SAN DIEGO — The investigational ultralong-acting inhaled beta2-agonist indacaterol outperformed salmeterol and placebo in a double-blind, randomized clinical trial involving 998 patients with moderate to severe COPD.
Once-daily indacaterol provided sustained bronchodilation throughout the 24-hour day at 12 and 26 weeks that was superior to that of twice-daily salmeterol (Serevent) or placebo.
Moreover, indacaterol-treated patients experienced significantly less dyspnea and need for rescue medication and greater improvement in health status than patients in the other two study arms, Dr. Oliver Kornmann reported at the annual meeting of the American College of Chest Physicians.
The results of INLIGHT 2 (Indacaterol: Efficacy Evaluation Using 150 Mcg Doses With COPD Patients–2) indicate that indacaterol administered via single-dose dry powder inhaler will be a good option for maintenance therapy in patients with moderate-to-severe COPD, according to Dr. Kornmann, a pulmonologist at Mainz (Germany) University Hospital.
The primary study end point was trough forced expiratory volume in 1 second (FEV1) at week 12, which was 60 mL greater with indacaterol than salmeterol and 170 mL more than with placebo. Although these differences were statistically significant, the prespecified definition of clinical significance was a 120 mL difference, he noted.
A key secondary end point was health status as assessed using the St. George's Respiratory Questionnaire. At week 12, the total score in the indacaterol group was improved over baseline by 6.3 points more than placebo and 2.1 points more than salmeterol, which was dosed at 50 mcg twice daily using its proprietary dry powder inhaler. A total of 58% of indacaterol-treated patients achieved at least a 4-point improvement, as did 47% on salmeterol and 39% on placebo.
The odds of achieving a clinically meaningful improvement in health status by this measure with indacaterol therapy were 1.6-fold greater than with salmeterol and 2.4-fold greater than with placebo.
The indacaterol group didn't require rescue albuterol on 60% of days over the course of 26 weeks of follow-up. That was significantly better than the 55% rate with salmeterol and 42% with placebo.
At week 12, 60% of indacaterol-treated patients had achieved a clinically meaningful reduction in dyspnea as defined by at least a 1-point improvement in Transition Dyspnea Index total score, as did 51% of the salmeterol group and 40% on placebo. All these differences were significant.
Serious adverse events occurred in 8.8% of patients on indacaterol, 5.7% on salmeterol, and 7.8% on placebo.
A total of 18% of the indacaterol group experienced worsening of COPD, as did 15% on salmeterol and 19% on placebo, although most exacerbations were mild to moderate.
Of note, prolongation of the QT interval on ECG in excess of 450 milliseconds for men and 470 milliseconds for women occurred in 5.2% of the indacaterol group, 1.8% of the salmeterol group, and 3.3% with placebo.
Bacterial or viral upper respiratory infections occurred in 7.2% of the indacaterol group, 1.8% of salmeterol-treated patients, and 3.6% with placebo.
INLIGHT 2 participants averaged 63 years of age and had a smoking history of 20 pack-years or more.
The study was sponsored by Novartis. Dr. Kornmann is a consultant to the company.
The Food and Drug Administration has deemed the application for U.S. licensure not approvable at present and has requested more data from Novartis.