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Clinical Trial Results:
A Phase II, multicentre, randomised, double-blind, placebo controlled, proof of concept study of efficacy and safety of Rifamycin SV-MMX® 600 mg tablets administered three or two times daily to patients with diarrhoea-predominant irritable bowel syndrome (IBS-D)

Summary
EudraCT number	2016-004977-42
Trial protocol	BE ES DE IT
Global end of trial date	10 Sep 2020

Results information
Results version number	v1(current)
This version publication date	04 Oct 2022
First version publication date	04 Oct 2022
Other versions
Summary report(s)	Protocol

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

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Trial information

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Sponsor protocol code

CB-01-11/28

ISRCTN number

US NCT number

NCT03099785

WHO universal trial number (UTN)

Sponsor organisation name

Cosmo Technologies

Sponsor organisation address

Riverside 2, 49 Sir John Rogerson's Quay, Grand Canal Dock, Dublin,, Dublin, Italy, D02 KV60

Public contact

Cristina Banyai, Cosmo Technologies Ltd, +353 867015703, cbanyai@cosmopharma.com

Scientific contact

Luigi Longo, Cosmo Technologies Ltd, +353 867015703, cbanyai@cosmopharma.com

Sponsor organisation name

Cosmo Technologies

Sponsor organisation address

Riverside 2, 49 Sir John Rogerson's Quay, Grand Canal Dock , Dublin, Ireland, D02 KV60

Public contact

Cristina Banyai, Luigi Longo, cbanyai@cosmopharma.com

Scientific contact

Cristina Banyai, Luigi Longo, LLongo@cosmopharma.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

01 Apr 2021

Is this the analysis of the primary completion data?

Yes

Primary completion date

10 Sep 2020

Global end of trial reached?

Yes

Global end of trial date

10 Sep 2020

Was the trial ended prematurely?

Yes

Main objective of the trial

To compare two dose regimens of Rifamycin SV-MMX® 600 mg tablets versus matching placebo in terms of proportion of subjects with adequate relief of the composite of abdominal pain and stool consistency.

Protection of trial subjects

Subjects were followed for safety and tolerability assessments: Treatment-emergent adverse events (TEAEs); vital signs (blood pressure, heart rate, body temperature, body weight), physical examinations; laboratory tests; electrocardiogram (ECG).

Background therapy

There were no additional treatments or comparators used in this study across all arms/groups of the study.

Evidence for comparator

The present proof of concept trial is designed to preliminarily investigate the efficacy of rifamycin SV in the indicated pathology versus matching placebo. Moreover, the efficacy will be also compared between two different rifamycin SV dose regimens. There were no comparators used in the study.

Actual start date of recruitment

09 Nov 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Spain: 60

Country: Number of subjects enrolled

Belgium: 50

Country: Number of subjects enrolled

Germany: 136

Country: Number of subjects enrolled

Italy: 33

Worldwide total number of subjects

279

EEA total number of subjects

279

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)

244

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

342 subjects were planned to be enrolled. The study was prematurely terminate on 31OCT20, due to also the pandemic situation. The enrolment stopped with the randomisation of 279 subjects. First patient enrolled 09Nov2017. There were study 25 centres/4 countries including Spain, Belgium, Italy and Germany.

Screening details

The study protocol foresaw a screening phase including a baseline symptom evaluation period, followed by a treatment period of 2 weeks (visits 2, 3 and 4) and by a follow-up period of 10 weeks (visits 5 to 7, telephonic follow-ups 1 to 7). Screening window Day-21 till Day-15.

Period 1 title

Treatment period- overall study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Blinding implementation details

The code for specific subjects will be documented in the source, in the eCRF and in the clinical study report. Breaking of an individual randomisation code by the investigator during the study is allowed only when knowledge of the code is essential for the subject's health. In these cases, the investigator will access the individual code of the concerned subject in the integrated eCRF system, where the unblinding action will be audit trailed.

Are arms mutually exclusive

Yes

Treatment group 1: dose regimen 1

Arm description

Rifamycin SV-MMX® 600 mg modified release tablets, three times daily (t.i.d.) Morning: one 600 mg tablet Afternoon: one 600 mg tablet Evening: one 600 mg tablet

Arm type

Active comparator

Investigational medicinal product name

Rifamycin SV-MMX® 600 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Rifamycin SV-MMX® 600 mg modified release tablets, three times daily (t.i.d.) Morning: one 600 mg tablet Afternoon: one 600 mg tablet Evening: one 600 mg tablet All the subjects will take the assigned tablets t.i.d., ideally at the following times: 07:30±2 h, 15:30±2 h and 23:30±2 h, for 14 days.

Treatment group 2: dose regimen 2

Arm description

Rifamycin SV-MMX® 600 mg modified release tablets, two times daily (b.i.d.) + matching placebo daily (q.d.) Morning. one 600 mg tablet Afternoon: one matching placebo tablet Evening: one 600 mg tablet

Arm type

Active comparator

Investigational medicinal product name

Rifamycin SV-MMX®

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Ocular use

Dosage and administration details

Rifamycin SV-MMX® 600mg

Treatment group 3: matching placebo

Arm description

Rifamycin SV-MMX® matching placebo tablets, t.i.d. Morning. one matching placebo tablet Afternoon: one matching placebo tablet Evening: one matching placebo tablet

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Matching Placebo tablets

Number of subjects in period 1	Treatment group 1: dose regimen 1	Treatment group 2: dose regimen 2	Treatment group 3: matching placebo
Started	87	95	97
Completed	79	88	91
Not completed	8	7	6
Consent withdrawn by subject	1	2	2
Physician decision	1	-	-
Early termination due to holiday	1	-	-
Adverse event, non-fatal	1	1	1
Incompliant with study drug and the visits	-	-	1
Shouldn't be randomised	-	1	-
Lost to follow-up	2	2	-
Discontinued before treatment	2	1	1
Lack of efficacy	-	-	1

Baseline characteristics

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Reporting group title

Treatment period- overall study

Reporting group description

Reporting group values	Treatment period- overall study	Total
Number of subjects	279	279
Age categorical
Units: Subjects
Adults (18-64 years)	257	257
From 65-84 years	22	22
85 years and over	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	40.6 ( 14.7 )	-
Gender categorical
Units: Subjects
Female	169	169
Male	110	110
Race
Units: Subjects
White	274	274
Other	2	2
Black	2	2
Asian	1	1
BW
Units: kg
arithmetic mean (standard deviation)	74.01 ( 16.55 )	-
Height
Units: cm
arithmetic mean (standard deviation)	170.2 ( 9.4 )	-

Subject analysis set title

The intent-to-treat (ITT)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Intention-To-Treat Set (ITT): all randomised subjects. This analysis set was used for sensitivity analyses

Subject analysis set title

Full Analysis Set (FAS)

Subject analysis set type

Full analysis

Subject analysis set description

All randomised subjects, who receive at least one dose of the investigational medicinal product and have at least one post randomisation assessment of the primary efficacy data. This analysis set will be used for the primary efficacy analysis

Subject analysis set title

Per Protocol Set (PP)

Subject analysis set type

Per protocol

Subject analysis set description

Per Protocol Set (PP): all randomised subjects who fulfil the study protocol requirements in terms of IMP intake and collection of primary efficacy data and with no major deviations that may affect study results. This analysis set will be used for sensitivity analyses

Subject analysis set title

Safety Set

Subject analysis set type

Safety analysis

Subject analysis set description

All subjects who receive at least one dose of the IMP. This analysis set will be used for the safety analyses

Subject analysis set title

mFAS

Subject analysis set type

Sub-group analysis

Subject analysis set description

The modified FAS (mFAS) is a subset of the FAS including all the subjects who fulfilled the protocol in terms of treatment compliance in the first week of treatment and had at least 6 (out of 7) daily assessments of abdominal pain score and stool consistency in both the last available week of screening and the first week of treatment and with no major deviations that could affect primary efficacy analysis

Subject analysis set title

Dose Regimen 1 (Full Analysis Set)

Subject analysis set type

Full analysis

Subject analysis set description

Dose Regimen 1 (Full Analysis Set)

Subject analysis set title

Dose Regimen 2 (Full Analysis Set)

Subject analysis set type

Full analysis

Subject analysis set description

Dose Regimen 2 (Full Analysis Set)

Subject analysis set title

Dose Regimen 3 (Full Analysis Set)

Subject analysis set type

Full analysis

Subject analysis set description

Dose Regimen 3 (Full Analysis Set)

Subject analysis set title

Dose Regimen 1 (IIT)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Dose Regimen 1 (Intention to Treat)

Subject analysis set title

Dose Regimen 2 (IIT)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Dose Regimen 2 (Intention to Treat)

Subject analysis set title

Dose Regimen 3 (IIT)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Dose Regimen 3 (Intention to Treat)

Subject analysis set title

Dose Regimen 1 (Per Protocol Set)

Subject analysis set type

Per protocol

Subject analysis set description

Dose Regimen 1 (Per Protocol Set)

Subject analysis set title

Dose Regimen 2 (Per Protocol Set)

Subject analysis set type

Per protocol

Subject analysis set description

Dose Regimen 2 (Per Protocol Set)

Subject analysis set title

Dose Regimen 3 (Per Protocol Set)

Subject analysis set type

Per protocol

Subject analysis set description

Dose Regimen 3 (Per Protocol Set)

Subject analysis set title

Dose Regimen 1 (mFAS)

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Dose Regimen 1 (modified Full Analysis Set)

Subject analysis set title

Dose Regimen 2 (mFAS)

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Dose Regimen 2 (modified Full Analysis Set)

Subject analysis set title

Dose Regimen 3 (mFAS)

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Dose Regimen 3 (modified Full Analysis Set)

Subject analysis sets values	The intent-to-treat (ITT)	Full Analysis Set (FAS)	Per Protocol Set (PP)	Safety Set	mFAS	Dose Regimen 1 (Full Analysis Set)	Dose Regimen 2 (Full Analysis Set)	Dose Regimen 3 (Full Analysis Set)	Dose Regimen 1 (IIT)	Dose Regimen 2 (IIT)	Dose Regimen 3 (IIT)	Dose Regimen 1 (Per Protocol Set)	Dose Regimen 2 (Per Protocol Set)	Dose Regimen 3 (Per Protocol Set)	Dose Regimen 1 (mFAS)	Dose Regimen 2 (mFAS)	Dose Regimen 3 (mFAS)
Number of subjects	279	264	207	275	235	81	88	95	87	95	97	63	65	79	74	75	86
Age categorical
Units: Subjects
Adults (18-64 years)	257	243	192	254	218	74	82	87	80	88	89	58	60	74	68	70	80
From 65-84 years	22	21	15	21	17	7	6	8	7	7	8	5	5	5	6	5	6
85 years and over	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	40.6 ( 14.7 )	40.5 ( 14.6 )	40.2 ( 14.5 )	40.5 ( 14.6 )	40.1 ( 14.4 )	40.6 ( 15.6 )	41.1 ( 13.4 )	39.9 ( 15.0 )	40.1 ( 15.3 )	41.5 ( 13.7 )	40.2 ( 15.1 )	40.8 ( 15.9 )	41.8 ( 13.1 )	38.5 ( 14.5 )	40.2 ( 15.7 )	41.2 ( 13.2 )	38.9 ( 14.4 )
Gender categorical
Units: Subjects
Female	169	162	117	167	140	48	55	59	52	58	59	33	36	48	42	44	54
Male	110	102	90	108	95	33	33	36	35	37	38	30	29	31	32	31	32
Race
Units: Subjects
White	274	259	202	270	230	79	87	93	85	94	95	61	64	77	72	74	84
Other	2	2	2	2	2	1	0	1	1	0	1	1	0	1	1	0	1
Black	2	2	2	2	2	0	1	1	0	1	1	0	1	1	0	1	1
Asian	1	1	1	1	1	1	0	0	1	0	0	1	0	0	1	0	0
BW
Units: kg
arithmetic mean (standard deviation)	74.01 ( 16.55 )	74.07 ( 16.77 )	74.83 ( 16.70 )	74.12 ( 16.59 )	74.39 ( 17.02 )	74.20 ( 17.06 )	75.40 ( 16.64 )	72.72 ( 16.71 )	73.70 ( 16.91 )	75.55 ( 16.21 )	72.77 ( 16.61 )	74.16 ( 15.59 )	77.97 ( 17.13 )	72.76 ( 17.02 )	74.46 ( 17.69 )	76.23 ( 16.79 )	72.70 ( 16.65 )
Height
Units: cm
arithmetic mean (standard deviation)	170.2 ( 9.4 )	170.2 ( 9.5 )	170.5 ( 9.8 )	170.1 ( 9.5 )	170.2 ( 9.7 )	170.3 ( 9.1 )	170.5 ( 9.2 )	169.8 ( 10.2 )	170.2 ( 9.1 )	170.4 ( 9.1 )	169.9 ( 10.2 )	170.9 ( 8.9 )	170.9 ( 10.0 )	169.9 ( 10.3 )	170.5 ( 9.1 )	170.5 ( 9.7 )	169.6 ( 10.2 )

End points

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Reporting group title

Treatment group 1: dose regimen 1

Reporting group description

Rifamycin SV-MMX® 600 mg modified release tablets, three times daily (t.i.d.) Morning: one 600 mg tablet Afternoon: one 600 mg tablet Evening: one 600 mg tablet

Reporting group title

Treatment group 2: dose regimen 2

Reporting group description

Reporting group title

Treatment group 3: matching placebo

Reporting group description

Rifamycin SV-MMX® matching placebo tablets, t.i.d. Morning. one matching placebo tablet Afternoon: one matching placebo tablet Evening: one matching placebo tablet

Subject analysis set title

The intent-to-treat (ITT)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Intention-To-Treat Set (ITT): all randomised subjects. This analysis set was used for sensitivity analyses

Subject analysis set title

Full Analysis Set (FAS)

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Per Protocol Set (PP)

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Safety Set

Subject analysis set type

Safety analysis

Subject analysis set description

All subjects who receive at least one dose of the IMP. This analysis set will be used for the safety analyses

Subject analysis set title

mFAS

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

Dose Regimen 1 (Full Analysis Set)

Subject analysis set type

Full analysis

Subject analysis set description

Dose Regimen 1 (Full Analysis Set)

Subject analysis set title

Dose Regimen 2 (Full Analysis Set)

Subject analysis set type

Full analysis

Subject analysis set description

Dose Regimen 2 (Full Analysis Set)

Subject analysis set title

Dose Regimen 3 (Full Analysis Set)

Subject analysis set type

Full analysis

Subject analysis set description

Dose Regimen 3 (Full Analysis Set)

Subject analysis set title

Dose Regimen 1 (IIT)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Dose Regimen 1 (Intention to Treat)

Subject analysis set title

Dose Regimen 2 (IIT)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Dose Regimen 2 (Intention to Treat)

Subject analysis set title

Dose Regimen 3 (IIT)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Dose Regimen 3 (Intention to Treat)

Subject analysis set title

Dose Regimen 1 (Per Protocol Set)

Subject analysis set type

Per protocol

Subject analysis set description

Dose Regimen 1 (Per Protocol Set)

Subject analysis set title

Dose Regimen 2 (Per Protocol Set)

Subject analysis set type

Per protocol

Subject analysis set description

Dose Regimen 2 (Per Protocol Set)

Subject analysis set title

Dose Regimen 3 (Per Protocol Set)

Subject analysis set type

Per protocol

Subject analysis set description

Dose Regimen 3 (Per Protocol Set)

Subject analysis set title

Dose Regimen 1 (mFAS)

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Dose Regimen 1 (modified Full Analysis Set)

Subject analysis set title

Dose Regimen 2 (mFAS)

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Dose Regimen 2 (modified Full Analysis Set)

Subject analysis set title

Dose Regimen 3 (mFAS)

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Dose Regimen 3 (modified Full Analysis Set)

Primary: Proportion of weekly responders with adequate relief of the composite of abdominal pain and stool consistency in the 1st week of treatment

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End point title

Proportion of weekly responders with adequate relief of the composite of abdominal pain and stool consistency in the 1st week of treatment

End point description

Relief of abdominal pain is defined as a decrease in the weekly average of abdominal pain score of at least 30% compared with baseline and relief of stool consistency is defined as a 50% or greater reduction in the number of days per week with at least one stool that has a consistency of Type 6 or 7 compared with baseline.

