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Clinical Trial Results:
Double-blind, randomised, placebo-controlled, parallel-group phase II study to evaluate the effect of oral ibodutant in irritable bowel syndrome with diarrhoea (IBS-D) - The Iris-2 Study.

Summary
EudraCT number	2010-018300-85
Trial protocol	CZ DE ES SE IT DK BG
Global end of trial date	11 May 2012

Results information
Results version number	v1(current)
This version publication date	15 Nov 2018
First version publication date	15 Nov 2018
Other versions

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

NAK-04

ISRCTN number

US NCT number

NCT01303224

WHO universal trial number (UTN)

Sponsor organisation name

Menarini Ricerche S.p.A.

Sponsor organisation address

Via Sette Santi 1, Florence, Italy, 50131

Public contact

Corporate Director of Clinical Sciences, Corporate Clinical Sciences, +39 05556809990, acapriati@menarini-ricerche.it

Scientific contact

Corporate Director of Clinical Sciences, Corporate Clinical Sciences, +39 05556809990, acapriati@menarini-ricerche.it

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

11 May 2012

Is this the analysis of the primary completion data?

Yes

Primary completion date

11 May 2012

Global end of trial reached?

Yes

Global end of trial date

11 May 2012

Was the trial ended prematurely?

Main objective of the trial

To evaluate the efficacy of 3 oral doses of ibodutant on IBS symptoms relief and abdominal pain/discomfort relief as compared to placebo in IBS-D patients following an 8-week oral treatment course.

Protection of trial subjects

If any event(s) related to the conduct of the study or the development of the IMP which affected the safety of the study participants, the sponsor and the investigator were to take appropriate urgent safety measures to protect the patients against any immediate hazard. The CAs and IRB/ECs were to be informed forthwith about these new events and the measures taken. For patients participating in the study, Menarini Ricerche S.p.A. had stipulated an insurance policy in accordance with local regulatory requirements.

Background therapy

Evidence for comparator

The choice of placebo as control group also complied with requirements of institutional and academic guidelines and was justified because there was unison agreement that there were no standard therapy for IBS. Moreover, the “placebo effect” in IBS was known to be high with response rates ranging from 0% to 84% (median: 47%) so that demonstration of superiority over placebo was most likely to reflect a true advantage for the patient.

Actual start date of recruitment

06 Oct 2010

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 188

Country: Number of subjects enrolled

Spain: 23

Country: Number of subjects enrolled

Sweden: 26

Country: Number of subjects enrolled

Bulgaria: 162

Country: Number of subjects enrolled

Czech Republic: 50

Country: Number of subjects enrolled

Denmark: 67

Country: Number of subjects enrolled

Germany: 35

Country: Number of subjects enrolled

Italy: 14

Worldwide total number of subjects

565

EEA total number of subjects

565

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)

519

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The first patient was screened on 06 Oct 2010 and the first subject was randomised on 22 Oct 2010. The last patient completed the study on 11 May 2012. The study was conducted at 78 investigational sites in 8 European countries.

Screening details

A total of 1054 entered into the 2-week screening period. Of these, 565 patients were eligible for randomisation, indicating a screening failure rate of 53.6%. A total of 559 patients took at least one dose of study medication and provided at least one primary endpoint assessment (ITT-population)

Period 1 title

8-week Double-blind Treatment (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

Double-blind conditions were ensured by the identical appearance and weight of the three different strengths of ibodutant tablets as well as the placebo tablets. In order to preserve the double-blind conditions of the study, persons who were involved in the preparation or the handling of the randomisation list were not involved in the study conduct and statistical analysis. This remained in effect until the database was completed and locked.

Are arms mutually exclusive

Yes

Ibodutant 1mg

Arm description

Ibodutant 1mg, oral tablet to be given once daily for 8 weeks of treatment.

Arm type

Experimental

Investigational medicinal product name

Ibodutant

Investigational medicinal product code

MEN 15596

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Ibodutant 1 mg oral tablet, to be given once daily in fasting conditions.

