Download PDF

Clinical Trial Results:
A double-blind, randomised, placebo-controlled study on the efficacy of Iberogast® (STW 5) in patients with irritable bowel syndrome

Summary
EudraCT number	2011-002613-10
Trial protocol	DE
Global end of trial date	25 Oct 2017

Results information
Results version number	v1(current)
This version publication date	09 Nov 2018
First version publication date	09 Nov 2018
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

BAY98-7411/17063

ISRCTN number

US NCT number

NCT01940848

WHO universal trial number (UTN)

Sponsor organisation name

Bayer AG

Sponsor organisation address

Kaiser-Wilhelm-Allee, D-51368 Leverkusen, Germany,

Public contact

Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com

Scientific contact

Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

25 Oct 2017

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

25 Oct 2017

Was the trial ended prematurely?

Main objective of the trial

The primary objective of this study was to show the efficacy of STW 5 (Iberogast, BAY98-7411) on pain related symptoms of subjects with irritable bowel syndrome (IBS).

Protection of trial subjects

The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with ethical principles that have their origin in the Declaration of Helsinki and the International Council for Harmonization guideline E6: Good Clinical Practice. Before entering the study, the informed consent was read by and explained to all the subjects. Participating subjects signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.

Background therapy

Evidence for comparator

Actual start date of recruitment

11 Oct 2013

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Germany: 243

Worldwide total number of subjects

243

EEA total number of subjects

243

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

205

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Study was conducted at 19 active study centers in Germany, between 11 October 2013 (first subject first visit) and 05 July 2017 (last subject last visit).

Screening details

Overall, 320 subjects were screened, of them 77 subjects failed screening: 68 did not fulfil eligibility criteria, 3 lost to follow up, 5 withdrew informed consent and 1 due to other reason. A total of 243 subjects were randomized and received at least one dose of study medication.

Period 1 title

Overall Trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

STW 5 (Iberogast)

Arm description

Subjects received STW 5 orally 20 drops three times daily (3*20 drops per day) before or during the meals for 4 weeks (from Day 1 to Day 29).

Arm type

Experimental

Investigational medicinal product name

STW 5

Investigational medicinal product code

BAY98-7411

Other name

Iberogast

Pharmaceutical forms

Oral drops, liquid

Routes of administration

Oral use

Dosage and administration details

Subjects received STW 5 orally 20 drops three times daily (3*20 drops per day) before or during the meals for 4 weeks (from Day 1 to Day 29).

Placebo

Arm description

Subjects received placebo matched to STW 5 orally 20 drops three times daily (3*20 drops per day) before or during the meals for 4 weeks (from Day 1 to Day 29).

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral drops, liquid

Routes of administration

Oral use

Dosage and administration details

Subjects received placebo matched to STW 5 orally 20 drops three times daily (3*20 drops per day) before or during the meals for 4 weeks (from Day 1 to Day 29).

Number of subjects in period 1	STW 5 (Iberogast)	Placebo
Started	167	76
Completed	152	72
Not completed	15	4
Eligibility criteria not fulfilled	-	1
Lack of therapeutic response	1	1
Adverse event, other reason	1	-
Adverse event	4	-
Other reason	2	1
Withdrawal of informed consent	3	1
Subject lost to follow up	4	-

Baseline characteristics

Top of page

Reporting group title

STW 5 (Iberogast)

Reporting group description

Subjects received STW 5 orally 20 drops three times daily (3*20 drops per day) before or during the meals for 4 weeks (from Day 1 to Day 29).

Reporting group title

Placebo

Reporting group description

Subjects received placebo matched to STW 5 orally 20 drops three times daily (3*20 drops per day) before or during the meals for 4 weeks (from Day 1 to Day 29).

Reporting group values	STW 5 (Iberogast)	Placebo	Total
Number of subjects	167	76	243
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	46.7 ± 16.59	46.9 ± 17.24	-
Gender categorical
Units: Subjects
Female	129	61	190
Male	38	15	53
IBS type
IBS is chronic, relapsing gastrointestinal disorder, characterized by abdominal pain, bloating and changes in bowel habit. IBS regarding ROME III is associated with recurrent abdominal pain or discomfort at least 3 days /month in last 3 months is associated with two or more of following: 1)improvement with defecation, 2)onset associated with change in frequency of stool, 3)onset associated with change in form (appearance) of stool. Diarrhoea-predominant IBS (IBS-D), Constipation-predominant- IBS (IBS-C) were included in the study.
Units: Subjects
IBS-C	50	25	75
IBS-D	63	27	90
Not classifiable	54	24	78
Time from date of first diagnosis of IBS
Time from date of first diagnosis of IBS until date of informed consent was described by statistical characteristics according to the nature and distribution of the data.
Units: years
arithmetic mean (standard deviation)	8.1 ± 9.80	7.4 ± 7.47	-
Irritable bowel syndrome-quality of life measure (IBS-QoL) total score
IBS-QoL is a self-report QoL measure to assess impact of IBS and its treatment. It consists of 34 items, each with a 5-point response scale. Individual responses to 34 items were summed up, averaged for total score, then transformed to 0-100 scale. Higher scores indicate better IBS specific quality of life. The number of subjects analysed signifies subjects who were evaluable for this parameter, for each arm respectively, (n=225, STW 5 = 154, placebo = 71).
Units: score on a scale
arithmetic mean (standard deviation)	59.19 ± 19.184	55.21 ± 17.629	-
Feeling of complete evacuation
Evacuation is defined as mean daily number of defecations during analyzed period multiplied by 7 for the weekly standardization. The FAS (N=237) included all randomized subjects who received at least one dose of study medication and whose post randomization assessment of data of efficacy were available at least.
Units: number of defecations per day*7
arithmetic mean (standard deviation)	5.05 ± 4.226	5.29 ± 6.190	-
Feeling of incomplete evacuation
Evacuation is defined as mean daily number of defecations during analyzed period multiplied by 7 for the weekly standardization. The FAS (N=237) included all randomized subjects who received at least one dose of study medication and whose post randomization assessment of data of efficacy were available at least.
Units: number of defecations per day*7
arithmetic mean (standard deviation)	5.73 ± 5.729	5.10 ± 4.792	-
Stool consistency in IBS-C subgroup
Stool consistency was assessed in subjects with constipation-predominant IBS by the bristol stool form scale (BSS). The BSS provides a pictorial and verbal description of stool consistency, and form and is an appropriate instrument for capturing stool consistency. As per BSS: types 1-2, hard (suggestive of constipation); types 3-5, normal; types 6-7, loose/liquid (associated with diarrhoea). IBS-C (N=74) included all subjects with constipation-predominant IBS in the FAS.
Units: stool consistency
arithmetic mean (standard deviation)	2.88 ± 0.613	2.49 ± 0.796	-
Stool consistency in IBS-D subgroup
Stool consistency was assessed in subjects with diarrhoea-predominant IBS by the BSS. The BSS provides a pictorial and verbal description of stool consistency, and form and is an appropriate instrument for capturing stool consistency. As per BSS: types 1-2, hard (suggestive of constipation); types 3-5, normal; types 6-7, loose/liquid (associated with diarrhoea). IBS-D (N=88) included all subjects with diarrhoea-predominant IBS in the FAS.
Units: stool consistency
arithmetic mean (standard deviation)	5.15 ± 0.671	5.04 ± 0.663	-
Weekly usage of bisacodyl tablets
Subjects were instructed to use bisacodyl only in case of absence of bowel movements for more than three days. Investigators dispensed the rescue medication bisacodyl for treatment of severe constipation. The FAS (N=237) included all randomized subjects who received at least one dose of study medication and whose post randomization assessment of data of efficacy were available at least.
Units: number of tablets
arithmetic mean (standard deviation)	0.18 ± 0.591	0.47 ± 1.425	-
Weekly usage of loperamid tablets
Subjects were instructed to use loperamide only in case of three consecutive bowel movements with type 6 according to BSS or in case of first bowel movement with type 7 according to BSS. As per BSS: types 1-2, hard(suggestive of constipation); types 3-5, normal; types 6-7, loose/liquid (associated with diarrhoea). Investigators dispensed the rescue medication loperamide for treatment of severe diarrhoea. The FAS (N=237) included all randomized subjects who received at least one dose of study medication and whose post randomization assessment of data of efficacy were available at least.
Units: number of tablets
arithmetic mean (standard deviation)	0.22 ± 1.060	0.16 ± 0.616	-
Birmingham IBS symptom questionnaire total score
Birmingham IBS symptom score comprises a self-completed questionnaire which consists of 11 questions based on frequency of IBS related symptoms. Birmingham IBS symptom questionnaire completed by subjects provides assessment in 3 dimensions pain, constipation and diarrhoea based on frequency of symptoms. All single items of questionnaire were then transformed to a total score ranging from 0 (no symptoms) to 100 (all symptoms). The number of subjects analysed signifies subjects who were evaluable for this parameter, for each arm respectively, (n=230, STW 5 = 158, placebo =72).
Units: score on a scale
arithmetic mean (standard deviation)	37.62 ± 11.810	36.31 ± 11.295	-
Birmingham IBS symptom pain sub scale
Birmingham IBS symptom score comprises a self-completed questionnaire. This questionnaire completed by the subjects provides assessment in three dimensions pain, constipation and diarrhoea based on the frequency of symptoms. Pain subscale included questions related to ‘Pain’, ‘Pain after eating’ and ‘Sleep problem.’ The items within each dimension were summed up and transformed to a scale ranging from 0 (no symptoms) to 100 (all symptoms). The number of subjects analysed signifies subjects who were evaluable for this parameter, for each arm respectively, (n=236, STW 5 = 161, placebo =75).
Units: score on a scale
arithmetic mean (standard deviation)	55.20 ± 16.197	54.04 ± 16.424	-
Birmingham IBS symptom constipation sub scale
Birmingham IBS symptom score comprises a self-completed questionnaire. Questionnaire completed by subjects provides assessment in 3 dimensions pain, constipation, diarrhoea based on frequency of symptoms. Constipation subscale included questions related to ‘hard bowel motions’, ‘straining’, ‘constipation’. Items within each dimension were summed up, transformed to a scale ranging from 0 (no symptoms) to 100 (all symptoms). The number of subjects analysed signifies subjects who were evaluable for this parameter, for each arm respectively, (n = 235, STW 5 = 162, placebo = 73).
Units: score on a scale
arithmetic mean (standard deviation)	33.29 ± 25.958	35.53 ± 32.031	-
Birmingham IBS symptom diarrhoea sub scale
Birmingham IBS symptom score comprises a self-completed questionnaire. Questionnaire completed by subjects provides assessment in 3 dimensions pain, constipation and diarrhoea based on frequency of symptoms. Diarrhoea subscale included questions related to Loose, watery stools, diarrhoea, leaked or soiled, urgency, mucus or slime. Items within each dimension were summed up, transformed to a scale ranging from 0 (no symptoms) to 100 (all symptoms). Number of subjects analysed signifies subjects who were evaluable for this parameter, for each arm respectively, (n= 231, STW 5 = 158, placebo =73).
Units: score on a scale
arithmetic mean (standard deviation)	29.39 ± 18.126	26.41 ± 19.087	-
IBS-C: Birmingham IBS symptom questionnaire total score
Birmingham IBS symptom score comprises a self-completed questionnaire. It consists of 11 questions based on frequency of IBS related symptoms. Questionnaire completed by subjects provides assessment in 3 dimensions pain, constipation, diarrhoea based on frequency of symptoms. All single items of questionnaire were then transformed to a total score ranging from 0 (no symptoms) to 100 (all symptoms). Number of subjects analysed signifies subjects who were evaluable for this parameter, for each arm respectively, (n= 73, STW 5 = 48, placebo =25).
Units: score on a scale
arithmetic mean (standard deviation)	37.61 ± 10.204	37.75 ± 11.645	-
IBS-D: Birmingham IBS symptom questionnaire total score
Birmingham IBS symptom score comprises a self-completed questionnaire. It consists of 11 questions based on frequency of IBS related symptoms. This questionnaire completed by the subjects provides assessment in three dimensions pain, constipation and diarrhoea based on the frequency of symptoms. All single items of the questionnaire were then transformed to a total score ranging from 0 (no symptoms) to 100 (all symptoms). Number of subjects analysed signifies subjects who were evaluable for this parameter, for each arm respectively, (n= 84, STW 5 = 59, placebo =25).
Units: score on a scale
arithmetic mean (standard deviation)	39.91 ± 11.785	37.75 ± 9.305	-
IBS-C: Birmingham IBS symptom pain dimension sub scale
Birmingham IBS symptom score comprises a self-completed questionnaire. This questionnaire completed by subjects provides assessment in three dimensions pain, constipation, diarrhoea based on frequency of symptoms. Pain subscale included questions related to ‘Pain’, ‘Pain after eating’ and ‘Sleep problem.’ The items within each dimension were summed up and transformed to a scale ranging from 0 (no symptoms) to 100 (all symptoms). Number of subjects analysed signifies subjects who were evaluable for this parameter, for each arm respectively, (n= 73, STW 5 = 48, placebo =25).
Units: score on a scale
arithmetic mean (standard deviation)	54.86 ± 18.412	56.53 ± 16.791	-
IBS-C: Birmingham IBS symptom constipation dimension sub scale
Birmingham IBS symptom score comprises a self-completed questionnaire. Questionnaire completed by subjects provides assessment in three dimensions pain, constipation and diarrhoea based on frequency of symptoms. Constipation subscale included questions related to hard bowel motions, straining, constipation’. Items within each dimension were summed up and transformed to a scale ranging from 0 (no symptoms) to 100 (all symptoms). IBS-C (N=74, STW 5 = 49, placebo =25) included all subjects with constipation-predominant IBS in the FAS.
Units: score on a scale
arithmetic mean (standard deviation)	50.34 ± 23.494	62.67 ± 30.852	-
IBS-C: Birmingham IBS symptom diarrhea dimension sub scale
Birmingham IBS symptom score comprises a self-completed questionnaire. Questionnaire completed by subjects provides assessment in 3 dimensions pain, constipation, diarrhoea based on frequency of symptoms. Diarrhoea subscale included questions related to Loose, watery stools, diarrhoea, leaked or soiled, urgency, mucus or slime. Items within each dimension were summed up, transformed to a scale ranging from 0 (no symptoms) to 100 (all symptoms). The number of subjects analysed signifies subjects who were evaluable for this parameter, for each arm respectively, (n= 74, STW 5 = 48, placebo =25).
Units: score on a scale
arithmetic mean (standard deviation)	19.58 ± 12.922	11.52 ± 11.450	-
IBS-D: Birmingham IBS symptom pain dimension sub scale
Birmingham IBS symptom score comprises a self-completed questionnaire. This questionnaire completed by subjects provides assessment in three dimensions pain, constipation, diarrhoea based on frequency of symptoms. Pain subscale included questions related to Pain, Pain after eating and Sleep problem. The items within each dimension were summed up and transformed to a scale ranging from 0 (no symptoms) to 100 (all symptoms). IBS-D (N=88, STW 5=61, placebo= 27) included all subjects with diarrhoea-predominant IBS in the FAS.
Units: score on a scale
arithmetic mean (standard deviation)	57.70 ± 14.084	56.05 ± 16.357	-
IBS-D: Birmingham IBS symptom constipation dimension sub scale
Birmingham IBS symptom score comprises a self-completed questionnaire. Questionnaire completed by subjects provides assessment in three dimensions pain, constipation and diarrhoea based on frequency of symptoms. Constipation subscale included questions related to hard bowel motions, straining, constipation’. Items within each dimension were summed up and transformed to a scale ranging from 0 (no symptoms) to 100 (all symptoms). Number of subjects analysed signifies subjects who were evaluable for this parameter, for each arm respectively, (n= 87, STW 5 = 61, placebo =26).
Units: score on a scale
arithmetic mean (standard deviation)	20.44 ± 20.399	14.36 ± 12.746	-
IBS-D: Birmingham IBS symptom diarrhea dimension sub scale
Birmingham IBS symptom score comprises a self-completed questionnaire. Questionnaire completed by subjects provides assessment in 3 dimensions pain, constipation, diarrhoea based on frequency of symptoms. Diarrhoea subscale included questions related to Loose, watery stools, diarrhoea, leaked or soiled, urgency, mucus or slime. Items within each dimension were summed up, transformed to a scale ranging from 0 (no symptoms) to 100 (all symptoms). Number of subjects analysed signifies subjects who were evaluable for this parameter, for each arm respectively, (n= 85, STW 5 = 59, placebo =26).
Units: score on a scale
arithmetic mean (standard deviation)	40.68 ± 17.983	41.54 ± 14.841	-