End point type

Primary

End point timeframe

1st week of treatment

End point values	Treatment group 1: dose regimen 1	Treatment group 2: dose regimen 2	Treatment group 3: matching placebo	Dose Regimen 1 (Full Analysis Set)	Dose Regimen 2 (Full Analysis Set)	Dose Regimen 3 (Full Analysis Set)	Dose Regimen 1 (IIT)	Dose Regimen 2 (IIT)	Dose Regimen 3 (IIT)	Dose Regimen 1 (Per Protocol Set)	Dose Regimen 2 (Per Protocol Set)	Dose Regimen 3 (Per Protocol Set)	Dose Regimen 1 (mFAS)	Dose Regimen 2 (mFAS)	Dose Regimen 3 (mFAS)
Number of subjects analysed	87	95	97	81	88	95	87	95	97	63	65	79	74	75	86
Units: subjects	10	22	9	10	22	9	10	22	9	7	18	7	9	21	9

DOSE REGIMEN 1 vs. DOSE REGIMEN 3 (FAS)

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 1 vs. DOSE REGIMEN 3 (Full Analysis Set)

Comparison groups

Dose Regimen 1 (Full Analysis Set) v Dose Regimen 3 (Full Analysis Set)

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority ^[1]

P-value

= 0.5892

Method

Wald Chi-Square

Parameter type

Odds ratio (OR)

Point estimate

1.35

Confidence interval

level

95%

sides

2-sided

lower limit

0.52

upper limit

3.49

Notes
[1] - Subjects with missing data on primary endpoint are defined as non-responders according to EMA guidance

DOSE REGIMEN 1 vs. DOSE REGIMEN 3 (mFAS)

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 1 vs. DOSE REGIMEN 3 (mFAS)

Comparison groups

Dose Regimen 1 (mFAS) v Dose Regimen 3 (mFAS)

Number of subjects included in analysis

160

Analysis specification

Pre-specified

Analysis type

superiority ^[2]

P-value

= 0.4758

Method

Wald Chi-Square

Parameter type

Odds ratio (OR)

Point estimate

1.18

Confidence interval

level

95%

sides

2-sided

lower limit

0.44

upper limit

3.16

Notes
[2] - Subjects with missing data on primary endpoint are defined as non-responders according to EMA guidance

DOSE REGIMEN 1 vs. DOSE REGIMEN 3 (IIT)

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 1 vs. DOSE REGIMEN 3 (IIT)

Comparison groups

Dose Regimen 1 (IIT) v Dose Regimen 3 (IIT)

Number of subjects included in analysis

184

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.593

Method

Wald Chi-Square

Parameter type

Odds ratio (OR)

Point estimate

1.33

Confidence interval

level

95%

sides

2-sided

lower limit

0.51

upper limit

3.45

DOSE REGIMEN 2 vs. DOSE REGIMEN 3 (FAS)

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 2 vs. DOSE REGIMEN 3 (Full Analysis Set)

Comparison groups

Dose Regimen 3 (Full Analysis Set) v Dose Regimen 2 (Full Analysis Set)

Number of subjects included in analysis

183

Analysis specification

Pre-specified

Analysis type

superiority ^[3]

P-value

= 0.0066

Method

Wald Chi-Square

Parameter type

Odds ratio (OR)

Point estimate

3.19

Confidence interval

level

95%

sides

2-sided

lower limit

1.38

upper limit

7.37

Notes
[3] - Subjects with missing data on primary endpoint are defined as non-responders according to EMA guidance

DOSE REGIMEN 1 vs. DOSE REGIMEN 2 (FAS)

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 1 vs. DOSE REGIMEN 2 (Full Analysis Set)

Comparison groups

Dose Regimen 1 (Full Analysis Set) v Dose Regimen 2 (Full Analysis Set)

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority ^[4]

P-value

= 0.0314

Method

Wald Chi-Square

Parameter type

Odds ratio (OR)

Point estimate

0.42

Confidence interval

level

95%

sides

2-sided

lower limit

0.19

upper limit

0.96

Notes
[4] - Subjects with missing data on primary endpoint are defined as non-responders according to EMA guidance

DOSE REGIMEN 2 vs. DOSE REGIMEN 3 (mFAS)

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 2 vs. DOSE REGIMEN 3 (mFAS)

Comparison groups

Dose Regimen 3 (mFAS) v Dose Regimen 2 (mFAS)

Number of subjects included in analysis

161

Analysis specification

Pre-specified

Analysis type

superiority ^[5]

P-value

= 0.0015

Method

Wald Chi-Square

Parameter type

Odds ratio (OR)

Point estimate

3.33

Confidence interval

level

95%

sides

2-sided

lower limit

1.42

upper limit

7.82

Notes
[5] - Subjects with missing data on primary endpoint are defined as non-responders according to EMA guidance

DOSE REGIMEN 1 vs. DOSE REGIMEN 2 (mFAS)

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 1 vs. DOSE REGIMEN 2 (mFAS)

Comparison groups

Dose Regimen 2 (mFAS) v Dose Regimen 1 (mFAS)

Number of subjects included in analysis

149

Analysis specification

Pre-specified

Analysis type

superiority ^[6]

P-value

= 0.0124

Method

Wald Chi-Square

Parameter type

Odds ratio (OR)

Point estimate

0.36

Confidence interval

level

95%

sides

2-sided

lower limit

0.15

upper limit

0.84

Notes
[6] - Subjects with missing data on primary endpoint are defined as non-responders according to EMA guidance

DOSE REGIMEN 2 vs. DOSE REGIMEN 3 (IIT)

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 2 vs. DOSE REGIMEN 3 (IIT)

Comparison groups

Dose Regimen 3 (IIT) v Dose Regimen 2 (IIT)

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0101

Method

Wald Chi-Square

Parameter type

Odds ratio (OR)

Point estimate

3.06

Confidence interval

level

95%

sides

2-sided

lower limit

1.32

upper limit

7.07

DOSE REGIMEN 1 vs. DOSE REGIMEN 2 (IIT)

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 1 vs. DOSE REGIMEN 2 (IIT)

Comparison groups

Dose Regimen 2 (IIT) v Dose Regimen 1 (IIT)

Number of subjects included in analysis

182

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0438

Method

Wald Chi-Square

Parameter type

Odds ratio (OR)

Point estimate

0.44

Confidence interval

level

95%

sides

2-sided

lower limit

0.19

upper limit

0.99

DOSE REGIMEN 1 vs. DOSE REGIMEN 3 (PP)

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 1 vs. DOSE REGIMEN 3 (PP Analysis Set)

Comparison groups

Dose Regimen 3 (Per Protocol Set) v Dose Regimen 1 (Per Protocol Set)

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7975

Method

Wald Chi-Square

Parameter type

Odds ratio (OR)

Point estimate

1.29

Confidence interval

level

95%

sides

2-sided

lower limit

0.43

upper limit

3.88

DOSE REGIMEN 2 vs. DOSE REGIMEN 3 (PP)

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 1 vs. DOSE REGIMEN 3 (PP Analysis Set)

Comparison groups

Dose Regimen 3 (Per Protocol Set) v Dose Regimen 2 (Per Protocol Set)

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004

Method

Wald Chi-Square

Parameter type

Odds ratio (OR)

Point estimate

3.94

Confidence interval

level

95%

sides

2-sided

lower limit

1.53

upper limit

10.16

DOSE REGIMEN 1 vs. DOSE REGIMEN 2 (PP)

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 1 vs. DOSE REGIMEN 2 (PP Analysis Set)

Comparison groups

Dose Regimen 2 (Per Protocol Set) v Dose Regimen 1 (Per Protocol Set)

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.011

Method

Wald Chi-Square

Parameter type

Odds ratio (OR)

Point estimate

0.33

Confidence interval

level

95%

sides

2-sided

lower limit

0.13

upper limit

0.85

Secondary: Proportion of subjects with adequate relief of global IBS symptoms for at least 2 (consecutive or not) of the 10 weeks during the follow-up period

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End point title

Proportion of subjects with adequate relief of global IBS symptoms for at least 2 (consecutive or not) of the 10 weeks during the follow-up period

End point description

Adequate relief of global IBS symptoms is defined as a response of "yes" to the following question, which was asked weekly (every 7 days): "In regard to all your symptoms of IBS, as compared to the way you felt before you started study medication, have you, in the past 7 days, had adequate relief of your IBS symptoms? [Yes/No]"

End point type

Secondary

End point timeframe

Weeks 3-12

End point values	Treatment group 1: dose regimen 1	Treatment group 2: dose regimen 2	Treatment group 3: matching placebo	Dose Regimen 1 (Full Analysis Set)	Dose Regimen 2 (Full Analysis Set)	Dose Regimen 3 (Full Analysis Set)	Dose Regimen 1 (IIT)	Dose Regimen 2 (IIT)	Dose Regimen 3 (IIT)	Dose Regimen 1 (Per Protocol Set)	Dose Regimen 2 (Per Protocol Set)	Dose Regimen 3 (Per Protocol Set)
Number of subjects analysed	87	95	97	81	88	95	87	95	97	63	65	79
Units: Subjects	45	59	55	43	58	54	45	59	55	38	45	46

Dose regimen 1 vs. Dose Regimen 3 (FAS)

Statistical analysis description

Odds ratios and their 95% confidence intervals for Dose Regimen 1 vs Dose Regimen 3 (FAS)

Comparison groups

Dose Regimen 1 (Full Analysis Set) v Dose Regimen 3 (Full Analysis Set)

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.53

upper limit

2.04

Dose regimen 2 vs. Dose Regimen 3 (FAS)

Statistical analysis description

Odds ratios and their 95% confidence intervals for Dose Regimen 2 vs Dose Regimen 3 (FAS)

Comparison groups

Dose Regimen 3 (Full Analysis Set) v Dose Regimen 2 (Full Analysis Set)

Number of subjects included in analysis

183

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

3.36

Dose regimen 1 vs. Dose Regimen 2 (FAS)

Statistical analysis description

Odds ratios and their 95% confidence intervals for Dose Regimen 1 vs Dose Regimen 2 (FAS)

Comparison groups

Dose Regimen 2 (Full Analysis Set) v Dose Regimen 1 (Full Analysis Set)

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.61

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

1.26

Dose regimen 1 vs. Dose Regimen 3 (ITT)

Statistical analysis description

Odds ratios and their 95% confidence intervals for Dose Regimen 1 vs Dose Regimen 3 (ITT)

Comparison groups

Dose Regimen 1 (IIT) v Dose Regimen 3 (IIT)

Number of subjects included in analysis

184

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.53

upper limit

1.99

Dose regimen 2 vs. Dose Regimen 3 (ITT)

Statistical analysis description

Odds ratios and their 95% confidence intervals for Dose Regimen 2 vs Dose Regimen 3 (ITT)

Comparison groups

Dose Regimen 3 (IIT) v Dose Regimen 2 (IIT)

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.61

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

3.16

Dose regimen 1 vs. Dose Regimen 2 (ITT)

Statistical analysis description

Odds ratios and their 95% confidence intervals for Dose Regimen 1 vs Dose Regimen 2 (ITT)

Comparison groups

Dose Regimen 2 (IIT) v Dose Regimen 1 (IIT)

Number of subjects included in analysis

182

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.64

Confidence interval

level

95%

sides

2-sided

lower limit

0.31

upper limit

1.29

Dose regimen 1 vs. Dose Regimen 3 (PP)

Statistical analysis description

Odds ratios and their 95% confidence intervals for Dose Regimen 1 vs Dose Regimen 3 (PP)

Comparison groups

Dose Regimen 1 (Per Protocol Set) v Dose Regimen 3 (Per Protocol Set)

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.29

Confidence interval

level

95%

sides

2-sided

lower limit

0.62

upper limit

2.67

Dose regimen 2 vs. Dose Regimen 3 (PP)

Statistical analysis description

Odds ratios and their 95% confidence intervals for Dose Regimen 2 vs Dose Regimen 3 (PP)

Comparison groups

Dose Regimen 3 (Per Protocol Set) v Dose Regimen 2 (Per Protocol Set)

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.83

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

3.86

Dose regimen 1 vs. Dose Regimen 2 (PP)

Statistical analysis description

Odds ratios and their 95% confidence intervals for Dose Regimen 1 vs Dose Regimen 2 (PP)

Comparison groups

Dose Regimen 2 (Per Protocol Set) v Dose Regimen 1 (Per Protocol Set)

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.31

upper limit

1.58

Secondary: Proportion of subjects with adequate relief of global IBS symptoms during at least 2 weeks (consecutive or not) per month (“monthly response”) during month 1, during month 1 through 2 and during month 1 through 3

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End point title

Proportion of subjects with adequate relief of global IBS symptoms during at least 2 weeks (consecutive or not) per month (“monthly response”) during month 1, during month 1 through 2 and during month 1 through 3

End point description

End point type

Secondary

End point timeframe

during month 1, during month 1 through 2 and during month 1 through 3

End point values	Treatment group 1: dose regimen 1	Treatment group 2: dose regimen 2	Treatment group 3: matching placebo	Dose Regimen 1 (Full Analysis Set)	Dose Regimen 2 (Full Analysis Set)	Dose Regimen 3 (Full Analysis Set)	Dose Regimen 1 (IIT)	Dose Regimen 2 (IIT)	Dose Regimen 3 (IIT)	Dose Regimen 1 (Per Protocol Set)	Dose Regimen 2 (Per Protocol Set)	Dose Regimen 3 (Per Protocol Set)
Number of subjects analysed	87	95	97	81	88	95	87	95	97	63	65	79
Units: Subjects
Month 1	42	53	34	41	50	34	42	53	34	34	38	28
Month 1 through 2	34	49	36	34	48	36	34	49	36	27	37	32
Month 1 through 3	28	40	33	28	39	33	28	40	33	23	29	30

Dose Regimen 1 vs. Dose Regimen 3 (FAS)

Statistical analysis description

Odds ratios and their 95% confidence intervals for Dose Regimen 1 vs Dose Regimen 3 (FAS)

Comparison groups

Dose Regimen 1 (Full Analysis Set) v Dose Regimen 3 (Full Analysis Set)

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

Confidence interval

level

90%

sides

1-sided

lower limit

upper limit

Dose Regimen 2 vs. Dose Regimen 3 (FAS)

Statistical analysis description

Odds ratios and their 95% confidence intervals for Dose Regimen 2 vs Dose Regimen 3 (FAS)

Comparison groups

Dose Regimen 3 (Full Analysis Set) v Dose Regimen 2 (Full Analysis Set)

Number of subjects included in analysis

183

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

3.36

Dose Regimen 1 vs. Dose Regimen 2 (FAS)

Statistical analysis description

Odds ratios and their 95% confidence intervals for Dose Regimen 1 vs Dose Regimen 2 (FAS)

Comparison groups

Dose Regimen 2 (Full Analysis Set) v Dose Regimen 1 (Full Analysis Set)

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.61

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

1.26

Dose Regimen 1 vs. Dose Regimen 3 (ITT)

Statistical analysis description

Odds ratios and their 95% confidence intervals for Dose Regimen 1 vs Dose Regimen 3 (ITT)

Comparison groups

Dose Regimen 1 (IIT) v Dose Regimen 3 (IIT)

Number of subjects included in analysis

184

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.53

upper limit

1.99

Dose Regimen 2 vs. Dose Regimen 3 (ITT)

Statistical analysis description

Odds ratios and their 95% confidence intervals for Dose Regimen 2 vs Dose Regimen 3 (ITT)

Comparison groups

Dose Regimen 3 (IIT) v Dose Regimen 2 (IIT)

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.61

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

3.16

Dose Regimen 1 vs. Dose Regimen 2 (ITT)

Statistical analysis description

Odds ratios and their 95% confidence intervals for Dose Regimen 1 vs Dose Regimen 2 (ITT)

Comparison groups

Dose Regimen 2 (IIT) v Dose Regimen 1 (IIT)

Number of subjects included in analysis

182

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.64

Confidence interval

level

95%

sides

2-sided

lower limit

0.31

upper limit

1.29

Dose Regimen 1 vs. Dose Regimen 3 (PP)

Statistical analysis description

Odds ratios and their 95% confidence intervals for Dose Regimen 1 vs Dose Regimen 3 (PP)

Comparison groups

Dose Regimen 1 (Per Protocol Set) v Dose Regimen 3 (Per Protocol Set)

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.29

Confidence interval

level

95%

sides

2-sided

lower limit

0.62

upper limit

2.67

Dose Regimen 2 vs. Dose Regimen 3 (PP)

Statistical analysis description

Odds ratios and their 95% confidence intervals for Dose Regimen 2 vs Dose Regimen 3 (PP)

Comparison groups

Dose Regimen 3 (Per Protocol Set) v Dose Regimen 2 (Per Protocol Set)

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.83

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

3.86

Dose Regimen 1 vs. Dose Regimen 2 (PP)

Statistical analysis description

Odds ratios and their 95% confidence intervals for Dose Regimen 1 vs Dose Regimen 2 (PP)

Comparison groups

Dose Regimen 2 (Per Protocol Set) v Dose Regimen 1 (Per Protocol Set)

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.31

upper limit

1.58

Secondary: Proportion of subjects with adequate relief of IBS-related bloating for at least 2 (consecutive or not) of the 10 weeks during the follow-up period (i.e., weeks 3 through 12).

