A prospective, randomised, multi-centre, double-blind, placebo-controlled Phase III trial to investigate the efficacy and safety of lozenges with benzydamine hydrochloride and dichlorobenzyl alcohol in the symptomatic treatment of patients suffering from acute pharyngitis

The primary objective is to investigate the efficacy of lozenges containing benzydamine hydrochloride and dichlorobenzyl alcohol in the symptomatic treatment of patients with acute pharyngitis. The evaluation aims to demonstrate non-inferiority compared to an active comparator and superiority compared to placebo. This objective addresses the clinical need for effective symptomatic relief in acute pharyngitis, a common condition characterized by throat inflammation and pain.

The secondary objective is to investigate the safety and tolerability of lozenges with benzydamine hydrochloride and dichlorobenzyl alcohol compared to placebo and an active comparator in the symptomatic treatment of patients suffering from acute pharyngitis. This assessment is clinically relevant for establishing the overall benefit-risk profile of the investigational treatment in this patient population.

The sponsor did not provide information regarding the total number of participants enrolled in this clinical trial. The study population consisted of **adult patients** aged **18 years and older** diagnosed with **acute pharyngitis**. Both **male** and **female** subjects were eligible for inclusion. Participants were required to have a clinically confirmed diagnosis with recent symptom onset of no more than 30 hours and a minimum throat soreness severity score. The trial enrolled **patients** presenting with acute symptoms rather than individuals from the general healthy population. Access to a private internet-enabled electronic device for the trial duration was a practical requirement for participation. No vulnerable populations were included in this study.

This is a prospective, randomized, multi-centre, double-blind, placebo-controlled Phase III clinical trial designed to investigate the efficacy and safety of lozenges containing **benzydamine hydrochloride** and **2,4 dichlorobenzyl alcohol** in the symptomatic treatment of patients with **acute pharyngitis**. The trial employs a three-arm design comparing the investigational medicinal product against an active comparator and placebo. The study is classified as a category 2 trial and utilizes **oropharyngeal** administration of the study medication. The trial design incorporates randomization procedures to ensure unbiased allocation of participants across treatment groups, with blinding maintained throughout the study period to minimize bias in assessment and reporting of outcomes.

The primary objective is to demonstrate superiority of the investigational product compared to placebo and non-inferiority compared to the active comparator in terms of symptomatic relief. The **primary endpoint** is defined as the area under curve of changes from baseline in Throat Soreness Intensity Scale over a two-hour period following the first application on Day 0. Principal inclusion criteria require participants to be at least 18 years of age with clinically diagnosed acute pharyngitis defined as a Tonsillopharyngitis Assessment value of at least 5 points, recent onset of symptoms within 30 hours, and a **Throat Soreness Scale** score of at least 7 points. Participants must provide signed informed consent and possess a private internet-enabled electronic device for use throughout the trial duration.

The maximum daily dose for all treatment arms is **25.2 mg**, with a maximum total dose of **84 mg** administered over a treatment period of 4 days. The estimated recruitment start date is November 2025, with an anticipated trial completion date of May 2026. Participants will be required to use their personal electronic devices to record study-related data throughout their involvement in the trial. The study protocol includes provisions for early termination of individual participants under specific conditions, though the exact circumstances are determined by the investigator based on safety considerations and protocol adherence.

The experimental medication **DoriDuo** is formulated as a **lozenge** containing two active substances: **benzydamine hydrochloride** and **2,4 dichlorobenzyl alcohol**. The product exhibits anti-inflammatory and locally numbing properties. The pharmaceutical form is administered via **oropharyngeal use**. The maximum daily dose is **25.2 mg**, with a maximum total dose of **84 mg** over the treatment period. The maximum treatment period is **4 weeks**. All active substances in this formulation are of chemical origin. This product is not a paediatric formulation and is not designated as an orphan drug.

The comparator treatment **Mebocaína Anti-Inflam** is presented as **compressed lozenges** containing **1.2 mg** and **3 mg** of the same active substances: benzydamine hydrochloride and 2,4 dichlorobenzyl alcohol. The route of administration is oropharyngeal use. The maximum daily dose amount is 25.2 mg, with a maximum total dose of 84 mg administered over a maximum treatment period of 4 weeks. The product has undergone new packaging for unblinding purposes. This comparator is manufactured by STADA LDA and holds marketing authorization in Portugal with authorization number 5407382.

A **placebo** matching both the test and comparator products is included in the trial design. The placebo is administered via oropharyngeal use with the same dosing schedule as the active treatments: a maximum daily dose of 25.2 mg and a maximum total dose of 84 mg over a maximum treatment period of 4 weeks. The placebo formulation does not contain active pharmaceutical ingredients.

Efficacy will be assessed using the **Throat Soreness Intensity Scale (TSS)** as the primary endpoint parameter. The primary efficacy evaluation is defined as the area under the curve (AUC) of changes from baseline in TSS over a 2-hour time course following the first application on Day 0. This assessment will enable determination of superiority of the investigational medicinal product containing **benzydamine hydrochloride** and **dichlorobenzyl alcohol** compared to placebo, as well as non-inferiority compared to the active comparator. The primary endpoint focuses on the symptomatic treatment of **acute pharyngitis**, with measurements collected during the initial treatment period to evaluate the immediate therapeutic effect on throat soreness intensity.