End points

Top of page

Reporting group title

STW 5 (Iberogast)

Reporting group description

Subjects received STW 5 orally 20 drops three times daily (3*20 drops per day) before or during the meals for 4 weeks (from Day 1 to Day 29).

Reporting group title

Placebo

Reporting group description

Subjects received placebo matched to STW 5 orally 20 drops three times daily (3*20 drops per day) before or during the meals for 4 weeks (from Day 1 to Day 29).

Subject analysis set title

Safety analysis set (SAF)

Subject analysis set type

Safety analysis

Subject analysis set description

SAF (N= 243) included all randomized subjects who received at least one dose of study medication.

Subject analysis set title

Full analysis set (FAS)

Subject analysis set type

Full analysis

Subject analysis set description

FAS (N=237) included all randomized subjects who received at least one dose of study medication and whose post randomization assessment of data of efficacy were available at least. The FAS includes subjects with treatment effects measured, according to the intention-to-treat principle.

Subject analysis set title

IBS with predominant constipation (IBS-C)

Subject analysis set type

Sub-group analysis

Subject analysis set description

IBS-C (N=74) included all subjects with constipation-predominant IBS in the FAS.

Subject analysis set title

IBS with predominant diarrhoea (IBS-D)

Subject analysis set type

Sub-group analysis

Subject analysis set description

IBS-D (N=88) included all subjects with diarrhoea-predominant IBS in the FAS.

Primary: Response Rate for Abdominal Pain Intensity After 4 Weeks of Treatment

Top of page

End point title

Response Rate for Abdominal Pain Intensity After 4 Weeks of Treatment

End point description

The abdominal pain intensity was evaluated by using an 10 centimeters (cm) visual analogue scale (VAS) ranging from no pain to worst pain that asked subjects daily to rate their ‘worst abdominal pain over the past 24-hours’. Rate of responders with decrease of worst abdominal pain in past 24 hours score of greater than or equal to (>=) 30 percentage (%) compared with baseline for at least 14 single days within the first 4 weeks of study treatment determined by daily assessment on a VAS was measured.

End point type

Primary

End point timeframe

From start of study drug administration up to 4 weeks of treatment

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	162 ^[1]	75 ^[2]
Units: percentage of subjects
number (not applicable)	40.7	42.7

Notes
[1] - FAS
[2] - FAS

Statistical analysis 1

Statistical analysis description

Within a Cochran-Mantel-Haenszel chi-square test controlling for centre, the odds ratio for the treatment comparison was determined together with the respective 95% confidence interval two-sided and the respective p-value.

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8678

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.54

upper limit

1.68

Secondary: Response Rate for Abdominal Pain Intensity After 2 Weeks of Treatment

Top of page

End point title

Response Rate for Abdominal Pain Intensity After 2 Weeks of Treatment

End point description

The abdominal pain intensity was evaluated using a 10 cm VAS ranging from no pain to worst pain that asked subjects daily to rate their “worst abdominal pain over the past 24-hours”. Rate of responders with decrease of worst abdominal pain in past 24 hours score of >= 30% compared with baseline for at least 7 single days within the first 2 weeks of study treatment determined by daily assessment on a VAS was measured.

End point type

Secondary

End point timeframe

From start of study drug administration up to 2 weeks of treatment

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	162 ^[3]	75 ^[4]
Units: percentage of subjects
number (not applicable)	39.5	42.7

Notes
[3] - FAS
[4] - FAS

Statistical analysis 1

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6552

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

1.54

Secondary: Irritable Bowel Syndrome - Quality of Life Measure (IBS-QoL): Change From Baseline for the Transformed Total Score at Week 4

Top of page

End point title

Irritable Bowel Syndrome - Quality of Life Measure (IBS-QoL): Change From Baseline for the Transformed Total Score at Week 4

End point description

IBS-QoL is a self-report QoL measure to assess impact of IBS and its treatment. It consists of 34 items, each with a 5-point response scale. Individual responses to 34 items were summed up, averaged for total score, then transformed to 0-100 scale. Higher scores indicate better IBS specific quality of life.

