Clinical Trial Results:
A monocentric, observer-blind, randomized clinical study using an abrasive wound model with an intra-individual comparison to investigate the wound healing properties of a topical wound healing product in comparison to untreated and a reference product in 36 healthy subjects.
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Summary
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EudraCT number |
2014-001374-34 |
Trial protocol |
DE |
Global end of trial date |
17 Jul 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
04 Aug 2016
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First version publication date |
04 Aug 2016
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Other versions |
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Summary report(s) |
Wound healing properties of a topical wound healing product |
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 |
6630-0450-01
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
MEDICE Arzneimittel Pütter GmbH & Co. KG
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Sponsor organisation address |
Kuhloweg 37, Iserlohn, Germany, 58638
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Public contact |
Medical Department OTC, MEDICE Arzneimittel Pütter GmbH & Co. KG, +49 023719370, info@medice.de
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Scientific contact |
Medical Department OTC, MEDICE Arzneimittel Pütter GmbH & Co. KG, +49 023719370, info@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 |
13 Jan 2015
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
17 Jul 2014
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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 primary objective was the comparison of the investigational product versus untreated on the size of the open wound area/crusts assessed by quantitative image analysis at the different assessment time points (Area Under the Curve (AUC) over time on relative differences to Baseline).
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Protection of trial subjects |
At each visit at the test center from Day 1 on, the study nurse looked for signs of inflammation/infection (erythema, edema, pain, odor, non-healing, excessive exudates, hyperthermia) and/or allergic reactions (erythema, edema, itching). In case of signs for a strong allergic reaction or signs for strong inflammation/infection, the treatment of the respective test area had to be discontinued. The test area had to be follow-up for safety reasons as long as the allergic reaction or inflammation/infection was resovled or a stable condition was reached.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
18 Jun 2014
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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: 36
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Worldwide total number of subjects |
36
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EEA total number of subjects |
36
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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) |
36
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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 |
- | ||||||||||||
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Pre-assignment
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Screening details |
A total of 42 healthy subjects were enrolled and screened. Excluded: not meeting inclusion/exclusion criteria (N=5) and Reserve (N=1). 36 subjects were randomised in this study. | ||||||||||||
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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 |
Single blind [1] | ||||||||||||
Roles blinded |
Monitor, Data analyst, Assessor, Investigator [2] | ||||||||||||
Blinding implementation details |
The trial was conducted under observer-blind conditions. Since there were untreated and treated areas and since the kind application and the dosage differed between the two test products, all persons (carer, subject) involved in the application were not blinded. Personnel responsible for the skin assessments and the visual & instrumental measurements including the investigator remained blinded.
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Arms
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Are arms mutually exclusive |
No
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Arm title
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Soventol Wund- und Heilgel | ||||||||||||
Arm description |
Soventol® Wund- und Heilgel is a certified medical device and is indicated for the treatment of acute and chronic wounds such as abrasions, cuts, scratches, laceration, blistering burns, and sunburns | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Soventol Wund- und Heilgel
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Cream
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Routes of administration |
Cutaneous use
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Dosage and administration details |
The investigational and reference products were applied twice daily (mornings and evenings) on the abrasive wounds on the left volar forearm. The test areas were then covered with a standard plaster. On study days with visits at the test center (Days 1, 3, 5, 8, 9, 10, and 12) the first daily application was done by a technician after instrumental measurements and visual assessments. The second daily application was done by the subjects at home (evening). On Days 2, 4, 6, 7, 11, 13, and 14 the test products were applied by the subjects themselves at home according to the instruction by a technician. Applications were always performed between 8 and 11 a.m. in the morning and 8 and 11 p.m. in the evening.
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Arm title
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Bepanthen Wund- und Heilsalbe | ||||||||||||
Arm description |
Indications for Bepanthen® Wund- und Heilsalbe are promotion of healing in superficial minor skin and mucosa injuries | ||||||||||||
Arm type |
Active comparator | ||||||||||||
Investigational medicinal product name |
Bepanthen Wund- und Heilsalbe
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Ointment
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Routes of administration |
Cutaneous use
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Dosage and administration details |
The investigational and reference products were applied twice daily (mornings and evenings) on the abrasive wounds on the left volar forearm. The test areas were then covered with a standard plaster. On study days with visits at the test center (Days 1, 3, 5, 8, 9, 10, and 12) the first daily application was done by a technician after instrumental measurements and visual assessments. The second daily application was done by the subjects at home (evening). On Days 2, 4, 6, 7, 11, 13, and 14 the test products were applied by the subjects themselves at home according to the instruction by a technician. Applications were always performed between 8 and 11 a.m. in the morning and 8 and 11 p.m. in the evening.
