A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Ambroxol Hard-Boiled Lozenges in Patients with Acute Pharyngitis

Abstract

Introduction: The aim of this study was to evaluate the efficacy and safety of a new hard-boiled lozenge formulation containing ambroxol 20 mg versus placebo for the relief of sore throat in patients with acute pharyngitis.

Methods: This was a phase 3, randomized, double-blind, placebo-controlled, parallel-group multicenter trial conducted between June and September 2018 in South Africa. Patients with a diagnosis of acute pharyngitis, onset ≤ 72 h, and sore throat pain of at least moderate intensity were randomized to receive either ambroxol 20 mg or placebo hard-boiled lozenges. The primary efficacy endpoint was the normalized time-weighted sum of pain intensity differences (SPID) from baseline over 3 h following administration of the first lozenge (SPIDnorm,0-3h). Secondary efficacy endpoints included SPID 24 h after the first lozenge intake (SPIDnorm,0-24h) and patient assessment of efficacy at 3 and 24 h after the first lozenge.

Results: Of 422 patients from 11 centers, 390 were randomized to one of the two treatment groups (n = 196, ambroxol; n = 194, placebo) and 388 were analyzed (modified intention-to-treat). The mean ± standard deviation SPIDnorm,0-3h values were -0.386 (0.259) and -0.366 (0.243) in the ambroxol and placebo groups, respectively, and the adjusted mean ± standard error SPIDnorm0-3h difference between ambroxol and placebo was -0.020 (0.025) (p = 0.443). Comparable results between treatment groups were also found for SPIDnorm,0-24h and patient assessment of efficacy at 3 and 24 h after the first lozenge. The incidence of treatment-emergent adverse events (TEAEs) was similar between treatment groups (11.7% for ambroxol versus 9.3% for placebo).

Conclusion: Although marked pain relief was observed over the first 3 h of treatment, superiority of ambroxol 20 mg hard-boiled lozenges versus placebo was not demonstrated in this study.

Trial registration: NCT03583658.

Funding: Sanofi-Aventis Group.

Keywords: Acute pharyngitis; Ambroxol; Local anesthetic; Lozenges; Sore throat.

Figures

Fig. 1

Study design. AESI adverse event of special interest, SAE serious adverse event, V visit

Fig. 2

Patient disposition. mITT modified intention-to-treat

Fig. 3

Change from baseline in throat pain intensity 3 h after the first lozenge (mITT population). CI confidence interval, LS least square, mITT modified intention-to-treat, SD standard deviation

Fig. 4

LS mean (SE) for the time course of PID from pre-dose baseline over the first 24 h (mITT population). LS least square, mITT modified intention-to-treat, PID pain intensity difference, SE standard error

Fig. 5

a Patient assessments of efficacy at 3 and 24 h and b final patient and investigator assessments of efficacy (mITT population). mITT modified intention-to-treat population