End point type

Secondary

End point timeframe

Baseline, Week 4

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	141 ^[5]	66 ^[6]
Units: score on a scale
arithmetic mean (standard deviation)	10.13 ± 15.365	9.98 ± 16.010

Notes
[5] - FAS with number of evaluable subjects for this specific end point.
[6] - FAS with number of evaluable subjects for this specific end point.

Statistical analysis 1

Statistical analysis description

IBS-QoL was tested using an analysis of covariance (ANCOVA) model with treatment, center and underlying IBS type as fixed effects and the baseline value as covariate. Results were presented by differences in least-square means (LS mean difference) together with the corresponding p-values and 95% confidence intervals.

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

207

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3607

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

1.9

Confidence interval

level

95%

sides

2-sided

lower limit

-2.19

upper limit

Secondary: Responders Regarding Stool Frequency in IBS-C Subgroup After 4 Weeks of Treatment

Top of page

End point title

Responders Regarding Stool Frequency in IBS-C Subgroup After 4 Weeks of Treatment

End point description

Stool frequency responder in constipation-predominant-IBS sub group is defined as subject with increase of one or more complete spontaneous bowel movements (CSBM) per week compared with baseline for at least 50% of analyzed weeks.

End point type

Secondary

End point timeframe

From start of study drug administration up to 4 weeks of treatment

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	49 ^[7]	25 ^[8]
Units: count of subjects
number (not applicable)	20	11

Notes
[7] - IBS-C subgroup of FAS.
[8] - IBS-C subgroup of FAS.

Statistical analysis 1

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9753

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

0.98

Confidence interval

level

95%

sides

2-sided

lower limit

0.33

upper limit

2.9

Secondary: Responders Regarding Stool Consistency in IBS-D Subgroup After 4 Weeks of Treatment

Top of page

End point title

Responders Regarding Stool Consistency in IBS-D Subgroup After 4 Weeks of Treatment

End point description

Stool consistency responder in IBS with diarrhoea-predominant sub group is defined as subject with decrease in weekly average of greater than (>) 1 in terms of BSS for at least 50% of analyzed weeks. Stool consistency was assessed by Bristol Stool Form Scale (BSS). The BSS provides a pictorial and verbal description of stool consistency and form. It is an appropriate instrument for capturing stool consistency in IBS trials. As per BSS: types 1-2, hard (suggestive of constipation); types 3-5, normal; types 6-7, loose/liquid (associated with diarrhoea).

End point type

Secondary

End point timeframe

From start of study drug administration up to 4 weeks of treatment

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	61 ^[9]	27 ^[10]
Units: count of subjects
number (not applicable)	16	10

Notes
[9] - IBS-D subgroup of FAS.
[10] - IBS-D subgroup of FAS.

Statistical analysis 1

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2952

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

0.58

Confidence interval

level

95%

sides

2-sided

lower limit

0.21

upper limit

1.6

Secondary: Responders Regarding Stool Frequency for IBS-C Subgroup After 2 Weeks of Treatment

Top of page

End point title

Responders Regarding Stool Frequency for IBS-C Subgroup After 2 Weeks of Treatment

End point description

Stool frequency responder in constipation-predominant-IBS sub group is defined as subject with increase of one or more CSBM per week compared with baseline for at least 50% of analyzed weeks.

End point type

Secondary

End point timeframe

From start of study drug administration up to 2 weeks of treatment

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	49 ^[11]	25 ^[12]
Units: count of subjects
number (not applicable)	22	11

Notes
[11] - IBS-C subgroup of FAS.
[12] - IBS-C subgroup of FAS.

Statistical analysis 1

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7125

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

1.22

Confidence interval

level

95%

sides

2-sided

lower limit

0.44

upper limit

3.35

Secondary: Responders Regarding Stool Consistency in IBS-D Subgroup After 2 Weeks of Treatment

Top of page

End point title

Responders Regarding Stool Consistency in IBS-D Subgroup After 2 Weeks of Treatment

End point description

Stool consistency responder in IBS with diarrhoea-predominant sub group is defined as subject with decrease in weekly average of >1 in terms of BSS for at least 50% of analyzed weeks. Stool consistency was assessed by Bristol Stool Form Scale (BSS). The BSS provides a pictorial and verbal description of stool consistency and form. It is an appropriate instrument for capturing stool consistency in IBS trials. As per BSS: types 1-2, hard (suggestive of constipation); types 3-5, normal; types 6-7, loose/liquid (associated with diarrhoea).

End point type

Secondary

End point timeframe

From start of study drug administration up to 2 weeks of treatment

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	61 ^[13]	27 ^[14]
Units: count of subjects
number (not applicable)	20	10

Notes
[13] - IBS-D subgroup of FAS.
[14] - IBS-D subgroup of FAS.

Statistical analysis 1

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6279

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.29

upper limit

2.08

Secondary: Change of Pain Intensity From Baseline to Week 4

Top of page

End point title

Change of Pain Intensity From Baseline to Week 4

End point description

The abdominal pain intensity was evaluated by using the 10 cm VAS ranging from no pain to worst pain that asked subjects daily to rate their ‘worst abdominal pain over the past 24-hours’.

End point type

Secondary

End point timeframe

Baseline, Week 4

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	144 ^[15]	69 ^[16]
Units: centimeter (cm)
arithmetic mean (standard deviation)	-1.91 ± 2.599	-2.29 ± 3.009

Notes
[15] - FAS with number of evaluable subjects for this specific end point.
[16] - FAS with number of evaluable subjects for this specific end point.

Statistical analysis 1

Statistical analysis description

Change of pain intensity was tested using an ANCOVA model with last VAS value at Week 4 adjusted for treatment, center and underlying IBS type and last VAS baseline value. Results were presented by differences in least-square means (LS mean difference) together with the corresponding p-values and 95% confidence intervals.

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

213

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5943

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

0.17

Confidence interval

level

95%

sides

2-sided

lower limit

-0.47

upper limit

0.81

Secondary: Change of Pain Intensity From Baseline to Week 2

Top of page

End point title

Change of Pain Intensity From Baseline to Week 2

End point description

The abdominal pain intensity was evaluated by using an 10 cm VAS ranging from no pain to worst pain that asked subjects daily to rate their ‘worst abdominal pain over the past 24-hours’.

End point type

Secondary

End point timeframe

Baseline, Week 2

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	158 ^[17]	73 ^[18]
Units: centimeter (cm)
arithmetic mean (standard deviation)	-1.57 ± 2.589	-1.62 ± 2.568

Notes
[17] - FAS with number of evaluable subjects for this specific end point.
[18] - FAS with number of evaluable subjects for this specific end point.

Statistical analysis 1

Statistical analysis description

Change of pain intensity was tested using an ANCOVA model with last VAS value at Week 2 adjusted for treatment, center and underlying IBS type and last VAS baseline value. Results were presented by differences in least-square means (LS mean difference) together with the corresponding p-values and 95% confidence intervals.

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

231

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5637

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-0.19

Confidence interval

level

95%

sides

2-sided

lower limit

-0.83

upper limit

0.45

Secondary: Response Rate for Abdominal Pain Intensity After First 7 Days of Treatment (Early Responders)

Top of page

End point title

Response Rate for Abdominal Pain Intensity After First 7 Days of Treatment (Early Responders)

End point description

Early responders were defined as subjects responding regarding pain intensity for at least 4 days during the first 7 days of the treatment period. The abdominal pain intensity was evaluated by using an 10 cm VAS ranging from no pain to worst pain that asked subjects daily to rate their ‘worst abdominal pain over the past 24-hours’.

End point type

Secondary

End point timeframe

From the start of study drug administration until first 7 days of treatment

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	162 ^[19]	75 ^[20]
Units: percentage of subjects
number (not applicable)	30.2	28.0

Notes
[19] - FAS
[20] - FAS

Statistical analysis 1

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5692

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

1.2

Confidence interval

level

95%

sides

2-sided

lower limit

0.64

upper limit

2.26

Secondary: Response Rate for Abdominal Pain Intensity in the Last 14 Days of Treatment (Late Responders)

Top of page

End point title

Response Rate for Abdominal Pain Intensity in the Last 14 Days of Treatment (Late Responders)

End point description

Late responders were defined as subjects responding regarding pain intensity for at least 7 days during the last 14 days of the treatment period. The abdominal pain intensity was evaluated by using an 10 cm VAS ranging from no pain to worst pain that asked subjects daily to rate their ‘worst abdominal pain over the past 24-hours’.

End point type

Secondary

End point timeframe

From the start of study drug administration until last 14 days of treatment

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	162 ^[21]	75 ^[22]
Units: percentage of subjects
number (not applicable)	50.6	53.3

Notes
[21] - FAS
[22] - FAS

Statistical analysis 1

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7926

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

0.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.52

upper limit

1.65

Secondary: Feeling of Completed Evacuation - Change From Baseline to Week 4

Top of page

End point title

Feeling of Completed Evacuation - Change From Baseline to Week 4

End point description

Evacuation is defined as mean daily number of defecations during analyzed period multiplied by 7 for the weekly standardization.

End point type

Secondary

End point timeframe

Baseline, Week 4

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	151 ^[23]	71 ^[24]
Units: number of defecations per day*7
arithmetic mean (standard deviation)	0.54 ± 2.554	0.68 ± 3.485

Notes
[23] - FAS with number of evaluable subjects for this specific end point.
[24] - FAS with number of evaluable subjects for this specific end point.

Statistical analysis 1

Comparison groups

Placebo v STW 5 (Iberogast)

Number of subjects included in analysis

222

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4411

Method

Wilcoxon rank sum test

Confidence interval

Secondary: Feeling of Incomplete Evacuation – Change From Baseline to Week 4

Top of page

End point title

Feeling of Incomplete Evacuation – Change From Baseline to Week 4

End point description

Evacuation is defined as mean daily number of defecations during analyzed period multiplied by 7 for the weekly standardization.

End point type

Secondary

End point timeframe

Baseline, Week 4

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	151 ^[25]	71 ^[26]
Units: number of defecations per day*7
arithmetic mean (standard deviation)	-1.33 ± 3.731	-1.45 ± 4.722

Notes
[25] - FAS with number of evaluable subjects for this specific end point.
[26] - FAS with number of evaluable subjects for this specific end point.

Statistical analysis 1

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

222

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5169

Method

Wilcoxon rank sum test

Confidence interval

Secondary: Stool Consistency in IBS-C and IBS-D Subgroups-Change From Baseline to Week 4

Top of page

End point title

Stool Consistency in IBS-C and IBS-D Subgroups-Change From Baseline to Week 4

End point description

Stool consistency was assessed by the BSS. The BSS provides a pictorial and verbal description of stool consistency and form and is an appropriate instrument for capturing stool consistency. As per BSS: types 1-2, hard (suggestive of constipation); types 3-5, normal; types 6-7, loose/liquid (associated with diarrhoea). In the below table, ‘n’ signifies those subjects who were evaluable for this measure at given time points for each group.

