Trial Outcomes & Findings for 52-Week Efficacy and Safety Study of Ibodutant in Women With Irritable Bowel Syndrome With Diarrhea (IBS-D) (NCT NCT02120027)

NCT ID: NCT02120027

Last Updated: 2017-03-03

Results Overview

The patient will be considered a weekly responder if she meets both of the following criteria in the same week: * Abdominal pain response: decrease in weekly average of worst abdominal pain score in the past 24 hours of at least 30% compared with baseline (patients reported their worst abdominal pain on a 0 to 10 NRS scale, where 0 corresponds to no pain and 10 corresponds to worst possible pain); * Stool consistency response: decrease of at least 50% in the number of days per week with at least one stool that has a consistency of Type 6 or 7 compared with baseline (patients reported their stool consistency response using the Bristol Stool Chart score based on a 1 to 7 NRS scale where 1 corresponds to hard stool and 7 corresponds to watery diarrhoea).

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

558 participants

Primary outcome timeframe

24 weeks

Results posted on

2017-03-03

Participant Flow

The first patient was screened on 26th February 2014 and the first patient randomised on 24th March 2014. The last patient completed the study on 03rd November 2015. The study was conducted at 139 clinical sites in 9 countries (Czech Rep, Germany, Hungary, Latvia, Poland, Slovakia, Sweden, the USA and the United Kingdom)

A total of 1300 patients entered a 2-week Screening period, 1072 entered the qualifying 2-week Run-in period and 558 of them were randomised. Two patients randomised to placebo never took the study medication.

Participant milestones

Participant milestones
Measure	Ibodutant 10 mg Oral tablet to be given once daily for 24 weeks of treatment. Patients randomised to the ibodutant 10 mg arm will continue on ibodutant 10 mg for additional 28 weeks of treatment via mock-re-randomisation at week 25 . Ibodutant 10 mg: Oral tablet, to be given once daily.	Placebo Oral tablet to be given once daily for 24 weeks of treatment. Patients randomised to the placebo arm will be re-randomised at week 25 in a 1:1 ratio to ibodutant or placebo for additional 28 weeks of treatment. Placebo: Oral tablet (identical in appearance and weight to ibodutant tablets) to be given once daily.
Overall Study STARTED	277	279
Overall Study COMPLETED	161	160
Overall Study NOT COMPLETED	116	119

Reasons for withdrawal

Reasons for withdrawal
Measure	Ibodutant 10 mg Oral tablet to be given once daily for 24 weeks of treatment. Patients randomised to the ibodutant 10 mg arm will continue on ibodutant 10 mg for additional 28 weeks of treatment via mock-re-randomisation at week 25 . Ibodutant 10 mg: Oral tablet, to be given once daily.	Placebo Oral tablet to be given once daily for 24 weeks of treatment. Patients randomised to the placebo arm will be re-randomised at week 25 in a 1:1 ratio to ibodutant or placebo for additional 28 weeks of treatment. Placebo: Oral tablet (identical in appearance and weight to ibodutant tablets) to be given once daily.
Overall Study Adverse Event	4	5
Overall Study Lack of Efficacy	3	5
Overall Study Lost to Follow-up	5	13
Overall Study Other	4	0
Overall Study Physician Decision	4	3
Overall Study Protocol Violation	18	21
Overall Study Study terminated by Sponsor	45	47
Overall Study Withdrawal by Subject	33	25

