Clinical Trial Results:
Phase IV study comparing the efficacy and safety of Benzydamine hydrochloride 0,3% oromucosal spray and Benzydamine hydrochloride 3 mg lozenges in patients with acute sore throat.
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Summary
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EudraCT number |
2019-003257-29 |
Trial protocol |
HU PL |
Global end of trial date |
30 Jun 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
13 Jul 2022
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First version publication date |
13 Jul 2022
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
030(Z)WO19176
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04941976 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Angelini Pharma S.p.A
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Sponsor organisation address |
Via Amelia 70, Roma, Italy, 00181
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Public contact |
Study Manager, Angelini S.p.A., 39 0691045567, carmelina.valerio@angelinipharma.com
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Scientific contact |
Study Manager, Angelini S.p.A., 39 0691045567, carmelina.valerio@angelinipharma.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
30 Jun 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
30 Jun 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Jun 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The main objective of this study was to assess the pain relief in patients with acute sore throat, at 2 minutes (T2 min), after a single dose administration of benzydamine hydrochloride 0,3% oromucosal spray or benzydamine hydrochloride 3 mg lozenges. Moreover, safety and efficacy evaluations up to a 7-days treatment period, were performed.
The study was initiated at 16 sites and enrolment was performed at 12 sites located among Poland (4 sites), Hungary (1 site) and Russia (7 sites).
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Protection of trial subjects |
This trial was conducted in accordance with the study protocol, GCPs, Declaration of Helsinki (including up-to-date versions) and applicable regulatory requirements and started after the Institutional Review Board/Ethics Committee written approval and in absence of any non-acceptance grounds by the Competent Authority.
Before entering the study, patients were fully informed about the purposes of the research, possible benefits, any potential personal reasonable risk or discomfort, the expected duration of their participation in the trial. The patient was also informed by the Investigator of all aspects related to his/her personal data processing, as well as his/her rights on this matter.
Before recruitment, a copy of the ICF (including the information sheet) and DCPPD (including the Information on Processing of Personal Data) was given to the patient. The patient entered the study by signing the ICF and DCPPD
A temporary suspension of the study was performed on April 3rd, 2020 in Hungary according to the EMA Guidance for the management of COVID-19 and Hungarian RA recommendations. Sponsor and its delegate have promptly informed all Investigators conducting the trial about the suspension of clinical phase, which was re-started on June 24th, 2020 after official communication to the RA.
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Background therapy |
Not applicable | ||
Evidence for comparator |
The benzydamine lozenges formulations was used as a comparator drug with the aim to better understand if a difference exists in terms of onset of pain relief between spray and lozenges, with the final goal to provide patients with two different treatment formats to choose from, according to their own preferences: some patients, for example, could prefer the demulcent effect of a lozenge and other the convenience of a spray. | ||
Actual start date of recruitment |
13 Aug 2020
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Russian Federation: 256
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Country: Number of subjects enrolled |
Poland: 78
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Country: Number of subjects enrolled |
Hungary: 29
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Worldwide total number of subjects |
363
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EEA total number of subjects |
107
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
342
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From 65 to 84 years |
21
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 363 male and female patients (aged 18 – 75 years, limits included) were randomized to benzydamine hydrochloride 0.3% spray or lozenges 3 mg mint flavour. Patients enrolment was competitive among clinical sites. | |||||||||
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Pre-assignment
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Screening details |
At Visit 0 (Screening/Baseline), the Investigator assigned the Screening number to each potentially eligible patient, following a sequential order, after the relevant ICF was signed and dated. | |||||||||
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Period 1
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Period 1 title |
PERIOD 1 (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||
Blinding implementation details |
The two different pharmaceutical forms of the investigated drugs did not permit to mask the two treatments, for this reason an open label design has been selected.