End point type

Secondary

End point timeframe

Baseline, Week 4

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	52 ^[27]	27 ^[28]
Units: score on BSS scale
arithmetic mean (standard deviation)
IBS-C (n= 47, 22)	0.53 ± 1.020	0.39 ± 0.705
IBS-D (n= 52, 27)	-0.43 ± 0.752	-0.51 ± 1.076

Notes
[27] - FAS with number of evaluable subjects for this end point.
[28] - FAS with number of evaluable subjects for this end point.

No statistical analyses for this end point

Secondary: Change From Baseline in Weekly Usage of Bisacodyl Tablets

Top of page

End point title

Change From Baseline in Weekly Usage of Bisacodyl Tablets

End point description

Subjects were instructed to use bisacodyl only in case of absence of bowel movements for more than three days. Investigators dispensed the rescue medication bisacodyl for treatment of severe constipation. The weekly usage of rescue medication was analysed descriptively and differences between the treatment groups were additionally assessed with a Wilcoxon rank sum test. In the below table, ‘n’ signifies those subjects who were evaluable for this measure at given time points for each group.

End point type

Secondary

End point timeframe

Baseline, Weeks 1, 2, 3 and 4

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	161 ^[29]	75 ^[30]
Units: number of tablets
arithmetic mean (standard deviation)
Change at Week 1 (n= 161,75)	-0.02 ± 0.474	-0.20 ± 0.737
Change at Week 2 (n= 160,73)	-0.06 ± 0.630	-0.22 ± 0.821
Change at Week 3 (n= 155,73)	-0.01 ± 0.938	-0.28 ± 1.096
Change at Week 4 (n= 151,71)	-0.09 ± 0.431	-0.29 ± 1.171

Notes
[29] - FAS with number of evaluable subjects for this end point.
[30] - FAS with number of evaluable subjects for this end point.

No statistical analyses for this end point

Secondary: Change From Baseline in Weekly Usage of Loperamid Tablets

Top of page

End point title

Change From Baseline in Weekly Usage of Loperamid Tablets

End point description

Subjects were instructed to use loperamide only in case of three consecutive bowel movements with type 6 according to BSS or in case of first bowel movement with type 7 according to BSS. As per BSS: types 1-2, hard (suggestive of constipation); types 3-5, normal; types 6-7, loose/liquid (associated with diarrhoea). Investigators dispensed the rescue medication loperamide for treatment of severe diarrhoea. The weekly usage of rescue medication was analysed descriptively and differences between the treatment groups were additionally assessed with a Wilcoxon rank sum test. In the below table, ‘n’ signifies those subjects who were evaluable for this measure at given time points for each group.

End point type

Secondary

End point timeframe

Baseline, Weeks 1, 2, 3 and 4

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	161 ^[31]	75 ^[32]
Units: number of tablets
arithmetic mean (standard deviation)
Change at Week 1 (n= 161,75)	-0.01 ± 0.981	0.01 ± 0.822
Change at Week 2 (n= 160,73)	-0.04 ± 0.563	-0.03 ± 0.616
Change at Week 3 (n= 155,73)	-0.01 ± 0.983	-0.07 ± 0.486
Change at Week 4 (n= 151,71)	0.03 ± 0.660	0.04 ± 0.881

Notes
[31] - FAS with number of evaluable subjects for this end point.
[32] - FAS with number of evaluable subjects for this end point.

No statistical analyses for this end point

Secondary: Birmingham IBS Symptom Questionnaire – Change Between Week 1 and Week 4 for the Total Score

Top of page

End point title

Birmingham IBS Symptom Questionnaire – Change Between Week 1 and Week 4 for the Total Score

End point description

The Birmingham IBS symptom score comprises a self-completed questionnaire which consists of 11 questions based on the frequency of IBS related symptoms. The Birmingham IBS symptom questionnaire completed by the subjects provides assessment in the three dimensions pain, constipation and diarrhoea based on the frequency of symptoms. All single items of the questionnaire were then transformed to a total score ranging from 0 (no symptoms) to 100 (all symptoms).

End point type

Secondary

End point timeframe

Week 1 (Baseline), Week 4

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	143 ^[33]	64 ^[34]
Units: score on a scale
arithmetic mean (standard deviation)	-11.04 ± 13.011	-10.80 ± 13.571

Notes
[33] - FAS with number of evaluable subjects for this end point.
[34] - FAS with number of evaluable subjects for this end point.

No statistical analyses for this end point

Secondary: Birmingham IBS Symptom Questionnaire – Change Between Week 1 and Week 4 for the 3 Dimensions

Top of page

End point title

Birmingham IBS Symptom Questionnaire – Change Between Week 1 and Week 4 for the 3 Dimensions

End point description

Birmingham IBS symptom score comprises a self-completed questionnaire. It consists of 11 questions based on frequency of IBS related symptoms. This questionnaire completed by the subjects provides assessment in three dimensions pain, constipation and diarrhoea based on the frequency of symptoms. All single items of the questionnaire were then transformed to a total score ranging from 0 (no symptoms) to 100 (all symptoms). In the below table ‘n’ signifies those subjects who were evaluable for this measure at given time points for each group.

End point type

Secondary

End point timeframe

Week 1 (Baseline), Week 4

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	151 ^[35]	68 ^[36]
Units: score on a scale
arithmetic mean (standard deviation)
Birmingham IBS symptom pain sub scale (n=151,68)	-18.06 ± 20.332	-16.57 ± 20.329
BirminghamIBSsymptomconstipationsubscale(n=151,68)	-8.57 ± 20.431	-8.14 ± 19.474
Birmingham IBSsymptom diarrhoea subscale(n=144,67)	-8.14 ± 15.520	-8.96 ± 16.508

Notes
[35] - FAS with number of evaluable subjects for this end point.
[36] - FAS with number of evaluable subjects for this end point.

No statistical analyses for this end point

Secondary: Birmingham IBS Symptom Questionnaire – Change Between Week 1 and Week 4 for the 3 Single Items of Questionnaire

Top of page

End point title

Birmingham IBS Symptom Questionnaire – Change Between Week 1 and Week 4 for the 3 Single Items of Questionnaire

End point description

The Birmingham IBS symptom score comprises a self-completed questionnaire which consists of 11 questions based on the frequency of IBS related symptoms. Each question has a standard response scale with symptoms all being measured on a 6-point Likert scale ranging from 0=none of the time to 5=all of the time. The Birmingham IBS symptom questionnaire completed by the subjects provides assessment in the three dimensions pain, constipation and diarrhoea based on the frequency of symptoms. Birmingham IBS questionnaire three single items ‘Diarrhoea’, ‘Constipation’ and ‘Urgency’ were provided. In the below table, shifts in the scores from the baseline were analysed and reported. ‘n’ signifies those subjects who were evaluable for this measure at given time points for each group. '99999' signifies no subjects fall under the below mentioned criteria in the category for the given time points for respective reporting groups.

End point type

Secondary

End point timeframe

Week 1 (Baseline), Week 4

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	152 ^[37]	70 ^[38]
Units: count of subjects
Diarrhoea item score -4 (n= 149,68)	99999	1
Diarrhoea item score -3 (n= 149,68)	4	1
Diarrhoea item score -2 (n= 149,68)	13	13
Diarrhoea item score -1 (n= 149,68)	41	15
Diarrhoea item score 0 (n= 149,68)	69	30
Diarrhoea item score 1 (n= 149,68)	19	7
Diarrhoea item score 2 (n= 149,68)	1	1
Diarrhoea item score 3 (n= 149,68)	2	99999
Constipation item score -5 (n= 152,68)	99999	1
Constipation item score -4 (n= 152,68)	1	99999
Constipation item score -3 (n= 152,68)	7	5
Constipation item score -2 (n= 152,68)	17	3
Constipation item score -1 (n= 152,68)	34	16
Constipation item score 0 (n= 152,68)	66	36
Constipation item score 1 (n= 152,68)	23	5
Constipation item score 2 (n= 152,68)	4	2
Urgency item score -5 (n= 152,70)	2	99999
Urgency item score -4 (n= 152,70)	4	4
Urgency item score -3 (n= 152,70)	3	3
Urgency item score -2 (n= 152,70)	24	8
Urgency item score -1 (n= 152,70)	50	16
Urgency item score 0 (n= 152,70)	46	18
Urgency item score 1 (n= 152,70)	16	16
Urgency item score 2 (n= 152,70)	5	2
Urgency item score 3 (n= 152,70)	1	2
Urgency item score 4 (n= 152,70)	1	1

Notes
[37] - FAS with number of evaluable subjects for this end point.
[38] - FAS with number of evaluable subjects for this end point.

No statistical analyses for this end point

Secondary: Birmingham IBS Symptom Questionnaire in IBS-C and IBS-D Subgroups – Change Between Week 1 and Week 4 for the Total Score

Top of page

End point title

Birmingham IBS Symptom Questionnaire in IBS-C and IBS-D Subgroups – Change Between Week 1 and Week 4 for the Total Score

End point description

Birmingham IBS symptom questionnaire was evaluated in IBS-C and IBS-D subgroups for the total score. Birmingham IBS symptom score comprises a self-completed questionnaire. It consists of 11 questions based on frequency of IBS related symptoms. This questionnaire completed by the subjects provides assessment in three dimensions pain, constipation and diarrhoea based on the frequency of symptoms. All single items of the questionnaire were then transformed to a total score ranging from 0 (no symptoms) to 100 (all symptoms). In the below table, ‘n’ signifies those subjects who were evaluable for this measure at given time points for each group.

End point type

Secondary

End point timeframe

Week 1 (Baseline), Week 4

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	48 ^[39]	25 ^[40]
Units: score on a scale
arithmetic mean (standard deviation)
IBS-C (n= 44, 22)	-10.45 ± 13.205	-9.34 ± 12.181
IBS-D (n= 48, 25)	-13.98 ± 12.258	-14.47 ± 13.941

Notes
[39] - FAS with number of evaluable subjects for this end point.
[40] - FAS with number of evaluable subjects for this end point.