Baseline Characteristics

52-Week Efficacy and Safety Study of Ibodutant in Women With Irritable Bowel Syndrome With Diarrhea (IBS-D)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ibodutant 10 mg n=277 Participants Oral tablet to be given once daily for 24 weeks of treatment. Patients randomised to the ibodutant 10 mg arm will continue on ibodutant 10 mg for additional 28 weeks of treatment via mock-re-randomisation at week 25 . Ibodutant 10 mg: Oral tablet, to be given once daily.	Placebo n=279 Participants Oral tablet to be given once daily for 24 weeks of treatment. Patients randomised to the placebo arm will be re-randomised at week 25 in a 1:1 ratio to ibodutant or placebo for additional 28 weeks of treatment. Placebo: Oral tablet, (identical in appearance and weight to ibodutant tablets), to be given once daily.	Total n=556 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	269 Participants n=5 Participants	269 Participants n=7 Participants	538 Participants n=5 Participants
Age, Categorical >=65 years	8 Participants n=5 Participants	10 Participants n=7 Participants	18 Participants n=5 Participants
Age, Continuous	42.6 years STANDARD_DEVIATION 12.2 • n=5 Participants	43.8 years STANDARD_DEVIATION 11.8 • n=7 Participants	43.2 years STANDARD_DEVIATION 12.0 • n=5 Participants
Sex: Female, Male Female	277 Participants n=5 Participants	279 Participants n=7 Participants	556 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	124 Participants n=5 Participants	131 Participants n=7 Participants	255 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	153 Participants n=5 Participants	148 Participants n=7 Participants	301 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	32 Participants n=5 Participants	28 Participants n=7 Participants	60 Participants n=5 Participants
Race (NIH/OMB) White	241 Participants n=5 Participants	247 Participants n=7 Participants	488 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Geographic Region Eastern Europe	35 Participants n=5 Participants	30 Participants n=7 Participants	65 Participants n=5 Participants
Geographic Region North America	211 Participants n=5 Participants	214 Participants n=7 Participants	425 Participants n=5 Participants
Geographic Region Western Europe	31 Participants n=5 Participants	35 Participants n=7 Participants	66 Participants n=5 Participants
Body Mass Index, Continuous	29.6 kg/m² STANDARD_DEVIATION 6.92 • n=5 Participants	29.6 kg/m² STANDARD_DEVIATION 7.02 • n=7 Participants	29.6 kg/m² STANDARD_DEVIATION 6.96 • n=5 Participants
Abdominal Pain Severity, Categorical Abdominal Pain Severity < 5	55 Participants n=5 Participants	54 Participants n=7 Participants	109 Participants n=5 Participants
Abdominal Pain Severity, Categorical Abdominal Pain Severity ≥ 5 and < 8	172 Participants n=5 Participants	172 Participants n=7 Participants	344 Participants n=5 Participants
Abdominal Pain Severity, Categorical Abdominal Pain Severity ≥ 8	50 Participants n=5 Participants	53 Participants n=7 Participants	103 Participants n=5 Participants
IBS-Signs and Symptoms Score, Categorical Mild IBS	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
IBS-Signs and Symptoms Score, Categorical Moderate IBS	60 Participants n=5 Participants	58 Participants n=7 Participants	118 Participants n=5 Participants
IBS-Signs and Symptoms Score, Categorical Severe IBS	210 Participants n=5 Participants	214 Participants n=7 Participants	424 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks

Population: Modified ITT (mITT) Population: all patients included in the ITT population excluding patients from site 00179 (N=48), where a potential serious breach of Good Clinical Practice was reported, and site 00186 (N=34), where disqualification proceedings against the Investigator were initiated by the US Food and Drug Administration.

Outcome measures

Outcome measures
Measure	Ibodutant 10 mg n=236 Participants Oral tablet to be given once daily for 24 weeks of treatment. Patients randomised to the ibodutant 10 mg arm will continue on ibodutant 10 mg for additional 28 weeks of treatment via mock-re-randomisation at week 25 . Ibodutant 10 mg: Oral tablet, to be given once daily.	Placebo n=238 Participants Oral tablet to be given once daily for 24 weeks of treatment. Patients randomised to the placebo arm will be re-randomised at week 25 in a 1:1 ratio to ibodutant or placebo for additional 28 weeks of treatment. Placebo: Oral tablet, (identical in appearance and weight to ibodutant tablets), to be given once daily.
Weekly Response for Abdominal Pain Intensity AND Stool Consistency Over the First 24 Weeks of Treatment in at Least 50% of the Weeks of Treatment (12 Out of 24 Weeks).	51 Participants	52 Participants

SECONDARY outcome

Timeframe: 24 weeks

The patient will be considered a weekly abdominal pain responder if she meets the following criterion: * Decrease in weekly average of worst abdominal pain score in the past 24 hours of at least 30% compared with baseline.