Ibodutant 3mg

Arm description

Ibodutant 3mg, oral tablet to be given once daily for 8 weeks of treatment.

Arm type

Experimental

Investigational medicinal product name

Ibodutant

Investigational medicinal product code

MEN 15596

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Ibodutant 3 mg oral tablet, to be given once daily in fasting conditions.

Ibodutant 10mg

Arm description

Ibodutant 10mg, oral tablet to be given once daily for 8 weeks of treatment.

Arm type

Experimental

Investigational medicinal product name

Ibodutant

Investigational medicinal product code

MEN 15596

Other name

Pharmaceutical forms

Tablet

Routes of administration

Other use

Dosage and administration details

Ibodutant 10 mg oral tablet, to be given once daily in fasting conditions.

Placebo

Arm description

Placebo, oral tablet to be given once daily for 8 weeks of treatment.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Sugar pill

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo oral tablet (identical in appearance and weight to ibodutant tablets) to be given once daily in fasting conditions.

Number of subjects in period 1	Ibodutant 1mg	Ibodutant 3mg	Ibodutant 10mg	Placebo
Started	141	142	139	143
Completed	130	131	133	133
Not completed	11	11	6	10
Consent withdrawn by subject	4	8	2	4
unk	2	1	2	3
Adverse event, non-fatal	2	1	1	-
Sponsor request	1	-	-	-
Lost to follow-up	1	1	1	3
Protocol deviation	1	-	-	-

Baseline characteristics

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Reporting group title

Ibodutant 1mg

Reporting group description

Ibodutant 1mg, oral tablet to be given once daily for 8 weeks of treatment.

Reporting group title

Ibodutant 3mg

Reporting group description

Ibodutant 3mg, oral tablet to be given once daily for 8 weeks of treatment.

Reporting group title

Ibodutant 10mg

Reporting group description

Ibodutant 10mg, oral tablet to be given once daily for 8 weeks of treatment.

Reporting group title

Placebo

Reporting group description

Placebo, oral tablet to be given once daily for 8 weeks of treatment.

Reporting group values	Ibodutant 1mg	Ibodutant 3mg	Ibodutant 10mg	Placebo	Total
Number of subjects	141	142	139	143	565
Age categorical
Units: Subjects
Adults (18-70 years)	141	142	139	143	565
Age continuous
Units: years
arithmetic mean (standard deviation)	46.1 ( 13.3 )	46.8 ( 13.5 )	47.0 ( 12.8 )	44.2 ( 14.0 )	-
Gender categorical
Units: Subjects
Female	89	89	79	79	336
Male	52	53	60	64	229
Time since onset of IBS symptoms
Units: Years
arithmetic mean (standard deviation)	( )	( )	( )	( )	-
IBS symptoms at baseline/randomisation: abdominal pain
Abdominal pain
Units: Scores on a scale
arithmetic mean (standard deviation)	( )	( )	( )	( )	-
IBS symptoms at baseline/randomisation: bloating
Bloating
Units: Scores on a scale
arithmetic mean (standard deviation)	( )	( )	( )	( )	-
IBS symptoms at baseline/randomisation: urgency
Urgency
Units: Scores on a scale
arithmetic mean (standard deviation)	( )	( )	( )	( )	-
IBS symptoms at baseline/randomisation: severity
IBS symptom severity rate
Units: Scores on a scale
arithmetic mean (standard deviation)	( )	( )	( )	( )	-
Stool frequency/day
Units: Bowel movements/day
arithmetic mean (standard deviation)	( )	( )	( )	( )	-
Stool consistency
Units: Scores on a scale
arithmetic mean (standard deviation)	( )	( )	( )	( )	-
IBS symptomes severity scale score
IBS symptomes severity scale score
Units: Scores on a scale
arithmetic mean (standard deviation)	( )	( )	( )	( )	-
QoL questionnaire EQ-5D VAS
Quality of Life questionnaire EQ-5D Visual analog scales
Units: Scores on a scale
arithmetic mean (standard deviation)	( )	( )	( )	( )	-

Subject analysis set title

ITT 1 mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

All patients randomised to the 1 mg Ibudutant group who took at least one dose of the study medication and provided at least one primary endpoint assessment.

