Efficacy and tolerability of ambroxol hydrochloride lozenges in sore throat. Randomised, double-blind, placebo-controlled trials regarding the local anaesthetic properties

Abstract

Two confirmatory clinical trials were performed to investigate the efficacy and tolerability of ambroxol lozenges at doses of 20 mg and 30 mg relative to placebo in relieving the symptoms of sore throat of at least moderately severe intensity in patients suffering from oro-pharyngeal catarrh accompanied by pain on swallowing, feeling of scratchiness, burning and urge to cough.

Objective: Description and comparison of the efficacy and tolerability of lozenges containing 20 mg or 30 mg ambroxol hydrochloride (trans-4-[(2-amino-3,5-dibrom-benzyl)amino]cyclohexano hydrochloride, CAS 18683-91-5) in relieving acute sore throat, in comparison to placebo.

Design: Two similar, multi-centre, prospective, placebo-controlled, randomised, double-blind trials involving three days of treatment with up to 6 lozenges containing 20 or 30 mg ambroxol hydrochloride per day.

Subjects: There were enrolled three-hundred-thirty-one (331, study I) and three-hundred-eighty-three (383, study II) outpatients with acute uncomplicated sore throat of at least moderately severe intensity which is not suspected to be due to bacterial pharyngitis.

Treatments: Double-blind treatment with up to six lozenges per day containing either 20 mg or 30 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 (SPIDnorm) and the patients' evaluation of efficacy and tolerability at the end of each day of the three days treatment.

Results: All treatments led to a reduction of pain intensity; the means (+/- SD) SPIDnorm after the 1st lozenge were 0.53 +/- 0.28 or 0.50 +/- 0.30 or 0.38 +/- 0.28 with 20 mg or 30 mg ambroxol hydrochloride or placebo respectively in study I, and 0.53 +/- 0.30 or 0.60 +/- 0.28 or 0.39 +/- 0.31 in study II; the effect of treatment was statistically significant (p: 0.0002 or p: 0.0033 in study I and p: 0.0005 or p: 0.0001 in study II, respectively, for the comparison of 20 mg or 30 mg ambroxol hydrochloride vs. placebo). The improvement with the active treatments was greater than with placebo (95% confidence interval (CI) estimates of the mean treatment differences vs. placebo were 0.08 to 0.23 or 0.05 to 0.20 for lozenges with 20 mg or 30 mg ambroxol hydrochloride, respectively, in study I, and 0.06 to 0.21 or 0.13 to 0.28 in study II). At the end of each subsequent ambulatory treatment day with up to six 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 treatments investigated were equally well tolerated.

Conclusions: Sucking lozenges containing 20 mg or 30 mg ambroxol hydrochloride has a beneficial pain-relieving effect in patients with acute sore throat, superior to that achieved by sucking a placebo lozenge. While both strengths were equally well tolerated, the higher strength of 30 mg ambroxol hydrochloride did not prove more effective. The findings confirm that the previously discovered local anaesthetic properties of ambroxol hydrochloride do have beneficial clinical implications.