Outcome measures

Outcome measures
Measure	Ibodutant 10 mg n=236 Participants Oral tablet to be given once daily for 24 weeks of treatment. Patients randomised to the ibodutant 10 mg arm will continue on ibodutant 10 mg for additional 28 weeks of treatment via mock-re-randomisation at week 25 . Ibodutant 10 mg: Oral tablet, to be given once daily.	Placebo n=238 Participants Oral tablet to be given once daily for 24 weeks of treatment. Patients randomised to the placebo arm will be re-randomised at week 25 in a 1:1 ratio to ibodutant or placebo for additional 28 weeks of treatment. Placebo: Oral tablet, (identical in appearance and weight to ibodutant tablets), to be given once daily.
Weekly Response for Abdominal Pain Intensity Over the First 24 Weeks of Treatment in at Least 50% of the Weeks of Treatment (12 Out of 24 Weeks).	96 Participants	83 Participants

SECONDARY outcome

Timeframe: 24 weeks

The patient was considered a weekly stool consistency responder if she met the following criterion: * Decrease of at least 50% in the number of days per week with at least one stool that has a consistency of Type 6 or 7 compared with baseline.

Outcome measures

Outcome measures
Measure	Ibodutant 10 mg n=236 Participants Oral tablet to be given once daily for 24 weeks of treatment. Patients randomised to the ibodutant 10 mg arm will continue on ibodutant 10 mg for additional 28 weeks of treatment via mock-re-randomisation at week 25 . Ibodutant 10 mg: Oral tablet, to be given once daily.	Placebo n=238 Participants Oral tablet to be given once daily for 24 weeks of treatment. Patients randomised to the placebo arm will be re-randomised at week 25 in a 1:1 ratio to ibodutant or placebo for additional 28 weeks of treatment. Placebo: Oral tablet, (identical in appearance and weight to ibodutant tablets), to be given once daily.
Weekly Response for Stool Consistency Over the First 24 Weeks of Treatment in at Least 50% of the Weeks of Treatment (12 Out of 24 Weeks).	72 Participants	71 Participants

SECONDARY outcome

Timeframe: 24 weeks

The patient was considered a weekly responder if she has an IBS degree-of-relief equal to "completely relieved/improved" or "considerably relieved/improved". Weekly e-diary assessment of IBS degree-of-relief of overall on signs or symptoms over the last 7 days was collected using a balanced 7-point Likert scale with 1= Completely relieved/improved, 2= Considerably relieved/improved, 3=Somewhat relieved/improved, 4= Unchanged, 5= Somewhat worse, 6=Considerably worse, 7= As bad as I can imagine.

Outcome measures

Outcome measures
Measure	Ibodutant 10 mg n=236 Participants Oral tablet to be given once daily for 24 weeks of treatment. Patients randomised to the ibodutant 10 mg arm will continue on ibodutant 10 mg for additional 28 weeks of treatment via mock-re-randomisation at week 25 . Ibodutant 10 mg: Oral tablet, to be given once daily.	Placebo n=238 Participants Oral tablet to be given once daily for 24 weeks of treatment. Patients randomised to the placebo arm will be re-randomised at week 25 in a 1:1 ratio to ibodutant or placebo for additional 28 weeks of treatment. Placebo: Oral tablet, (identical in appearance and weight to ibodutant tablets), to be given once daily.
Weekly Response for Relief of Overall IBS Signs and Symptoms Over the First 24 Weeks of Treatment in at Least 50% of the Weeks (12 Out of 24)	37 Participants	29 Participants

SECONDARY outcome

Timeframe: 24 weeks

Weekly response for abdominal pain intensity AND stool consistency over the first 24 weeks of treatment in at least 50% of the weeks of treatment (12 out of 24 weeks) with at least 2 weeks of response in the last 4 weeks of treatment (week 21 to 24). The patient will be considered a weekly responder as defined for the primary endpoint.

Outcome measures

Outcome measures
Measure	Ibodutant 10 mg n=236 Participants Oral tablet to be given once daily for 24 weeks of treatment. Patients randomised to the ibodutant 10 mg arm will continue on ibodutant 10 mg for additional 28 weeks of treatment via mock-re-randomisation at week 25 . Ibodutant 10 mg: Oral tablet, to be given once daily.	Placebo n=238 Participants Oral tablet to be given once daily for 24 weeks of treatment. Patients randomised to the placebo arm will be re-randomised at week 25 in a 1:1 ratio to ibodutant or placebo for additional 28 weeks of treatment. Placebo: Oral tablet, (identical in appearance and weight to ibodutant tablets), to be given once daily.
Sustained Analysis of Response for Abdominal Pain AND Stool Consistency Over First 24-week Double-blind Treatment Period	50 Participants	45 Participants

