Clinical Trial Results:
Phase IV study on the feasibility of a preventative/therapeutic approach with Benzydamine Oromucosal solution in radiation-induced Oral Mucositis (OM) in patients with head and neck cancer (HNC)
Summary
|
|
EudraCT number |
2020-003306-32 |
Trial protocol |
HU PL |
Global end of trial date |
05 Sep 2022
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
30 Sep 2023
|
First version publication date |
30 Sep 2023
|
Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
030(Z)WO19247
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT05055726 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
Angelini Pharma S.p.A.
|
||
Sponsor organisation address |
Via Amelia 70, Rome, Italy, 00181
|
||
Public contact |
Valeria Tellone, Angelini Pharma S.p.A., +39 3452493461, valeria.tellone@angelinipharma.com
|
||
Scientific contact |
Valeria Tellone, Angelini Pharma S.p.A., +39 3452493461, valeria.tellone@angelinipharma.com
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
05 Sep 2022
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
05 Sep 2022
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
05 Sep 2022
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
To assess the effectiveness of benzydamine oromucosal solution (mouthwash) in the prevention/treatment of radiation-induced oral mucositis, in Head and Neck Cancer (HNC) patients, from first day of radiation therapy (RT) through end of RT/Early Treatment Termination visit (ETTV).
|
||
Protection of trial subjects |
The study was conducted in accordance with the Declaration of Helsinki, GCP principals and all applicable regulatory requirement. The clinical trial was initiated when a written and dated positive opinion by all relevant Regulatory Authorities and Ethics Committees of the country involved was obtained.
Before entering the study, a written and signed informed consent form (ICF) and the Declaration of Consent for Processing of Personal Data (DCPPD) were obtained from all patients. Patients were enrolled only if both the ICF and DCPPD were obtained in writing.
|
||
Background therapy |
Not applicable | ||
Evidence for comparator |
Not applicable. This was a Phase IV, multicentre, international, open label, single-group study. The single-group design was chosen since there was no other comparable product with the same mechanism of action as benzydamine in this indication, nor a standard of care recognised at the European level. Moreover, placebo or similar mouthwash solutions were not selected as comparators due to ethical reasons related to the importance of treating the severe symptomatology that characterises RT-induced OM. | ||
Actual start date of recruitment |
06 Dec 2021
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Hungary: 31
|
||
Country: Number of subjects enrolled |
Poland: 58
|
||
Worldwide total number of subjects |
89
|
||
EEA total number of subjects |
89
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
58
|
||
From 65 to 84 years |
31
|
||
85 years and over |
0
|
|
|||||||||||
Recruitment
|
|||||||||||
Recruitment details |
A total of 89 patients diagnosed with stages III or IV NHC, who were candidates and about to start RT, were enrolled into the study and 67 of the patients included in the enrolled population completed the study per protocol from 7 sites (4 sites in Hungary and 3 sites in Poland). | ||||||||||
Pre-assignment
|
|||||||||||
Screening details |
At the screening visit, patients with prior head and neck RT (in the previous 6 months), or patients who received a palliative treatment; patients with distant metastatic disease and/or severe cognitive impairment and/or clinically symptomatic brain metastases and/or patients with significant comorbid conditions; or patients with mucositis due to o | ||||||||||
Period 1
|
|||||||||||
Period 1 title |
OVERALL PERIOD
|
||||||||||
Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
|
||||||||||
Blinding used |
Not blinded | ||||||||||
Blinding implementation details |
This was an open-label study: both the Investigator and patient were aware of the assigned medication.