Subject analysis set title

ITT 3 mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

All patients randomised to the 3 mg Ibudutant group who took at least one dose of the study medication and provided at least one primary endpoint assessment.

Subject analysis set title

ITT 10 mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

All patients randomised to the 10 mg Ibudutant group who took at least one dose of the study medication and provided at least one primary endpoint assessment.

Subject analysis set title

ITT placebo

Subject analysis set type

Intention-to-treat

Subject analysis set description

All patients randomised to the placebo group who took at least one dose of the study medication and provided at least one primary endpoint assessment.

Subject analysis sets values	ITT 1 mg	ITT 3 mg	ITT 10 mg	ITT placebo
Number of subjects	140	138	139	142
Age categorical
Units: Subjects
Adults (18-70 years)	140	138	139	142
Age continuous
Units: years
arithmetic mean (standard deviation)	45.9 ( 13.7 )	47.1 ( 13.4 )	47.0 ( 12.8 )	44.1 ( 14.0 )
Gender categorical
Units: Subjects
Female	89	87	79	78
Male	51	51	60	64
Time since onset of IBS symptoms
Units: Years
arithmetic mean (standard deviation)	6.2 ( 7.3 )	6.3 ( 7.5 )	6.3 ( 6.9 )	4.6 ( 6.2 )
IBS symptoms at baseline/randomisation: abdominal pain
Abdominal pain
Units: Scores on a scale
arithmetic mean (standard deviation)	2.5 ( 0.6 )	2.3 ( 0.5 )	2.3 ( 0.5 )	2.3 ( 0.6 )
IBS symptoms at baseline/randomisation: bloating
Bloating
Units: Scores on a scale
arithmetic mean (standard deviation)	2.4 ( 0.8 )	2.2 ( 0.7 )	2.2 ( 0.7 )	2.2 ( 0.6 )
IBS symptoms at baseline/randomisation: urgency
Urgency
Units: Scores on a scale
arithmetic mean (standard deviation)	2.5 ( 0.7 )	2.5 ( 0.6 )	2.4 ( 0.6 )	2.4 ( 0.6 )
IBS symptoms at baseline/randomisation: severity
IBS symptom severity rate
Units: Scores on a scale
arithmetic mean (standard deviation)	2.7 ( 0.7 )	2.6 ( 0.6 )	2.6 ( 0.6 )	2.6 ( 0.6 )
Stool frequency/day
Units: Bowel movements/day
arithmetic mean (standard deviation)	4.6 ( 1.5 )	4.4 ( 1.3 )	4.4 ( 1.5 )	4.4 ( 1.2 )
Stool consistency
Units: Scores on a scale
arithmetic mean (standard deviation)	5.7 ( 0.6 )	5.7 ( 0.5 )	5.7 ( 0.6 )	5.7 ( 0.6 )
IBS symptomes severity scale score
IBS symptomes severity scale score
Units: Scores on a scale
arithmetic mean (standard deviation)	343.4 ( 68.8 )	333.3 ( 78.3 )	332.6 ( 74.3 )	335.7 ( 69.4 )
QoL questionnaire EQ-5D VAS
Quality of Life questionnaire EQ-5D Visual analog scales
Units: Scores on a scale
arithmetic mean (standard deviation)	54.5 ( 22.9 )	55.5 ( 21.9 )	58.1 ( 22.9 )	55.3 ( 22.3 )

End points

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Reporting group title

Ibodutant 1mg

Reporting group description

Ibodutant 1mg, oral tablet to be given once daily for 8 weeks of treatment.

Reporting group title

Ibodutant 3mg

Reporting group description

Ibodutant 3mg, oral tablet to be given once daily for 8 weeks of treatment.