Top of page

End point title

Proportion of subjects with adequate relief of IBS-related bloating for at least 2 (consecutive or not) of the 10 weeks during the follow-up period (i.e., weeks 3 through 12).

End point description

Adequate relief of bloating is defined as a response of "yes" to the following question, which was asked weekly (every 7 days): "In regard to your symptom of bloating, as compared to the way you felt before you started study medication, have you, in the past 7 days, had adequate relief of your IBS symptom of bloating? [Yes/No]."

End point type

Secondary

End point timeframe

Weeks 3 through 12

End point values	Treatment group 1: dose regimen 1	Treatment group 2: dose regimen 2	Treatment group 3: matching placebo	Dose Regimen 1 (Full Analysis Set)	Dose Regimen 2 (Full Analysis Set)	Dose Regimen 3 (Full Analysis Set)	Dose Regimen 1 (IIT)	Dose Regimen 2 (IIT)	Dose Regimen 3 (IIT)	Dose Regimen 1 (Per Protocol Set)	Dose Regimen 2 (Per Protocol Set)	Dose Regimen 3 (Per Protocol Set)
Number of subjects analysed	87	95	97	81	88	95	87	95	97	63	65	79
Units: Subjects	48	59	54	47	57	53	48	59	54	39	44	46

Dose Regimen 1 vs Dose Regimen 3 (FAS)

Statistical analysis description

Odds ratios and their 95% confidence intervals for Dose Regimen 1 vs Dose Regimen 3 (FAS)

Comparison groups

Dose Regimen 1 (Full Analysis Set) v Dose Regimen 3 (Full Analysis Set)

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.45

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

2.89

Dose Regimen 2 vs Dose Regimen 3 (FAS)

Statistical analysis description

Odds ratios and their 95% confidence intervals for Dose Regimen 2 vs Dose Regimen 3 (FAS)

Comparison groups

Dose Regimen 3 (Full Analysis Set) v Dose Regimen 2 (Full Analysis Set)

Number of subjects included in analysis

183

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.67

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

3.27

Dose Regimen 1 vs Dose Regimen 2 (FAS)

Statistical analysis description

Odds ratios and their 95% confidence intervals for Dose Regimen 1 vs Dose Regimen 2 (FAS)

Comparison groups

Dose Regimen 2 (Full Analysis Set) v Dose Regimen 1 (Full Analysis Set)

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.87

Confidence interval

level

95%

sides

2-sided

lower limit

0.42

upper limit

1.81

Dose Regimen 1 vs Dose Regimen 3 (ITT)

Statistical analysis description

Odds ratios and their 95% confidence intervals for Dose Regimen 1 vs Dose Regimen 3 (ITT)

Comparison groups

Dose Regimen 1 (IIT) v Dose Regimen 3 (IIT)

Number of subjects included in analysis

184

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.31

Confidence interval

level

95%

sides

2-sided

lower limit

0.67

upper limit

2.58

Dose Regimen 2 vs Dose Regimen 3 (ITT)

Statistical analysis description

Odds ratios and their 95% confidence intervals for Dose Regimen 2 vs Dose Regimen 3 (ITT)

Comparison groups

Dose Regimen 3 (IIT) v Dose Regimen 2 (IIT)

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.61

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

3.14

Dose Regimen 1 vs Dose Regimen 2 (ITT)

Statistical analysis description

Odds ratios and their 95% confidence intervals for Dose Regimen 1 vs Dose Regimen 2(ITT)

Comparison groups

Dose Regimen 2 (IIT) v Dose Regimen 1 (IIT)

Number of subjects included in analysis

182

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

1.66

Dose Regimen 1 vs Dose Regimen 3 (PP)

Statistical analysis description

Odds ratios and their 95% confidence intervals for Dose Regimen 1 vs Dose Regimen 3(PP)

Comparison groups

Dose Regimen 1 (Per Protocol Set) v Dose Regimen 3 (Per Protocol Set)

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.48

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

3.13

Dose Regimen 2 vs Dose Regimen 3 (PP)

Statistical analysis description

Odds ratios and their 95% confidence intervals for Dose Regimen 2 vs Dose Regimen 3(PP)

Comparison groups

Dose Regimen 3 (Per Protocol Set) v Dose Regimen 2 (Per Protocol Set)

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.67

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

3.51

Dose Regimen 1 vs Dose Regimen 2 (PP)

Statistical analysis description

Odds ratios and their 95% confidence intervals for Dose Regimen 1 vs Dose Regimen 2(PP)

Comparison groups

Dose Regimen 2 (Per Protocol Set) v Dose Regimen 1 (Per Protocol Set)

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.39

upper limit

Secondary: Proportion of subjects with relief (weekly responders) determined from the subjects’ daily assessments of IBS symptoms, bloating, and abdominal pain

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End point title

Proportion of subjects with relief (weekly responders) determined from the subjects’ daily assessments of IBS symptoms, bloating, and abdominal pain

End point description

Relief of IBS symptoms and bloating is defined as a score of either 0 (not at all) or 1 (hardly) for at least 50% of the days in a given week or a score of 0 (not at all), 1 (hardly), or 2 (somewhat) for 100% of the days in a given week for at least 2 (consecutive or not) of the 4 weeks during a given month. Relief of abdominal pain is defined as a decrease by ≥30% from baseline in weekly mean rating of IBS-related abdominal pain.

End point type

Secondary

End point timeframe

During treatment and follow up period

End point values	Treatment group 1: dose regimen 1	Treatment group 2: dose regimen 2	Treatment group 3: matching placebo	Dose Regimen 1 (Full Analysis Set)	Dose Regimen 2 (Full Analysis Set)	Dose Regimen 3 (Full Analysis Set)	Dose Regimen 1 (IIT)	Dose Regimen 2 (IIT)	Dose Regimen 3 (IIT)	Dose Regimen 1 (Per Protocol Set)	Dose Regimen 2 (Per Protocol Set)	Dose Regimen 3 (Per Protocol Set)
Number of subjects analysed	87	95	97	81	88	95	87	95	97	63	65	79
Units: Subjects
IBS Symptoms	22	29	19	21	29	19	22	29	19	17	24	16
Bloating	22	33	16	20	32	16	22	33	16	17	26	13
Abdominal Pain	46	52	55	44	51	55	46	52	55	34	40	47

Dose Regimen 1 vs Dose Regimen 3(FAS)-IBS Symptoms

Statistical analysis description

Odds ratio and 95% CI: Dose Regimen 1 vs Dose Regimen 3 (FAS) - IBS Symptoms

Comparison groups

Dose Regimen 1 (Full Analysis Set) v Dose Regimen 3 (Full Analysis Set)

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

2.84

Dose Regimen 2 vs Dose Regimen 3(FAS)-IBS Symptoms

Statistical analysis description

Odds ratio and 95% CI: Dose Regimen 2 vs Dose Regimen 3 (FAS) - IBS Symptoms

Comparison groups

Dose Regimen 3 (Full Analysis Set) v Dose Regimen 2 (Full Analysis Set)

Number of subjects included in analysis

183

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.97

Confidence interval

level

95%

sides

2-sided

lower limit

1.01

upper limit

3.85

Dose Regimen 1 vs Dose Regimen 2(FAS)-IBS Symptoms

Statistical analysis description

Odds ratio and 95% CI: Dose Regimen 1 vs Dose Regimen 2 (FAS) - IBS Symptoms

Comparison groups

Dose Regimen 2 (Full Analysis Set) v Dose Regimen 1 (Full Analysis Set)

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.71

Confidence interval

level

95%

sides

2-sided

lower limit

0.37

upper limit

1.39

Dose Regimen 1 vs Dose Regimen 3(ITT)-IBS Symptom

Statistical analysis description

Odds ratio and 95% CI: Dose Regimen 1 vs Dose Regimen 3 (ITT)-IBS Symptoms

Comparison groups

Dose Regimen 1 (IIT) v Dose Regimen 3 (IIT)

Number of subjects included in analysis

184

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.44

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

2.89

Dose Regimen 2 vs Dose Regimen 3(ITT)-IBS Symptoms

Statistical analysis description

Odds ratio and 95% CI: Dose Regimen 2 vs Dose Regimen 3 (ITT) - IBS Symptoms

Comparison groups

Dose Regimen 3 (IIT) v Dose Regimen 2 (IIT)

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.87

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

3.64

Dose Regimen 1 vs Dose Regimen 2(ITT)-IBS Symptoms

Statistical analysis description

Odds ratio and 95% CI: Dose Regimen 1 vs Dose Regimen 2 (ITT) - IBS Symptoms

Comparison groups

Dose Regimen 2 (IIT) v Dose Regimen 1 (IIT)

Number of subjects included in analysis

182

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.77

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

1.49

Dose Regimen 1 vs Dose Regimen 3 (PP)-IBS Symptoms

Statistical analysis description

Odds ratio and 95% CI: Dose Regimen 1 vs Dose Regimen 3 (PP Set) - IBS Symptoms

Comparison groups

Dose Regimen 1 (Per Protocol Set) v Dose Regimen 3 (Per Protocol Set)

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.46

Confidence interval

level

95%

sides

2-sided

lower limit

0.67

upper limit

3.18

Dose Regimen 2 vs Dose Regimen 3(PP)-IBS Symptoms

Statistical analysis description

Odds ratio and 95% CI: Dose Regimen 2 vs Dose Regimen 3 (PP Set) - IBS Symptoms

Comparison groups

Dose Regimen 3 (Per Protocol Set) v Dose Regimen 2 (Per Protocol Set)

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

2.3

Confidence interval

level

95%

sides

2-sided

lower limit

1.09

upper limit

4.85

Dose Regimen 1 vs Dose Regimen 2(PP)-IBS Symptoms

Statistical analysis description

Odds ratio and 95% CI: Dose Regimen 1 vs Dose Regimen 2 (PP Set) - IBS Symptoms

Comparison groups

Dose Regimen 2 (Per Protocol Set) v Dose Regimen 1 (Per Protocol Set)

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.63

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

1.34

Dose Regimen 1 vs Dose Regimen 3 (FAS) - Bloating

Statistical analysis description

Odds ratio and 95% CI: Dose Regimen 1 vs Dose Regimen 3 (FAS) - Bloating

Comparison groups

Dose Regimen 3 (Full Analysis Set) v Dose Regimen 1 (Full Analysis Set)

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.62

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

3.38

Dose Regimen 2 vs Dose Regimen 3 (FAS) - Bloating

Statistical analysis description

Odds ratio and 95% CI: Dose Regimen 2 vs Dose Regimen 3 (FAS) - Bloating

Comparison groups

Dose Regimen 3 (Full Analysis Set) v Dose Regimen 2 (Full Analysis Set)

Number of subjects included in analysis

183

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

2.82

Confidence interval

level

95%

sides

2-sided

lower limit

1.41

upper limit

5.63

Dose Regimen 1 vs Dose Regimen 2 (FAS) - Bloating

Statistical analysis description

Odds ratio and 95% CI: Dose Regimen 1 vs Dose Regimen 2 (FAS) - Bloating

Comparison groups

Dose Regimen 2 (Full Analysis Set) v Dose Regimen 1 (Full Analysis Set)

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.57

Confidence interval

level

95%

sides

2-sided

lower limit

0.29

upper limit

1.12

Dose Regimen 1 vs Dose Regimen 3 (ITT) -Bloating

Statistical analysis description

Odds ratio and 95% CI: Dose Regimen 1 vs Dose Regimen 3 (ITT) - Bloating

Comparison groups

Dose Regimen 1 (IIT) v Dose Regimen 3 (IIT)

Number of subjects included in analysis

184

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.77

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

3.66

Dose Regimen 2 vs Dose Regimen 3 (ITT) - Bloating

Statistical analysis description

Odds ratio and 95% CI: Dose Regimen 2 vs Dose Regimen 3 (ITT) - Bloating

Comparison groups

Dose Regimen 3 (IIT) v Dose Regimen 2 (IIT)

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

2.8

Confidence interval

level

95%

sides

2-sided

lower limit

1.41

upper limit

5.55

Dose Regimen 1 vs Dose Regimen 2 (ITT) - Bloating

Statistical analysis description

Odds ratio and 95% CI: Dose Regimen 1 vs Dose Regimen 2 (ITT) - Bloating

Comparison groups

Dose Regimen 2 (IIT) v Dose Regimen 1 (IIT)

Number of subjects included in analysis

182

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.63

Confidence interval

level

95%

sides

2-sided

lower limit

0.33

upper limit

1.21

Dose Regimen 1 vs Dose Regimen 3 (PP) - Bloating

Statistical analysis description

Odds ratio and 95% CI: Dose Regimen 1 vs Dose Regimen 3 (PP Set) - Bloating

Comparison groups

Dose Regimen 1 (Per Protocol Set) v Dose Regimen 3 (Per Protocol Set)

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

4.24

Dose Regimen 2 vs Dose Regimen 3 (PP) - Bloating

Statistical analysis description

Odds ratio and 95% CI: Dose Regimen 2 vs Dose Regimen 3 (PP Set) - Bloating

Comparison groups

Dose Regimen 3 (Per Protocol Set) v Dose Regimen 2 (Per Protocol Set)

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

3.38

Confidence interval

level

95%

sides

2-sided

lower limit

1.56

upper limit

7.34

Dose Regimen 1 vs Dose Regimen 2 (PP) - Bloating

Statistical analysis description

Odds ratio and 95% CI: Dose Regimen 1 vs Dose Regimen 2 (PP Set) - Bloating

Comparison groups

Dose Regimen 2 (Per Protocol Set) v Dose Regimen 1 (Per Protocol Set)

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.55

Confidence interval

level

95%

sides

2-sided

lower limit

0.26

upper limit

1.17

Dose Regimen 1 vs Dose Regimen 3 (FAS)-Abdom. Pain

Statistical analysis description

Odds ratio and 95% CI: Dose Regimen 1 vs Dose Regimen 3 (FAS) - Abdominal Pain

Comparison groups

Dose Regimen 1 (Full Analysis Set) v Dose Regimen 3 (Full Analysis Set)

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.48

upper limit

1.57

Dose Regimen 2 vs Dose Regimen 3 (FAS)-Abdom. Pain

Statistical analysis description

Odds ratio and 95% CI: Dose Regimen 2 vs Dose Regimen 3 (FAS) - Abdominal Pain

Comparison groups

Dose Regimen 3 (Full Analysis Set) v Dose Regimen 2 (Full Analysis Set)

Number of subjects included in analysis

183

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.56

upper limit

1.8

Dose Regimen 1 vs Dose Regimen 2 (FAS)-Abdom. Pain

Statistical analysis description

Odds ratio and 95% CI: Dose Regimen 1 vs Dose Regimen 2 (FAS) - Abdominal Pain

Comparison groups

Dose Regimen 1 (Full Analysis Set) v Dose Regimen 2 (Full Analysis Set)

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.47

upper limit

1.59

Dose Regimen 1 vs Dose Regimen 3 (ITT)-Abdom. Pain

Statistical analysis description

Odds ratio and 95% CI: Dose Regimen 1 vs Dose Regimen 3 (ITT) - Abdominal Pain

Comparison groups

Dose Regimen 1 (IIT) v Dose Regimen 3 (IIT)

Number of subjects included in analysis

184

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

1.63

Dose Regimen 2 vs Dose Regimen 3 (ITT)-Abdom. Pain

Statistical analysis description

Odds ratio and 95% CI: Dose Regimen 2 vs Dose Regimen 3 (ITT) - Abdominal Pain

Comparison groups

Dose Regimen 3 (IIT) v Dose Regimen 2 (IIT)

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.54

upper limit

1.73

Dose Regimen 1 vs Dose Regimen 2 (ITT)-Abdom. Pain

Statistical analysis description

Odds ratio and 95% CI: Dose Regimen 1 vs Dose Regimen 2 (ITT) - Abdominal Pain

Comparison groups

Dose Regimen 2 (IIT) v Dose Regimen 1 (IIT)

Number of subjects included in analysis

182

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.51

upper limit

1.69

Dose Regimen 1 vs Dose Regimen 3 (PP)-Abdom. Pain

Statistical analysis description

Odds ratio and 95% CI: Dose Regimen 1 vs Dose Regimen 3 (PP Set) - Abdominal Pain

Comparison groups

Dose Regimen 1 (Per Protocol Set) v Dose Regimen 3 (Per Protocol Set)

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.41

upper limit

1.56

Dose Regimen 2 vs Dose Regimen 3 (PP)-Abdom. Pain

Statistical analysis description

Odds ratio and 95% CI: Dose Regimen2 vs Dose Regimen 3 (PP Set) - Abdominal Pain

Comparison groups

Dose Regimen 2 (Per Protocol Set) v Dose Regimen 3 (Per Protocol Set)

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.09

Confidence interval

level

95%

sides

2-sided

lower limit

0.56

upper limit

2.13

Dose Regimen 1 vs Dose Regimen 2 (PP)-Abdom. Pain

Statistical analysis description

Odds ratio and 95% CI: Dose Regimen 1 vs Dose Regimen 2 (PP Set) - Abdominal Pain

Comparison groups

Dose Regimen 2 (Per Protocol Set) v Dose Regimen 1 (Per Protocol Set)

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.73

Confidence interval

level

95%

sides

2-sided

lower limit

0.36

upper limit

1.48

Secondary: Change from baseline to week 12 in daily IBS symptoms, bloating and abdominal pain.