No statistical analyses for this end point

Secondary: Birmingham IBS Symptom Questionnaire in IBS-C and IBS-D Subgroups – Change Between Week 1 and Week 4 for the 3 Dimensions

Top of page

End point title

Birmingham IBS Symptom Questionnaire in IBS-C and IBS-D Subgroups – Change Between Week 1 and Week 4 for the 3 Dimensions

End point description

Birmingham IBS symptom questionnaire was evaluated in IBS-C and IBS-D subgroups for the 3 dimensions (pain, constipation, diarrhoea sub scales). Birmingham IBS symptom score comprises a self-completed questionnaire. It consists of 11 questions based on frequency of IBS related symptoms. This questionnaire completed by the subjects provides assessment in three dimensions pain, constipation and diarrhoea based on the frequency of symptoms. All single items of the questionnaire were then transformed to a total score ranging from 0 (no symptoms) to 100 (all symptoms). In the below table, ‘n’ signifies those subjects who were evaluable for this measure at given time points for each group.

End point type

Secondary

End point timeframe

Week 1 (Baseline), Week 4

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	52 ^[41]	27 ^[42]
Units: score on a scale
arithmetic mean (standard deviation)
IBS-C: IBS pain subscale (n=47,22)	-20.57 ± 21.120	-16.67 ± 23.254
IBS-C: IBS constipation subscale(n=47,23)	-13.19 ± 23.488	-14.49 ± 24.997
IBS-C: IBS diarrhoea subscale (n=45,23)	-2.58 ± 12.363	-1.04 ± 8.199
IBS-D: IBS pain subscale (n=52,27)	-21.54 ± 17.092	-22.22 ± 17.735
IBS-D: IBS constipation subscale (n=52,26)	-6.67 ± 14.995	-1.54 ± 12.119
IBS-D: IBS diarrhoea subscale (n=48,26)	-13.92 ± 18.761	-18.00 ± 17.933

Notes
[41] - FAS with number of evaluable subjects for this end point.
[42] - FAS with number of evaluable subjects for this end point.

No statistical analyses for this end point

Secondary: Birmingham IBS Symptom Questionnaire in IBS-C and IBS-D Subgroups –Change Between Week 1 and Week 4 for 3 Single Items of Questionnaire

Top of page

End point title

Birmingham IBS Symptom Questionnaire in IBS-C and IBS-D Subgroups –Change Between Week 1 and Week 4 for 3 Single Items of Questionnaire

End point description

Birmingham IBS symptom questionnaire was evaluated in IBS-C and IBS-D subgroups for 3 single items of questionnaire (diarrhoea, constipation, urgency items). The Birmingham IBS symptom score comprises a self-completed questionnaire which consists of 11 questions based on the frequency of IBS related symptoms. Each question has a standard response scale with symptoms all being measured on a 6-point Likert scale ranging from 0=none of the time to 5=all of the time. The Birmingham IBS symptom questionnaire completed by the subjects provides assessment in the three dimensions pain, constipation and diarrhoea based on the frequency of symptoms.In the below table, shifts in the scores from the baseline were analysed and reported. ‘n’ signifies those subjects who were evaluable for this measure at given time points for each group. '99999' signifies no subjects fall under the below mentioned criteria in the category for the given time points for respective reporting groups.

End point type

Secondary

End point timeframe

Week 1 (Baseline), Week 4

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	52 ^[43]	27 ^[44]
Units: count of subjects
number (not applicable)
IBS-C: Diarrhoea item score -2 (n= 47,23)	2	1
IBS-C: Diarrhoea item score -1 (n= 47,23)	7	4
IBS-C: Diarrhoea item score 0 (n= 47,23)	28	14
IBS-C: Diarrhoea item score 1 (n= 47,23)	7	3
IBS-C: Diarrhoea item score 2 (n= 47,23)	1	1
IBS-C: Diarrhoea item score 3 (n= 47,23)	2	99999
IBS-C: Constipation item score -5 (n= 48,23)	99999	1
IBS-C: Constipation item score -3 (n= 48,23)	5	3
IBS-C: Constipation item score -2 (n= 48,23)	6	3
IBS-C: Constipation item score -1 (n= 48,23)	14	5
IBS-C: Constipation item score 0 (n= 48,23)	12	9
IBS-C: Constipation item score 1 (n= 48,23)	8	1
IBS-C: Constipation item score 2 (n= 48,23)	3	1
IBS-C: Urgency item score -5 (n= 48,23)	1	99999
IBS-C: Urgency item score -4 (n= 48,23)	99999	1
IBS-C: Urgency item score -2 (n= 48,23)	7	1
IBS-C: Urgency item score -1 (n= 48,23)	9	6
IBS-C: Urgency item score 0 (n= 48,23)	23	7
IBS-C: Urgency item score 1 (n= 48,23)	6	6
IBS-C: Urgency item score 2 (n= 48,23)	2	2
IBS-D: Diarrhoea item score -4 (n= 50,27)	99999	1
IBS-D: Diarrhoea item score -3 (n= 50,27)	2	99999
IBS-D: Diarrhoea item score -2 (n= 50,27)	8	9
IBS-D: Diarrhoea item score -1 (n= 50,27)	17	6
IBS-D: Diarrhoea item score 0 (n= 50,27)	17	8
IBS-D: Diarrhoea item score 1 (n= 50,27)	6	3
IBS-D: Constipation item score -3 (n= 52,26)	1	99999
IBS-D: Constipation item score -2 (n= 52,26)	4	99999
IBS-D: Constipation item score -1 (n= 52,26)	12	7
IBS-D: Constipation item score 0 (n= 52,26)	31	16
IBS-D: Constipation item score 1 (n= 52,26)	4	3
IBS-D: Urgency item score -4 (n= 52,27)	4	3
IBS-D: Urgency item score -3 (n= 52,27)	1	3
IBS-D: Urgency item score -2 (n= 52,27)	12	5
IBS-D: Urgency item score -1 (n= 52,27)	16	5
IBS-D: Urgency item score 0 (n= 52,27)	10	5
IBS-D: Urgency item score 1 (n= 52,27)	6	5
IBS-D: Urgency item score 2 (n= 52,27)	3	99999
IBS-D: Urgency item score 3 (n= 52,27)	99999	1

Notes
[43] - FAS with number of evaluable subjects for this end point.
[44] - FAS with number of evaluable subjects for this end point.

No statistical analyses for this end point

Secondary: Number of Subjects with Global Assessment of Tolerability on a 5-point Likert Scale by Investigator and Subject

Top of page

End point title

Number of Subjects with Global Assessment of Tolerability on a 5-point Likert Scale by Investigator and Subject

End point description

The investigator and subjects assessed the tolerability of the study treatment by using a five point Likert scale (1 = very good, 2 = good, 3 = moderate, 4 = poor, 5 = very poor). In the below table, ‘n’ signifies those subjects who were evaluable for this measure at given time points for each group, and '99999' signifies no subjects fall under the below mentioned criteria in the category for the given time points for respective reporting groups.

End point type

Secondary

End point timeframe

Weeks 2 and 4

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	159 ^[45]	74 ^[46]
Units: count of subjects
Investigator: Week 2 (n=159,74): very good	71	33
Investigator: Week 2 (n=159,74): good	75	38
Investigator: Week 2 (n=159,74): moderate	11	3
Investigator: Week 2 (n=159,74): poor	1	99999
Investigator: Week 2 (n=159,74): very poor	1	99999
Investigator: Week 4 (n=153,72): very good	63	34
Investigator: Week 4 (n=153,72): good	77	35
Investigator: Week 4 (n=153,72): moderate	9	3
Investigator: Week 4 (n=153,72): poor	4	99999
Investigator: Week 4 (n=153,72): very poor	99999	99999
Subject: Week 2 (n=159,74): very good	72	32
Subject: Week 2 (n=159,74): good	73	36
Subject: Week 2 (n=159,74): moderate	12	6
Subject: Week 2 (n=159,74): poor	1	99999
Subject: Week 2 (n=159,74): very poor	1	99999
Subject: Week 4 (n=153,72): very good	62	31
Subject: Week 4 (n=153,72): good	77	36
Subject: Week 4 (n=153,72): moderate	10	5
Subject: Week 4 (n=153,72): poor	1	99999
Subject: Week 4 (n=153,72): very poor	3	99999

Notes
[45] - SAF with number of evaluable subjects for this specific end point.
[46] - SAF with number of evaluable subjects for this specific end point.

No statistical analyses for this end point

Secondary: IBS-QoL for IBS-C and IBS-D Subgroups: Change From Baseline for the Transformed Total Score at Week 4

Top of page

End point title

IBS-QoL for IBS-C and IBS-D Subgroups: Change From Baseline for the Transformed Total Score at Week 4

End point description

End point type

Secondary

End point timeframe

Baseline, Week 4

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	48 ^[47]	27 ^[48]
Units: score on a scale
arithmetic mean (standard deviation)
IBS-C (n= 44, 21)	9.88 ± 17.772	10.36 ± 12.595
IBS-D (n= 48, 27)	13.01 ± 16.092	12.96 ± 19.277

Notes
[47] - FAS with number of evaluable subjects for this specific end point.
[48] - FAS with number of evaluable subjects for this specific end point.

Statistical analyis 1: IBS-C

Statistical analysis description

IBS-QoL transformed total score was tested based on ANCOVA model with transformed total score at Week 4 adjusted for treatment, center and week 1 value. Results were presented by differences in LS mean difference together with the corresponding p-values and 95% confidence intervals.

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5276

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

2.67

Confidence interval

level

95%

sides

2-sided

lower limit

-5.74

upper limit

11.07

Statistical analyis 2: IBS-D

Statistical analysis description

IBS-QoL transformed total score was tested based on ANCOVA model with transformed total score at Week 4 adjusted for treatment, center and Week 1 value. Results were presented by differences in LS mean difference together with the corresponding p-values and 95% confidence intervals.

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.792

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

-6.37

upper limit

8.32

Secondary: IBS-QoL: Change From Baseline for the 8 Transformed Subscale Scores at Week 4

Top of page

End point title

IBS-QoL: Change From Baseline for the 8 Transformed Subscale Scores at Week 4

End point description

IBS-QoL is a self-report Qol measure to assess impact of IBS and its treatment. It consists of 34 items, each with a 5-point response scale. Individual responses to 34 items were summed up, averaged for total score, then transformed to 0-100 scale. Higher scores indicate better IBS specific quality of life. There were also eight subscale scores for the IBS-QOL (dysphoria, interference with activity, body image, health worry, food avoidance, social reaction, sexual relationships). In the below table, TS means transformed subscale, and here, ‘n’ signifies those subjects who were evaluable for this measure at given time points for each group.

