Clinical Trial Results:
EPs® 7630 film-coated tablets in subjects (≥18 years old) suffering from common cold symptoms in a general practice setting.
A prospective, multi-center, single-arm, open-label, phase IV clinical post-marketing safety study
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Summary
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EudraCT number |
2010-022441-21 |
Trial protocol |
AT |
Global end of trial date |
22 Aug 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Mar 2016
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First version publication date |
29 Jul 2015
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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 |
701004.01.012
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Additional study identifiers
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ISRCTN number |
ISRCTN65790556 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Dr. Willmar Schwabe GmbH & Co. KG
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Sponsor organisation address |
Dr. Willmar Schwabe Str. 4, Karlsruhe, Germany, 76227
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Public contact |
Clinical Research Department, Dr. Willmar Schwabe GmbH & Co. KG, +49 7214005573,
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Scientific contact |
Clinical Research Department, Dr. Willmar Schwabe GmbH & Co. KG, +49 7214005573,
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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 |
22 Aug 2013
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
22 Aug 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
22 Aug 2013
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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 objective of the present post-marketing study is to gain further information about the safety and treatment outcome with EPs® 7630 film-coated tablets (Kaloba 20 mg Filmtabletten) in adult subjects (≥ 18 years old) suffering from common cold.
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Protection of trial subjects |
Possibility to withdraw consent by patient. Monitoring of adverse events and laboratory parameters.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
12 Jan 2011
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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 |
Austria: 120
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Worldwide total number of subjects |
120
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EEA total number of subjects |
120
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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) |
120
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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 |
Subjects were recruited in eight investigational sites | |||||||||||||||||||||
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Pre-assignment period milestones
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Number of subjects started |
120 | |||||||||||||||||||||
Number of subjects completed |
120 | |||||||||||||||||||||
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Period 1
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Period 1 title |
Treatment period (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not 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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Baseline | |||||||||||||||||||||
Arm description |
Baseline before starting EPs® 7630 treatment | |||||||||||||||||||||
Arm type |
Baseline | |||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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EPs® 7630 | |||||||||||||||||||||
Arm description |
Investigational medical product containing EPs® 7630, 20 mg per film-coated tablet (Kaloba 20 mg Filmtabletten) | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
EPs® 7630
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
1 film-coated tablet 3 times a day for 10 consecutive days
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Baseline characteristics reporting groups
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Reporting group title |
Treatment period (overall period)
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Reporting group description |
Investigational medical product containing EPs® 7630, 20 mg per film-coated tablet (Kaloba 20 mg Filmtabletten) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 |
The Full analysis set (FAS) consisted of all subjects having received study medication at least once and having at least one measurement of one of the efficiency parameters during the treatment period.
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End points reporting groups
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Reporting group title |
Baseline
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Reporting group description |
Baseline before starting EPs® 7630 treatment | ||
Reporting group title |
EPs® 7630
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Reporting group description |
Investigational medical product containing EPs® 7630, 20 mg per film-coated tablet (Kaloba 20 mg Filmtabletten) | ||
Subject analysis set title |
Full analysis set
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The Full analysis set (FAS) consisted of all subjects having received study medication at least once and having at least one measurement of one of the efficiency parameters during the treatment period.
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End point title |
Change in total score of common cold symptoms (CCS) between baseline and end of treatment as assessed by the investigator | ||||||||||||
End point description |
Common cold symptoms: Nasal discharge, sore throat, nasal congestion, sneezing, scratchy throat, hoarseness, cough, headache, malaise, fever; each symptom assessed according to a 4-point verbal rating scale from "0 = not present" to "3 = severe".
Note: There were no primary end points defined for analysis. Because at least one primary end point is required to enter study results into the database, all outcome variables are presented using the end point type primary.
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End point type |
Primary
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End point timeframe |
Baseline and end of Treatment (10-day Treatment period)
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Statistical analysis title |
Non-parametric analysis | ||||||||||||
Statistical analysis description |
Baseline and end of treatment values available for 117 subjects with arithmetic mean (standard deviation) of change between baseline and end of treatment: -8.6 (±4.0) points;
LOCF, two-sided . The number of subjects included in analysis was summarized to 237 (Baseline 120, End of treatment 117) because of requirements of the Eudra-CT data base.