Top of page

End point title

Change from baseline to week 12 in daily IBS symptoms, bloating and abdominal pain.

End point description

Values at week 12 were calculated as: - IBS symptoms, bloating, abdominal pain, stool consistency: week 12 average of daily values, - the sense of urgency is calculated as 100* (number of days with urgency/number of days with data). The value at week 12 and change from baseline to week 12 in daily IBS symptoms, bloating and abdominal pain was summarised by treatment using descriptive statistics.

End point type

Secondary

End point timeframe

From baseline to week 12

End point values	Dose Regimen 1 (Full Analysis Set)	Dose Regimen 2 (Full Analysis Set)	Dose Regimen 3 (Full Analysis Set)	Dose Regimen 1 (IIT)	Dose Regimen 2 (IIT)	Dose Regimen 3 (IIT)	Dose Regimen 1 (Per Protocol Set)	Dose Regimen 2 (Per Protocol Set)	Dose Regimen 3 (Per Protocol Set)
Number of subjects analysed	78	85	93	81	87	93	63	65	79
Units: Change in symptoms
arithmetic mean (standard deviation)
Global IBS Symptoms	-1.2 ( 1.6 )	-1.3 ( 1.5 )	-1.1 ( 1.4 )	-1.1 ( 1.6 )	-1.2 ( 1.5 )	-1.0 ( 1.4 )	-1.3 ( 1.6 )	-1.2 ( 1.5 )	-1.1 ( 1.3 )
IBS-Related Bloating	-0.9 ( 1.6 )	-0.9 ( 1.6 )	-0.8 ( 1.4 )	-0.8 ( 1.5 )	-0.9 ( 1.6 )	-0.8 ( 1.4 )	-0.9 ( 1.6 )	-0.9 ( 1.6 )	-0.8 ( 1.4 )
Abdominal Pain	-1.6 ( 2.2 )	-1.9 ( 2.1 )	-1.8 ( 2.1 )	-1.5 ( 2.1 )	-1.9 ( 2.1 )	-1.7 ( 2.1 )	-1.6 ( 2.2 )	-1.8 ( 2.2 )	-1.7 ( 2.2 )

No statistical analyses for this end point

Secondary: Proportion of monthly responders during month 1, during month 1 through 2 and during month 1 through 3 determined from the subjects’ daily assessments of IBS symptoms, bloating, and abdominal pain and stool consistency

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End point title

Proportion of monthly responders during month 1, during month 1 through 2 and during month 1 through 3 determined from the subjects’ daily assessments of IBS symptoms, bloating, and abdominal pain and stool consistency

End point description

Relief of IBS symptoms and bloating is defined as a score of either 0 (not at all) or 1 (hardly) for at least 50% of the days in a given month or a score of 0 (not at all), 1 (hardly), or 2 (somewhat) for 100% of the days in a given month. Relief of abdominal pain is defined as a decrease by ≥30% from baseline in weekly mean rating of IBS-related abdominal pain. Relief of stool consistency is defined as a 50% or greater reduction in the number of days per month with at least one stool that has a consistency of Type 6 or 7 compared with baseline.

End point type

Secondary

End point timeframe

During month 1, during month 1 through 2 and during month 1 through 3

End point values	Treatment group 1: dose regimen 1	Treatment group 2: dose regimen 2	Treatment group 3: matching placebo	Dose Regimen 1 (Full Analysis Set)	Dose Regimen 2 (Full Analysis Set)	Dose Regimen 3 (Full Analysis Set)	Dose Regimen 1 (IIT)	Dose Regimen 2 (IIT)	Dose Regimen 3 (IIT)	Dose Regimen 1 (Per Protocol Set)	Dose Regimen 2 (Per Protocol Set)	Dose Regimen 3 (Per Protocol Set)
Number of subjects analysed	87	95	97	81	88	95	87	95	97	63	65	79
Units: Subjects
IBS Symptoms (Month 1)	10	17	8	9	17	8	10	17	8	8	15	6
IBS Symptoms (Month 1 through 2)	13	20	11	12	19	11	13	20	11	10	15	10
IBS Symptoms (Month 1 through 3)	12	19	13	12	18	13	12	19	13	11	13	12
Bloating (Month 1)	15	22	10	14	18	10	15	18	10	12	16	9
Bloating (Month 1 through 2)	13	25	14	13	22	14	13	22	14	11	16	13
Bloating (Month 1 through 3)	16	25	15	16	24	15	16	25	15	14	18	13
Abdominal Pain (Month 1)	40	55	51	38	54	51	40	55	51	31	40	45
Abdominal Pain (Month 1 through 2)	42	52	51	40	51	51	42	52	51	34	38	48
Abdominal Pain (Month 1 through 3)	41	55	52	39	54	52	41	55	52	32	41	46
Stool Consistency (Month 1)	50	61	54	48	59	54	50	61	54	41	44	46
Stool Consistency (Month 1 through 2)	53	57	52	51	56	52	53	57	52	44	42	46
Stool Consistency (Month 1 through 3)	51	56	55	50	55	55	51	56	55	45	40	48

No statistical analyses for this end point

Secondary: Change from baseline to each week during the 12 week follow up for daily IBS symptoms, bloating, abdominal pain, stool consistency and sense of urgency

Top of page

End point title

Change from baseline to each week during the 12 week follow up for daily IBS symptoms, bloating, abdominal pain, stool consistency and sense of urgency

End point description

Sense of urgency asked as "Have you felt or experienced a sense of urgency today? [Yes/No]" and calculated as 100x (number of days with urgency/number of days with data), and daily number of stools.

