The safety and efficacy of CKD-497 in patients with acute upper respiratory tract infection and bronchitis symptoms: a multicenter, double-blind, double-dummy, randomized, controlled, phase II clinical trial

Background: Acute upper respiratory tract infection (AURI) together with acute bronchitis is the most common illness worldwide. Botanical medicines used as expectorants and antitussives have proven to be effective while also having excellent safety margins. We aimed at evaluating the efficacy and safety of a new botanical drug, CKD-497, in patients with AURI and acute bronchitis. Methods: In this phase 2 study, 225 patients were enrolled and randomly assigned to one of four treatment groups: placebo (n=55), Synatura (R) (n=49), CKD-497 200 mg (n=68), or CKD-497 300 mg (n=53). The study drugs were administered three times daily over the course of 7 days. Primary endpoint was the change in the bronchitis severity score (BSS) from baseline to day 7. Secondary endpoint was evaluated based on clinical response rates on days 4 and 7. A safety analysis was also performed. Results: Between baseline and day 7, the mean BSS scores decreased significantly in each group (P<0.001): -4.04 +/- 1.85, -4.31 +/- 1.47, -4.09 +/- 1.48, and -4.28 +/- 1.69. However, neither the CKD-497 nor Synatura (R) group showed any significant effect on the difference in BSS change (P=0.75). The rate of clinical response was higher in the CKD-497 300 mg group as compared to the placebo only on day 4 (36% vs. 18%; P<0.05) and those having more severe bronchitis (phlegm score >= 3) showed a significant reduction of total BSS in the Synatura (R) and CKD-497 groups (P=0.042). No significant adverse events were observed in either of the CKD-497 groups. Conclusions: CKD-497 and even the positive control drug had no significant effect on BSS change in this phase 2 clinical trial. However, CKD-497 300 mg had a mild but significant clinical improvement in early bronchitis patients with more severe phlegm. Considering both efficacy and safety, a future study using 300 mg of CKD-497 with a shorter-term endpoint is warranted in patients with more severe bronchitis symptoms.