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Comparison groups |
Baseline v EPs® 7630
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Number of subjects included in analysis |
237
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | ||||||||||||
P-value |
< 0.0001 | ||||||||||||
Method |
Wilcoxon signed-rank test | ||||||||||||
Confidence interval |
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| Notes [1] - Within-subject change between baseline and end of treatment |
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End point title |
Change in further common cold relevant complaints between baseline and end of treatment as assessed by the investigator | ||||||||||||
End point description |
Further common cold relevant complaints: Pulmonary rates at auscultation, sputum production, chest pain during coughing, chilliness, exhaustion, loss of appetite, diarrhea, muscle aches;
each symptom assessed according to a 4-point verbal rating scale from "0 = not present" to "3 = severe"
Note: There were no primary end points defined for analysis. Because at least one primary end point is required to enter study results into the database, all outcome variables are presented using the end point type primary.
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End point type |
Primary
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End point timeframe |
Baseline and end of Treatment (10-day Treatment period)
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Statistical analysis title |
Non-parametric analysis | ||||||||||||
Statistical analysis description |
Baseline and end of treatment values available for 117 subjects with arithmetic mean (standard deviation) of change between baseline and end of treatment: -2.8 (±2.6) points; LOCF, two-sided. The number of subjects included in analysis was summarized to 237 (Baseline 120, End of treatment 117) because of requirements of the Eudra-CT data base.
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Comparison groups |
Baseline v EPs® 7630
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Number of subjects included in analysis |
237
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Analysis specification |
Pre-specified
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Analysis type |
other [2] | ||||||||||||
P-value |
< 0.0001 | ||||||||||||
Method |
Wilcoxon signed-rank test | ||||||||||||
Confidence interval |
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| Notes [2] - Within-subject change between baseline and end of treatment |
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End point title |
Change in total score of common cold symptoms and further common cold relevant complaints between baseline and end of treatment as assessed by the investigator | ||||||||||||
End point description |
Common cold symptoms: Nasal discharge, sore throat, nasal congestion, sneezing, scratchy throat, hoarseness, cough, headache, malaise, fever;
Further common cold relevant complaints: Pulmonary rates at auscultation, sputum production, chest pain during coughing, chilliness, exhaustion, loss of appetite, diarrhea, muscle aches;
each symptom assessed according to a 4-point verbal rating scale from "0 = not present" to "3 = severe"
Note: There were no primary end points defined for analysis. Because at least one primary end point is required to enter study results into the database, all outcome variables are presented using the end point type primary.
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End point type |
Primary
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End point timeframe |
Baseline and end of Treatment (10-day Treatment period)
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Statistical analysis title |
Non-parametric analysis | ||||||||||||
Statistical analysis description |
Baseline and end of treatment values available for 117 subjects with arithmetic mean (standard deviation) of change between baseline and end of treatment: -11.4 (±5.6) points; LOCF, two-sided. The number of subjects included in analysis was summarized to 237 (Baseline 120, End of treatment 117) because of requirements of the Eudra-CT data base.
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Comparison groups |
Baseline v EPs® 7630
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Number of subjects included in analysis |
237
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Analysis specification |
Pre-specified
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Analysis type |
other [3] | ||||||||||||
P-value |
< 0.0001 | ||||||||||||
Method |
Wilcoxon signed-rank test | ||||||||||||
Confidence interval |
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| Notes [3] - Within-subject change between baseline and end of treatment |
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End point title |
Change in common cold symptoms (CCS) as rated by the subject in the subject’s diary | ||||||||||||
End point description |
15 common cold symptoms (not comparable with the common cold symptoms assessed by the investigator): Runny nose, sore throat, congested nose, sneezing, scratchy throat, hoarseness, cough, headache, malaise, chilliness, chest pain during coughing, lost of appetite, restless sleep, limited usual daily activity, muscle aches;
each symptom rated by the subject according to a 5-point rating scale from "0 = not present" to "4 = severe".
Note: There were no primary end points defined for analysis. Because at least one primary end point is required to enter study results into the database, all outcome variables are presented using the end point type primary.
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End point type |
Primary
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End point timeframe |
Baseline and Day 10 (10-day Treatment period)
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| Notes [4] - 111 subjects assessed CCS at Day 1 (baseline) [5] - 92 subjects assessed CCS at Day 10 |
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Statistical analysis title |
Non-parametric analysis | ||||||||||||
Statistical analysis description |
Day 1 and Day 10 values available for 84 subjects with arithmetic mean (standard deviation) of change between Day 1 and Day 10: -18.2 (±9.7) points; two-sided. The number of subjects included in analysis was summarized to 203 (Baseline 111, End of treatment 92) because of requirements of the Eudra-CT data base.
