent of patients who experienced asthma exacerbations overall was not different between groups (i.e., 16.2% in the salmeterol group versus 17.9% in the higher-dose beclomethasone dipropionate group). Two randomized, double-blind, parallel-group clinical trials (N = 925) enrolled patients (ages 12 to 78 years) with persistent asthma who were previously maintained but not adequately controlled on prior therapy. During the 2-to 4-week run-in period, all patients were switched to fluticasone propionate 88 mcg twice daily. Patients still not adequately controlled were randomized to either the addition of SEREVENT Inhalation Aerosol 42 mcg twice daily or an increase of fluticasone propionate to 220 mcg twice daily. As compared to the increased (2.5 times) dose of fluticasone propionate, the addition of salmeterol resulted in statistically significantly greater improvements in pulmonary function and asthma symptoms, and statistically significantly greater reduction in supplemental albuterol use. Fewer patients receiving salmeterol experienced asthma exacerbations than those receiving the higher dose of fluticasone propionate (8.8% versus 13.8%). Salmeterol Multi-center Asthma Research Trial The Salmeterol Multi-center Asthma Research Trial (SMART) enrolled long-acting beta2-agonist–naive patients with asthma (average age of 39 years, 71% Caucasian, 18% African-American, 8% Hispanic) to assess the safety of salmeterol (SEREVENT Inhalation Aerosol, 42 mcg twice daily over 28 weeks) compared to placebo when added to usual asthma therapy. The primary endpoint was the combined number of respiratory-related deaths or respiratory-related life-threatening experiences (intubation and mechanical ventilation). Other endpoints included combined asthma-related deaths or life-threatening experiences and asthma-related deaths. A planned interim analysis was conducted when approximately half of the intended number of patients had been enrolled (N = 26,353). Due to the low rate of primary events in the study, the findings of the planned interim analysis were not conclusive. The analysis showed no significant difference for the primary endpoint for the total population. However, a higher number of asthma-related deaths or life-threatening experiences (36 vs. 23) and a higher number of asthma-related deaths (13 vs. 4) occurred in the patients treated with salmeterol. Post hoc subgroup analyses revealed no significant increase in respiratory-or asthma-related episodes, including deaths, in Caucasian patients. In African-Americans, the study showed a small, though statistically significantly greater, number of primary events (20 vs. 7), asthma-related deaths or life-threatening experiences (19 vs. 4), and asthma-related deaths (8 vs. 1) in patients taking salmeterol compared to those taking placebo. The numbers of patients from other ethnic groups were too small to draw any conclusions in these populations. Even though SMART did not reach predetermined stopping criteria for the total population, the study was stopped due to the findings in African-American patients and difficulties in enrollment. Exercise-Induced Bronchospasm Protection against exercise-induced bronchospasm (EIB) was examined in 3 controlled studies. Based on median values, patients who received SEREVENT Inhalation Aerosol had consistently less exercise-induced fall in FEV1 than patients who received placebo, and they were protected for a longer period of time than patients who received albuterol (see Table 2). There were, however, some patients who were not protected from EIB after SEREVENT administration and others in whom protection against EIB decreased with continued administration over a period of 4 weeks. Table 2. Exercise-Induced Bronchospasm Mean Percentage Fall in Postexercise FEV1
Treatment Clinical Trials/Time After Dose Placebo
SEREVENT
Inhalation Aerosol
Albuterol
Inhalation Aerosol
Study A: 1st Dose
6 hours
12 hours
37
27
9 *
16 * Study A: 4th Week
6 hours
12 hours
30
24
19
12 Study B:
1 hour
6 hours
12 hours 37
37
34 0 *
5 *†
6 *† 2 *
27
33 Study C:
0.5 hour
2.5 hours
4.5 hours
6.0 hours 43
33
--
-- 16 *
12 *†
12 †
19 † 8 *
30
36
41 *
Statistically superior to placebo (p 0.05). †
Statistically superior to albuterol (p 0.05).
Chronic Obstructive Pulmonary Disease
In 2 large randomized, double-blind studies, SEREVENT Inhalation Aerosol administered twice daily was compared with placebo and ipratropium bromide inhalation aerosol administered 4 times daily in patients with COPD (emphysema and chronic bronchitis), including patients who were reversible ( 12% and 200 mL increase in baseline FEV1 after albuterol treatment) and nonreversible to albuterol.
After a single 42-mcg dose of SEREVENT, significant improvement in pulmonary function (mean FEV1 increase of 12% or more) occurred within 30 minutes, reached a peak within
4 hours on average, and persisted for 12 hours with no loss in effectiveness observed over a 12-week treatment period. Figure 2 displays serial 12-hour measurements of FEV1 from these two 12-week trials for both the first and last treatment days. Figure 2. FEV1 From 2 Large 12-Week Clinical Trials
First Treatment Day * Ipratropium inhalation aerosol (or matching placebo) administered immediately
following hour 6 assessment. Last Treatment Day (Week 12) * Ipratropium inhalation aerosol (or matching placebo) administered immediately following hour 6 assessment.
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