End point type

Secondary

End point timeframe

From baseline to each week during the 12 week follow up

End point values	Treatment group 1: dose regimen 1	Treatment group 2: dose regimen 2	Treatment group 3: matching placebo	Dose Regimen 1 (Full Analysis Set)	Dose Regimen 2 (Full Analysis Set)	Dose Regimen 3 (Full Analysis Set)	Dose Regimen 1 (IIT)	Dose Regimen 2 (IIT)	Dose Regimen 3 (IIT)	Dose Regimen 1 (Per Protocol Set)	Dose Regimen 2 (Per Protocol Set)	Dose Regimen 3 (Per Protocol Set)
Number of subjects analysed	81	86	93	78	82	92	81	87	94	63	63	78
Units: Change in symptoms
arithmetic mean (standard deviation)
Global IBS Symptoms (Week 3)	-1.0 ( 1.2 )	-1.2 ( 1.3 )	-1.0 ( 1.3 )	-1.0 ( 1.2 )	-1.2 ( 1.3 )	-1.0 ( 1.3 )	-1.0 ( 1.2 )	-1.2 ( 1.3 )	-1.0 ( 1.3 )	-1.0 ( 1.2 )	-1.1 ( 1.3 )	-1.0 ( 1.2 )
Global IBS Symptoms (Week 4)	-0.9 ( 1.3 )	-1.2 ( 1.4 )	-0.9 ( 1.3 )	-1.0 ( 1.3 )	-1.2 ( 1.4 )	-1.0 ( 1.3 )	-0.9 ( 1.3 )	-1.2 ( 1.4 )	-0.9 ( 1.3 )	-1.1 ( 1.2 )	-1.1 ( 1.4 )	-1.0 ( 1.3 )
Global IBS Symptoms (Week 5)	-1.1 ( 1.2 )	-1.2 ( 1.5 )	-1.0 ( 1.3 )	-1.2 ( 1.2 )	-1.2 ( 1.5 )	-1.0 ( 1.3 )	-1.1 ( 1.2 )	-1.2 ( 1.5 )	-1.0 ( 1.3 )	-1.2 ( 1.2 )	-1.2 ( 1.4 )	-1.0 ( 1.4 )
Global IBS Symptoms (Week 6)	-1.1 ( 1.2 )	-1.2 ( 1.5 )	-1.0 ( 1.3 )	-1.2 ( 1.2 )	-1.3 ( 1.4 )	-1.0 ( 1.3 )	-1.1 ( 1.2 )	-1.2 ( 1.5 )	-1.0 ( 1.3 )	-1.2 ( 1.2 )	-1.2 ( 1.4 )	-1.0 ( 1.3 )
Global IBS Symptoms (Week 7)	-1.1 ( 1.4 )	-1.3 ( 1.4 )	-1.1 ( 1.2 )	-1.2 ( 1.3 )	-1.3 ( 1.4 )	-1.1 ( 1.2 )	-1.1 ( 1.4 )	-1.3 ( 1.4 )	-1.1 ( 1.2 )	-1.2 ( 1.3 )	-1.3 ( 1.3 )	-1.1 ( 1.2 )
Global IBS Symptoms (Week 8)	-1.1 ( 1.5 )	-1.3 ( 1.5 )	-1.0 ( 1.4 )	-1.1 ( 1.4 )	-1.3 ( 1.4 )	-1.0 ( 1.4 )	-1.1 ( 1.5 )	-1.3 ( 1.5 )	-1.0 ( 1.4 )	-1.3 ( 1.5 )	-1.3 ( 1.4 )	-1.1 ( 1.3 )
Global IBS Symptoms (Week 9)	-1.1 ( 1.5 )	-1.3 ( 1.4 )	-1.0 ( 1.4 )	-1.1 ( 1.5 )	-1.3 ( 1.4 )	-1.0 ( 1.4 )	-1.1 ( 1.5 )	-1.3 ( 1.4 )	-1.0 ( 1.4 )	-1.3 ( 1.5 )	-1.2 ( 1.4 )	-1.0 ( 1.4 )
Global IBS Symptoms (Week 10)	-1.2 ( 1.4 )	-1.3 ( 1.5 )	-1.1 ( 1.4 )	-1.2 ( 1.4 )	-1.3 ( 1.5 )	-1.1 ( 1.4 )	-1.2 ( 1.4 )	-1.3 ( 1.5 )	-1.1 ( 1.4 )	-1.3 ( 1.5 )	-1.3 ( 1.5 )	-1.1 ( 1.3 )
Global IBS Symptoms (Week 11)	-1.2 ( 1.6 )	-1.3 ( 1.5 )	-1.1 ( 1.4 )	-1.3 ( 1.5 )	-1.3 ( 1.5 )	-1.1 ( 1.4 )	-1.2 ( 1.6 )	-1.3 ( 1.5 )	-1.1 ( 1.4 )	-1.4 ( 1.5 )	-1.3 ( 1.5 )	-1.1 ( 1.3 )
Global IBS Symptoms (Week 12)	-1.1 ( 1.6 )	-1.2 ( 1.5 )	-1.0 ( 1.4 )	-1.2 ( 1.6 )	-1.3 ( 1.5 )	-1.1 ( 1.4 )	-1.1 ( 1.6 )	-1.2 ( 1.5 )	-1.0 ( 1.4 )	-1.3 ( 1.6 )	-1.2 ( 1.5 )	-1.1 ( 1.3 )
IBS-related bloating (Week 3)	-0.7 ( 1.3 )	-0.9 ( 1.3 )	-0.7 ( 1.3 )	-0.7 ( 1.3 )	-0.9 ( 1.4 )	-0.7 ( 1.3 )	-0.7 ( 1.3 )	-0.9 ( 1.3 )	-0.7 ( 1.3 )	-0.7 ( 1.3 )	-0.9 ( 1.4 )	-0.7 ( 1.2 )
IBS-related bloating (Week 4)	-0.6 ( 1.4 )	-0.9 ( 1.4 )	-0.9 ( 1.3 )	-0.6 ( 1.4 )	-0.9 ( 1.4 )	-0.9 ( 1.3 )	-0.6 ( 1.4 )	-0.9 ( 1.4 )	-0.9 ( 1.3 )	-0.7 ( 1.4 )	-0.9 ( 1.5 )	-0.9 ( 1.3 )
IBS-related bloating (Week 5)	-0.7 ( 1.4 )	-0.9 ( 1.5 )	-0.9 ( 1.3 )	-0.8 ( 1.4 )	-0.9 ( 1.5 )	-0.9 ( 1.3 )	-0.7 ( 1.4 )	-0.9 ( 1.5 )	-0.9 ( 1.3 )	-0.8 ( 1.4 )	-0.9 ( 1.5 )	-0.9 ( 1.3 )
IBS-related bloating (Week 6)	-0.8 ( 1.3 )	-0.9 ( 1.5 )	-1.0 ( 1.4 )	-0.9 ( 1.4 )	-1.0 ( 1.5 )	-1.0 ( 1.4 )	-0.8 ( 1.3 )	-0.9 ( 1.5 )	-1.0 ( 1.4 )	-0.9 ( 1.4 )	-1.0 ( 1.5 )	-1.0 ( 1.3 )
IBS-related bloating (Week 7)	-0.8 ( 1.5 )	-0.9 ( 1.5 )	-1.0 ( 1.4 )	-0.8 ( 1.5 )	-0.9 ( 1.5 )	-1.0 ( 1.4 )	-0.8 ( 1.5 )	-0.9 ( 1.5 )	-1.0 ( 1.4 )	-0.9 ( 1.5 )	-0.9 ( 1.5 )	-1.0 ( 1.4 )
IBS-related bloating (Week 8)	-0.8 ( 1.4 )	-0.9 ( 1.6 )	-1.0 ( 1.4 )	-0.8 ( 1.4 )	-0.9 ( 1.6 )	-1.0 ( 1.4 )	-0.8 ( 1.4 )	-0.9 ( 1.6 )	-1.0 ( 1.4 )	-1.0 ( 1.4 )	-0.9 ( 1.7 )	-1.0 ( 1.4 )
IBS-related bloating (Week 9)	-0.8 ( 1.4 )	-1.0 ( 1.6 )	-0.9 ( 1.4 )	-0.9 ( 1.4 )	-1.0 ( 1.6 )	-0.9 ( 1.4 )	-0.8 ( 1.4 )	-1.0 ( 1.6 )	-0.9 ( 1.4 )	-1.0 ( 1.4 )	-1.0 ( 1.6 )	-0.8 ( 1.4 )
IBS-related bloating (Week 10)	-0.9 ( 1.4 )	-1.0 ( 1.6 )	-0.9 ( 1.4 )	-0.9 ( 1.4 )	-1.0 ( 1.6 )	-0.9 ( 1.4 )	-0.9 ( 1.4 )	-1.0 ( 1.6 )	-0.9 ( 1.4 )	-1.0 ( 1.5 )	-1.1 ( 1.6 )	-0.9 ( 1.4 )
IBS-related bloating (Week 11)	-0.9 ( 1.4 )	-1.0 ( 1.6 )	-1.0 ( 1.4 )	-0.9 ( 1.4 )	-1.0 ( 1.6 )	-1.0 ( 1.4 )	-0.9 ( 1.4 )	-1.0 ( 1.6 )	-1.0 ( 1.4 )	-0.9 ( 1.5 )	-1.0 ( 1.6 )	-1.0 ( 1.4 )
IBS-related bloating (Week 12)	-0.8 ( 1.5 )	-0.9 ( 1.6 )	-0.8 ( 1.4 )	-0.9 ( 1.6 )	-0.9 ( 1.6 )	-0.8 ( 1.4 )	-0.8 ( 1.5 )	-0.9 ( 1.6 )	-0.8 ( 1.4 )	-0.9 ( 1.6 )	-0.9 ( 1.6 )	-0.8 ( 1.4 )
Abdominal Pain (Week 3)	-1.4 ( 1.7 )	-1.9 ( 2.0 )	-1.6 ( 1.9 )	-1.4 ( 1.7 )	-1.9 ( 1.9 )	-1.6 ( 1.9 )	-1.4 ( 1.7 )	-1.9 ( 2.0 )	-1.6 ( 1.9 )	-1.3 ( 1.7 )	-1.8 ( 1.9 )	-0.8 ( 1.9 )
Abdominal Pain (Week 4)	-1.3 ( 1.7 )	-1.8 ( 2.1 )	-1.7 ( 2.1 )	-1.4 ( 1.7 )	-1.8 ( 2.1 )	-1.7 ( 2.1 )	-1.3 ( 1.7 )	-1.8 ( 2.1 )	-1.7 ( 2.1 )	-1.5 ( 1.8 )	-1.7 ( 2.0 )	-1.9 ( 2.1 )
Abdominal Pain (Week 5)	-1.5 ( 1.7 )	-1.9 ( 2.1 )	-1.7 ( 2.1 )	-1.6 ( 1.7 )	-1.9 ( 2.0 )	-1.7 ( 2.1 )	-1.5 ( 1.7 )	-1.9 ( 2.1 )	-1.7 ( 2.1 )	-1.6 ( 1.7 )	-1.9 ( 2.0 )	-1.7 ( 2.2 )
Abdominal Pain (Week 6)	-1.5 ( 1.8 )	-2.0 ( 2.1 )	-1.6 ( 2.1 )	-1.6 ( 1.8 )	-2.1 ( 2.0 )	-1.7 ( 2.1 )	-1.5 ( 1.8 )	-2.0 ( 2.1 )	-1.6 ( 2.1 )	-1.6 ( 1.8 )	-2.0 ( 2.1 )	-1.8 ( 2.2 )
Abdominal Pain (Week 7)	-1.5 ( 2.0 )	-2.1 ( 2.1 )	-1.8 ( 2.0 )	-1.6 ( 2.0 )	-2.1 ( 2.0 )	-1.8 ( 2.0 )	-1.5 ( 2.0 )	-2.1 ( 2.1 )	-1.8 ( 2.0 )	-1.6 ( 1.9 )	-2.0 ( 2.0 )	-1.9 ( 2.0 )
Abdominal Pain (Week 8)	-1.5 ( 1.9 )	-2.1 ( 2.2 )	-1.8 ( 2.2 )	-1.5 ( 1.9 )	-2.1 ( 2.2 )	-1.8 ( 2.2 )	-1.5 ( 1.9 )	-2.1 ( 2.2 )	-1.8 ( 2.2 )	-1.6 ( 1.9 )	-2.1 ( 2.2 )	-2.0 ( 2.1 )
Abdominal Pain (Week 9)	-1.5 ( 2.0 )	-2.1 ( 2.0 )	-1.7 ( 2.3 )	-1.5 ( 2.0 )	-2.1 ( 1.9 )	-1.7 ( 2.3 )	-1.5 ( 2.0 )	-2.1 ( 2.0 )	-1.7 ( 2.3 )	-1.6 ( 2.1 )	-2.0 ( 2.0 )	-1.7 ( 2.3 )
Abdominal Pain (Week 10)	-1.6 ( 2.3 )	-2.1 ( 2.1 )	-1.9 ( 2.2 )	-1.6 ( 2.2 )	-2.1 ( 2.0 )	-1.9 ( 2.2 )	-1.6 ( 2.3 )	-2.1 ( 2.1 )	-1.9 ( 2.2 )	-1.6 ( 2.3 )	-2.1 ( 2.1 )	-1.9 ( 2.2 )
Abdominal Pain (Week 11)	-1.6 ( 2.1 )	-2.1 ( 2.1 )	-1.9 ( 2.2 )	-1.6 ( 2.1 )	-2.1 ( 2.0 )	-1.9 ( 2.2 )	-1.6 ( 2.1 )	-2.1 ( 2.1 )	-1.9 ( 2.2 )	-1.7 ( 2.2 )	-2.0 ( 2.1 )	-2.0 ( 2.3 )
Abdominal Pain (Week 12)	-1.5 ( 2.1 )	-1.9 ( 2.1 )	-1.7 ( 2.1 )	-1.6 ( 2.2 )	-1.9 ( 2.1 )	-1.8 ( 2.1 )	-1.5 ( 2.1 )	-1.9 ( 2.1 )	-1.7 ( 2.1 )	-1.6 ( 2.2 )	-1.8 ( 2.2 )	-1.7 ( 2.2 )
Sense of Urgency (Week 3)	-21.2 ( 33.7 )	-28.9 ( 40.0 )	-20.7 ( 34.9 )	-21.3 ( 34.2 )	-28.4 ( 40.0 )	-20.5 ( 35.0 )	-21.2 ( 33.7 )	-28.9 ( 40.0 )	-20.7 ( 34.9 )	-20.3 ( 34.6 )	-30.0 ( 40.0 )	-19.1 ( 33.4 )
Sense of Urgency (Week 4)	-18.2 ( 35.4 )	-24.0 ( 40.1 )	-22.4 ( 34.4 )	-19.0 ( 35.8 )	-23.8 ( 40.6 )	-22.2 ( 34.5 )	-18.2 ( 35.4 )	-24.0 ( 40.1 )	-22.4 ( 34.4 )	-19.4 ( 37.0 )	-24.2 ( 42.0 )	-21.5 ( 33.7 )
Sense of Urgency (Week 5)	-24.0 ( 34.6 )	-31.2 ( 38.2 )	-20.2 ( 34.5 )	-23.9 ( 35.1 )	-30.1 ( 37.5 )	-20.1 ( 34.7 )	-24.0 ( 34.6 )	-31.2 ( 38.2 )	-20.2 ( 34.5 )	-23.9 ( 35.8 )	-27.9 ( 36.9 )	-19.4 ( 34.7 )
Sense of Urgency (Week 6)	-21.2 ( 35.1 )	-25.4 ( 39.3 )	-21.0 ( 34.6 )	-20.6 ( 35.5 )	-24.1 ( 38.5 )	-20.8 ( 34.7 )	-21.2 ( 35.1 )	-25.4 ( 39.3 )	-21.0 ( 34.6 )	-20.5 ( 36.8 )	-23.6 ( 37.3 )	-20.1 ( 34.4 )
Sense of Urgency (Week 7)	-24.8 ( 35.4 )	-29.5 ( 40.4 )	-22.4 ( 35.2 )	-24.6 ( 36.0 )	-28.4 ( 39.8 )	-22.2 ( 35.3 )	-24.8 ( 35.4 )	-29.5 ( 40.4 )	-22.4 ( 35.2 )	-24.5 ( 35.9 )	-26.5 ( 39.1 )	-21.4 ( 33.8 )
Sense of Urgency (Week 8)	-24.8 ( 35.3 )	-24.5 ( 39.7 )	-22.1 ( 35.2 )	-24.5 ( 35.9 )	-23.7 ( 39.8 )	-22.0 ( 35.4 )	-24.8 ( 35.3 )	-24.5 ( 39.7 )	-22.1 ( 35.2 )	-25.7 ( 37.0 )	-20.3 ( 38.4 )	-22.7 ( 34.6 )
Sense of Urgency (Week 9)	-22.6 ( 35.0 )	-28.4 ( 40.0 )	-22.0 ( 35.2 )	-22.7 ( 35.3 )	-28.1 ( 40.1 )	-21.9 ( 35.4 )	-22.6 ( 35.0 )	-28.4 ( 40.0 )	-22.0 ( 35.2 )	-23.2 ( 35.9 )	-25.2 ( 37.8 )	-19.9 ( 34.0 )
Sense of Urgency (Week 10)	-24.2 ( 34.8 )	-27.9 ( 39.1 )	-22.8 ( 37.6 )	-23.8 ( 35.3 )	-27.7 ( 39.5 )	-22.6 ( 37.8 )	-24.2 ( 34.8 )	-27.9 ( 39.1 )	-22.8 ( 37.6 )	-25.4 ( 36.6 )	-24.0 ( 39.6 )	-20.3 ( 36.0 )
Sense of Urgency (Week 11)	-23.5 ( 36.1 )	-29.9 ( 38.5 )	-20.9 ( 37.6 )	-23.6 ( 36.6 )	-28.6 ( 37.5 )	-20.6 ( 37.7 )	-23.5 ( 36.1 )	-29.9 ( 38.5 )	-20.9 ( 37.6 )	-25.0 ( 37.4 )	-25.7 ( 36.7 )	-20.4 ( 37.1 )
Sense of Urgency (Week 12)	-25.6 ( 36.8 )	-25.7 ( 40.6 )	-21.9 ( 37.0 )	-26.0 ( 37.4 )	-25.1 ( 40.2 )	-21.7 ( 37.1 )	-25.6 ( 36.8 )	-25.7 ( 40.6 )	-21.9 ( 37.0 )	-28.3 ( 37.8 )	-20.6 ( 39.5 )	-19.8 ( 35.8 )
Stool Consistency (Week 3)	-1.1 ( 1.2 )	-1.1 ( 1.2 )	-1.0 ( 1.1 )	-1.1 ( 1.1 )	-1.1 ( 1.1 )	-1.0 ( 1.1 )	-1.1 ( 1.2 )	-1.1 ( 1.2 )	-1.0 ( 1.1 )	-1.2 ( 1.1 )	-1.0 ( 1.1 )	-1.0 ( 1.1 )
Stool Consistency (Week 4)	-1.0 ( 1.3 )	-1.0 ( 1.2 )	-1.0 ( 1.2 )	-1.1 ( 1.3 )	-1.0 ( 1.2 )	-1.0 ( 1.2 )	-1.0 ( 1.3 )	-1.0 ( 1.2 )	-1.0 ( 1.2 )	-1.1 ( 1.3 )	-1.0 ( 1.3 )	-1.0 ( 1.2 )
Stool Consistency (Week 5)	-1.1 ( 1.3 )	-1.0 ( 1.0 )	-0.9 ( 1.2 )	-1.2 ( 1.3 )	-1.0 ( 1.0 )	-0.9 ( 1.3 )	-1.1 ( 1.3 )	-1.0 ( 1.0 )	-0.9 ( 1.2 )	-1.2 ( 1.3 )	-0.9 ( 1.0 )	-0.9 ( 1.3 )
Stool Consistency (Week 6)	-1.1 ( 1.3 )	-1.0 ( 1.1 )	-0.9 ( 1.2 )	-1.1 ( 1.3 )	-1.0 ( 1.1 )	-0.9 ( 1.2 )	-1.1 ( 1.3 )	-1.0 ( 1.1 )	-0.9 ( 1.2 )	-1.2 ( 1.3 )	-1.0 ( 1.2 )	-0.9 ( 1.2 )
Stool Consistency (Week 7)	-1.0 ( 1.4 )	-1.0 ( 1.2 )	-0.9 ( 1.1 )	-1.1 ( 1.3 )	-1.0 ( 1.2 )	-0.9 ( 1.1 )	-1.0 ( 1.4 )	-1.0 ( 1.2 )	-0.9 ( 1.1 )	-1.0 ( 1.3 )	-1.0 ( 1.1 )	-0.9 ( 1.1 )
Stool Consistency (Week 8)	-1.0 ( 1.4 )	-1.0 ( 1.3 )	-1.1 ( 1.3 )	-1.1 ( 1.4 )	-1.0 ( 1.3 )	-1.1 ( 1.3 )	-1.0 ( 1.4 )	-1.0 ( 1.3 )	-1.1 ( 1.3 )	-1.1 ( 1.3 )	-1.0 ( 1.2 )	-1.1 ( 1.3 )
Stool Consistency (Week 9)	-0.9 ( 1.3 )	-1.0 ( 1.3 )	-1.2 ( 1.4 )	-1.0 ( 1.2 )	-1.1 ( 1.2 )	-1.2 ( 1.4 )	-0.9 ( 1.3 )	-1.0 ( 1.3 )	-1.2 ( 1.4 )	-1.0 ( 1.3 )	-1.0 ( 1.1 )	-1.1 ( 1.2 )
Stool Consistency (Week 10)	-1.0 ( 1.2 )	-1.0 ( 1.0 )	-1.2 ( 1.3 )	-1.0 ( 1.2 )	-1.0 ( 1.0 )	-1.2 ( 1.3 )	-1.0 ( 1.2 )	-1.0 ( 1.0 )	-1.2 ( 1.3 )	-1.0 ( 1.2 )	-1.0 ( 1.0 )	-1.1 ( 1.2 )
Stool Consistency (Week 11)	-1.0 ( 1.3 )	-0.9 ( 1.0 )	-1.0 ( 1.3 )	-1.1 ( 1.3 )	-1.0 ( 1.0 )	-1.0 ( 1.3 )	-1.0 ( 1.3 )	-0.9 ( 1.0 )	-1.0 ( 1.3 )	-1.1 ( 1.4 )	-1.0 ( 1.0 )	-0.9 ( 1.2 )
Stool Consistency (Week 12)	-1.0 ( 1.4 )	-1.0 ( 1.1 )	-1.0 ( 1.2 )	-1.1 ( 1.4 )	-1.0 ( 1.1 )	-1.0 ( 1.2 )	-1.0 ( 1.4 )	-1.0 ( 1.1 )	-1.0 ( 1.2 )	-1.1 ( 1.5 )	-1.0 ( 1.1 )	-1.0 ( 1.2 )
Bowel Movements (Week 3)	-0.5 ( 1.3 )	-0.8 ( 1.3 )	-0.8 ( 1.5 )	-0.6 ( 1.3 )	-0.8 ( 1.3 )	-0.8 ( 1.5 )	-0.5 ( 1.3 )	-0.8 ( 1.3 )	-0.8 ( 1.5 )	-0.6 ( 1.3 )	-0.7 ( 1.1 )	-0.8 ( 1.5 )
Bowel Movements (Week 4)	-0.6 ( 1.2 )	-1.0 ( 1.4 )	-0.7 ( 1.7 )	-0.6 ( 1.2 )	-0.9 ( 1.3 )	-0.7 ( 1.7 )	-0.6 ( 1.2 )	-1.0 ( 1.4 )	-0.7 ( 1.7 )	-0.6 ( 1.2 )	-0.8 ( 1.2 )	-0.8 ( 1.7 )
Bowel Movements (Week 5)	-0.6 ( 1.3 )	-0.9 ( 1.3 )	-0.7 ( 1.6 )	-0.7 ( 1.3 )	-0.9 ( 1.3 )	-0.7 ( 1.6 )	-0.6 ( 1.3 )	-0.9 ( 1.3 )	-0.7 ( 1.6 )	-0.7 ( 1.2 )	-0.8 ( 1.2 )	-0.8 ( 1.7 )
Bowel Movements (Week 6)	-0.5 ( 1.3 )	-0.9 ( 1.4 )	-0.7 ( 1.5 )	-0.5 ( 1.4 )	-0.9 ( 1.3 )	-0.7 ( 1.5 )	-0.5 ( 1.3 )	-0.9 ( 1.4 )	-0.7 ( 1.5 )	-0.6 ( 1.4 )	-0.9 ( 1.2 )	-0.8 ( 1.5 )
Bowel Movements (Week 7)	-0.5 ( 1.5 )	-0.9 ( 1.4 )	-0.7 ( 1.5 )	-0.5 ( 1.5 )	-0.9 ( 1.3 )	-0.7 ( 1.5 )	-0.5 ( 1.5 )	-0.9 ( 1.4 )	-0.7 ( 1.5 )	-0.6 ( 1.6 )	-0.8 ( 1.1 )	-0.8 ( 1.5 )
Bowel Movements (Week 8)	-0.6 ( 1.4 )	-0.9 ( 1.4 )	-0.8 ( 1.6 )	-0.6 ( 1.4 )	-0.9 ( 1.4 )	-0.8 ( 1.6 )	-0.6 ( 1.4 )	-0.9 ( 1.4 )	-0.8 ( 1.6 )	-0.7 ( 1.4 )	-0.8 ( 1.3 )	-1.0 ( 1.5 )
Bowel Movements (Week 9)	-0.4 ( 1.4 )	-1.0 ( 1.3 )	-0.8 ( 1.5 )	-0.5 ( 1.4 )	-1.0 ( 1.2 )	-0.8 ( 1.6 )	-0.4 ( 1.4 )	-1.0 ( 1.3 )	-0.8 ( 1.5 )	-0.6 ( 1.4 )	-0.9 ( 1.0 )	-0.8 ( 1.5 )
Bowel Movements (Week 10)	-0.5 ( 1.4 )	-0.9 ( 1.4 )	-0.8 ( 1.3 )	-0.6 ( 1.4 )	-0.9 ( 1.4 )	0.8 ( 1.3 )	-0.5 ( 1.4 )	-0.9 ( 1.4 )	-0.8 ( 1.3 )	-0.6 ( 1.4 )	-0.8 ( 1.2 )	-0.8 ( 1.4 )
Bowel Movements (Week 11)	-0.6 ( 1.3 )	-1.0 ( 1.4 )	-0.8 ( 1.6 )	0.6 ( 1.3 )	-0.9 ( 1.4 )	-0.8 ( 1.6 )	-0.6 ( 1.3 )	-1.0 ( 1.4 )	-0.8 ( 1.6 )	-0.6 ( 1.3 )	-0.9 ( 1.2 )	-0.9 ( 1.5 )
Bowel Movements (Week 12)	-0.6 ( 1.4 )	-0.9 ( 1.4 )	-0.7 ( 1.4 )	-0.7 ( 1.4 )	-0.9 ( 1.4 )	-0.7 ( 1.4 )	-0.6 ( 1.4 )	-0.9 ( 1.4 )	-0.7 ( 1.4 )	-0.7 ( 1.5 )	-0.8 ( 1.2 )	-0.7 ( 1.4 )

No statistical analyses for this end point

Secondary: Number of weeks (consecutive or not) subjects achieved adequate relief of bloating during the follow up period.