After randomization, both the Investigator and patient were aware of the assigned medication.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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BNZ hydrochloride 0,3% spray | |||||||||
Arm description |
One administration (2-4 nebulizations) up to 6 times a day. Each nebulization contains 0.17 ml of the solution; a total of 4 nebulizations corresponds to 2.04 mg of benzydamine | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Benzydamine hydrochloride spray oromucosal solution
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Investigational medicinal product code |
030
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Other name |
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Pharmaceutical forms |
Oromucosal solution
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Routes of administration |
Oromucosal use
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Dosage and administration details |
Single application of 0.3% benzydamine hydrochloride spray oromucosal solution, corresponding to 2.04 mg of benzydamine, for a total of 4 nebulizations;
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Arm title
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BNZ hydrochloride 3 mg LOZENGE (mint flavour) | |||||||||
Arm description |
One lozenge corresponding to 2.68 mg of benzydamine 3 times a day (Poland and Russia); One lozenge corresponding to 2.68 mg of benzydamine 3-4 times a day (Hungary); | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Benzydamine hydrochloride lozenge (mint flavour)
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Investigational medicinal product code |
030
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Other name |
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Pharmaceutical forms |
Lozenge
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Routes of administration |
Oral use
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Dosage and administration details |
Single 3 mg lozenge of benzydamine hydrochloride (mint flavour), corresponding to 2.68 mg of benzydamine.
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Baseline characteristics reporting groups
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Reporting group title |
PERIOD 1 (overall period)
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Per Protocol (PP) population
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All randomized patients who took at least the first dose of the study medication and having all Day 0 (up to 120 minutes) STRRS evaluations, with no major protocol violations.
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Subject analysis set title |
Modified Intention-to Treat (m-IIT) population
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Subject analysis set type |
Modified intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All randomized patients who took at least one dose of the study medication and performed the 2 minutes post-treatment efficacy assessment with STRRS.
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Subject analysis set title |
Safety population
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All patients who took at least one dose of the study medication
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End points reporting groups
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Reporting group title |
BNZ hydrochloride 0,3% spray
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Reporting group description |
One administration (2-4 nebulizations) up to 6 times a day. Each nebulization contains 0.17 ml of the solution; a total of 4 nebulizations corresponds to 2.04 mg of benzydamine | ||
Reporting group title |
BNZ hydrochloride 3 mg LOZENGE (mint flavour)
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Reporting group description |
One lozenge corresponding to 2.68 mg of benzydamine 3 times a day (Poland and Russia); One lozenge corresponding to 2.68 mg of benzydamine 3-4 times a day (Hungary); | ||
Subject analysis set title |
Per Protocol (PP) population
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
All randomized patients who took at least the first dose of the study medication and having all Day 0 (up to 120 minutes) STRRS evaluations, with no major protocol violations.
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Subject analysis set title |
Modified Intention-to Treat (m-IIT) population
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
All randomized patients who took at least one dose of the study medication and performed the 2 minutes post-treatment efficacy assessment with STRRS.
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Subject analysis set title |
Safety population
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All patients who took at least one dose of the study medication
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End point title |
STRRS at 2 minutes | ||||||||||||
End point description |
Percentage of responders defined as patients who reported at least a “slight relief” (STRRS score ≥1) at 2 minutes after the first application of benzydamine hydrochloride 0.3% spray or benzydamine hydrochloride 3mg lozenges
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End point type |
Primary
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End point timeframe |
2 minutes after post study drug application
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| Notes [1] - Percentage of responders [2] - Percentage of responders |
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Statistical analysis title |
95% Confidence Interval | ||||||||||||
Statistical analysis description |
Lower limit of the two-sided 95% Confidence Interval (95% CI) of the difference between the study drugs in the responder rates
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Comparison groups |
BNZ hydrochloride 0,3% spray v BNZ hydrochloride 3 mg LOZENGE (mint flavour)
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Number of subjects included in analysis |
363
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
Method |
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Parameter type |
95% CI | ||||||||||||
Point estimate |
1.05
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Confidence interval |
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95% | ||||||||||||
sides |
2-sided
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lower limit |
-4.78 | ||||||||||||
upper limit |
6.88 | ||||||||||||
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End point title |
STRRS at 1 minute | ||||||||||||
End point description |
A “slight relief” in STRRS (score ≥ 1) will be considered as the first perceived pain relief;
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End point type |
Secondary
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End point timeframe |
At 1 minute after a single dose administration.
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Statistical analysis title |
Cochran-Mantel-Haenszel test | ||||||||||||
Comparison groups |
BNZ hydrochloride 0,3% spray v BNZ hydrochloride 3 mg LOZENGE (mint flavour)
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Number of subjects included in analysis |
363
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.0041 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Confidence interval |
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End point title |
STRRS at 5 minutes | ||||||||||||
End point description |
Percentage of patients recording a meaningful sore throat relief assessed at T5 min after a single dose administration. A “meaningful sore throat relief” was considered as a score ≥ 3 (moderate relief) in the STRRS;
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End point type |
Secondary
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End point timeframe |
At 5 minutes
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Statistical analysis title |
Cochran-Mantel-Haenszel test | ||||||||||||
Comparison groups |
BNZ hydrochloride 0,3% spray v BNZ hydrochloride 3 mg LOZENGE (mint flavour)
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Number of subjects included in analysis |
363
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.0058 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Confidence interval |
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End point title |
STRRS at 10 minutes | ||||||||||||
End point description |
Percentage of patients recording a meaningful sore throat relief assessed at T10 min after a single dose administration. A “meaningful sore throat relief” was considered as a score ≥ 3 (moderate relief) in the STRRS.
