Clinical Trial Results:
A multi-centre, randomized, placebo-controlled, double-blind, parallel-group study investigating safety and efficacy of a sore throat lozenge in the symptomatic treatment of patients with acute pharyngitis.
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Summary
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EudraCT number |
2016-003962-24 |
Trial protocol |
DE |
Global end of trial date |
03 Jul 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
17 Sep 2020
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First version publication date |
17 Sep 2020
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Other versions |
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Summary report(s) |
DoriPha Results 6632-9050-04 |
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 |
6632-9050-04
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Medice Arzneimitel Pütter GmbH & Co. KG
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Sponsor organisation address |
Kuhloweg 37, Iserlohn, Germany, 58638
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Public contact |
Medizinische Abteilung, Medice Arzneimitel Pütter GmbH & Co. KG , 0049 023719370, dori@medice.de
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Scientific contact |
Medizinische Abteilung, Medice Arzneimitel Pütter GmbH & Co. KG , 0049 023719370, dori@medice.de
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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 |
15 Nov 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
03 Jul 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
03 Jul 2017
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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 |
Safety and efficacy of Dorithricin® Halstabletten Classic (lozenges)
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Protection of trial subjects |
Each study patient could be withdrawn from the study at any time. There was no detriment for the patient due to the discontinuation. The investigator should have tried to find out the reason for withdrawal, if possible. However, the patient was not obliged to disclose the reason for the withdrawal.
The investigator could exclude patients from the study for one of the following reasons:
- Occurrence of inacceptable adverse events (definition: inacceptable according to patient's or investigator´s assessment)
- Change in health conditions that put a patient at risk
- Investigator considered it medically necessary
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
19 Jan 2017
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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 |
Germany: 321
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Worldwide total number of subjects |
321
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EEA total number of subjects |
321
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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) |
313
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From 65 to 84 years |
8
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Overall, 328 adult male or female patients with acute pharyngitis were screened at 17 investigational study sites (centres) in Germany. Seven out of 328 patients (2.1%) failed to meet the inclusion- and/or exclusion criteria (screening failures), and 321 patients (97.9%) were randomized to one of the two treatment groups. | |||||||||||||||||||||||||||
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Period 1
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Period 1 title |
overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | |||||||||||||||||||||||||||
Blinding implementation details |
The blinding of the study medication is achieved through the following measures:
- active medication and placebo are identically in appearance, shape, size and taste
- the study medication contains the same batch number and expiry date (traceability is ensured by the randomization list) Patients will be allocated to the respective treatment arm based on the random number on the blisters and the secondary package.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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triple active combination | |||||||||||||||||||||||||||
Arm description |
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Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
Dorithricin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Lozenge
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Routes of administration |
Oromucosal use
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Dosage and administration details |
The initial dose (2 lozenges simultaneously) was administered at the study site. Patients were instructed to administer at home 1 lozenge at intervals of 2 hours (±15 minutes) up to a maximum of 8 lozenges per day. The number of lozenges taken on Day 0 or Day 3 could be less than 8, depending on the clock time of Visit 1 (Day 0) and Visit 2 (Day 3).
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Arm title
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Placebo | |||||||||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo lozenge
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Lozenge
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Routes of administration |
Oromucosal use
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Dosage and administration details |
The initial dose (2 lozenges simultaneously) was administered at the study site. Patients were instructed to administer at home 1 lozenge at intervals of 2 hours (±15 minutes) up to a maximum of 8 lozenges per day. The number of lozenges taken on Day 0 or Day 3 could be less than 8, depending on the clock time of Visit 1 (Day 0) and Visit 2 (Day 3).
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Baseline characteristics reporting groups
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Reporting group title |
triple active combination
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Reporting group description |
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Reporting group title |
Placebo
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
triple active combination
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Reporting group description |
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Reporting group title |
Placebo
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Reporting group description |
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Subject analysis set title |
FAS
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The FAS for the efficacy analyses includes all randomized patients with at least one documented application of trial medication (Dorithricin® or placebo) and post-baseline efficacy
data for the primary endpoint (Visit 2). In the case an emergency envelope was opened during the study, this “unblinded” patient would have been excluded from the FAS.
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Subject analysis set title |
PP
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The PP for the efficacy analyses includes all FAS patients who have no protocol deviations that might have a relevant influence on the assessment of the primary endpoint (major protocol violation). This means, that patients who prematurely discontinued the study due to AE, lack of efficacy or any other reason that could have been associated with lack of efficacy or safety, were also included in the PP if major protocol violation did not occur.
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Subject analysis set title |
SES
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The safety population described by the SES includes all randomized patients with at least one documented application of study medication (Dorithricin® or placebo) and any post-baseline safety data. The SES was analysed mainly with respect to drug safety.
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End point title |
percentage of total responders 72 hours p.i.d. (full analysis set) | |||||||||
End point description |
Total Responders: complete resolution of throat pain + difficulty in swallowing 72 hours p.i.d.
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End point type |
Primary
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End point timeframe |
72 hours post initial dose
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Statistical analysis title |
analysis of total responder | |||||||||
Comparison groups |
triple active combination v Placebo
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Number of subjects included in analysis |
316
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.0022 | |||||||||
Method |
generalized estimation equation | |||||||||
Parameter type |
difference in Total Responder rates | |||||||||
Point estimate |
17.4
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
5.8 | |||||||||
upper limit |
29.7 | |||||||||
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End point title |
percentage of early responders 48 hours p.i.d. (full analysis set) | |||||||||
End point description |
Early Responders (complete resolution of throat pain + difficulty in swallowing 48 hours p.i.d.) and remaining symptom-free
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End point type |
Secondary
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End point timeframe |
48 hours p.i.d.
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Statistical analysis title |
analysis of early responder | |||||||||
Comparison groups |
triple active combination v Placebo
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Number of subjects included in analysis |
316
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.0115 | |||||||||
Method |
generalized estimation equation | |||||||||
Parameter type |
difference in early responder rates | |||||||||
Point estimate |
7.9
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
1.1 | |||||||||
upper limit |
22.5 | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
During the 3 days of investigational treatment with Dorithricin® and placebo (Visit 1 – Visit 2).
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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 |
19.1
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Reporting groups
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Reporting group title |
Dorithricin
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Reporting group description |
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Reporting group title |
Placebo
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Reporting group description |
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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? Yes | |||
Date |
Amendment |
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04 Apr 2017 |
Inclusion criterion “pain intensity of ≥8 on a 11-point numeric rating scale” was changed to “pain intensity of ≥7 on a 11-point numeric rating scale”. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
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 | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/30329199 |
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