Top of page

End point title

Number of weeks (consecutive or not) subjects achieved adequate relief of bloating during the follow up period.

End point description

Relief of IBS bloating is defined as a score of either 0 (not at all) or 1 (hardly) for at least 50% of the days in a given week or a score of 0 (not at all), 1 (hardly), or 2 (somewhat) for 100% of the days in a given week for at least 2 (consecutive or not) of the 4 weeks during a given month.

End point type

Secondary

End point timeframe

Weeks 3 through 12

Treatment group 1: dose regimen 1

Treatment group 2: dose regimen 2

Treatment group 3: matching placebo

Dose Regimen 1 (Full Analysis Set)

Dose Regimen 2 (Full Analysis Set)

Dose Regimen 3 (Full Analysis Set)

Dose Regimen 1 (IIT)

Dose Regimen 2 (IIT)

Dose Regimen 3 (IIT)

Dose Regimen 1 (Per Protocol Set)

Dose Regimen 2 (Per Protocol Set)

Dose Regimen 3 (Per Protocol Set)

Number of subjects analysed

Units: Weeks

median (full range (min-max))

2.0 (0 to 10)

4.0 (0 to 10)

3.0 (0 to 10)

2.0 (0 to 10)

4.0 (0 to 10)

3.0 (0 to 10)

2.0 (0 to 10)

4.0 (0 to 10)

3.0 (0 to 10)

2.0 (0 to 10)

4.0 (0 to 10)

3.0 (0 to 10)

Dose Regimen 1 vs Dose Regimen 3 (FAS)

Statistical analysis description

Comparison between treatment groups of the number of weeks subjects achieved adequate relief of bloating during follow-up phase (Full analysis set): Dose Regimen 1 vs Dose Regimen 3

Comparison groups

Dose Regimen 1 (Full Analysis Set) v Dose Regimen 3 (Full Analysis Set)

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7582

Method

Wilcoxon (Mann-Whitney)

Parameter type

Wilcoxon Rank-Sum Statistics

Point estimate

6279.5

Confidence interval

level

95%

sides

1-sided

lower limit

upper limit

Dose Regimen 2 vs Dose Regimen 3 (FAS)

Statistical analysis description

Comparison between treatment groups of the number of weeks subjects achieved adequate relief of bloating during follow-up phase (Full analysis set): Dose Regimen 2 vs Dose Regimen 3

Comparison groups

Dose Regimen 3 (Full Analysis Set) v Dose Regimen 2 (Full Analysis Set)

Number of subjects included in analysis

183

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2362

Method

Wilcoxon (Mann-Whitney)

Parameter type

Wilcoxon Rank-Sum Statistics

Point estimate

7561

Confidence interval

level

95%

sides

1-sided

lower limit

upper limit

Dose Regimen 1 vs Dose Regimen 2(FAS)

Statistical analysis description

Comparison between treatment groups of the number of weeks subjects achieved adequate relief of bloating during follow-up phase (Full analysis set): Dose Regimen 1 vs Dose Regimen 2

Comparison groups

Dose Regimen 2 (Full Analysis Set) v Dose Regimen 1 (Full Analysis Set)

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3324

Method

Wilcoxon (Mann-Whitney)

Parameter type

Wilcoxon Rank-Sum Statistics

Point estimate

5686.5

Confidence interval

level

95%

sides

1-sided

lower limit

upper limit

Dose Regimen 1 vs Dose Regimen 3(IIT)

Statistical analysis description

Comparison between treatment groups of the number of weeks subjects achieved adequate relief of bloating during follow-up phase (ITT): Dose Regimen 1 vs Dose Regimen 3

Comparison groups

Dose Regimen 1 (IIT) v Dose Regimen 3 (IIT)

Number of subjects included in analysis

184

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8789

Method

Wilcoxon (Mann-Whitney)

Parameter type

Wilcoxon Rank-Sum Statistics

Point estimate

6638.5

Confidence interval

level

95%

sides

1-sided

lower limit

upper limit

Dose Regimen 2 vs Dose Regimen 3(IIT)

Statistical analysis description

Comparison between treatment groups of the number of weeks subjects achieved adequate relief of bloating during follow-up phase (ITT): Dose Regimen 2 vs Dose Regimen 3

Comparison groups

Dose Regimen 3 (IIT) v Dose Regimen 2 (IIT)

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2666

Method

Wilcoxon (Mann-Whitney)

Parameter type

Wilcoxon Rank-Sum Statistics

Point estimate

7981.5

Confidence interval

level

95%

sides

1-sided

lower limit

upper limit

Dose Regimen 1 vs Dose Regimen 2(IIT)

Statistical analysis description

Comparison between treatment groups of the number of weeks subjects achieved adequate relief of bloating during follow-up phase (ITT): Dose Regimen 1 vs Dose Regimen 2

Comparison groups

Dose Regimen 2 (IIT) v Dose Regimen 1 (IIT)

Number of subjects included in analysis

182

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2915

Method

Wilcoxon (Mann-Whitney)

Parameter type

Wilcoxon Rank-Sum Statistics

Point estimate

6117.5

Confidence interval

level

95%

sides

1-sided

lower limit

upper limit

Dose Regimen 1 vs Dose Regimen 3(PP Set)

Statistical analysis description

Comparison between treatment groups of the number of weeks subjects achieved adequate relief of bloating during follow-up phase (PP Set): Dose Regimen 1 vs Dose Regimen 3

Comparison groups

Dose Regimen 1 (Per Protocol Set) v Dose Regimen 3 (Per Protocol Set)

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.685

Method

Wilcoxon (Mann-Whitney)

Parameter type

Wilcoxon Rank-Sum Statistics

Point estimate

4434.5

Confidence interval

level

95%

sides

1-sided

lower limit

upper limit

Dose Regimen 2 vs Dose Regimen 3(PP Set)

Statistical analysis description

Comparison between treatment groups of the number of weeks subjects achieved adequate relief of bloating during follow-up phase (PP Set): Dose Regimen 2 vs Dose Regimen 3

Comparison groups

Dose Regimen 3 (Per Protocol Set) v Dose Regimen 2 (Per Protocol Set)

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4077

Method

Wilcoxon (Mann-Whitney)

Parameter type

Wilcoxon Rank-Sum Statistics

Point estimate

4847

Confidence interval

level

95%

sides

1-sided

lower limit

upper limit

Dose Regimen 1 vs Dose Regimen 2(PP Set)

Statistical analysis description

Comparison between treatment groups of the number of weeks subjects achieved adequate relief of bloating during follow-up phase (PP Set): Dose Regimen 1 vs Dose Regimen 2

Comparison groups

Dose Regimen 2 (Per Protocol Set) v Dose Regimen 1 (Per Protocol Set)

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5554

Method

Wilcoxon (Mann-Whitney)

Parameter type

Wilcoxon Rank-Sum Statistics

Point estimate

3846.5

Confidence interval

level

95%

sides

1-sided

lower limit

upper limit

Secondary: Number of weeks (consecutive or not) subjects achieved adequate relief of IBS symptoms during the follow up period.

Top of page

End point title

Number of weeks (consecutive or not) subjects achieved adequate relief of IBS symptoms during the follow up period.

End point description

End point type

Secondary

End point timeframe

Weeks 3 through 12

Treatment group 1: dose regimen 1

Treatment group 2: dose regimen 2

Treatment group 3: matching placebo

Dose Regimen 1 (Full Analysis Set)

Dose Regimen 2 (Full Analysis Set)

Dose Regimen 3 (Full Analysis Set)

Dose Regimen 1 (IIT)

Dose Regimen 2 (IIT)

Dose Regimen 3 (IIT)

Dose Regimen 1 (Per Protocol Set)

Dose Regimen 2 (Per Protocol Set)

Dose Regimen 3 (Per Protocol Set)

Number of subjects analysed

Units: Weeks

median (full range (min-max))

3.0 (0 to 10)

4.5 (0 to 10)

3.0 (0 to 10)

5.0 (0 to 10)

3.0 (0 to 10)

4.5 (0 to 10)

3.0 (0 to 10)

4.0 (0 to 10)

3.0 (0 to 10)

Dose Regimen 1 vs Dose Regimen 3 (FAS)

Statistical analysis description

Comparison between treatment groups of the number of weeks subjects achieved adequate relief of IBS symptoms during follow-up phase (Full analysis set): Dose Regimen 1 vs Dose Regimen 3

Comparison groups

Dose Regimen 1 (Full Analysis Set) v Dose Regimen 3 (Full Analysis Set)

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8797

Method

Wilcoxon (Mann-Whitney)

Parameter type

Wilcoxon Rank-Sum Statistics

Point estimate

6233

Confidence interval

level

95%

sides

1-sided

lower limit

upper limit

Dose Regimen 2 vs Dose Regimen 3 (FAS)

Statistical analysis description

Comparison between treatment groups of the number of weeks subjects achieved adequate relief of IBS symptoms during follow-up phase (Full analysis set): Dose Regimen 2 vs Dose Regimen 3

Comparison groups

Dose Regimen 3 (Full Analysis Set) v Dose Regimen 2 (Full Analysis Set)

Number of subjects included in analysis

183

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1965

Method

Wilcoxon (Mann-Whitney)

Parameter type

Wilcoxon Rank-Sum Statistics

Point estimate

7596.5

Confidence interval

level

95%

sides

1-sided

lower limit

upper limit

Dose Regimen 1 vs Dose Regimen 2 (FAS)

Statistical analysis description

Comparison between treatment groups of the number of weeks subjects achieved adequate relief of IBS symptoms during follow-up phase (Full analysis set): Dose Regimen 1 vs Dose Regimen 2

Comparison groups

Dose Regimen 2 (Full Analysis Set) v Dose Regimen 1 (Full Analysis Set)

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2353

Method

Wilcoxon (Mann-Whitney)

Parameter type

Wilcoxon Rank-Sum Statistics

Point estimate

5624

Confidence interval

level

95%

sides

1-sided

lower limit

upper limit

Dose Regimen 1 vs Dose Regimen 3 (IIT)

Statistical analysis description

Comparison between treatment groups of the number of weeks subjects achieved adequate relief of IBS symptoms during follow-up phase (IIT): Dose Regimen 1 vs Dose Regimen 3

Comparison groups

Dose Regimen 1 (IIT) v Dose Regimen 3 (IIT)

Number of subjects included in analysis

184

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9059

Method

Wilcoxon (Mann-Whitney)

Parameter type

Wilcoxon Rank-Sum Statistics

Point estimate

6628

Confidence interval

level

95%

sides

1-sided

lower limit

upper limit

Dose Regimen 2 vs Dose Regimen 3 (IIT)

Statistical analysis description

Comparison between treatment groups of the number of weeks subjects achieved adequate relief of IBS symptoms during follow-up phase (IIT): Dose Regimen 2 vs Dose Regimen 3

Comparison groups

Dose Regimen 3 (IIT) v Dose Regimen 2 (IIT)

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2708

Method

Wilcoxon (Mann-Whitney)

Parameter type

Wilcoxon Rank-Sum Statistics

Point estimate

7979

Confidence interval

level

95%

sides

1-sided

lower limit

upper limit

Dose Regimen 1 vs Dose Regimen 2 (IIT)

Statistical analysis description

Comparison between treatment groups of the number of weeks subjects achieved adequate relief of IBS symptoms during follow-up phase (IIT): Dose Regimen 1 vs Dose Regimen 2

Comparison groups

Dose Regimen 2 (IIT) v Dose Regimen 1 (IIT)

Number of subjects included in analysis

182

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2849

Method

Wilcoxon (Mann-Whitney)

Parameter type

Wilcoxon Rank-Sum Statistics

Point estimate

6112.5

Confidence interval

level

95%

sides

1-sided

lower limit

upper limit

Dose Regimen 1 vs Dose Regimen 3 (PP Set)

Statistical analysis description

Comparison between treatment groups of the number of weeks subjects achieved adequate relief of IBS symptoms during follow-up phase (PP Set): Dose Regimen 1 vs Dose Regimen 3

Comparison groups

Dose Regimen 1 (Per Protocol Set) v Dose Regimen 3 (Per Protocol Set)

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5842

Method

Wilcoxon (Mann-Whitney)

Parameter type

Wilcoxon Rank-Sum Statistics

Point estimate

6233

Confidence interval

level

95%

sides

1-sided

lower limit

upper limit

Variability estimate

Standard deviation

Dose Regimen 2 vs Dose Regimen 3 (PP Set)

Statistical analysis description

Comparison between treatment groups of the number of weeks subjects achieved adequate relief of IBS symptoms during follow-up phase (PP Set): Dose Regimen 2 vs Dose Regimen 3

Comparison groups

Dose Regimen 3 (Per Protocol Set) v Dose Regimen 2 (Per Protocol Set)

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4254

Method

Wilcoxon (Mann-Whitney)

Parameter type

Wilcoxon Rank-Sum Statistics

Point estimate

4840

Confidence interval

level

95%

sides

1-sided

lower limit

upper limit

Dose Regimen 1 vs Dose Regimen 2 (PP Set)

Statistical analysis description

Comparison between treatment groups of the number of weeks subjects achieved adequate relief of IBS symptoms during follow-up phase (PP Set): Dose Regimen 1 vs Dose Regimen 2

Comparison groups

Dose Regimen 2 (Per Protocol Set) v Dose Regimen 1 (Per Protocol Set)

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8042

Method

Wilcoxon (Mann-Whitney)

Parameter type

Wilcoxon Rank-Sum Statistics

Point estimate

3916.5

Confidence interval

level

95%

sides

1-sided

lower limit

upper limit

Secondary: Proportion of subjects with adequate relief of bloating during at least 2 weeks (consecutive or not) per month (“monthly response”)

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End point title

Proportion of subjects with adequate relief of bloating during at least 2 weeks (consecutive or not) per month (“monthly response”)

End point description

End point type

Secondary

End point timeframe

Month 1 through Month 3

End point values	Treatment group 1: dose regimen 1	Treatment group 2: dose regimen 2	Treatment group 3: matching placebo	Dose Regimen 1 (Full Analysis Set)	Dose Regimen 2 (Full Analysis Set)	Dose Regimen 3 (Full Analysis Set)	Dose Regimen 1 (IIT)	Dose Regimen 2 (IIT)	Dose Regimen 3 (IIT)	Dose Regimen 1 (Per Protocol Set)	Dose Regimen 2 (Per Protocol Set)	Dose Regimen 3 (Per Protocol Set)
Number of subjects analysed	87	95	97	81	88	95	87	95	97	63	65	79
Units: Subjects
Month 1	42	53	34	41	50	34	42	53	34	34	38	28
Month 1 through 2	34	49	36	34	48	36	34	49	36	27	37	32
Month 1 through 3	28	40	33	28	39	33	28	40	33	23	29	30

Dose regimen 1 vs. Dose Regimen 3 (FAS) -Month 1-2

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 1 vs. DOSE REGIMEN 3 (FAS) - Month 1 through 2

Comparison groups

Dose Regimen 1 (Full Analysis Set) v Dose Regimen 3 (Full Analysis Set)

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.29

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

2.43

Dose regimen 2 vs. Dose Regimen 3 (FAS) -Month 1-2

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 2 vs. DOSE REGIMEN 3 (FAS) - Month 1 through 2

Comparison groups

Dose Regimen 3 (Full Analysis Set) v Dose Regimen 2 (Full Analysis Set)

Number of subjects included in analysis

183

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.98

Confidence interval

level

95%

sides

2-sided

lower limit

1.07

upper limit

3.67

Dose regimen 1 vs. Dose Regimen 2 (FAS)-Month 1-2

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 1 vs. DOSE REGIMEN 2 (FAS) - Month 1 through 2

Comparison groups

Dose Regimen 2 (Full Analysis Set) v Dose Regimen 1 (Full Analysis Set)

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.65

Confidence interval

level

95%

sides

2-sided

lower limit

0.34

upper limit

1.24

Dose regimen 1 vs. Dose Regimen 3 (ITT)-Month 1-2

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 1 vs. DOSE REGIMEN 3 (ITT) - Month 1 through 2

Comparison groups

Dose Regimen 1 (IIT) v Dose Regimen 3 (IIT)

Number of subjects included in analysis

184

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.21

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

2.27

Dose regimen 2 vs. Dose Regimen 3 (ITT)-Month 1-2

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 2 vs. DOSE REGIMEN 3 (ITT) - Month 1 through 2

Comparison groups

Dose Regimen 3 (IIT) v Dose Regimen 2 (IIT)

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

1.09

upper limit

3.69

Dose regimen 1 vs. Dose Regimen 2 (ITT)-Month 1-2

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 1 vs. DOSE REGIMEN 2 (ITT) - Month 1 through 2

Comparison groups

Dose Regimen 2 (IIT) v Dose Regimen 1 (IIT)

