A prospective, multi-centre, randomised, 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. This evaluation focuses on demonstrating non-inferiority compared to an active comparator and superiority compared to placebo. The clinical relevance lies in establishing the therapeutic benefit of this combination formulation in reducing pharyngeal symptoms through both anti-inflammatory and locally numbing mechanisms.

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.

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 participation. Participants were selected based on clinically diagnosed acute pharyngitis with recent onset of symptoms not exceeding 30 hours prior to enrollment. Eligible individuals were required to have a minimum throat soreness scale score of 7 points and a tonsillopharyngitis assessment value of at least 5 points. Additionally, participants needed to possess a private internet-enabled electronic device such as a mobile phone, smartphone, tablet, or personal computer for use throughout the trial duration. The study did not involve vulnerable populations.

This is a prospective, multi-centre, **randomized**, **double-blind**, **placebo-controlled** **Phase III trial** designed to investigate the efficacy and safety of lozenges containing **benzydamine hydrochloride** and **dichlorobenzyl alcohol** in the symptomatic treatment of patients with **acute pharyngitis**. The trial employs a three-arm design comparing the investigational medicinal product (test product DoriDuo) against an active comparator (Mebocaína Anti-Inflam) and a placebo. All products are administered via **oropharyngeal use** in lozenge form. The primary objective is to demonstrate superiority of the test 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** (AUC) of changes from baseline in the **Throat Soreness Intensity Scale** (TSS) over a two-hour period following the first application on Day 0. This endpoint will assess both superiority against placebo and non-inferiority against the reference product. The trial is categorized as a Category 2 clinical trial, as Phase III trials are classified under this category according to regulatory guidelines.

Participants eligible for inclusion must be aged 18 years or older with clinically diagnosed acute pharyngitis, defined by a **Tonsillopharyngitis Assessment** (TPA) value of at least 5 points. Symptoms must have onset within 30 hours prior to enrollment, and participants must present with a throat soreness scale score of at least 7 points. All participants are required to provide signed informed consent and must have access to a private internet-enabled electronic device (such as a mobile phone, smartphone, tablet, or personal computer) for the entire duration of the trial.

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 September 1, 2025, with an anticipated trial completion date of April 30, 2026. The trial involves multiple study visits including a screening visit to assess eligibility criteria, treatment visits during the 4-day intervention period, and an end-of-study visit to evaluate outcomes and safety parameters.

Participant involvement extends from the initial screening through the completion of the 4-day treatment period and subsequent follow-up assessments. Throughout the study, participants will be monitored for efficacy outcomes and adverse events. Early termination from the study may occur under specific conditions including withdrawal of consent, protocol violations, adverse events requiring discontinuation, or at the discretion of the investigator if continuation poses risks to participant safety or compromises data integrity.

The experimental medication **DoriDuo** is formulated as a **lozenge** containing two active pharmaceutical ingredients: **benzydamine hydrochloride** and **2,4 dichlorobenzyl alcohol**. This product functions as an anti-inflammatory and locally numbing agent. The medication is administered via the **oropharyngeal route**. The maximum daily dose is 25.2 mg, with a maximum total dose of 84 mg over the treatment period. The maximum treatment duration is 4 days. The product is manufactured by MEDICE ARZNEIMITTEL PÜTTER GMBH & CO KG and is classified under ATC code R02AX.

The active **comparator** treatment consists of **Mebocaína Anti-Inflam**, presented as a **compressed lozenge** with a strength of 1.2 mg + 3 mg. This product contains the same active substances as the test medication: benzydamine hydrochloride and 2,4 dichlorobenzyl alcohol. The comparator is administered via oropharyngeal use, with an identical dosing regimen to the experimental medication, including a maximum daily dose of 25.2 mg and a maximum total dose of 84 mg. The maximum treatment period is 4 days. This product holds marketing authorization in Portugal (authorization number 5407382) and is manufactured by STADA LDA. The product has been modified with new packaging specifically for unblinding purposes in the context of this clinical trial.

A **placebo** matching both the test medication and the active comparator is included in the study design. The placebo is administered via the oropharyngeal route following the same dosing schedule as the active treatments, with a maximum daily dose of 25.2 mg and a maximum total dose of 84 mg. The maximum treatment period for the placebo is 4 days. The placebo formulation is designed to be indistinguishable from the active treatments to maintain the double-blind nature of the trial.

Efficacy will be assessed using the primary endpoint defined as the area under curve (AUC) of changes from baseline in the **Throat Soreness Intensity Scale (TSS)** over the time course of 2 hours after first application on Day 0. The primary endpoint evaluation will establish superiority of the investigational medicinal product containing **benzydamine hydrochloride** and **dichlorobenzyl alcohol** in comparison to placebo and non-inferiority in comparison to the active comparator. Patients must present with clinically diagnosed **acute pharyngitis** defined as a Tonsillopharyngitis Assessment (TPA) value of at least 5 points and a baseline throat soreness scale score of at least 7 points. Eligibility criteria specify that symptoms must have a recent onset of 30 hours or less at the time of enrollment.