End point type

Secondary

End point timeframe

Baseline, Week 4

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	150 ^[49]	70 ^[50]
Units: score on a scale
arithmetic mean (standard deviation)
TS dysphoria (n=149,68)	12.84 ± 17.919	12.13 ± 20.977
TS interference with activity (n= 146, 68)	8.34 ± 18.500	10.24 ± 19.725
TS body image (n=148,69)	11.06 ± 19.752	10.24 ± 17.709
TS health worry (n=149,68)	10.91 ± 18.682	10.78 ± 21.016
TS food avoidance (n=147,70)	9.52 ± 25.359	12.50 ± 22.556
TS social reaction (n=150,68)	9.00 ± 17.143	9.38 ± 20.417
TS sexual (n=148,69)	6.67 ± 21.499	4.35 ± 20.654
TS relationships (n=150,66)	7.00 ± 18.723	6.82 ± 20.564

Notes
[49] - FAS with number of evaluable subjects for this specific end point.
[50] - FAS with number of evaluable subjects for this specific end point.

IBS-QoL: Transformed subscale dysphoria

Statistical analysis description

IBS-QoL transformed subscale score was tested based on ANCOVA model with transformed subscale score at Week 4 adjusted for treatment, center, underlying IBS type and Week 1 value. Results were presented by differences in least-square means (LS mean difference) together with the corresponding p-values and 95% confidence intervals.

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

220

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3021

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

2.55

Confidence interval

level

95%

sides

2-sided

lower limit

-2.31

upper limit

7.41

Transformed subscale interference with activity

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

220

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6357

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

1.15

Confidence interval

level

95%

sides

2-sided

lower limit

-3.63

upper limit

5.94

IBS-QoL: Transformed subscale body image

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

220

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5711

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

1.37

Confidence interval

level

95%

sides

2-sided

lower limit

-3.39

upper limit

6.12

IBS-QoL: Transformed subscale health worry

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

220

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4424

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

1.91

Confidence interval

level

95%

sides

2-sided

lower limit

-2.99

upper limit

6.82

IBS-QoL: Transformed subscale food avoidance

Statistical analysis description

IBS-QoL transformed subscale score was tested based on ANCOVA model with transformed subscale score at Week 4 adjusted for treatment, center, underlying IBS type and week 1 value. Results were presented by differences in least-square means (LS mean difference) together with the corresponding p-values and 95% confidence intervals.

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

220

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8031

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-0.83

Confidence interval

level

95%

sides

2-sided

lower limit

-7.38

upper limit

5.72

IBS-QoL: Transformed subscale social reaction

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

220

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.592

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

1.32

Confidence interval

level

95%

sides

2-sided

lower limit

-3.54

upper limit

6.18

IBS-QoL: Transformed subscale sexual

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

220

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2725

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

2.95

Confidence interval

level

95%

sides

2-sided

lower limit

-2.34

upper limit

8.24

IBS-QoL: Transformed subscale relationships

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

220

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5177

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

1.54

Confidence interval

level

95%

sides

2-sided

lower limit

-3.15

upper limit

6.24

Secondary: IBS-QoL for IBS-C and IBS-D Subgroups: Change From Baseline for the 8 Transformed Subscale Scores at Week 4

Top of page

End point title

IBS-QoL for IBS-C and IBS-D Subgroups: Change From Baseline for the 8 Transformed Subscale Scores at Week 4

End point description

End point type

Secondary

End point timeframe

Baseline, Week 4

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	52 ^[51]	27 ^[52]
Units: score on a scale
arithmetic mean (standard deviation)
IBS-C: TS dysphoria (n=47,22)	13.30 ± 20.476	15.06 ± 18.791
IBS-D: TS dysphoria (n=50,27)	17.38 ± 17.303	14.93 ± 25.155
IBS-C: TS interference with activity (n=46,22)	7.07 ± 18.725	8.60 ± 14.691
IBS-D: TS interference with activity (n=49,27)	12.54 ± 21.343	13.89 ± 23.216
IBS-C: TS body image (n=45,22)	8.61 ± 23.548	10.80 ± 13.933
IBS-D: TS body image (n=51,27)	14.58 ± 17.707	13.43 ± 21.350
IBS-C: TS health worry (n=47,22)	12.59 ± 21.343	15.15 ± 21.461
IBS-D: TS health worry (n=51,27)	11.60 ± 18.187	12.65 ± 18.253
IBS-C: TS food avoidance (n=46,23)	8.33 ± 25.154	11.23 ± 20.506
IBS-D: TS food avoidance (n=51,27)	13.40 ± 24.099	17.59 ± 19.657
IBS-C: TS social reaction (n=47,22)	9.18 ± 18.145	11.08 ± 17.565
IBS-D: TS social reaction (n=51,27)	9.19 ± 18.301	10.88 ± 24.119
IBS-C: TS sexual (n=45,23)	8.89 ± 23.929	7.07 ± 21.594
IBS-D: TS sexual (n=51,27)	7.11 ± 24.142	6.94 ± 21.183
IBS-C: TS relationships (n=46,21)	6.34 ± 17.496	7.94 ± 20.152
IBS-D: TS relationships (n=52,27)	10.26 ± 23.257	7.41 ± 23.721

Notes
[51] - FAS with number of evaluable subjects for this end point.
[52] - FAS with number of evaluable subjects for this end point.

IBS-C: TS dysphoria

Statistical analysis description

IBS-QoL transformed subscale score was tested based on ANCOVA model with transformed subscale score at Week 4 adjusted for treatment, center and Week 1 value. Results were presented by differences in least-square means (LS mean difference) together with the corresponding p-values and 95% confidence intervals.

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.51

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

3.3

Confidence interval

level

95%

sides

2-sided

lower limit

-6.66

upper limit

13.26

IBS-D: TS dysphoria

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6331

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

2.08

Confidence interval

level

95%

sides

2-sided

lower limit

-6.59

upper limit

10.75

IBS-C: TS interference with activity

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9393

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

0.32

Confidence interval

level

95%

sides

2-sided

lower limit

-8.17

upper limit

8.82

IBS-D: TS interference with activity

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6475

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

2.12

Confidence interval

level

95%

sides

2-sided

lower limit

-7.1

upper limit

11.34

IBS-C: TS body image

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8943

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

0.68

Confidence interval

level

95%

sides

2-sided

lower limit

-9.51

upper limit

10.87

IBS-D: TS body image

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9489

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

0.25

Confidence interval

level

95%

sides

2-sided

lower limit

-7.57

upper limit

8.07

IBS-C: TS health worry

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4863

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

3.54

Confidence interval

level

95%

sides

2-sided

lower limit

-6.56

upper limit

13.63

IBS-D: TS health worry

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7329

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-1.32

Confidence interval

level

95%

sides

2-sided

lower limit

-9.02

upper limit

6.37

IBS-C: TS food avoidance

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8417

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

1.12

Confidence interval

level

95%

sides

2-sided

lower limit

-10.07

upper limit

12.32

IBS-D: TS food avoidance

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8468

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-1.06

Confidence interval

level

95%

sides

2-sided

lower limit

-12.02

upper limit

9.89

IBS-C: TS social reaction

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4717

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

3.13

Confidence interval

level

95%

sides

2-sided

lower limit

-5.51

upper limit

11.77

IBS-D: TS social reaction

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5524

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-2.73

Confidence interval

level

95%

sides

2-sided

lower limit

-11.84

upper limit

6.39

IBS-C: TS sexual

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4729

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

3.71

Confidence interval

level

95%

sides

2-sided

lower limit

-6.57

upper limit

IBS-D: TS sexual

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7376

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

1.66

Confidence interval

level

95%

sides

2-sided

lower limit

-8.19

upper limit

11.51

IBS-C: TS relationships

Statistical analysis description

Comparison groups

Placebo v STW 5 (Iberogast)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6652

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

1.97

Confidence interval

level

95%

sides

2-sided

lower limit

-7.09

upper limit

11.02

IBS-D: TS relationships

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9849

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-0.08

Confidence interval

level

95%

sides

2-sided

lower limit

-8.75

upper limit

8.58

Secondary: Change of Pain Intensity From Baseline to Week 4 in the Subgroups IBS-C and IBS-D

Top of page

End point title

Change of Pain Intensity From Baseline to Week 4 in the Subgroups IBS-C and IBS-D

End point description

Pain intensity was assessed in subjects suffering from diarrhoea-predominant IBS and constipation-predominant IBS in the evening. The abdominal pain intensity was evaluated by using an 10 cm VAS ranging from no pain to worst pain that asked subjects daily to rate their ‘worst abdominal pain over the past 24-hours’. In the below table, ‘n’ signifies those subjects who were evaluable for this measure at given time points for each group.

End point type

Secondary

End point timeframe

Baseline, Week 4

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	51 ^[53]	25 ^[54]
Units: centimeter (cm)
arithmetic mean (standard deviation)
IBS-C (n= 47,22)	-1.52 ± 2.683	-2.22 ± 3.142
IBS-D (n= 51,25)	-2.43 ± 2.562	-2.81 ± 2.701

Notes
[53] - FAS with number of evaluable subjects for this specific end point.
[54] - FAS with number of evaluable subjects for this specific end point.

Statistical analysis 1: IBS-C

Statistical analysis description

Change of pain intensity from baseline to week 4 was tested using an ANCOVA model with treatment, center and underlying IBS type as fixed effects and the baseline value as covariate. Results are presented by LS mean difference together with the corresponding p-values and 95% confidence intervals.

Comparison groups

Placebo v STW 5 (Iberogast)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7802

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

1.2

Statistical analysis 1: IBS-D

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3497

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

0.47

Confidence interval

level

95%

sides

2-sided

lower limit

-0.52

upper limit

1.46

Secondary: Change of Pain Intensity From Baseline to Week 2 in the Subgroups IBS-C and IBS-D

Top of page

End point title

Change of Pain Intensity From Baseline to Week 2 in the Subgroups IBS-C and IBS-D

End point description

End point type

Secondary

End point timeframe

Baseline, Week 2

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	59 ^[55]	27 ^[56]
Units: centimeter (cm)
arithmetic mean (standard deviation)
IBS-C (n= 49,23)	-1.28 ± 2.730	-1.26 ± 2.002
IBS-D (n= 59,27)	-2.14 ± 2.412	-2.36 ± 2.705

Notes
[55] - FAS with number of evaluable subjects for this specific end point.
[56] - FAS with number of evaluable subjects for this specific end point.