Reporting group title

Ibodutant 10mg

Reporting group description

Ibodutant 10mg, oral tablet to be given once daily for 8 weeks of treatment.

Reporting group title

Placebo

Reporting group description

Placebo, oral tablet to be given once daily for 8 weeks of treatment.

Subject analysis set title

ITT 1 mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

All patients randomised to the 1 mg Ibudutant group who took at least one dose of the study medication and provided at least one primary endpoint assessment.

Subject analysis set title

ITT 3 mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

All patients randomised to the 3 mg Ibudutant group who took at least one dose of the study medication and provided at least one primary endpoint assessment.

Subject analysis set title

ITT 10 mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

All patients randomised to the 10 mg Ibudutant group who took at least one dose of the study medication and provided at least one primary endpoint assessment.

Subject analysis set title

ITT placebo

Subject analysis set type

Intention-to-treat

Subject analysis set description

All patients randomised to the placebo group who took at least one dose of the study medication and provided at least one primary endpoint assessment.

Primary: Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort at the End of 8 Weeks of Treatment, Where the Response is Defined as at Least 6 Weeks With Satisfactory Relief During 8 Weeks of Treatment (75% Rule)

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End point title

Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort at the End of 8 Weeks of Treatment, Where the Response is Defined as at Least 6 Weeks With Satisfactory Relief During 8 Weeks of Treatment (75% Rule)

End point description

Weekly binary questions (yes/no) from Interactive Voice/Web Response (IV/WRS) diary records: "Did you have satisfactory relief of your overall IBS symptoms during the last week?" and "Did you have satisfactory relief of your abdominal pain or discomfort during the last week?" Responder: Report of satisfactory overall IBS symptom relief ="Yes" and of satisfactory abdominal pain/discomfort relief = "Yes" 6/8 weeks (75% rule)

End point type

Primary

End point timeframe

Eight weeks

End point values	ITT 1 mg	ITT 3 mg	ITT 10 mg	ITT placebo
Number of subjects analysed	140	138	139	142
Units: Number of Responders
Responder	45	46	55	39
Non Responder	95	92	84	103

Cochran-Mantel-Haenszel Test

Statistical analysis description

Mantel-Haenszel-Test was used to compare separately each of the 3 active treatment groups with placebo using a two-sided overall significance level of 5%. The proportion of responders was tested with the following hypotheses: H0 (placebo) vs H1(Ibodutant:1mg/3mg/10mg). Approximately 80% power based on the assumptions: rate placebo 40%, expected mean therapeutic gain over placebo 15% for at least one dose of Ibodutant.

Comparison groups

ITT 3 mg v ITT 1 mg v ITT 10 mg v ITT placebo

Number of subjects included in analysis

559

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.05 ^[1]

Method

t-test, 2-sided

Confidence interval

Notes
[1] - Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance: Multiplicity was adjusted by using the Hochberg Procedure.

Secondary: Response of satisfactory relief of overall IBS symptoms AND abdominal pain/discomfort during 8 weeks of treatment according to the 50% rule

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End point title

Response of satisfactory relief of overall IBS symptoms AND abdominal pain/discomfort during 8 weeks of treatment according to the 50% rule

End point description

Weekly binary questions (yes/no) from IV/WRS diary records: "Did you have satisfactory relief of your overall IBS symptoms during the last week?" and "Did you have satisfactory relief of your abdominal pain or discomfort during the last week?" Responder: Report of satisfactory overall IBS symptom relief ="Yes" and of satisfactory abdominal pain/discomfort relief = "Yes" 4/8 weeks with at least 2 consecutive weeks of satisfactory relief during Week 5 to Week 8(50% rule)

End point type

Secondary

End point timeframe

Eight weeks

End point values	ITT 1 mg	ITT 3 mg	ITT 10 mg	ITT placebo
Number of subjects analysed	140	138	139	142
Units: Number of responders
Responder	72	61	74	55
Non-Responder	68	77	65	87

Mantel Haenszel

Comparison groups

ITT 1 mg v ITT 3 mg v ITT 10 mg v ITT placebo

Number of subjects included in analysis

559

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.05 ^[2]

Method

Mantel-Haenszel

Confidence interval

Notes
[2] - Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance: Multiplicity was adjusted using the Hochberg procedure.

