Randomized, Double-Blind, Multicenter, Phase 3 Study of AG NPP709 Compared With Ivy Leaf Extract in Patients With Acute or Chronic Respiratory Symptoms

Abstract

Background: AG NPP709, formulated with extracts of ivy leaves and Coptis chinensis rhizomes, has antitussive and expectorant effects in preclinical rodent studies. We conducted a clinical trial to establish the efficacy and safety of the product compared with a widely prescribed ivy leaf extract product for the treatment of respiratory symptoms. Methods: In this randomized, double-blind, active-controlled, non-inferiority phase 3 trial, conducted in six hospitals in South Korea, symptomatic patients with acute upper respiratory infections (URIs) or chronic inflammatory bronchitis were randomized to receive either AG NPP709 or ivy leaf extract (control drug) for 5 days (n = 118 in each group). The primary efficacy endpoint was the clinical improvement rate, defined as the percentage of patients with symptoms evaluated as the top two scores on a five-point Likert scale at the end of the study (with a non-inferiority margin set at-15.0%). Results: The overall patient age ranged from 2 to 70 years, with a mean age of 24.9 years in the AG NPP709 group and 21.7 years in the control group. No statistical difference was observed in the clinical improvement rate, with a between-group difference of 4.3% (95% confidence interval: -8.9, 17.5). The symptom clearance rates (AG NPP709 vs. control) for cough and sputum were 43.0% vs. 40.0% (P = 0.655) and 34.6% vs. 25.5% (P = 0.142), respectively. The incidence of adverse events was similar in both groups (11.0% vs. 11.1%, P = 0.982), with most events being grade 1 or 2. Conclusion: AG NPP709 was non-inferior to ivy leaf extract and had an acceptable safety profile. AG NPP709 could be an alternative treatment option for alleviating the symptoms associated with acute URI and chronic bronchitis. Trial Registration: ClinicalTrials.gov Identifier: NCT01151202