Adverse Events

Ibodutant 10 mg for 24-week Treatment

Serious events: 3 serious events

Other events: 75 other events

Deaths: 0 deaths

Placebo for 24-week Treatment

Serious events: 2 serious events

Other events: 82 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ibodutant 10 mg for 24-week Treatment n=277 participants at risk Oral tablet to be given once daily for 24 weeks of treatment. Ibodutant 10 mg: Oral tablet, to be given once daily.	Placebo for 24-week Treatment n=279 participants at risk Oral tablet to be given once daily for 24 weeks of treatment. Placebo: Oral tablet, (identical in appearance and weight to ibodutant tablets), to be given once daily.
Musculoskeletal and connective tissue disorders Cervical spinal stenosis	0.36% 1/277 • Number of events 1 • Adverse Events were reported for the safety population (all enrolled patients who received at least 1 dose of study drug) over a period of 24 weeks (first 24-week double-blind treatment period). AEs were categorized as Treatment-Emergent Signs and Symptoms (TESS) or Non-TESS for each of the study periods based on the onset date/time of AE. Number of events and number of patients (%) are presented by System Organ Class (SOC) and Preferred Term (PT). All serious TESS are reported for patients in any arm for the first 24-week period. No change in incidence of serious TESS was observed over the entire 52-weeks of study treatment with respect to the first 24-week treatment period.	0.00% 0/279 • Adverse Events were reported for the safety population (all enrolled patients who received at least 1 dose of study drug) over a period of 24 weeks (first 24-week double-blind treatment period). AEs were categorized as Treatment-Emergent Signs and Symptoms (TESS) or Non-TESS for each of the study periods based on the onset date/time of AE. Number of events and number of patients (%) are presented by System Organ Class (SOC) and Preferred Term (PT). All serious TESS are reported for patients in any arm for the first 24-week period. No change in incidence of serious TESS was observed over the entire 52-weeks of study treatment with respect to the first 24-week treatment period.
Injury, poisoning and procedural complications Post-traumatic neck syndrome	0.00% 0/277 • Adverse Events were reported for the safety population (all enrolled patients who received at least 1 dose of study drug) over a period of 24 weeks (first 24-week double-blind treatment period). AEs were categorized as Treatment-Emergent Signs and Symptoms (TESS) or Non-TESS for each of the study periods based on the onset date/time of AE. Number of events and number of patients (%) are presented by System Organ Class (SOC) and Preferred Term (PT). All serious TESS are reported for patients in any arm for the first 24-week period. No change in incidence of serious TESS was observed over the entire 52-weeks of study treatment with respect to the first 24-week treatment period.	0.36% 1/279 • Number of events 1 • Adverse Events were reported for the safety population (all enrolled patients who received at least 1 dose of study drug) over a period of 24 weeks (first 24-week double-blind treatment period). AEs were categorized as Treatment-Emergent Signs and Symptoms (TESS) or Non-TESS for each of the study periods based on the onset date/time of AE. Number of events and number of patients (%) are presented by System Organ Class (SOC) and Preferred Term (PT). All serious TESS are reported for patients in any arm for the first 24-week period. No change in incidence of serious TESS was observed over the entire 52-weeks of study treatment with respect to the first 24-week treatment period.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/277 • Adverse Events were reported for the safety population (all enrolled patients who received at least 1 dose of study drug) over a period of 24 weeks (first 24-week double-blind treatment period). AEs were categorized as Treatment-Emergent Signs and Symptoms (TESS) or Non-TESS for each of the study periods based on the onset date/time of AE. Number of events and number of patients (%) are presented by System Organ Class (SOC) and Preferred Term (PT). All serious TESS are reported for patients in any arm for the first 24-week period. No change in incidence of serious TESS was observed over the entire 52-weeks of study treatment with respect to the first 24-week treatment period.	0.36% 1/279 • Number of events 1 • Adverse Events were reported for the safety population (all enrolled patients who received at least 1 dose of study drug) over a period of 24 weeks (first 24-week double-blind treatment period). AEs were categorized as Treatment-Emergent Signs and Symptoms (TESS) or Non-TESS for each of the study periods based on the onset date/time of AE. Number of events and number of patients (%) are presented by System Organ Class (SOC) and Preferred Term (PT). All serious TESS are reported for patients in any arm for the first 24-week period. No change in incidence of serious TESS was observed over the entire 52-weeks of study treatment with respect to the first 24-week treatment period.