Number of subjects included in analysis

182

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.32

upper limit

1.14

Dose regimen 1 vs. Dose Regimen 3 (PPS)-Month 1-2

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 1 vs. DOSE REGIMEN 3 (PP Set) - Month 1 through 2

Comparison groups

Dose Regimen 1 (Per Protocol Set) v Dose Regimen 3 (Per Protocol Set)

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.17

Confidence interval

level

95%

sides

2-sided

lower limit

0.59

upper limit

2.33

Dose regimen 2 vs. Dose Regimen 3 (PPS)-Month 1-2

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 2 vs. DOSE REGIMEN 3 (PP Set) - Month 1 through 2

Comparison groups

Dose Regimen 3 (Per Protocol Set) v Dose Regimen 2 (Per Protocol Set)

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.91

upper limit

3.47

Dose regimen 1 vs. Dose Regimen 2 (PPS)-Month 1-2

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 1 vs. DOSE REGIMEN 2 (PP Set) - Month 1 through 2

Comparison groups

Dose Regimen 2 (Per Protocol Set) v Dose Regimen 1 (Per Protocol Set)

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.66

Confidence interval

level

95%

sides

2-sided

lower limit

0.32

upper limit

1.34

Dose regimen 1 vs. Dose Regimen 3 (FAS)- Month 1

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 1 vs. DOSE REGIMEN 3 (FAS) - Month 1

Comparison groups

Dose Regimen 1 (Full Analysis Set) v Dose Regimen 3 (Full Analysis Set)

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.98

Confidence interval

level

95%

sides

2-sided

lower limit

1.05

upper limit

3.75

Dose regimen 2 vs. Dose Regimen 3 (FAS) - Month 1

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 2 vs. DOSE REGIMEN 3 (FAS) - Month 1

Comparison groups

Dose Regimen 3 (Full Analysis Set) v Dose Regimen 2 (Full Analysis Set)

Number of subjects included in analysis

183

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

2.59

Confidence interval

level

95%

sides

2-sided

lower limit

1.38

upper limit

4.86

Dose regimen 1 vs. Dose Regimen 2 (FAS) - Month 1

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 1 vs. DOSE REGIMEN 2 (FAS) - Month 1

Comparison groups

Dose Regimen 2 (Full Analysis Set) v Dose Regimen 1 (Full Analysis Set)

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.77

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

1.47

Dose regimen 1 vs. Dose Regimen 3 (ITT) - Month 1

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 1 vs. DOSE REGIMEN 3 (ITT) - Month 1

Comparison groups

Dose Regimen 1 (IIT) v Dose Regimen 3 (IIT)

Number of subjects included in analysis

184

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.95

Confidence interval

level

95%

sides

2-sided

lower limit

1.04

upper limit

3.65

Dose regimen 2 vs. Dose Regimen 3 (ITT) - Month 1

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 2 vs. DOSE REGIMEN 3 (ITT) - Month 1

Comparison groups

Dose Regimen 3 (IIT) v Dose Regimen 2 (IIT)

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

1.45

upper limit

5.03

Dose regimen 1 vs. Dose Regimen 2 (ITT) - Month 1

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 1 vs. DOSE REGIMEN 2 (ITT) - Month 1

Comparison groups

Dose Regimen 2 (IIT) v Dose Regimen 1 (IIT)

Number of subjects included in analysis

182

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.72

Confidence interval

level

95%

sides

2-sided

lower limit

0.38

upper limit

1.36

Dose regimen 1 vs. Dose Regimen 3(PP) - Month 1

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 1 vs. DOSE REGIMEN 3 (PP Set) - Month 1

Comparison groups

Dose Regimen 1 (Per Protocol Set) v Dose Regimen 3 (Per Protocol Set)

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

2.1

Confidence interval

level

95%

sides

2-sided

lower limit

1.05

upper limit

4.21

Dose regimen 2 vs. Dose Regimen 3 (PP) - Month 1

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 2 vs. DOSE REGIMEN 3 (PP Set) - Month 1

Comparison groups

Dose Regimen 3 (Per Protocol Set) v Dose Regimen 2 (Per Protocol Set)

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

2.54

Confidence interval

level

95%

sides

2-sided

lower limit

1.27

upper limit

5.1

Dose regimen 1 vs. Dose Regimen 2 (PP) - Month 1

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 1 vs. DOSE REGIMEN 2 (PP Set) - Month 1

Comparison groups

Dose Regimen 2 (Per Protocol Set) v Dose Regimen 1 (Per Protocol Set)

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.83

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

1.7

Dose regimen 1 vs. Dose Regimen 3 (FAS) -Month 1-3

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 1 vs. DOSE REGIMEN 3 (FAS) - Month 1 through 3

Comparison groups

Dose Regimen 1 (Full Analysis Set) v Dose Regimen 3 (Full Analysis Set)

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.53

upper limit

1.96

Dose regimen 2 vs. Dose Regimen 3 (FAS)- Month 1-3

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 2 vs. DOSE REGIMEN 3 (FAS) - Month 1 through 3

Comparison groups

Dose Regimen 3 (Full Analysis Set) v Dose Regimen 2 (Full Analysis Set)

Number of subjects included in analysis

183

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.58

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

2.97

Dose regimen 1 vs. Dose Regimen 2 (FAS) -Month 1-3

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 1 vs. DOSE REGIMEN 2 (FAS) - Month 1 through 3

Comparison groups

Dose Regimen 2 (Full Analysis Set) v Dose Regimen 1 (Full Analysis Set)

Number of subjects included in analysis

169

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.65

Confidence interval

level

95%

sides

2-sided

lower limit

0.33

upper limit

1.25

Dose regimen 1 vs. Dose Regimen 3 (ITT)-Month 1-3

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 1 vs. DOSE REGIMEN 3 (ITT) - Month 1 through 3

Comparison groups

Dose Regimen 1 (IIT) v Dose Regimen 3 (IIT)

Number of subjects included in analysis

184

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.51

upper limit

1.85

Dose regimen 2 vs. Dose Regimen 3 (ITT)- Month 1-3

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 2 vs. DOSE REGIMEN 3 (ITT) - Month 1 through 3

Comparison groups

Dose Regimen 3 (IIT) v Dose Regimen 2 (IIT)

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.61

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

3.01

Dose regimen 1 vs. Dose Regimen 2 (ITT)- Month 1-3

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 1 vs. DOSE REGIMEN 2 (ITT) - Month 1 through 3

Comparison groups

Dose Regimen 2 (IIT) v Dose Regimen 1 (IIT)

Number of subjects included in analysis

182

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.31

upper limit

1.16

Dose regimen 1 vs. Dose Regimen 3 (PP)- Month 1-3

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 1 vs. DOSE REGIMEN 3 (PP Set) - Month 1 through 3

Comparison groups

Dose Regimen 1 (Per Protocol Set) v Dose Regimen 3 (Per Protocol Set)

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.47

upper limit

1.92

Dose regimen 2 vs. Dose Regimen 3 (PP)- Month 1-3

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 2 vs. DOSE REGIMEN 3 (PP Set) - Month 1 through 3

Comparison groups

Dose Regimen 3 (Per Protocol Set) v Dose Regimen 2 (Per Protocol Set)

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.35

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

2.71

Dose regimen 1 vs. Dose Regimen 2 (PP)-Month 1-3

Statistical analysis description

Odds Ratio and 95% CI of DOSE REGIMEN 1 vs. DOSE REGIMEN 2 (PP Set) - Month 1 through 3

Comparison groups

Dose Regimen 2 (Per Protocol Set) v Dose Regimen 1 (Per Protocol Set)

Number of subjects included in analysis

128

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.34

upper limit

1.46

Secondary: Change from baseline in quality of life inquired as IBS-QoL

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End point title

Change from baseline in quality of life inquired as IBS-QoL

End point description

End point type

Secondary

End point timeframe

At week 4, 8 and 12

End point values	Treatment group 1: dose regimen 1	Treatment group 2: dose regimen 2	Treatment group 3: matching placebo	Dose Regimen 1 (Full Analysis Set)	Dose Regimen 2 (Full Analysis Set)	Dose Regimen 3 (Full Analysis Set)	Dose Regimen 1 (IIT)	Dose Regimen 2 (IIT)	Dose Regimen 3 (IIT)	Dose Regimen 1 (Per Protocol Set)	Dose Regimen 2 (Per Protocol Set)	Dose Regimen 3 (Per Protocol Set)
Number of subjects analysed	68 ^[7]	72 ^[8]	80 ^[9]	65 ^[10]	71 ^[11]	80 ^[12]	68 ^[13]	72 ^[14]	80 ^[15]	54 ^[16]	57 ^[17]	70 ^[18]
Units: Change from Baseline in QoL scores
arithmetic mean (standard deviation)
Day 29	12.9 ( 15.5 )	16.2 ( 15.5 )	11.5 ( 14.6 )	12.4 ( 15.7 )	16.0 ( 15.4 )	11.5 ( 14.6 )	12.9 ( 15.5 )	16.2 ( 15.5 )	11.5 ( 14.6 )	13.6 ( 16.0 )	15.3 ( 14.8 )	12.4 ( 14.0 )
Day 57	13.4 ( 16.7 )	16.1 ( 17.9 )	12.0 ( 17.8 )	12.8 ( 16.9 )	15.8 ( 17.9 )	12.0 ( 17.8 )	13.4 ( 16.7 )	16.1 ( 17.9 )	12.0 ( 17.8 )	12.2 ( 15.6 )	13.7 ( 15.5 )	12.7 ( 18.0 )
Day 85	14.2 ( 20.0 )	18.0 ( 18.3 )	13.7 ( 15.8 )	14.2 ( 20.3 )	18.0 ( 18.3 )	13.7 ( 15.8 )	14.2 ( 20.0 )	18.0 ( 18.3 )	13.7 ( 15.8 )	14.5 ( 19.8 )	15.6 ( 15.8 )	13.9 ( 15.6 )

Notes
[7] - Day 29: 68 Day 57: 68 Day 85: 55
[8] - Day 29: 72 Day 57: 73 Day 85: 62
[9] - Day 29: 80 Day 57: 78 Day 85: 68
[10] - Day 29: 65 Day 57: 65 Day 85: 53
[11] - Day 29: 71 Day 57: 72 Day 85: 62
[12] - Day 29: 80 Day 57: 78 Day 85: 68
[13] - Day 29: 68 Day 57: 68 Day 85: 55
[14] - Day 29: 72 Day 57: 73 Day 85: 62
[15] - Day 29: 80 Day 57: 78 Day 85: 68
[16] - Day 29: 54 Day 57: 56 Day 85: 43
[17] - Day 29: 57 Day 57: 57 Day 85: 49
[18] - Day 29: 70 Day 57: 68 Day 85: 61

No statistical analyses for this end point

Other pre-specified: Plasma levels of IL1β, IL6, IL8, IL12p70 and TNFα and those of the antibodies against vinculin and Campylobacter CdtB protein

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End point title

Plasma levels of IL1β, IL6, IL8, IL12p70 and TNFα and those of the antibodies against vinculin and Campylobacter CdtB protein

End point description

Immunomodulatory effect sub-study: To preliminarily investigate the potential anti-inflammatory and immunomodulatory effects of rifamycin SV in patients suffering from diarrhoea-predominant irritable bowel syndrome. Unreported values are BLQL. BLQL below the LQL of 0.03 pg/mL for IL1β, 0.1 pg/mL for IL6, IL8 and IL12p70 and 0.3 pg/mL for TNFα.

End point type

Other pre-specified

End point timeframe

Between Day -21 and Day 85

End point values	Treatment group 1: dose regimen 1	Treatment group 2: dose regimen 2	Treatment group 3: matching placebo
Number of subjects analysed	13	20	15
Units: Plasma concentration
arithmetic mean (standard deviation)
IL1B (pg/mL) - Day -21/-15	13 ( 0.023 )	20 ( 0.008 )	15 ( 0.100 )
IL1B (pg/mL) - Day 15	12 ( 0.043 )	19 ( 0.019 )	14 ( 0.020 )
IL1B (pg/mL) - Day 85	11 ( 0.036 )	20 ( 0.016 )	13 ( 0.020 )
IL6 (pg/mL) - Day -21/-15	13 ( 0.195 )	20 ( 0.090 )	15 ( 0.046 )
IL6 (pg/mL) - Day 15	12 ( 0.166 )	19 ( 0.340 )	14 ( 0.000 )
IL6 (pg/mL) - Day 85	11 ( 0.000 )	20 ( 0.118 )	13 ( 0.000 )
IL8 (pg/mL) - Day -21/-15	13 ( 0.152 )	20 ( 0.133 )	15 ( 0.140 )
IL8 (pg/mL) - Day 15	12 ( 0.201 )	19 ( 0.174 )	14 ( 0.264 )
IL8 (pg/mL) - Day 85	11 ( 0.187 )	20 ( 0.235 )	13 ( 0.152 )
IL12p70 (pg/mL) - Day -21/-15	13 ( 0.279 )	20 ( 0.054 )	15 ( 0.000 )
IL12p70 (pg/mL) - Day 15	12 ( 0.347 )	19 ( 0.144 )	14 ( 0.051 )
IL12p70 (pg/mL) - Day 85	11 ( 0.105 )	20 ( 0.193 )	13 ( 0.028 )
TNFa (pg/mL) - Day -21/-15	13 ( 0.368 )	20 ( 0.104 )	15 ( 0.113 )
TNFa (pg/mL) - Day 15	12 ( 0.298 )	19 ( 0.352 )	14 ( 0.131 )
TNFa (pg/mL) - Day 85	11 ( 0.379 )	20 ( 0.384 )	13 ( 0.182 )
Antibodies against vinculin (%) - Day -21/-15	13 ( 0.000 )	20 ( 0.000 )	15 ( 0.000 )
Antibodies against vinculin (%) - Day 15	12 ( 0.287 )	19 ( 0.190 )	14 ( 0.099 )
Antibodies against vinculin (%) - Day 85	11 ( 0.164 )	20 ( 0.216 )	13 ( 1.132 )
Antibodies against vinculin(OD at 450nm) -D-21/-15	0.631 ( 0.510 )	0.617 ( 0.578 )	0.342 ( 0.211 )
Antibodies against Campylobacter CdtB(%) -D-21/-15	13 ( 0.000 )	20 ( 0.000 )	15 ( 0.000 )
Antibodies against Campylobacter CdtB(%) -Day 15	12 ( 0.104 )	19 ( 0.117 )	14 ( 0.086 )
Antibodies against Campylobacter CdtB(%) -Day 85	11 ( 0.124 )	20 ( 0.139 )	13 ( 0.210 )
Campylobacter CdtB Antibodies(OD at450nm)-D-21/-15	13 ( 0.658 )	20 ( 0.939 )	15 ( 0.688 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