Statistical analysis 1: IBS-C

Statistical analysis description

Change of pain intensity from baseline to week 2 was tested using an ANCOVA model with treatment, center and underlying IBS type as fixed effects and the baseline value as covariate. Results are presented by LS mean difference together with the corresponding p-values and 95% confidence intervals.

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1891

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-0.84

Confidence interval

level

95%

sides

2-sided

lower limit

-2.11

upper limit

0.42

Statistical analysis 2: IBS-D

Statistical analysis description

Comparison groups

STW 5 (Iberogast) v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8358

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

0.11

Confidence interval

level

95%

sides

2-sided

lower limit

-0.93

upper limit

1.14

Secondary: Number of Subjects with Treatment Emergent Adverse Events

Top of page

End point title

Number of Subjects with Treatment Emergent Adverse Events

End point description

An adverse event (AE) was any untoward medical occurrence in subject who received study drug without regard to possibility of causal relationship. A treatment-emergent adverse event (TEAE) was defined as any event with onset or worsening after the start of investigational medicinal product administration.

End point type

Secondary

End point timeframe

Baseline up to Week 4

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	167 ^[57]	76 ^[58]
Units: count of subjects	37	18

Notes
[57] - SAF
[58] - SAF

No statistical analyses for this end point

Secondary: Number of Subjects with Clinically Significant Abnormal Changes in Vital Signs

Top of page

End point title

Number of Subjects with Clinically Significant Abnormal Changes in Vital Signs

End point description

The vital signs such as blood pressure, pulse and body weight were assessed for the clinically abnormal significant changes and reported.

End point type

Secondary

End point timeframe

Baseline up to Week 4

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	167 ^[59]	76 ^[60]
Units: count of subjects	0	0

Notes
[59] - SAF
[60] - SAF

No statistical analyses for this end point

Secondary: Number of Subjects with Clinically Significant Abnormal Changes in Laboratory Parameters

Top of page

End point title

Number of Subjects with Clinically Significant Abnormal Changes in Laboratory Parameters

End point description

The laboratory parameters such as haematology, blood chemistry, urinalysis were assessed for the clinically significant abnormal changes and reported.

End point type

Secondary

End point timeframe

Baseline up to Week 4

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	167 ^[61]	76 ^[62]
Units: count of subjects	3	2

Notes
[61] - SAF
[62] - SAF

No statistical analyses for this end point

Secondary: Number of Subjects with Global Assessment of Efficacy on a 5-point Likert Scale by Investigator and Subject

Top of page

End point title

Number of Subjects with Global Assessment of Efficacy on a 5-point Likert Scale by Investigator and Subject

End point description

The investigator and the subjects assessed the efficacy of the study treatment separately by using a five point Likert scale (1 = very good, 2 = good, 3 = moderate, 4 = poor, 5 = very poor). In the below table, ‘n’ signifies those subjects who were evaluable for this measure at given time points for each group, and '99999' signifies no subjects fall under the below mentioned criteria in the category for the given time points for respective reporting groups.

End point type

Secondary

End point timeframe

Weeks 2 and 4

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	159 ^[63]	74 ^[64]
Units: count of subjects
Investigator: Week 2 (n=159,74): very good	5	3
Investigator: Week 2 (n=159,74): good	61	21
Investigator: Week 2 (n=159,74): moderate	46	30
Investigator: Week 2 (n=159,74): poor	43	18
Investigator: Week 2 (n=159,74): very poor	4	2
Investigator: Week 4 (n=153,72): very good	11	9
Investigator: Week 4 (n=153,72): good	59	26
Investigator: Week 4 (n=153,72): moderate	38	22
Investigator: Week 4 (n=153,72): poor	42	15
Investigator: Week 4 (n=153,72): very poor	3	99999
Subject: Week 2 (n=159,74): very good	5	3
Subject: Week 2 (n=159,74): good	57	23
Subject: Week 2 (n=159,74): moderate	53	27
Subject: Week 2 (n=159,74): poor	40	17
Subject: Week 2 (n=159,74): very poor	4	4
Subject: Week 4 (n=153,72): very good	16	7
Subject: Week 4 (n=153,72): good	56	27
Subject: Week 4 (n=153,72): moderate	38	23
Subject: Week 4 (n=153,72): poor	37	14
Subject: Week 4 (n=153,72): very poor	6	1

Notes
[63] - FAS with number of evaluable subjects for this specific end point.
[64] - FAS with number of evaluable subjects for this specific end point.

No statistical analyses for this end point

Secondary: Weekly Usage of Bisacodyl Tablets

Top of page

End point title

Weekly Usage of Bisacodyl Tablets

End point description

Subjects were instructed to use bisacodyl only in case of absence of bowel movements for more than three days. Investigators dispensed the rescue medication bisacodyl for treatment of severe constipation. In the below table, ‘n’ signifies those subjects who were evaluable for this measure at given time points for each group.

End point type

Secondary

End point timeframe

Weeks 1, 2, 3 and 4

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	161 ^[65]	75 ^[66]
Units: number of tablets
arithmetic mean (standard deviation)
Week 1 (n= 161,75)	0.15 ± 0.577	0.27 ± 1.057
Week 2 (n= 160,73)	0.12 ± 0.552	0.26 ± 1.041
Week 3 (n= 155,73)	0.18 ± 1.197	0.21 ± 0.927
Week 4 (n= 151,71)	0.08 ± 0.382	0.21 ± 1.081

Notes
[65] - FAS with number of evaluable subjects for this end point.
[66] - FAS with number of evaluable subjects for this end point.

No statistical analyses for this end point

Secondary: Weekly Usage of Loperamid Tablets

Top of page

End point title

Weekly Usage of Loperamid Tablets

End point description

Subjects were instructed to use loperamide only in case of three consecutive bowel movements with type 6 according to BSS or in case of first bowel movement with type 7 according to BSS. As per BSS: types 1-2, hard (suggestive of constipation); types 3-5, normal; types 6-7, loose/liquid (associated with diarrhoea). Investigators dispensed the rescue medication loperamide for treatment of severe diarrhoea. In the below table, ‘n’ signifies those subjects who were evaluable for this measure at given time points for each group.

End point type

Secondary

End point timeframe

Weeks 1, 2, 3 and 4

End point values	STW 5 (Iberogast)	Placebo
Number of subjects analysed	161 ^[67]	75 ^[68]
Units: number of tablets
arithmetic mean (standard deviation)
Week 1 (n= 161,75)	0.20 ± 1.092	0.17 ± 0.665
Week 2 (n= 160,73)	0.18 ± 1.113	0.14 ± 0.535
Week 3 (n= 155,73)	0.22 ± 0.811	0.10 ± 0.414
Week 4 (n= 151,71)	0.24 ± 1.105	0.21 ± 0.747

Notes
[67] - FAS with number of evaluable subjects for this end point.
[68] - FAS with number of evaluable subjects for this end point.

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Baseline up to Week 4

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

18.0

Reporting group title

Placebo

Reporting group description

Subject received placebo matched to STW 5 orally 20 drops three times daily (3*20 drops per day) before or during the meals for 4 weeks (from Day 1 to Day 29).

Reporting group title

STW5 (Iberogast)

Reporting group description

Subjects received STW 5 orally 20 drops three times daily (3*20 drops per day) before or during the meals for 4 weeks (from Day 1 to Day 29).

Serious adverse events	Placebo	STW5 (Iberogast)
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 76 (0.00%)	0 / 167 (0.00%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events	0	0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Placebo	STW5 (Iberogast)
Total subjects affected by non serious adverse events
subjects affected / exposed	18 / 76 (23.68%)	37 / 167 (22.16%)
Vascular disorders
Varicose vein
subjects affected / exposed	0 / 76 (0.00%)	1 / 167 (0.60%)
occurrences all number	0	1
General disorders and administration site conditions
Drug intolerance
subjects affected / exposed	0 / 76 (0.00%)	1 / 167 (0.60%)
occurrences all number	0	1
Influenza like illness
subjects affected / exposed	0 / 76 (0.00%)	1 / 167 (0.60%)
occurrences all number	0	1
Malaise
subjects affected / exposed	0 / 76 (0.00%)	1 / 167 (0.60%)
occurrences all number	0	1
Soft tissue inflammation
subjects affected / exposed	1 / 76 (1.32%)	0 / 167 (0.00%)
occurrences all number	1	0
Immune system disorders
Seasonal allergy
subjects affected / exposed	0 / 76 (0.00%)	1 / 167 (0.60%)
occurrences all number	0	1
Investigations
Hepatic enzyme abnormal
subjects affected / exposed	1 / 76 (1.32%)	0 / 167 (0.00%)
occurrences all number	1	0
Injury, poisoning and procedural complications
Arthropod bite
subjects affected / exposed	1 / 76 (1.32%)	0 / 167 (0.00%)
occurrences all number	1	0
Muscle strain
subjects affected / exposed	1 / 76 (1.32%)	0 / 167 (0.00%)
occurrences all number	1	0
Cardiac disorders
Cardiovascular disorder
subjects affected / exposed	0 / 76 (0.00%)	1 / 167 (0.60%)
occurrences all number	0	1
Nervous system disorders
Epilepsy
subjects affected / exposed	1 / 76 (1.32%)	0 / 167 (0.00%)
occurrences all number	2	0
Headache
subjects affected / exposed	2 / 76 (2.63%)	1 / 167 (0.60%)
occurrences all number	2	1
Gastrointestinal disorders
Abdominal distension
subjects affected / exposed	1 / 76 (1.32%)	0 / 167 (0.00%)
occurrences all number	1	0
Abdominal pain
subjects affected / exposed	0 / 76 (0.00%)	3 / 167 (1.80%)
occurrences all number	0	3
Abdominal pain upper
subjects affected / exposed	1 / 76 (1.32%)	6 / 167 (3.59%)
occurrences all number	1	6
Diarrhoea
subjects affected / exposed	0 / 76 (0.00%)	1 / 167 (0.60%)
occurrences all number	0	1
Enteritis
subjects affected / exposed	0 / 76 (0.00%)	1 / 167 (0.60%)
occurrences all number	0	1
Flatulence
subjects affected / exposed	0 / 76 (0.00%)	2 / 167 (1.20%)
occurrences all number	0	2
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 76 (0.00%)	2 / 167 (1.20%)
occurrences all number	0	2
Haemorrhoids thrombosed
subjects affected / exposed	0 / 76 (0.00%)	1 / 167 (0.60%)
occurrences all number	0	1
Irritable bowel syndrome
subjects affected / exposed	1 / 76 (1.32%)	0 / 167 (0.00%)
occurrences all number	1	0
Nausea
subjects affected / exposed	0 / 76 (0.00%)	2 / 167 (1.20%)
occurrences all number	0	2
Hepatobiliary disorders
Liver disorder
subjects affected / exposed	1 / 76 (1.32%)	0 / 167 (0.00%)
occurrences all number	1	0
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	0 / 76 (0.00%)	1 / 167 (0.60%)
occurrences all number	0	1
Eczema
subjects affected / exposed	0 / 76 (0.00%)	1 / 167 (0.60%)
occurrences all number	0	1
Rash
subjects affected / exposed	1 / 76 (1.32%)	0 / 167 (0.00%)
occurrences all number	1	0
Renal and urinary disorders
Haematuria
subjects affected / exposed	0 / 76 (0.00%)	1 / 167 (0.60%)
occurrences all number	0	1
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	2 / 76 (2.63%)	3 / 167 (1.80%)
occurrences all number	2	3
Muscle spasms
subjects affected / exposed	0 / 76 (0.00%)	1 / 167 (0.60%)
occurrences all number	0	1
Infections and infestations
Bronchitis
subjects affected / exposed	2 / 76 (2.63%)	2 / 167 (1.20%)
occurrences all number	2	2
Cystitis
subjects affected / exposed	0 / 76 (0.00%)	3 / 167 (1.80%)
occurrences all number	0	3
Gastroenteritis
subjects affected / exposed	0 / 76 (0.00%)	2 / 167 (1.20%)
occurrences all number	0	2
Herpes simplex
subjects affected / exposed	0 / 76 (0.00%)	1 / 167 (0.60%)
occurrences all number	0	1
Influenza
subjects affected / exposed	0 / 76 (0.00%)	1 / 167 (0.60%)
occurrences all number	0	1
Nasopharyngitis
subjects affected / exposed	5 / 76 (6.58%)	8 / 167 (4.79%)
occurrences all number	5	8
Salpingo-oophoritis
subjects affected / exposed	0 / 76 (0.00%)	1 / 167 (0.60%)
occurrences all number	0	1
Sinobronchitis
subjects affected / exposed	1 / 76 (1.32%)	0 / 167 (0.00%)
occurrences all number	1	0
Sinusitis
subjects affected / exposed	0 / 76 (0.00%)	1 / 167 (0.60%)
occurrences all number	0	1
Urinary tract infection
subjects affected / exposed	0 / 76 (0.00%)	1 / 167 (0.60%)
occurrences all number	0	1
Viral infection
subjects affected / exposed	1 / 76 (1.32%)	1 / 167 (0.60%)
occurrences all number	1	1