Nervous system disorders Occipital neuralgia	0.36% 1/277 • Number of events 1 • Adverse Events were reported for the safety population (all enrolled patients who received at least 1 dose of study drug) over a period of 24 weeks (first 24-week double-blind treatment period). AEs were categorized as Treatment-Emergent Signs and Symptoms (TESS) or Non-TESS for each of the study periods based on the onset date/time of AE. Number of events and number of patients (%) are presented by System Organ Class (SOC) and Preferred Term (PT). All serious TESS are reported for patients in any arm for the first 24-week period. No change in incidence of serious TESS was observed over the entire 52-weeks of study treatment with respect to the first 24-week treatment period.	0.00% 0/279 • Adverse Events were reported for the safety population (all enrolled patients who received at least 1 dose of study drug) over a period of 24 weeks (first 24-week double-blind treatment period). AEs were categorized as Treatment-Emergent Signs and Symptoms (TESS) or Non-TESS for each of the study periods based on the onset date/time of AE. Number of events and number of patients (%) are presented by System Organ Class (SOC) and Preferred Term (PT). All serious TESS are reported for patients in any arm for the first 24-week period. No change in incidence of serious TESS was observed over the entire 52-weeks of study treatment with respect to the first 24-week treatment period.
Renal and urinary disorders Nephrolithiasis	0.36% 1/277 • Number of events 1 • Adverse Events were reported for the safety population (all enrolled patients who received at least 1 dose of study drug) over a period of 24 weeks (first 24-week double-blind treatment period). AEs were categorized as Treatment-Emergent Signs and Symptoms (TESS) or Non-TESS for each of the study periods based on the onset date/time of AE. Number of events and number of patients (%) are presented by System Organ Class (SOC) and Preferred Term (PT). All serious TESS are reported for patients in any arm for the first 24-week period. No change in incidence of serious TESS was observed over the entire 52-weeks of study treatment with respect to the first 24-week treatment period.	0.00% 0/279 • Adverse Events were reported for the safety population (all enrolled patients who received at least 1 dose of study drug) over a period of 24 weeks (first 24-week double-blind treatment period). AEs were categorized as Treatment-Emergent Signs and Symptoms (TESS) or Non-TESS for each of the study periods based on the onset date/time of AE. Number of events and number of patients (%) are presented by System Organ Class (SOC) and Preferred Term (PT). All serious TESS are reported for patients in any arm for the first 24-week period. No change in incidence of serious TESS was observed over the entire 52-weeks of study treatment with respect to the first 24-week treatment period.
Respiratory, thoracic and mediastinal disorders Dyspnoe	0.00% 0/277 • Adverse Events were reported for the safety population (all enrolled patients who received at least 1 dose of study drug) over a period of 24 weeks (first 24-week double-blind treatment period). AEs were categorized as Treatment-Emergent Signs and Symptoms (TESS) or Non-TESS for each of the study periods based on the onset date/time of AE. Number of events and number of patients (%) are presented by System Organ Class (SOC) and Preferred Term (PT). All serious TESS are reported for patients in any arm for the first 24-week period. No change in incidence of serious TESS was observed over the entire 52-weeks of study treatment with respect to the first 24-week treatment period.	0.36% 1/279 • Number of events 1 • Adverse Events were reported for the safety population (all enrolled patients who received at least 1 dose of study drug) over a period of 24 weeks (first 24-week double-blind treatment period). AEs were categorized as Treatment-Emergent Signs and Symptoms (TESS) or Non-TESS for each of the study periods based on the onset date/time of AE. Number of events and number of patients (%) are presented by System Organ Class (SOC) and Preferred Term (PT). All serious TESS are reported for patients in any arm for the first 24-week period. No change in incidence of serious TESS was observed over the entire 52-weeks of study treatment with respect to the first 24-week treatment period.

Other adverse events

Additional Information

Angela Capriati, MD PhD - Corporate Director Clinical Research

MENARINI Group

Phone: +39 055 5680

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Prior to submitting the results of this study for publication or presentation, the Investigator will allow the sponsor at least 30 days time to review and comment upon the publication manuscript. It is agreed, that the results of the study will not be submitted for presentation, abstract, poster exhibition, or publication by the investigator until Menarini Ricerche S.p.A. has reviewed/commented and agreed to any publication.
Publication restrictions are in place

Restriction type: OTHER