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Comparison groups |
Baseline v EPs® 7630
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Number of subjects included in analysis |
203
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Analysis specification |
Pre-specified
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Analysis type |
other [6] | ||||||||||||
P-value |
< 0.0001 | ||||||||||||
Method |
Wilcoxon signed-rank test | ||||||||||||
Confidence interval |
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| Notes [6] - Within-subject change between Day 1 (baseline) and Day 10 |
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End point title |
Need for subject’s treatment with antibiotics according to the medical decision of the investigator | |||||||||
End point description |
Subjects needed to be treated with antibiotics during the study are identified based on concomitant medication documentation.
Note: There were no primary end points defined for analysis. Because at least one primary end point is required to enter study results into the database, all outcome variables are presented using the end point type primary.
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End point type |
Primary
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End point timeframe |
Baseline and end of Treatment (10-day Treatment period)
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| Notes [7] - Need for subject's treatment with antibiotics not evaluated at baseline |
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Statistical analysis title |
Proportion of subjects | |||||||||
Statistical analysis description |
The proportion of subjects with need for treatment with antibiotics was identified with respect to the total study period and was based on all 120 subjects with EPs® 7630 Treatment. The number of subjects included in analysis was summarized to 240 (Baseline 120, End of treatment 120) because of requirements of the Eudra-CT data base.
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Comparison groups |
Baseline v EPs® 7630
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Number of subjects included in analysis |
240
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Analysis specification |
Pre-specified
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Analysis type |
other [8] | |||||||||
Method |
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Parameter type |
percentage | |||||||||
Point estimate |
1.7
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.2 | |||||||||
upper limit |
5.9 | |||||||||
| Notes [8] - Proportion of subjects and exact 95% confidence interval for the proportion |
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End point title |
Number of subjects who are 'not sick' or 'very mildly sick' as rated by the subject in the subject's diary | |||||||||
End point description |
Possible answer to the question "How sick do you feel today?" in the subject's diary: 'not present', 'very mild', 'mild', 'moderate', 'severe'.
Note: There were no primary end points defined for analysis. Because at least one primary end point is required to enter study results into the database, all outcome variables are presented using the end point type primary.
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End point type |
Primary
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End point timeframe |
Day 1 (Baseline) and Day 10 (10-day treatment period)
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Statistical analysis title |
Proportion of subjects | |||||||||
Statistical analysis description |
The proportion of subjects who are not sick or very mildly sick was calculated for the number of subjects with answer to the question "How sick do you feel today?" at Day 10 (in total, 92 subjects). The number of subjects included in analysis was summarized to 203 (Baseline 111, End of treatment 92) because of requirements of the Eudra-CT data base.
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Comparison groups |
EPs® 7630 v Baseline
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Number of subjects included in analysis |
203
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Analysis specification |
Pre-specified
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Analysis type |
other [9] | |||||||||
Method |
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Parameter type |
percentage | |||||||||
Point estimate |
94.6
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
87.8 | |||||||||
upper limit |
98.2 | |||||||||
| Notes [9] - Proportion of subjects and exact 95% confidence interval for the proportion |
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End point title |
Treatment outcome according to the Integrative Medicine Outcome Scale (IMOS) as assessed by the investigator | ||||||||||||||||||||||||
End point description |
The IMOS describes the general health status of the subject.
Note: There were no primary end points defined for analysis. Because at least one primary end point is
required to enter study results into the database, all outcome variables are presented using the end
point type primary.
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End point type |
Primary
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End point timeframe |
Assessment at end of Treatment (10-day Treatment period)
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| Notes [10] - Assessment of treatment outcome not applicable at baseline |
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Statistical analysis title |
Proportion of subjects with complete recovery | ||||||||||||||||||||||||
Statistical analysis description |
Treatment outcome according to IMOS as assessed by the investigator available for 117 subjects at the
end of the treatment period; LOCF. The number of subjects included in analysis was summarized to 237 (Baseline 120, End of treatment 117) because of requirements of the Eudra-CT data base.
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Comparison groups |
Baseline v EPs® 7630
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Number of subjects included in analysis |
237
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Analysis specification |
Pre-specified
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Analysis type |
other [11] | ||||||||||||||||||||||||
Method |
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Parameter type |
Percentage | ||||||||||||||||||||||||
Point estimate |
41.9
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||
sides |
2-sided
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lower limit |
32.8 | ||||||||||||||||||||||||
upper limit |
51.4 | ||||||||||||||||||||||||
| Notes [11] - Proportion of subjects and exact 95% confidence interval for proportion |
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End point title |
Treatment outcome according to the Integrative Medicine Outcome Scale (IMOS) as assessed by the subject | ||||||||||||||||||||||||
End point description |
The IMOS describes the general health status of the subject.
