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Clinical Trial Results:
Safety and tolerability of Pelargonium sidoides extract EPs® 7630 in children (1 to 5 years old) suffering from acute bronchitis

Summary
EudraCT number
 2011-002652-14
Trial protocol
 DE  
Global end of trial date
15 Jul 2013

Results information
Results version number
 v1(current)
This version publication date
30 Sep 2018
First version publication date
30 Sep 2018
Other versions
Summary report(s)
 701003.01.010 Summary of results of postin in eudra Ct database V1.0 2018_09_14

Trial information

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Trial identification
Sponsor protocol code
701003.01.010
Additional study identifiers
ISRCTN number
 ISRCTN77419032
US NCT number
 -
WHO universal trial number (UTN)
 -
Sponsors
Sponsor organisation name
Dr. Willmar Schwabe GmbH & Co. KG
Sponsor organisation address
Willmar Schwabe Str. 4, Karlsruhe, Germany, 76227
Public contact
Head of Clinical Research, Dr. Willmar Schwabe GmbH & Co. KG Clinical Research Department, +49 07214005573,
Scientific contact
Head of Clinical Research, Dr. Willmar Schwabe GmbH & Co. KG Clinical Research Department, +49 07214005573,
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)
No
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
Yes
Results analysis stage
Analysis stage
Final
Date of interim/final analysis
02 Apr 2013
Is this the analysis of the primary completion data?
Yes
Primary completion date
02 Apr 2012
Global end of trial reached?
Yes
Global end of trial date
15 Jul 2013
Was the trial ended prematurely?
No
General information about the trial
Main objective of the trial
To evaluate the safety and tolerability of a treatment with EPs® 7630 syrup in comparison to EPs® 7630 solution in patients between 1 and 5 years old suffering from acute bronchitis.
Protection of trial subjects
Possibility to withdraw consent by subject. Monitoring of adverse Events and laboratory Parameters.
Background therapy
 -
Evidence for comparator
 -
Actual start date of recruitment
28 Nov 2011
Long term follow-up planned
No
Independent data monitoring committee (IDMC) involvement?
No
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled
Germany: 602
Worldwide total number of subjects
602
EEA total number of subjects
602
Number of subjects enrolled per age group
In utero
0
Preterm newborn - gestational age
0
Newborns (0-27 days)
0
Infants and toddlers (28 days-23 months)
110
Children (2-11 years)
492
Adolescents (12-17 years)
0
Adults (18-64 years)
0
From 65 to 84 years
0
85 years and over
0

Subject disposition

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Recruitment
Recruitment details
 -

Pre-assignment
Screening details
 Subjects were recruited in 35 investigational sites. All 602 subjects were randomized.

Pre-assignment period milestones
Number of subjects started
 602
Number of subjects completed
 602

Period 1
Period 1 title
Treatment period (overall period)
Is this the baseline period?
 Yes
Allocation method
Randomised - controlled
Blinding used
 Not blinded

Arms
Are arms mutually exclusive
Yes

Arm title
 EPs® 7630 syrup
Arm description
 100 g (= 93.985 ml) syrup contain: Herbal drug preparation from the roots of Pelargonium sidoides (1 : 8 - 10), dried. Eight randomized children were drop-outs without any intake of the investigational product. These subjects were excluded from the safety analysis set. The full analysis set corresponded with the safety analysis set.
Arm type
 Active comparator

Investigational medicinal product name
EPs® 7630 syrup
Investigational medicinal product code
Other name
Pharmaceutical forms
Syrup
Routes of administration
Oral use
Dosage and administration details
2.5 ml syrup three times daily for 7 consecutive days (SMC 7651, batch no. 0201101)

Arm title
 EPs® 7630 solution
Arm description
 10 g (= 9.75 mL) of oral solution contain 8.0 g herbal drug preparation from the roots of Pelargonium sidoides (1 : 8 - 10) (EPs® 7630) Three randomized children were drop-outs without any intake of the investigational product. These subjects were excluded from the safety analysis set. The full analysis set corresponded with the safety analysis set.
Arm type
 Active comparator

