Clinical Trial Results:
Randomized, double-blind, cross-over efficacy and safety study based on the pharmacodynamic model of topical use of the new combination gel containing diphenhydramine hydrochloride 20 mg/g and lidocaine hydrochloride 10 mg/g versus placebo in the treatment of local skin inflammatory and allergic lesions induced by the provocative test with histamine in healthy subjects.
Summary
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EudraCT number |
2018-004502-26 |
Trial protocol |
PL |
Global end of trial date |
26 Aug 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
16 May 2021
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First version publication date |
16 May 2021
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Other versions |
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 |
DL/HL/09/18
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Przedsiębiorstwo Produkcji Farmaceutycznej (P.P.F.) HASCO-LEK S.A.
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Sponsor organisation address |
Żmigrodzka 242E , Wrocław, Poland, 51-131
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Public contact |
Clinical Trial Information Desk, Przedsiębiorstwo Produkcji Farmaceutycznej (P.P.F.) HASCO-LEK S.A., 48 71327 18 61 261, a.puchala@hasco-lek.pl
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Scientific contact |
Clinical Trial Information Desk, Przedsiębiorstwo Produkcji Farmaceutycznej (P.P.F.) HASCO-LEK S.A., 48 71327 18 61 261, a.puchala@hasco-lek.pl
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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 |
26 Aug 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
26 Aug 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
26 Aug 2019
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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 |
To evaluate efficacy and safety of the new combination topical gel containing diphenhydramine hydrochloride 20 mg/g and lidocaine hydrochloride 10 mg/g versus placebo in the treatment of local skin inflammatory and allergic lesions induced in the provocative test with histamine (skin prick test)
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Protection of trial subjects |
Observation per subject from enrolment to the study (screening examination) until the end-of study evaluation. Medical surveillance at site. Safety procedures: physical examination, vital signs, laboratory tests, safety monitoring (AEs).
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Background therapy |
Not applicable | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 Aug 2019
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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 |
Poland: 44
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Worldwide total number of subjects |
44
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EEA total number of subjects |
44
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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) |
44
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||
Pre-assignment
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Screening details |
The screening procedures applied. Volunteers who signed informed consent form (ICF), met all inclusion criteria and none of the exclusion criteria were enrolled into the study. | ||||||||||||||||||
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 | ||||||||||||||||||
Blinding implementation details |
The double-blind design was used for the study. The aim of this was to decrease the risk of systematic error. Especially, this ensured more results reliability at the point of asking subjects about symptoms intensity as well as during taking measurements by the Investigator. Blinding could have been only broken in emergency situations for reasons of subjects safety. IPs were packed and labelled in a way that prevented unblinding.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Sequence TP - Test product then Placebo | ||||||||||||||||||
Arm description |
- | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Diphenhydramine hydrochloride and lidocaine hydrochloride, 20 mg/g and 10 mg/g, gel
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Gel
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Routes of administration |
Topical use
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Dosage and administration details |
Dose: 0.16 mL of a product - single application
Mode of administration: Topical administration
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Investigational medicinal product name |
Placebo, gel
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Gel
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Routes of administration |
Topical use
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Dosage and administration details |
Dose: 0.16 mL of a product - single application
Mode of administration: Topical administration
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Arm title
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Sequence PT - Placebo than Test product | ||||||||||||||||||
Arm description |
- | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Placebo, gel
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Gel
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Routes of administration |
Topical use
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Dosage and administration details |
Dose: 0.16 mL of a product - single application
Mode of administration: Topical administration
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Investigational medicinal product name |
Diphenhydramine hydrochloride and lidocaine hydrochloride, 20 mg/g and 10 mg/g, gel
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Gel
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Routes of administration |
Topical use
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Dosage and administration details |
Dose: 0.16 mL of a product - single application
Mode of administration: Topical administration
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Test product
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Diphenhydramine hydrochloride and lidocaine hydrochloride, 20 mg/g and 10 mg/g, gel
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Subject analysis set title |
Placebo
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Placebo, gel
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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 subjects exposed to the study products were the part of the safety analysis
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End points reporting groups
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Reporting group title |
Sequence TP - Test product then Placebo
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Reporting group description |
- | ||
Reporting group title |
Sequence PT - Placebo than Test product
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Reporting group description |
- | ||
Subject analysis set title |
Test product
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Diphenhydramine hydrochloride and lidocaine hydrochloride, 20 mg/g and 10 mg/g, gel
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Subject analysis set title |
Placebo
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Placebo, gel
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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 subjects exposed to the study products were the part of the safety analysis
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End point title |
Difference in itching AUC | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Evaluation of itch using VAS scale was performed after histamine administration (time “0”) and at: 2, 4, 6, 8, 10, 15, 20, 30, 60 and 90 minutes after test product/placebo administration
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Statistical analysis title |
Comparison of itching AUC between products | ||||||||||||
Statistical analysis description |
Wilcoxon test for paired data
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Comparison groups |
Test product v Placebo
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Number of subjects included in analysis |
78
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.017 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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Statistical analysis title |
Comparison of logarithmically transformed itching | ||||||||||||
Statistical analysis description |
t-test for paired data
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Comparison groups |
Test product v Placebo
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Number of subjects included in analysis |
78
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.024 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
Change in diameter of the wheal | |||||||||||||||||||||||||||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Evaluation of the diameter of the wheal and the erythema was performed after histamine administration (time “0”) and at: 2, 4, 6, 8, 10, 15, 20, 30, 60 and 90 minutes after test product/placebo administration
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Statistical analysis title |
Change in diameter of the wheal | |||||||||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
Linear mixed effect model
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Comparison groups |
Test product v Placebo
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Number of subjects included in analysis |
78
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||||||||||||||||||||||||||||||||
P-value |
< 0.05 [1] | |||||||||||||||||||||||||||||||||||||||||||||
Method |
Mixed models analysis | |||||||||||||||||||||||||||||||||||||||||||||
Confidence interval |
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Notes [1] - NA |
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End point title |
Peak itching intensity | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Evaluation of itch using VAS scale was performed after histamine administration (time “0”) and at: 2, 4, 6, 8, 10, 15, 20, 30, 60 and 90 minutes after test product/placebo administration.