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Arm title
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untreated | ||||||||||||
Arm description |
One abrasive wound on the left volar forearm of each subject was left untreated but covered with a standard bandage. On study days with visits at the test center (Days 1, 3, 5, 8, 9, 10, and 12) the first daily application was done by a technician after instrumental measurements and visual assessments. The second daily application was done by the subjects at home (evening). On Days 2, 4, 6, 7, 11, 13, and 14 the test products were applied by the subjects themselves at home according to the instruction by a technician. Applications were always performed between 8 and 11 a.m. in the morning and 8 and 11 p.m. in the evening. | ||||||||||||
Arm type |
untreated control covered with standard bandage | ||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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| Notes [1] - The number of roles blinded appears inconsistent with a single blinded trial. It is expected that there will be one role blinded in a single blind trial. Justification: The trial was conducted under observer-blind conditions (see blinding implementation details) [2] - The roles blinded appear inconsistent with a simple blinded trial. Justification: The trial was conducted under observer-blind conditions (see blinding implementation details). |
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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 |
Full Analysis Set
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Full analysis set (FAS): includes all subjects who did not violate any in- or exclusion criteria at the beginning of the trial, who received at least one application of the test products and for whom at least one post-baseline assessment was performed.
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Subject analysis set title |
Safety Population
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Safety Population (SP): included all subjects who received at least one application of the test
products, regardless of the number of assessments
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End points reporting groups
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Reporting group title |
Soventol Wund- und Heilgel
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Reporting group description |
Soventol® Wund- und Heilgel is a certified medical device and is indicated for the treatment of acute and chronic wounds such as abrasions, cuts, scratches, laceration, blistering burns, and sunburns | ||
Reporting group title |
Bepanthen Wund- und Heilsalbe
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Reporting group description |
Indications for Bepanthen® Wund- und Heilsalbe are promotion of healing in superficial minor skin and mucosa injuries | ||
Reporting group title |
untreated
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Reporting group description |
One abrasive wound on the left volar forearm of each subject was left untreated but covered with a standard bandage. On study days with visits at the test center (Days 1, 3, 5, 8, 9, 10, and 12) the first daily application was done by a technician after instrumental measurements and visual assessments. The second daily application was done by the subjects at home (evening). On Days 2, 4, 6, 7, 11, 13, and 14 the test products were applied by the subjects themselves at home according to the instruction by a technician. Applications were always performed between 8 and 11 a.m. in the morning and 8 and 11 p.m. in the evening. | ||
Subject analysis set title |
Full Analysis Set
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Full analysis set (FAS): includes all subjects who did not violate any in- or exclusion criteria at the beginning of the trial, who received at least one application of the test products and for whom at least one post-baseline assessment was performed.
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Subject analysis set title |
Safety Population
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Safety Population (SP): included all subjects who received at least one application of the test
products, regardless of the number of assessments
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End point title |
Comparison of the investigational product versus untreated on the size of the open wound area/crusts [1] | ||||||||||||
End point description |
The primary objective was the comparison of the investigational product versus untreated on the size of the open wound area/crusts assessed by quantitative image analysis at the different assessment time points (AUC over time on relative differences to Baseline). The size of the open wound area (including area covered with crusts) was determined for defined time points by quantitative image analysis. The relative difference to Baseline was calculated. AUCs from Day 3 to Day 15 were calculated with the trapezoid formula for the three treatments on these relative differences to Baseline. The statistical analysis for the primary objective was done on the AUC values.
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End point type |
Primary
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End point timeframe |
AUC over time on relative differences to Baseline from Day 3 to Day 15
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| Notes [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Due to intra-individual comparison all patients were included in each arm. |
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Statistical analysis title |
open wound area/crusts - product versus untreated | ||||||||||||
Statistical analysis description |
Paired t-test or Wilcoxon signed-ranks test (depending on Normality test) should be performed to analyze the difference between treatments regarding AUC over time on relative differences to Baseline from Day 3 to Day 15. Normality was rejected based on Shapiro-Wilk test. Therefore Wilcoxon signed-ranks test was used to compare areas treated with investigational product and untreated areas and found a significantly higher AUC (p<0.0001) for the areas treated with the investigational product.
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Comparison groups |
Soventol Wund- und Heilgel v untreated
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Number of subjects included in analysis |
66
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 | ||||||||||||
Method |
Wilcoxon signed-rank test | ||||||||||||
Confidence interval |
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End point title |
Comparison of the investigational product versus reference on the size of the open wound area/crusts [2] | ||||||||||||
End point description |
Comparisons of the reference product versus the investigational product and versus untreated on the size of open wound area/crusts assessed by quantitative image analysis at the different assessment time points (AUC over time on relative differences to Baseline).
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End point type |
Secondary
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End point timeframe |
AUC over time on relative differences to Baseline from Day 3 to Day 15
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| Notes [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Due to intra-individual comparison all patients were included in each arm. |
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Statistical analysis title |
open wound area/crust product versus reference | ||||||||||||
Comparison groups |
Soventol Wund- und Heilgel v Bepanthen Wund- und Heilsalbe
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Number of subjects included in analysis |
66
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.2553 | ||||||||||||
Method |
Wilcoxon signed-ranked test | ||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
At each visit at the test center from Day 1 on
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Adverse event reporting additional description |
AEs and changes in concomitant medication were recorded at each visit at the test center from day 1 on. Assessment of possible signs of inflammation/infection and/or signs of allergic reactions.
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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 |
17.0
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Reporting groups
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Reporting group title |
Soventol Wund- und Heilgel
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Reporting group description |
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Reporting group title |
Bepanthen Wund- und Heilsalbe
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Reporting group description |
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Reporting group title |
untreated control
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 | |||