Investigational medicinal product name
EPs® 7630 solution
Investigational medicinal product code
Other name
Pharmaceutical forms
Oral solution
Routes of administration
Oral use
Dosage and administration details
10 drops three times daily for 7 consecutive days (SMC 7521, batch no. 0201102)

Number of subjects in period 1
EPs® 7630 syrup EPs® 7630 solution
Started
411
191
Completed
387
178
Not completed
24
13
     Other specifications
19
10
     Adverse event, non-fatal
4
-
     Consent withdrawn by subject
1
3

Baseline characteristics

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Baseline characteristics reporting groups
Reporting group title
EPs® 7630 syrup
Reporting group description
 100 g (= 93.985 ml) syrup contain: Herbal drug preparation from the roots of Pelargonium sidoides (1 : 8 - 10), dried. Eight randomized children were drop-outs without any intake of the investigational product. These subjects were excluded from the safety analysis set. The full analysis set corresponded with the safety analysis set.

Reporting group title
EPs® 7630 solution
Reporting group description
 10 g (= 9.75 mL) of oral solution contain 8.0 g herbal drug preparation from the roots of Pelargonium sidoides (1 : 8 - 10) (EPs® 7630) Three randomized children were drop-outs without any intake of the investigational product. These subjects were excluded from the safety analysis set. The full analysis set corresponded with the safety analysis set.

Reporting group values
 EPs® 7630 syrup EPs® 7630 solution Total
Number of subjects
 411 191 602
Age categorical
Units: Subjects
    In utero
 0 0 0
    Preterm newborn infants (gestational age < 37 wks)
 0 0 0
    Newborns (0-27 days)
 0 0 0
    Infants and toddlers (28 days-23 months)
 73 37 110
    Children (2-11 years)
 338 154 492
    Adolescents (12-17 years)
 0 0 0
    Adults (18-64 years)
 0 0 0
    From 65-84 years
 0 0 0
    85 years and over
 0 0 0
Age continuous
Units: years
    arithmetic mean (standard deviation)
 3.03 ± 1.34 2.97 ± 1.39 -
Gender categorical
Units: Subjects
    Female
 192 86 278
    Male
 219 105 324
Subject analysis sets

Subject analysis set title
Safety analysis set
Subject analysis set type
 Safety analysis
Subject analysis set description
The safety analysis set (SAF) included all subjects having taken their randomised EPs® 7630 medication at least once. The safety analysis set corresponded with the full analysis set (FAS). This document in its section "End points" specifies commercially confidential information of Dr. Willmar Schwabe GmbH & Co. KG, Karlsruhe referred to in Article 81 Section (4) b) Regulation (EU) 536/2014 that is a trade secret and released by the holder for purposes of Regulation (EU) 536/2014 only under the condition of confidence. Trade secrets may not - even in part - be published or released to third parties other than to competent authorities without express permission of the trade secret holder.

Subject analysis sets values
 Safety analysis set
Number of subjects
591
Age categorical
Units: Subjects
    In utero
0
    Preterm newborn infants (gestational age < 37 wks)
0
    Newborns (0-27 days)
0
    Infants and toddlers (28 days-23 months)
108
    Children (2-11 years)
483
    Adolescents (12-17 years)
0
    Adults (18-64 years)
0
    From 65-84 years
0
    85 years and over
0
Age continuous
Units: years
    arithmetic mean (standard deviation)
3.01 ± 1.35
Gender categorical
Units: Subjects
    Female
275
    Male
316

End points

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End points reporting groups
Reporting group title
EPs® 7630 syrup
Reporting group description
 100 g (= 93.985 ml) syrup contain: Herbal drug preparation from the roots of Pelargonium sidoides (1 : 8 - 10), dried. Eight randomized children were drop-outs without any intake of the investigational product. These subjects were excluded from the safety analysis set. The full analysis set corresponded with the safety analysis set.

Reporting group title
EPs® 7630 solution
Reporting group description
 10 g (= 9.75 mL) of oral solution contain 8.0 g herbal drug preparation from the roots of Pelargonium sidoides (1 : 8 - 10) (EPs® 7630) Three randomized children were drop-outs without any intake of the investigational product. These subjects were excluded from the safety analysis set. The full analysis set corresponded with the safety analysis set.