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Statistical analysis title |
Comparison of peak itching intensity | ||||||||||||
Statistical analysis description |
Wilcoxon signed rank test
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Comparison groups |
Test product v Placebo
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Number of subjects included in analysis |
78
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.311 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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End point title |
Rate of decrease in itching | |||||||||||||||||||||||||||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Evaluation of itch using VAS scale was performed after histamine administration (time “0”) and at: 2, 4, 6, 8, 10, 15, 20, 30, 60 and 90 minutes after test product/placebo administration.
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Statistical analysis title |
Rate of decrease in itching intensity | |||||||||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
Linear mixed effect model
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Comparison groups |
Placebo v Test product
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Number of subjects included in analysis |
78
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||||||||||||||||||||||||||||||||
P-value |
< 0.05 | |||||||||||||||||||||||||||||||||||||||||||||
Method |
Mixed models analysis | |||||||||||||||||||||||||||||||||||||||||||||
Confidence interval |
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End point title |
Change in area of the wheal | |||||||||||||||||||||||||||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Evaluation of the diameter of the wheal and the erythema was performed after histamine administration (time “0”) and at: 2, 4, 6, 8, 10, 15, 20, 30, 60 and 90 minutes after test product/placebo administration.
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Statistical analysis title |
Change in area of the wheal | |||||||||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
Linear mixed effect model
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Comparison groups |
Test product v Placebo
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Number of subjects included in analysis |
78
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||||||||||||||||||||||||||||||||
P-value |
< 0.05 | |||||||||||||||||||||||||||||||||||||||||||||
Method |
Mixed models analysis | |||||||||||||||||||||||||||||||||||||||||||||
Confidence interval |
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End point title |
Change in diameter of the erythema | |||||||||||||||||||||||||||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Evaluation of the diameter of the wheal and the erythema was performed after histamine administration (time “0”) and at: 2, 4, 6, 8, 10, 15, 20, 30, 60 and 90 minutes after test product/placebo administration.
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Statistical analysis title |
Change in diameter of the erythema | |||||||||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
Linear mixed effect model
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Comparison groups |
Test product v Placebo
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Number of subjects included in analysis |
78
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||||||||||||||||||||||||||||||||
P-value |
< 0.05 | |||||||||||||||||||||||||||||||||||||||||||||
Method |
Mixed models analysis | |||||||||||||||||||||||||||||||||||||||||||||
Confidence interval |
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End point title |
Change in area of the erythema | |||||||||||||||||||||||||||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Evaluation of the diameter of the wheal and the erythema was performed after histamine administration (time “0”) and at: 2, 4, 6, 8, 10, 15, 20, 30, 60 and 90 minutes after test product/placebo administration.
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Statistical analysis title |
Change in area of the erythema | |||||||||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
Linear mixed effect model
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Comparison groups |
Test product v Placebo
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Number of subjects included in analysis |
78
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||||||||||||||||||||||||||||||||
P-value |
< 0.05 | |||||||||||||||||||||||||||||||||||||||||||||
Method |
Mixed models analysis | |||||||||||||||||||||||||||||||||||||||||||||
Confidence interval |
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End point title |
Occurance of AEs | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
all subjects exposed to study product were included into the safety population
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No statistical analyses for this end point |
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Adverse events information [1]
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Timeframe for reporting adverse events |
All subjects exposed to the study products were a part of the safety analysis. All Adverse Events (AE) reported during the study should be included in this analysis.
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Assessment type |
Systematic | ||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||
Dictionary version |
20.0
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Reporting groups
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Reporting group title |
Safety population
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Reporting group description |
- | ||||||||||||||||||||
Reporting group title |
Test product
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Reporting group description |
- | ||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
- | ||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0.05% | |||||||||||||||||||||
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Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: During the study there were no adverse events (AEs) reported in the study subjects |
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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? 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 |