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End point type |
Secondary
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End point timeframe |
At 10 minutes
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Statistical analysis title |
Cochran-Mantel-Haenszel test | ||||||||||||
Comparison groups |
BNZ hydrochloride 0,3% spray v BNZ hydrochloride 3 mg LOZENGE (mint flavour)
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Number of subjects included in analysis |
363
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.0866 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Confidence interval |
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End point title |
STRRS at 15 minutes | ||||||||||||
End point description |
Percentage of patients recording a meaningful sore throat relief assessed at T15 min after a single dose administration. A “meaningful sore throat relief” was considered as a score ≥ 3 (moderate relief) in the STRRS.
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End point type |
Secondary
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End point timeframe |
At 15 minutes
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Statistical analysis title |
Cochran-Mantel-Haenszel test | ||||||||||||
Comparison groups |
BNZ hydrochloride 0,3% spray v BNZ hydrochloride 3 mg LOZENGE (mint flavour)
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Number of subjects included in analysis |
363
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.0634 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Confidence interval |
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End point title |
STRRS at 30 minutes | ||||||||||||
End point description |
Percentage of patients recording a meaningful sore throat relief assessed at T30 minutes after a single dose administration. A “meaningful sore throat relief” was considered as a score ≥ 3 (moderate relief) in the STRRS.
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End point type |
Secondary
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End point timeframe |
At 30 minutes
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Statistical analysis title |
Cochran-Mantel-Haenszel test | ||||||||||||
Comparison groups |
BNZ hydrochloride 0,3% spray v BNZ hydrochloride 3 mg LOZENGE (mint flavour)
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Number of subjects included in analysis |
363
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.0035 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Confidence interval |
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End point title |
STRRS at 60 minutes | ||||||||||||
End point description |
Percentage of patients recording a meaningful sore throat relief assessed at T60 minutes after a single dose administration. A “meaningful sore throat relief” was considered as a score ≥ 3 (moderate relief) in the STRRS.
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End point type |
Secondary
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End point timeframe |
At 60 minutes
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Statistical analysis title |
Cochran-Mantel-Haenszel test | ||||||||||||
Comparison groups |
BNZ hydrochloride 0,3% spray v BNZ hydrochloride 3 mg LOZENGE (mint flavour)
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Number of subjects included in analysis |
363
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.0327 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Confidence interval |
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End point title |
STRRS at 120 minutes | ||||||||||||
End point description |
Percentage of patients recording a meaningful sore throat relief assessed at T120 minutes after a single dose administration. A “meaningful sore throat relief” was considered as a score ≥ 3 (moderate relief) in the STRRS.
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End point type |
Secondary
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End point timeframe |
At 120 minutes
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Statistical analysis title |
Cochran-Mantel-Haenszel test | ||||||||||||
Comparison groups |
BNZ hydrochloride 0,3% spray v BNZ hydrochloride 3 mg LOZENGE (mint flavour)
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Number of subjects included in analysis |
363
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.216 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
The time frame for reporting adverse events is from Informed consent signature up to the last visit (visit 2 or ETV).
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Adverse event reporting additional description |
Treatment Emergent Adverse Events (TEAEs):any event started on or after the first study medication administration and was not a pre-existing medical condition.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.1
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Reporting groups
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Reporting group title |
BNZ hydrocloride 0.3% spray
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Reporting group description |
Patients randomized to the spray applied 4 nebulizations (1 dose) of benzydamine hydrochloride spray oromucosal solution, corresponding to 2.04 mg of benzydamine on the inflamed area. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
BNZ hydrocloride 3 mg LOZENGE (mint flavour)
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Reporting group description |
Patients who took one 3 mg lozenge of benzydamine hydrochloride mint flavour, corresponding to 2.68 mg of benzydamine | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 1% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||||||
Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
| None reported | |||||||