Subject analysis set title
Safety analysis set
Subject analysis set type
 Safety analysis
Subject analysis set description
The safety analysis set (SAF) included all subjects having taken their randomised EPs® 7630 medication at least once. The safety analysis set corresponded with the full analysis set (FAS). This document in its section "End points" specifies commercially confidential information of Dr. Willmar Schwabe GmbH & Co. KG, Karlsruhe referred to in Article 81 Section (4) b) Regulation (EU) 536/2014 that is a trade secret and released by the holder for purposes of Regulation (EU) 536/2014 only under the condition of confidence. Trade secrets may not - even in part - be published or released to third parties other than to competent authorities without express permission of the trade secret holder.

Primary: Number of subjects with adverse events related to gastrointestinal complaints

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End point title
 Number of subjects with adverse events related to gastrointestinal complaints
End point description
Note: Number of subjects with adverse events related to gastrointestinal complaints is one of several pre-specified endpoints. See document for a complete description of the endpoints. Codes related to gastrointestinal complaints according to MedDRA Version 14: (10000059), (10000081), (10000084), (10000087), (10000133), (10010774), (10012735), (10013781), (10013911), (10013946), (10013950), (10014866), (10015137), (10016101), (10016766), (10017367), (10017888), (10017944), (10028813), (10030973), (10042101), (10043951), (10047700), (10048714), (10052402), (10053155), (10056819), (10060961)
End point type
Primary
End point timeframe
Baseline and End of Treatment (Day 7)
End point values
 EPs® 7630 syrup EPs® 7630 solution
Number of subjects analysed
403
188
Units: Subjects
    Subjects affected
13
6
Statistical analysis title
 Chi-squared test for risk difference
Statistical analysis description
For each of the treatment arms the relative frequencies of patients with AEs and adverse drug reactions of the mentioned system group are estimated. In addition a 95% confidence interval is calculated for the risk difference according to Newcombe.
Comparison groups
EPs® 7630 syrup v EPs® 7630 solution
Number of subjects included in analysis
591
Analysis specification
Pre-specified
Analysis type
 other [1]
P-value
 = 0.982 [2]
Method
 Chi-squared
Parameter type
 Risk difference (RD)
Point estimate
0.0003
Confidence interval
     level
 95%
     sides
2-sided
     lower limit
 -0.038
     upper limit
 0.0284
Notes
[1] - Difference between treatment arms
[2] - two-sided

Adverse events

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Adverse events information [1]
Timeframe for reporting adverse events
14 days
Assessment type
 Systematic
Dictionary used for adverse event reporting
Dictionary name
 MedDRA
Dictionary version
14
Reporting groups
Reporting group title
EPs(R) 7630 Syrup
Reporting group description
 Pelargonium extract

Reporting group title
EPs(R) 7630 Solution
Reporting group description
 Pelargonium extract

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: The were no preferred Terms affected by more than than frequeny threshold of 5%.
Serious adverse events
 EPs(R) 7630 Syrup EPs(R) 7630 Solution
Total subjects affected by serious adverse events
     subjects affected / exposed
0 / 403 (0.00%)
1 / 188 (0.53%)
     number of deaths (all causes)
0
0
     number of deaths resulting from adverse events
0
0
Injury, poisoning and procedural complications
Concussion
     subjects affected / exposed
0 / 403 (0.00%)
1 / 188 (0.53%)
     occurrences causally related to treatment / all
0 / 0
0 / 1
     deaths causally related to treatment / all
0 / 0
0 / 0
Frequency threshold for reporting non-serious adverse events: 5%
Non-serious adverse events
 EPs(R) 7630 Syrup EPs(R) 7630 Solution
Total subjects affected by non serious adverse events
     subjects affected / exposed
0 / 403 (0.00%)
0 / 188 (0.00%)

More information

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Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? No

Interruptions (globally)
Were there any global interruptions to the trial? No

Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
None reported

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