Secondary: Quality of Life Changes

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End point title

Quality of Life Changes

End point description

Change in EQ-5D Quality of Life (visual analogue scale) score at the end of 8 weeks of treatment versus baseline (at randomisation). EQ-5D quality of life visual analogue scale ranges from “0”= worst imaginable health state to “100”=best imaginable health state. all ITT patients who provided EQ-5D data at Visit 2 (start of treatment) and Visit 4 (end of treatment). No statistical analysis provided for Quality of Life Changes (Using EuroQoL EQ-5D Questionnaire).

End point type

Secondary

End point timeframe

Eight weeks

End point values	ITT 1 mg	ITT 3 mg	ITT 10 mg	ITT placebo
Number of subjects analysed	131	133	133	131
Units: VAS
arithmetic mean (standard deviation)
Baseline	56.4 ( 20.6 )	58.2 ( 22.0 )	57.2 ( 22.0 )	58.7 ( 21.5 )
Visit 4	71.3 ( 17.2 )	72.1 ( 18.7 )	66.7 ( 20.7 )	72.2 ( 17.0 )

No statistical analyses for this end point

Other pre-specified: Subgroup Analysis: Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort According to the 75% Rule in the Female ITT Population

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End point title

Subgroup Analysis: Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort According to the 75% Rule in the Female ITT Population

End point description

Weekly binary questions (yes/no) from IV/WRS diary records: "Did you have satisfactory relief of your overall IBS symptoms during the last week?" and "Did you have satisfactory relief of your abdominal pain or discomfort during the last week?" Responder: Report of satisfactory overall IBS symptom relief ="Yes" and of satisfactory abdominal pain/discomfort relief = "Yes" 6/8 weeks (75% rule) Population: Female ITT Population No statistical analysis provided for Subgroup Analysis

End point type

Other pre-specified

End point timeframe

Eight weeks

End point values	ITT 1 mg	ITT 3 mg	ITT 10 mg	ITT placebo
Number of subjects analysed	89	87	79	78
Units: Participants
Responders	32	35	37	19
Non-Responders	57	52	42	59

No statistical analyses for this end point

Other pre-specified: Subgroup Analysis: Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort According to the 75% Rule in the Male ITT Population

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End point title

Subgroup Analysis: Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort According to the 75% Rule in the Male ITT Population

End point description

Weekly binary questions (yes/no) from IV/WRS diary records: "Did you have satisfactory relief of your overall IBS symptoms during the last week?" and "Did you have satisfactory relief of your abdominal pain or discomfort during the last week?" Responder: Report of satisfactory overall IBS symptom relief ="Yes" and of satisfactory abdominal pain/discomfort relief = "Yes" 6/8 weeks (75% rule) Population: Intention-to-Treat in the male population No statistical analysis provided for Subgroup Analysis.

End point type

Other pre-specified

End point timeframe

Eight weeks

End point values	ITT 1 mg	ITT 3 mg	ITT 10 mg	ITT placebo
Number of subjects analysed	51	51	60	64
Units: Participants
Responders	13	11	18	20
Non-Responders	38	40	42	44

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Adverse Events (AEs) for 12 weeks Treatment Emergent Signs and Symptoms (TESS) for 8 weeks

Adverse event reporting additional description

TESS (collected from first drug intake at Visit 2 (randomisation) during the treatment period of 8 weeks) were analysed for the Safety Population (all patients who took at least one dose of study medication, N = 565). Generally, Adverse Events were reported/patient for a period of 12 weeks (during the total individual study period).

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

13.0

Reporting group title

Ibodutant 1mg

Reporting group description

Ibodutant 1mg, oral tablet to be given once daily for 8 weeks of treatment.