Note: There were no primary end points defined for analysis. Because at least one primary end point is
required to enter study results into the database, all outcome variables are presented using the end
point type primary.
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End point type |
Primary
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End point timeframe |
Assessment at Day 10 (10-day Treatment period)
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| Notes [12] - Assessment of treatment outcome not applicable at baseline [13] - Data available for 90 subjects at Day 10 |
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Statistical analysis title |
Proportion of subjects with complete recovery | ||||||||||||||||||||||||
Statistical analysis description |
Treatment outcome according to IMOS as assessed by the subject available for 90 subjects at the
end of the treatment period (Day 10). The number of subjects included in analysis was summarized to 210 (Baseline 120, End of treatment 90) because of requirements of the Eudra-CT data base.
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Comparison groups |
Baseline v EPs® 7630
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Number of subjects included in analysis |
210
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Analysis specification |
Pre-specified
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Analysis type |
other [14] | ||||||||||||||||||||||||
Method |
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Parameter type |
Percentage | ||||||||||||||||||||||||
Point estimate |
43.3
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||
sides |
2-sided
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lower limit |
32.9 | ||||||||||||||||||||||||
upper limit |
54.2 | ||||||||||||||||||||||||
| Notes [14] - Proportion of subjects with complete recovery and exact 95% confidence interval for the proportion |
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End point title |
Satisfaction of the subject with the treatment according to the Integrative Medicine Patient Satisfaction Scale (IMPSS) as assessed by the subject in the subject's diary | |||||||||||||||||||||||||||
End point description |
The IMPSS uses a 5 point scale ranging from ‘very satisfied’ to ‘not satisfied at all’.
Note: There were no primary end points defined for analysis. Because at least one primary end point is
required to enter study results into the database, all outcome variables are presented using the end
point type primary.
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End point type |
Primary
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End point timeframe |
Assessment at Day 10 (10-day Treatment period)
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| Notes [15] - Rating of satisfaction with treatment not applicable at baseline |
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Statistical analysis title |
Proportion of subjects 'very satisfied' | |||||||||||||||||||||||||||
Statistical analysis description |
Satisfaction with treatment according to IMPSS as assessed by the subject at Day 10 of the 10-day treatment period available for 120 subjects. The number of subjects included in analysis was summarized to 240 (Baseline 120, End of treatment 120) because of requirements of the Eudra-CT data base.
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Comparison groups |
EPs® 7630 v Baseline
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Number of subjects included in analysis |
240
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Analysis specification |
Pre-specified
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Analysis type |
other [16] | |||||||||||||||||||||||||||
Method |
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Parameter type |
Percentage | |||||||||||||||||||||||||||
Point estimate |
31.7
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Confidence interval |
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level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
23.5 | |||||||||||||||||||||||||||
upper limit |
40.8 | |||||||||||||||||||||||||||
| Notes [16] - Proportion of subjects 'very satisfied' with treatment and exact 95% confidence interval for the proportion |
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Adverse events information [1]
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Timeframe for reporting adverse events |
10.5 months
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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 |
14.0
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Reporting groups
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Reporting group title |
No active treatment
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Reporting group description |
No active treatment | ||||||||||||||||||||||||||||||
Reporting group title |
EPs 7630
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Reporting group description |
Verum treatment | ||||||||||||||||||||||||||||||
| 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: Overall, 15 subjects experienced non-serious adverse events. This number could not be entered into the database, because each adverse event occurred with a frequency which did not exceed the frequency threshold of 5% for reporting non-serious adverse events. Therefore, the number of subjects with non-serious adverse events resulted in 0 when considering the 5% frequency threshold. |
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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? Yes | |||
Date |
Amendment |
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20 Dec 2010 |
Amendment No. 1:
Study Protocol: modification of the study title;
Informed consent and Patient information: elimination of footnote 1: modification of point 3 and point 6;
CRF: modification of the study title; nasal examination severe (right and left) is an exclusion; pharyngeal swab was changed in nasal brushing; modification of assessment of integrative medicine outcome scale (IMOS);
Patient Diaries: were expanded by muscle pain on page 5, 6, 7, 9, 10, 12, 13 (diary1) and page 5, 7, 8, 9, 10, 11, 13 (diary 2). |
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28 Sep 2011 |
Amendment No. 2:
Study protocol: extension of study Duration to 23 months; modification of trial schedule (Visit 1 and Visit 3); Further specification of the "AE" Definition and Duration of treatment. |
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20 Dec 2012 |
Amendment No. 3:
Study protocol: extension of study Duration to 35 months. |
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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 | |||