09Nov2017 - 10Sep2020

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

20.0

Reporting group title

Dose Regimen 1

Reporting group description

Rifamycin SV 600 mg TD

Reporting group title

Dose Regimen 2

Reporting group description

Rifamycin SV 600 mg BD

Reporting group title

Dose Regimen 3

Reporting group description

Placebo

Serious adverse events	Dose Regimen 1	Dose Regimen 2	Dose Regimen 3
Total subjects affected by serious adverse events
subjects affected / exposed	2 / 85 (2.35%)	1 / 94 (1.06%)	1 / 96 (1.04%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0
Cardiac disorders
Arteriosclerosis coronary artery
Additional description: Worsening of calcified atherosclerosis of the coronary
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Nephritis
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Urinary tract infection
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Erysipelas
Additional description: Erysipelas in the face left side
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Dose Regimen 1	Dose Regimen 2	Dose Regimen 3
Total subjects affected by non serious adverse events
subjects affected / exposed	15 / 85 (17.65%)	45 / 94 (47.87%)	9 / 96 (9.38%)
Vascular disorders
Flushing
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Vaginal haemorrhage
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	0	0	1
Surgical and medical procedures
Strabismus correction
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Tooth extraction
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	0	0	1
Pregnancy, puerperium and perinatal conditions
Pregnancy
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	1 / 96 (1.04%)
occurrences all number	0	1	1
General disorders and administration site conditions
Fatigue
subjects affected / exposed	2 / 85 (2.35%)	4 / 94 (4.26%)	2 / 96 (2.08%)
occurrences all number	2	5	2
Pyrexia
subjects affected / exposed	2 / 85 (2.35%)	3 / 94 (3.19%)	1 / 96 (1.04%)
occurrences all number	2	3	1
General symptom
subjects affected / exposed	0 / 85 (0.00%)	2 / 94 (2.13%)	1 / 96 (1.04%)
occurrences all number	0	3	1
Asthenia
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Discomfort
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Malaise
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Night sweats
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Spinal pain
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Temperature regulation disorder
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	2	0
Vaccination site pain
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Withdrawal syndrome
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Immune system disorders
Hypersensitivity
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	3 / 96 (3.13%)
occurrences all number	1	0	3
Allergy to arthropod bite
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Rhinitis allergic
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	0	0	1
Reproductive system and breast disorders
Dysmenorrhoea
subjects affected / exposed	2 / 85 (2.35%)	1 / 94 (1.06%)	2 / 96 (2.08%)
occurrences all number	2	1	3
Metrorrhagia
subjects affected / exposed	2 / 85 (2.35%)	2 / 94 (2.13%)	0 / 96 (0.00%)
occurrences all number	2	2	0
Hot flush
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Menorrhagia
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	2	0
Ovulation pain
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	0	0	1
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
subjects affected / exposed	1 / 85 (1.18%)	3 / 94 (3.19%)	4 / 96 (4.17%)
occurrences all number	1	3	4
Cough
subjects affected / exposed	0 / 85 (0.00%)	2 / 94 (2.13%)	3 / 96 (3.13%)
occurrences all number	0	2	3
Bronchiolitis
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Chronic obstructive pulmonary disease
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Dysphonia
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Dyspnoea
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Epistaxis
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Nasal discomfort
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Respiratory tract infection
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Psychiatric disorders
Depression
subjects affected / exposed	0 / 85 (0.00%)	3 / 94 (3.19%)	0 / 96 (0.00%)
occurrences all number	0	3	0
Insomnia
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	1	0	1
Anxiety
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Emotional distress
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Nervousness
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	0	0	1
Sleep disorder
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	0	0	1
Somnolence
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Investigations
Viral test negative
subjects affected / exposed	1 / 85 (1.18%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	1	1	0
Hepatic enzyme increased
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	0	0	1
Injury, poisoning and procedural complications
Barotitis media
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	2	0	0
Burn of internal organs
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	0	0	1
Contusion
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Congenital, familial and genetic disorders
Congenital mitral valve incompetence
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Cardiac disorders
Arteriosclerosis coronary artery
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	0	0	1
Bradycardia
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Palpitations
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	2	0
Tricuspid valve incompetence
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Nervous system disorders
Headache
subjects affected / exposed	15 / 85 (17.65%)	19 / 94 (20.21%)	6 / 96 (6.25%)
occurrences all number	21	31	9
Dizziness
subjects affected / exposed	1 / 85 (1.18%)	2 / 94 (2.13%)	3 / 96 (3.13%)
occurrences all number	1	3	3
Migraine
subjects affected / exposed	2 / 85 (2.35%)	1 / 94 (1.06%)	1 / 96 (1.04%)
occurrences all number	3	1	2
Tension headache
subjects affected / exposed	0 / 85 (0.00%)	2 / 94 (2.13%)	2 / 96 (2.08%)
occurrences all number	0	5	6
Cluster headache
subjects affected / exposed	0 / 85 (0.00%)	2 / 94 (2.13%)	0 / 96 (0.00%)
occurrences all number	0	3	0
Insomnia
subjects affected / exposed	0 / 85 (0.00%)	2 / 94 (2.13%)	0 / 96 (0.00%)
occurrences all number	0	2	0
Syncope
subjects affected / exposed	2 / 85 (2.35%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	2	1	0
Migraine with aura
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	2	0
Somnambulism
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	0	0	1
Paraesthesia
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	0	0	1
Ear and labyrinth disorders
Conductive deafness
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Otitis media
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Tinnitus
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Eye disorders
Cataract
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Conjunctival haemorrhage
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Conjunctivitis
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	1	0	1
Dry age-related macular degeneration
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Eye pain
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	0	0	1
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	7 / 85 (8.24%)	9 / 94 (9.57%)	8 / 96 (8.33%)
occurrences all number	9	13	10
Nausea
subjects affected / exposed	4 / 85 (4.71%)	7 / 94 (7.45%)	4 / 96 (4.17%)
occurrences all number	4	10	5
Abdominal distension
subjects affected / exposed	5 / 85 (5.88%)	4 / 94 (4.26%)	3 / 96 (3.13%)
occurrences all number	7	4	3
Abdominal pain upper
subjects affected / exposed	2 / 85 (2.35%)	5 / 94 (5.32%)	3 / 96 (3.13%)
occurrences all number	6	7	3
Diarrhoea
subjects affected / exposed	4 / 85 (4.71%)	5 / 94 (5.32%)	1 / 96 (1.04%)
occurrences all number	4	6	1
Irritable bowel syndrome
subjects affected / exposed	3 / 85 (3.53%)	4 / 94 (4.26%)	2 / 96 (2.08%)
occurrences all number	3	4	2
Gastrointestinal pain
subjects affected / exposed	4 / 85 (4.71%)	1 / 94 (1.06%)	3 / 96 (3.13%)
occurrences all number	5	1	4
Dyspepsia
subjects affected / exposed	2 / 85 (2.35%)	4 / 94 (4.26%)	1 / 96 (1.04%)
occurrences all number	2	4	1
Flatulence
subjects affected / exposed	3 / 85 (3.53%)	1 / 94 (1.06%)	1 / 96 (1.04%)
occurrences all number	5	1	1
Abdominal discomfort
subjects affected / exposed	2 / 85 (2.35%)	2 / 94 (2.13%)	1 / 96 (1.04%)
occurrences all number	2	2	1
Abnormal faeces
subjects affected / exposed	2 / 85 (2.35%)	2 / 94 (2.13%)	0 / 96 (0.00%)
occurrences all number	2	2	0
Gastroenteritis
subjects affected / exposed	2 / 85 (2.35%)	1 / 94 (1.06%)	1 / 96 (1.04%)
occurrences all number	2	1	1
Gastrooesophageal reflux disease
subjects affected / exposed	2 / 85 (2.35%)	1 / 94 (1.06%)	1 / 96 (1.04%)
occurrences all number	2	1	1
Haemorrhoids
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	2 / 96 (2.08%)
occurrences all number	1	0	2
Dry mouth
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	1	0	1
Frequent bowel movements
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	3	0	1
Gastroenteritis viral
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	2	0	1
Abdominal pain lower
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Anal fissure
subjects affected / exposed	2 / 85 (2.35%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	2	0	0
Anal haemorrhage
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Aphthous ulcer
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	0	0	1
Change of bowel habit
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Chapped lips
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	0	0	1
Colitis
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	0	0	1
Constipation
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	0	0	3
Dental pulp disorder
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Epigastric discomfort
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Gastrointestinal hypermotility
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	0	0	1
Gastrointestinal somatic symptom disorder
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	2	0	0
Gingivitis
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	1 / 96 (1.04%)
occurrences all number	0	1	1
Haemorrhoidal haemorrhage
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	0	0	1
Hyperchlorhydria
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Large intestine polyp
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Loose tooth
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Pulpitis dental
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	0	0	1
Vomiting
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Skin and subcutaneous tissue disorders
Laceration
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	1 / 96 (1.04%)
occurrences all number	0	1	1
Pruritus generalised
subjects affected / exposed	1 / 85 (1.18%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	1	1	0
Angular cheilitis
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Erythema
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	0	0	1
Pruritus
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Psoriasis
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Rash
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	2 / 96 (2.08%)
occurrences all number	0	0	3
Skin lesion
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Sunburn
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Renal and urinary disorders
Haematuria
subjects affected / exposed	1 / 85 (1.18%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	2	1	0
Cystitis
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	2	0
Dysuria
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Leukocyturia
subjects affected / exposed	0 / 85 (0.00%)	2 / 94 (2.13%)	0 / 96 (0.00%)
occurrences all number	0	3	0
Micturition disorder
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Micturition urgency
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	0	0	1
Nephritis
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Polyuria
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	0	0	1
Renal colic
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	2	0	0
Urinary tract infection
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 85 (0.00%)	6 / 94 (6.38%)	1 / 96 (1.04%)
occurrences all number	0	7	2
Neck pain
subjects affected / exposed	2 / 85 (2.35%)	1 / 94 (1.06%)	3 / 96 (3.13%)
occurrences all number	2	1	4
Arthralgia
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	3 / 96 (3.13%)
occurrences all number	0	1	3
Muscle contracture
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	2 / 96 (2.08%)
occurrences all number	1	0	2
Muscle spasms
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	1	0	1
Ligament injury
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Myalgia
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	0	0	1
Neuromuscular pain
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	0	0	1
Osteoarthritis
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Pain in extremity
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Tenosynovitis
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Musculoskeletal pain
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Infections and infestations
Influenza
subjects affected / exposed	10 / 85 (11.76%)	2 / 94 (2.13%)	7 / 96 (7.29%)
occurrences all number	11	2	8
Gastroenteritis
subjects affected / exposed	4 / 85 (4.71%)	2 / 94 (2.13%)	4 / 96 (4.17%)
occurrences all number	4	3	4
Vulvovaginal candidiasis
subjects affected / exposed	2 / 85 (2.35%)	2 / 94 (2.13%)	2 / 96 (2.08%)
occurrences all number	2	3	4
Urinary tract infection
subjects affected / exposed	5 / 85 (5.88%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	5	1	0
Viral infection
subjects affected / exposed	0 / 85 (0.00%)	3 / 94 (3.19%)	1 / 96 (1.04%)
occurrences all number	0	3	1
Cystitis
subjects affected / exposed	1 / 85 (1.18%)	1 / 94 (1.06%)	2 / 96 (2.08%)
occurrences all number	1	1	2
Acute sinusitis
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	1 / 96 (1.04%)
occurrences all number	0	1	1
Oral herpes
subjects affected / exposed	0 / 85 (0.00%)	2 / 94 (2.13%)	0 / 96 (0.00%)
occurrences all number	0	2	0
Pharyngitis
subjects affected / exposed	2 / 85 (2.35%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	2	0	0
Rhinitis
subjects affected / exposed	1 / 85 (1.18%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	1	1	0
Upper respiratory tract infection
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	1 / 96 (1.04%)
occurrences all number	0	1	2
Candida infection
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	0	0	1
Ear infection
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Erysipelas
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Groin abscess
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
H1N1 influenza
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	0	0	1
Infection
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	0	0	1
Laryngitis
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	1 / 96 (1.04%)
occurrences all number	0	0	1
Sinusitis
subjects affected / exposed	0 / 85 (0.00%)	0 / 94 (0.00%)	2 / 96 (2.08%)
occurrences all number	0	0	2
Tonsillitis
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Vaginal infection
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Viral pharyngitis
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	1 / 96 (1.04%)
occurrences all number	0	1	1
Cat scratch disease
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Genitourinary tract infection
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Metabolism and nutrition disorders
Chondropathy
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Contusion
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Diabetes mellitus
subjects affected / exposed	1 / 85 (1.18%)	0 / 94 (0.00%)	0 / 96 (0.00%)
occurrences all number	1	0	0
Iron deficiency
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0
Hypercholesterolaemia
subjects affected / exposed	0 / 85 (0.00%)	1 / 94 (1.06%)	0 / 96 (0.00%)
occurrences all number	0	1	0

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Were there any global substantial amendments to the protocol? Yes

27 Feb 2017

1) To complete all 14 days of treatment up to the evening of Day 14, the day of Visit 4 will be Day 15. To maintain 7-day intervals between subsequent visits, the day of Visits 3 to 7 and of all the Phone calls is rectified. 2) Since the bowel cleansing preparation and the colonoscopy may bias the baseline symptom data to be collected by the patients from Visit 1 to Day -1, the following changes are introduced to standardise the baseline data collection and to prevent any bias: the screening phase is extended to Day -21, the screening visit will be scheduled between Days -21 and -15, the colonoscopy, if needed, will be scheduled between Days -21 and -16, baseline data collected from Day -14 to Day -1 will be considered for the evaluation of inclusion criterion 4 at Visit 2 – Day 1. 3) Details of the co-ordinating site in Germany and of the CRO designated for monitoring and submissions in Belgium are added. 4) “Oral body temperature” is changed to “body temperature” to allow more measurement types since this parameter is not expected to vary critically during the study

20 Feb 2018

The aim of this substantial amendment is: 1) To replace the use of the electronic diary with the paper one. 2) To specify the permitted values of averages calculated for confirming the inclusion criterion 4 point b), when the values calculated is >4. 3) To specify the use the once-off medications related to the preparation or performance of the colonoscopy inside the study. 4) To amend the name of responsible person at ArisGlobal Ltd. (provider of EDC and randomisation system) 4) To integrate the Note to File 1 in the new protocol version. 5) To integrate the Amendment Nr. 01, Final version 1.0, 21JUL17 in the new protocol version. Sections affected: • Synopsis • Section 5.2, 5.3, 5.3.1 • Section 6.1.1 • Section 7.4.2, 7.4.3, 7.4.4, 7.4.5 • Section 7.6 • Section 8.1, 8.2 • Section 12.1 • Section 13.2 • Section 15.1 • Section 16.2.4.1 • Section 16.5

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
15 Jun 2020	Study was interrupted and completed earlier due to Covid-19 pandemic.	-

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

None reported

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Clinical trials

Clinical Trial Results: A Phase II, multicentre, randomised, double-blind, placebo controlled, proof of concept study of efficacy and safety of Rifamycin SV-MMX® 600 mg tablets administered three or two times daily to patients with diarrhoea-predominant irritable bowel syndrome (IBS-D)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Proportion of weekly responders with adequate relief of the composite of abdominal pain and stool consistency in the 1st week of treatment

Primary: Proportion of weekly responders with adequate relief of the composite of abdominal pain and stool consistency in the 1st week of treatment

Secondary: Proportion of subjects with adequate relief of global IBS symptoms for at least 2 (consecutive or not) of the 10 weeks during the follow-up period

Secondary: Proportion of subjects with adequate relief of global IBS symptoms for at least 2 (consecutive or not) of the 10 weeks during the follow-up period

Secondary: Proportion of subjects with adequate relief of global IBS symptoms during at least 2 weeks (consecutive or not) per month (“monthly response”) during month 1, during month 1 through 2 and during month 1 through 3

Secondary: Proportion of subjects with adequate relief of global IBS symptoms during at least 2 weeks (consecutive or not) per month (“monthly response”) during month 1, during month 1 through 2 and during month 1 through 3

Secondary: Proportion of subjects with adequate relief of IBS-related bloating for at least 2 (consecutive or not) of the 10 weeks during the follow-up period (i.e., weeks 3 through 12).

Secondary: Proportion of subjects with adequate relief of IBS-related bloating for at least 2 (consecutive or not) of the 10 weeks during the follow-up period (i.e., weeks 3 through 12).

Secondary: Proportion of subjects with relief (weekly responders) determined from the subjects’ daily assessments of IBS symptoms, bloating, and abdominal pain

Secondary: Proportion of subjects with relief (weekly responders) determined from the subjects’ daily assessments of IBS symptoms, bloating, and abdominal pain

Secondary: Change from baseline to week 12 in daily IBS symptoms, bloating and abdominal pain.

Secondary: Change from baseline to week 12 in daily IBS symptoms, bloating and abdominal pain.

Secondary: Proportion of monthly responders during month 1, during month 1 through 2 and during month 1 through 3 determined from the subjects’ daily assessments of IBS symptoms, bloating, and abdominal pain and stool consistency

Secondary: Proportion of monthly responders during month 1, during month 1 through 2 and during month 1 through 3 determined from the subjects’ daily assessments of IBS symptoms, bloating, and abdominal pain and stool consistency

Secondary: Change from baseline to each week during the 12 week follow up for daily IBS symptoms, bloating, abdominal pain, stool consistency and sense of urgency

Secondary: Change from baseline to each week during the 12 week follow up for daily IBS symptoms, bloating, abdominal pain, stool consistency and sense of urgency

Secondary: Number of weeks (consecutive or not) subjects achieved adequate relief of bloating during the follow up period.

Secondary: Number of weeks (consecutive or not) subjects achieved adequate relief of bloating during the follow up period.

Secondary: Number of weeks (consecutive or not) subjects achieved adequate relief of IBS symptoms during the follow up period.

Secondary: Number of weeks (consecutive or not) subjects achieved adequate relief of IBS symptoms during the follow up period.

Secondary: Proportion of subjects with adequate relief of bloating during at least 2 weeks (consecutive or not) per month (“monthly response”)

Secondary: Proportion of subjects with adequate relief of bloating during at least 2 weeks (consecutive or not) per month (“monthly response”)

Secondary: Change from baseline in quality of life inquired as IBS-QoL

Secondary: Change from baseline in quality of life inquired as IBS-QoL

Other pre-specified: Plasma levels of IL1β, IL6, IL8, IL12p70 and TNFα and those of the antibodies against vinculin and Campylobacter CdtB protein

Other pre-specified: Plasma levels of IL1β, IL6, IL8, IL12p70 and TNFα and those of the antibodies against vinculin and Campylobacter CdtB protein

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A Phase II, multicentre, randomised, double-blind, placebo controlled, proof of concept study of efficacy and safety of Rifamycin SV-MMX® 600 mg tablets administered three or two times daily to patients with diarrhoea-predominant irritable bowel syndrome (IBS-D)