Reporting group title

Ibodutant 3mg

Reporting group description

Ibodutant 3mg, oral tablet to be given once daily for 8 weeks of treatment.

Reporting group title

Ibodutant 10mg

Reporting group description

Ibodutant 10mg, oral tablet to be given once daily for 8 weeks of treatment.

Reporting group title

Placebo

Reporting group description

Placebo, oral tablet to be given once daily for 8 weeks of treatment.

Serious adverse events	Ibodutant 1mg	Ibodutant 3mg	Ibodutant 10mg	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 141 (0.00%)	1 / 142 (0.70%)	1 / 139 (0.72%)	3 / 143 (2.10%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterus myomatosus
subjects affected / exposed	0 / 141 (0.00%)	0 / 142 (0.00%)	0 / 139 (0.00%)	1 / 143 (0.70%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Mydriasis
subjects affected / exposed	0 / 141 (0.00%)	0 / 142 (0.00%)	0 / 139 (0.00%)	1 / 143 (0.70%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Worsened abdominal pain
subjects affected / exposed	0 / 141 (0.00%)	0 / 142 (0.00%)	0 / 139 (0.00%)	1 / 143 (0.70%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Acute appendicitis
subjects affected / exposed	0 / 141 (0.00%)	1 / 142 (0.70%)	0 / 139 (0.00%)	0 / 143 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Diabetes Mellitus type II
subjects affected / exposed	0 / 141 (0.00%)	0 / 142 (0.00%)	1 / 139 (0.72%)	0 / 143 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 2%

Non-serious adverse events	Ibodutant 1mg	Ibodutant 3mg	Ibodutant 10mg	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	42 / 141 (29.79%)	40 / 142 (28.17%)	42 / 139 (30.22%)	29 / 143 (20.28%)
Investigations
Blood creatine phosphokinase increased
subjects affected / exposed	3 / 141 (2.13%)	0 / 142 (0.00%)	1 / 139 (0.72%)	1 / 143 (0.70%)
occurrences all number	3	0	1	1
Nervous system disorders
Dizziness
subjects affected / exposed	3 / 141 (2.13%)	2 / 142 (1.41%)	1 / 139 (0.72%)	0 / 143 (0.00%)
occurrences all number	3	2	1	0
Headache
subjects affected / exposed	7 / 141 (4.96%)	3 / 142 (2.11%)	8 / 139 (5.76%)	4 / 143 (2.80%)
occurrences all number	7	3	11	4
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 141 (0.71%)	2 / 142 (1.41%)	0 / 139 (0.00%)	3 / 143 (2.10%)
occurrences all number	1	2	0	4
Nausea
subjects affected / exposed	1 / 141 (0.71%)	4 / 142 (2.82%)	5 / 139 (3.60%)	3 / 143 (2.10%)
occurrences all number	1	4	5	3
Infections and infestations
Gastroenteritis
subjects affected / exposed	0 / 141 (0.00%)	2 / 142 (1.41%)	3 / 139 (2.16%)	0 / 143 (0.00%)
occurrences all number	0	2	3	0
Influenza
subjects affected / exposed	0 / 141 (0.00%)	2 / 142 (1.41%)	3 / 139 (2.16%)	5 / 143 (3.50%)
occurrences all number	0	2	3	5
Nasopharyngitis
subjects affected / exposed	5 / 141 (3.55%)	4 / 142 (2.82%)	5 / 139 (3.60%)	3 / 143 (2.10%)
occurrences all number	6	4	5	3
Upper respiratory tract infection
subjects affected / exposed	0 / 141 (0.00%)	0 / 142 (0.00%)	3 / 139 (2.16%)	1 / 143 (0.70%)
occurrences all number	0	0	3	1

More information

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Were there any global substantial amendments to the protocol? Yes

05 Jul 2010

substantial; effective in the Czech Republic modified inclusion criterion no 2 in such a way that all patients older than 50 years OR patients with positive family history of colorectal cancer had to have normal results from a colonoscopy or flexible sigmoidoscopy that has been performed after onset of IBS symptoms and within one year before Screening. Moreover, amendment required all Czech patients to have a documented negative IgA antibodies against tissue transglutaminase and endomysium within the last 24 months in order to ascertain the absence of gluten enteropathy

