Local anaesthetic properties of ambroxol hydrochloride lozenges in view of sore throat clinical proof of concept

Acute oro-pharyngeal catarrh is characterised by mild to severe sore throat, such as pain on swallowing, feeling of scratchiness, burning and urge to cough. The present study was conducted to explore whether the test compound is going to show clinical relevance and is a suitable medication for the relief of these symptoms. Objective: Description and comparison of the efficacy and tolerability of lozenges containing 20 mg ambroxol hydrochloride (trans-4-[(2-amino-3,5-dibrombenzyl)amino]cyclohexano hydrochloride, CAS 18683-91-5) in relieving acute sore throat, in comparison to placebo. Design: Multi-centre, prospective, placebo-controlled, randomised, double-blind trial involving two days of treatment with up to 6 lozenges containing 20 mg ambroxol hydrochloride per day. Subjects: Two-hundred-eighteen (218) patients were enrolled (97 males, 121 females, average age: 39.4 ± 15 years, range: 17-81 years); 215 were treated: 107 with 20 mg ambroxol and 108 with placebo; 26 discontinued prematurely (13 in each treatment group). 208 patients constituted the intent-to-treat (ITT) dataset (105 and 103 for treatment with ambroxol and placebo, respectively); 196 patients constituted the perprotocol (PP) dataset (97 and 99, respectively); all treated patients were part of the dataset for safety analysis. Treatments: Double-blind treatment with up to 6 lozenges per day containing 20 mg ambroxol hydrochloride or placebo (a lozenge with a distinct minty flavour). Main outcome measures: The time-weighted average pain relief over the first 3 h after the first lozenge as a ratio of the baseline pain intensity of sore throat (SPID norm ) and the patients' evaluation of efficacy and tolerability at the end of each day of treatment. Results: Both treatments led to a reduction of pain intensity; the mean (± SD) SPID norm after the 1st lozenge were 0.39 ± 0.27 and 0.28 ± 0.25 for 20 mg ambroxol hydrochloride and placebo, respectively; the treatment effect of ambroxol was statistically significantly superior compared to placebo (p: 0.0029; 95 % confidence interval estimate of the mean treatment difference for ambroxol minus placebo: 0.04 to 0.18). At the end of each subsequent ambulatory treatment day with up to 6 lozenges per day, a statistically significantly higher proportion of patients scored a higher level of efficacy for the active treatments with ambroxol hydrochloride compared to placebo. The investigational treatments were equally well tolerated. Conclusions: Sucking lozenges containing 20 mg ambroxol hydrochloride has a beneficial pain relieving effect in patients with acute sore throat, superior to that which otherwise can be achieved by sucking a placebo lozenge. This finding confirms that the preclinical local anaesthetic properties of ambroxol hydrochloride may have beneficial clinical implications.