More information

Top of page

Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

'99999' signifies that no subjects fall under the mentioned criteria in the category for the given time points for respective reporting groups.

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A double-blind, randomised, placebo-controlled study on the efficacy of Iberogast® (STW 5) in patients with irritable bowel syndrome

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Response Rate for Abdominal Pain Intensity After 4 Weeks of Treatment

Primary: Response Rate for Abdominal Pain Intensity After 4 Weeks of Treatment

Secondary: Response Rate for Abdominal Pain Intensity After 2 Weeks of Treatment

Secondary: Response Rate for Abdominal Pain Intensity After 2 Weeks of Treatment

Secondary: Irritable Bowel Syndrome - Quality of Life Measure (IBS-QoL): Change From Baseline for the Transformed Total Score at Week 4

Secondary: Irritable Bowel Syndrome - Quality of Life Measure (IBS-QoL): Change From Baseline for the Transformed Total Score at Week 4

Secondary: Responders Regarding Stool Frequency in IBS-C Subgroup After 4 Weeks of Treatment

Secondary: Responders Regarding Stool Frequency in IBS-C Subgroup After 4 Weeks of Treatment

Secondary: Responders Regarding Stool Consistency in IBS-D Subgroup After 4 Weeks of Treatment

Secondary: Responders Regarding Stool Consistency in IBS-D Subgroup After 4 Weeks of Treatment

Secondary: Responders Regarding Stool Frequency for IBS-C Subgroup After 2 Weeks of Treatment

Secondary: Responders Regarding Stool Frequency for IBS-C Subgroup After 2 Weeks of Treatment

Secondary: Responders Regarding Stool Consistency in IBS-D Subgroup After 2 Weeks of Treatment

Secondary: Responders Regarding Stool Consistency in IBS-D Subgroup After 2 Weeks of Treatment

Secondary: Change of Pain Intensity From Baseline to Week 4

Secondary: Change of Pain Intensity From Baseline to Week 4

Secondary: Change of Pain Intensity From Baseline to Week 2

Secondary: Change of Pain Intensity From Baseline to Week 2

Secondary: Response Rate for Abdominal Pain Intensity After First 7 Days of Treatment (Early Responders)

Secondary: Response Rate for Abdominal Pain Intensity After First 7 Days of Treatment (Early Responders)

Secondary: Response Rate for Abdominal Pain Intensity in the Last 14 Days of Treatment (Late Responders)

Secondary: Response Rate for Abdominal Pain Intensity in the Last 14 Days of Treatment (Late Responders)

Secondary: Feeling of Completed Evacuation - Change From Baseline to Week 4

Secondary: Feeling of Completed Evacuation - Change From Baseline to Week 4

Secondary: Feeling of Incomplete Evacuation – Change From Baseline to Week 4

Secondary: Feeling of Incomplete Evacuation – Change From Baseline to Week 4

Secondary: Stool Consistency in IBS-C and IBS-D Subgroups-Change From Baseline to Week 4

Secondary: Stool Consistency in IBS-C and IBS-D Subgroups-Change From Baseline to Week 4

Secondary: Change From Baseline in Weekly Usage of Bisacodyl Tablets

Secondary: Change From Baseline in Weekly Usage of Bisacodyl Tablets

Secondary: Change From Baseline in Weekly Usage of Loperamid Tablets

Secondary: Change From Baseline in Weekly Usage of Loperamid Tablets

Secondary: Birmingham IBS Symptom Questionnaire – Change Between Week 1 and Week 4 for the Total Score

Secondary: Birmingham IBS Symptom Questionnaire – Change Between Week 1 and Week 4 for the Total Score

Secondary: Birmingham IBS Symptom Questionnaire – Change Between Week 1 and Week 4 for the 3 Dimensions

Secondary: Birmingham IBS Symptom Questionnaire – Change Between Week 1 and Week 4 for the 3 Dimensions

Secondary: Birmingham IBS Symptom Questionnaire – Change Between Week 1 and Week 4 for the 3 Single Items of Questionnaire

Secondary: Birmingham IBS Symptom Questionnaire – Change Between Week 1 and Week 4 for the 3 Single Items of Questionnaire

Secondary: Birmingham IBS Symptom Questionnaire in IBS-C and IBS-D Subgroups – Change Between Week 1 and Week 4 for the Total Score

Secondary: Birmingham IBS Symptom Questionnaire in IBS-C and IBS-D Subgroups – Change Between Week 1 and Week 4 for the Total Score

Secondary: Birmingham IBS Symptom Questionnaire in IBS-C and IBS-D Subgroups – Change Between Week 1 and Week 4 for the 3 Dimensions

Secondary: Birmingham IBS Symptom Questionnaire in IBS-C and IBS-D Subgroups – Change Between Week 1 and Week 4 for the 3 Dimensions

Secondary: Birmingham IBS Symptom Questionnaire in IBS-C and IBS-D Subgroups –Change Between Week 1 and Week 4 for 3 Single Items of Questionnaire

Secondary: Birmingham IBS Symptom Questionnaire in IBS-C and IBS-D Subgroups –Change Between Week 1 and Week 4 for 3 Single Items of Questionnaire

Secondary: Number of Subjects with Global Assessment of Tolerability on a 5-point Likert Scale by Investigator and Subject

Secondary: Number of Subjects with Global Assessment of Tolerability on a 5-point Likert Scale by Investigator and Subject

Secondary: IBS-QoL for IBS-C and IBS-D Subgroups: Change From Baseline for the Transformed Total Score at Week 4

Secondary: IBS-QoL for IBS-C and IBS-D Subgroups: Change From Baseline for the Transformed Total Score at Week 4

Secondary: IBS-QoL: Change From Baseline for the 8 Transformed Subscale Scores at Week 4

Secondary: IBS-QoL: Change From Baseline for the 8 Transformed Subscale Scores at Week 4

Secondary: IBS-QoL for IBS-C and IBS-D Subgroups: Change From Baseline for the 8 Transformed Subscale Scores at Week 4

Secondary: IBS-QoL for IBS-C and IBS-D Subgroups: Change From Baseline for the 8 Transformed Subscale Scores at Week 4

Secondary: Change of Pain Intensity From Baseline to Week 4 in the Subgroups IBS-C and IBS-D

Secondary: Change of Pain Intensity From Baseline to Week 4 in the Subgroups IBS-C and IBS-D

Secondary: Change of Pain Intensity From Baseline to Week 2 in the Subgroups IBS-C and IBS-D

Secondary: Change of Pain Intensity From Baseline to Week 2 in the Subgroups IBS-C and IBS-D

Secondary: Number of Subjects with Treatment Emergent Adverse Events

Secondary: Number of Subjects with Treatment Emergent Adverse Events

Secondary: Number of Subjects with Clinically Significant Abnormal Changes in Vital Signs

Secondary: Number of Subjects with Clinically Significant Abnormal Changes in Vital Signs

Secondary: Number of Subjects with Clinically Significant Abnormal Changes in Laboratory Parameters

Secondary: Number of Subjects with Clinically Significant Abnormal Changes in Laboratory Parameters

Secondary: Number of Subjects with Global Assessment of Efficacy on a 5-point Likert Scale by Investigator and Subject

Secondary: Number of Subjects with Global Assessment of Efficacy on a 5-point Likert Scale by Investigator and Subject

Secondary: Weekly Usage of Bisacodyl Tablets

Secondary: Weekly Usage of Bisacodyl Tablets

Secondary: Weekly Usage of Loperamid Tablets

Secondary: Weekly Usage of Loperamid Tablets

Adverse events

Adverse events

Clinical Trial Results:
A double-blind, randomised, placebo-controlled study on the efficacy of Iberogast® (STW 5) in patients with irritable bowel syndrome