06 Jul 2010

substantial; effective in Germany modified inclusion criterion no 2 in such a way that all study participants, irrespective of their age, had to have normal results from colonoscopy or flexible sigmoidoscopy performed within the last 5 years and after the onset of IBS symptoms, and completed before Screening

12 Jul 2011

non-substantial, administrative became necessary because of the changes in responsibilities resulting from the fact that on July 12, 2011 INC Research, LLC, a therapeutically focused Contract Research Organization (CRO) privately held by Avista Capital Partners and Ontario Teachers’ Pension Plan, announced its completed acquisition of Kendle International Inc.

Were there any global interruptions to the trial? No

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

None reported

http://www.ncbi.nlm.nih.gov/pubmed/27196574

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Clinical trials

Clinical Trial Results:
Double-blind, randomised, placebo-controlled, parallel-group phase II study to evaluate the effect of oral ibodutant in irritable bowel syndrome with diarrhoea (IBS-D) - The Iris-2 Study.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort at the End of 8 Weeks of Treatment, Where the Response is Defined as at Least 6 Weeks With Satisfactory Relief During 8 Weeks of Treatment (75% Rule)

Primary: Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort at the End of 8 Weeks of Treatment, Where the Response is Defined as at Least 6 Weeks With Satisfactory Relief During 8 Weeks of Treatment (75% Rule)

Secondary: Response of satisfactory relief of overall IBS symptoms AND abdominal pain/discomfort during 8 weeks of treatment according to the 50% rule

Secondary: Response of satisfactory relief of overall IBS symptoms AND abdominal pain/discomfort during 8 weeks of treatment according to the 50% rule

Secondary: Quality of Life Changes

Secondary: Quality of Life Changes

Other pre-specified: Subgroup Analysis: Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort According to the 75% Rule in the Female ITT Population

Other pre-specified: Subgroup Analysis: Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort According to the 75% Rule in the Female ITT Population

Other pre-specified: Subgroup Analysis: Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort According to the 75% Rule in the Male ITT Population

Other pre-specified: Subgroup Analysis: Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort According to the 75% Rule in the Male ITT Population

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

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

Clinical trials

Clinical Trial Results: Double-blind, randomised, placebo-controlled, parallel-group phase II study to evaluate the effect of oral ibodutant in irritable bowel syndrome with diarrhoea (IBS-D) - The Iris-2 Study.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort at the End of 8 Weeks of Treatment, Where the Response is Defined as at Least 6 Weeks With Satisfactory Relief During 8 Weeks of Treatment (75% Rule)

Primary: Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort at the End of 8 Weeks of Treatment, Where the Response is Defined as at Least 6 Weeks With Satisfactory Relief During 8 Weeks of Treatment (75% Rule)

Secondary: Response of satisfactory relief of overall IBS symptoms AND abdominal pain/discomfort during 8 weeks of treatment according to the 50% rule

Secondary: Response of satisfactory relief of overall IBS symptoms AND abdominal pain/discomfort during 8 weeks of treatment according to the 50% rule

Secondary: Quality of Life Changes

Secondary: Quality of Life Changes

Other pre-specified: Subgroup Analysis: Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort According to the 75% Rule in the Female ITT Population

Other pre-specified: Subgroup Analysis: Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort According to the 75% Rule in the Female ITT Population

Other pre-specified: Subgroup Analysis: Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort According to the 75% Rule in the Male ITT Population

Other pre-specified: Subgroup Analysis: Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort According to the 75% Rule in the Male ITT Population

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

Clinical Trial Results:
Double-blind, randomised, placebo-controlled, parallel-group phase II study to evaluate the effect of oral ibodutant in irritable bowel syndrome with diarrhoea (IBS-D) - The Iris-2 Study.