|
||||||||||
Arms
|
|||||||||||
Arm title
|
Benzydamine HCl 0.15% w/v oromucosal solution | ||||||||||
Arm description |
Treatment of 15 ml (1 tablespoon) of concentrated or diluted (with water) solution was taken at home, 2-3 times a day, but not more than 5 times a day. Patients were asked to wash the mouth and throat for 20-30 seconds, according to the Investigator’s indications and the local product’s SmPC. In Hungary, at the first treatment, the therapy was advised to be started with diluted product (15 ml of water + 15 ml of concentrated solution). After that, gargling could continue with 15 ml (1 tablespoon) of concentrated benzydamine oromucosal solution (mouthwash), generally 2 to 3 times a day, but not more than 5 times a day. In Poland, the solution was to be used 2 to 3 times daily; at a single time, approximately 15 ml of concentrated or diluted benzydamine oromucosal solution (mouthwash) with a small amount of water, wash the mouth and throat for 20 to 30 seconds. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Benzydamine Hydrochloride 0.15%
|
||||||||||
Investigational medicinal product code |
030
|
||||||||||
Other name |
|||||||||||
Pharmaceutical forms |
Oromucosal solution
|
||||||||||
Routes of administration |
Oromucosal use
|
||||||||||
Dosage and administration details |
Treatment of 15 ml (1 tablespoon) of concentrated or diluted (with water) solution was taken at home, 2-3 times a day, but not more than 5 times a day. Patients were asked to wash the mouth and throat for 20-30 seconds, according to the Investigator’s indications and the local product’s SmPC.
|
||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
OVERALL PERIOD
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis sets
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Safety population (SP)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The safety population (SP)was defined as all the patients who took at least one dose of the study medication.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Per Protocol Population
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The per protocol (PP) population was defined as all the patients with a treatment compliance to the study medication ≥ 80% and all NRS evaluations, from first day of RT through 4 weeks, with no major protocol violations
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Benzydamine HCl 0.15% w/v oromucosal solution
|
||
Reporting group description |
Treatment of 15 ml (1 tablespoon) of concentrated or diluted (with water) solution was taken at home, 2-3 times a day, but not more than 5 times a day. Patients were asked to wash the mouth and throat for 20-30 seconds, according to the Investigator’s indications and the local product’s SmPC. In Hungary, at the first treatment, the therapy was advised to be started with diluted product (15 ml of water + 15 ml of concentrated solution). After that, gargling could continue with 15 ml (1 tablespoon) of concentrated benzydamine oromucosal solution (mouthwash), generally 2 to 3 times a day, but not more than 5 times a day. In Poland, the solution was to be used 2 to 3 times daily; at a single time, approximately 15 ml of concentrated or diluted benzydamine oromucosal solution (mouthwash) with a small amount of water, wash the mouth and throat for 20 to 30 seconds. | ||
Subject analysis set title |
Safety population (SP)
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The safety population (SP)was defined as all the patients who took at least one dose of the study medication.
|
||
Subject analysis set title |
Per Protocol Population
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The per protocol (PP) population was defined as all the patients with a treatment compliance to the study medication ≥ 80% and all NRS evaluations, from first day of RT through 4 weeks, with no major protocol violations
|
|
|||||||||||||
End point title |
Percentage of responders [1] | ||||||||||||
End point description |
The number of responders is defined as the number of HNC patients with OM pain intensity <5 (numerical rating scale [NRS]), expressed in percentage, at Visits 0 to 7/ETTV.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Visits from 0 to 7/ETTV.
|
||||||||||||
Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Due to the nature of the single-arm study, all statistical analysis was descriptive. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Number of compliant patients | ||||||||||||
End point description |
The compliance was calculated at the end of the study by the Sponsor using relevant data entered by the Investigator into the eCRF.
A patient was considered compliant to the benzydamine treatment if he/she took ≥80% of the total dose assigned by the Investigator.
The number of compliant patients was expressed in percentage,
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Visits 0 to 7/ETTV.
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
AEs were monitored through the whole study period from the signature of the informed consent form (6th December 2021) to the last visit scheduled in the protocol (5th September 2022).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
In the SP (m-ITT), there were 135 TEAEs reported during the study. Of the 135 TEAEs, two were adverse drug reactions (ADRs) occurred in two separate patients. Nearly all (n=126, 93.3%) of the TEAEs were reported as unlikely to have a correlation with the IMP. There were two that were reported as possibly correlated, and seven were reported as unas
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Adverse Events
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
24 May 2021 |
The present substantial Study Amendment no. 2 of May 24th, 2021 proposes changes relevant to the AJCC staging system version to be used in the trial, prohibited medications and administrative changes. Applicable sections in the Study Protocol were modified in accordance with this amendment.
The changes proposed must be applied to all sites/Countries where the study has been already submitted/approved.
The present Study Amendment is submitted to the applicable Regulatory Authorities and Ethics Committees in accordance with the local regulation. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
Not applicable |