Trial Outcomes & Findings for Ibodutant for Relief of Irritable Bowel Syndrome With Diarrhoea (IBS-D) (NCT NCT01303224)

Last Updated: 2015-10-07

Results Overview

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)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

565 participants

Primary outcome timeframe

Eight weeks

Results posted on

2015-10-07

Participant Flow

First subject screened 06/10/2010, first subject randomised 22/10/2010, last subject out 11/05/2012, at 78 study sites in 8 European countries (Bulgaria, Czech Republic, Denmark, Germany, Italy, Poland, Spain, and Sweden)

A run-in period was planned to confirm eligibility criteria. 5 more patients were randomized instead of the planned number (560) because due to the high screen fail rate it was impossible to predict with how many patients the enrollment goal would be reached. Although the enrollment goal was reached these 5 patients in screening continued the study

Participant milestones

Participant milestones
Measure	Ibodutant 1 mg oral tablet, once daily	Ibodutant 3 mg oral tablet, once daily	Ibodutant 10 mg oral tablet, once daily	Placebo oral tablet, once daily
Overall Study STARTED	141	142	139	143
Overall Study Intention To Treat	140	138	139	142
Overall Study COMPLETED	130	131	133	133
Overall Study NOT COMPLETED	11	11	6	10

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Ibodutant for Relief of Irritable Bowel Syndrome With Diarrhoea (IBS-D)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ibodutant 1 mg n=140 Participants oral tablet, once daily	Ibodutant 3 mg n=138 Participants oral tablet, once daily	Ibodutant 10 mg n=139 Participants oral tablet, once daily	Placebo n=142 Participants oral tablet, once daily	Total n=559 Participants Total of all reporting groups
Age, Continuous	45.9 years STANDARD_DEVIATION 13.7 • n=5 Participants	47.1 years STANDARD_DEVIATION 13.4 • n=7 Participants	47.0 years STANDARD_DEVIATION 12.8 • n=5 Participants	44.1 years STANDARD_DEVIATION 14.0 • n=4 Participants	46.0 years STANDARD_DEVIATION 13.5 • n=21 Participants
Sex: Female, Male Female	89 Participants n=5 Participants	87 Participants n=7 Participants	79 Participants n=5 Participants	78 Participants n=4 Participants	333 Participants n=21 Participants
Sex: Female, Male Male	51 Participants n=5 Participants	51 Participants n=7 Participants	60 Participants n=5 Participants	64 Participants n=4 Participants	226 Participants n=21 Participants
Time since onset of IBS symptoms	6.2 years STANDARD_DEVIATION 7.3 • n=5 Participants	6.3 years STANDARD_DEVIATION 7.5 • n=7 Participants	6.3 years STANDARD_DEVIATION 6.9 • n=5 Participants	4.6 years STANDARD_DEVIATION 6.2 • n=4 Participants	5.8 years STANDARD_DEVIATION 7.0 • n=21 Participants
IBS symptoms at baseline/ randomisation) Abdominal pain score	2.5 Scores on a scale STANDARD_DEVIATION 0.6 • n=5 Participants	2.3 Scores on a scale STANDARD_DEVIATION 0.5 • n=7 Participants	2.3 Scores on a scale STANDARD_DEVIATION 0.5 • n=5 Participants	2.3 Scores on a scale STANDARD_DEVIATION 0.6 • n=4 Participants	2.3 Scores on a scale STANDARD_DEVIATION 0.5 • n=21 Participants
IBS symptoms at baseline/ randomisation) Bloating score	2.4 Scores on a scale STANDARD_DEVIATION 0.8 • n=5 Participants	2.2 Scores on a scale STANDARD_DEVIATION 0.7 • n=7 Participants	2.2 Scores on a scale STANDARD_DEVIATION 0.7 • n=5 Participants	2.2 Scores on a scale STANDARD_DEVIATION 0.6 • n=4 Participants	2.3 Scores on a scale STANDARD_DEVIATION 0.7 • n=21 Participants
IBS symptoms at baseline/ randomisation) Urgency score	2.5 Scores on a scale STANDARD_DEVIATION 0.7 • n=5 Participants	2.5 Scores on a scale STANDARD_DEVIATION 0.6 • n=7 Participants	2.4 Scores on a scale STANDARD_DEVIATION 0.6 • n=5 Participants	2.4 Scores on a scale STANDARD_DEVIATION 0.6 • n=4 Participants	2.4 Scores on a scale STANDARD_DEVIATION 0.7 • n=21 Participants
IBS symptoms at baseline/ randomisation) IBS symptom severity rate	2.7 Scores on a scale STANDARD_DEVIATION 0.7 • n=5 Participants	2.6 Scores on a scale STANDARD_DEVIATION 0.6 • n=7 Participants	2.6 Scores on a scale STANDARD_DEVIATION 0.6 • n=5 Participants	2.6 Scores on a scale STANDARD_DEVIATION 0.6 • n=4 Participants	2.7 Scores on a scale STANDARD_DEVIATION 0.6 • n=21 Participants
Stool frequency/day	4.6 bowel movements/day STANDARD_DEVIATION 1.5 • n=5 Participants	4.4 bowel movements/day STANDARD_DEVIATION 1.3 • n=7 Participants	4.4 bowel movements/day STANDARD_DEVIATION 1.5 • n=5 Participants	4.4 bowel movements/day STANDARD_DEVIATION 1.2 • n=4 Participants	4.5 bowel movements/day STANDARD_DEVIATION 1.4 • n=21 Participants
Stool consistency	5.7 Scores on a scale STANDARD_DEVIATION 0.6 • n=5 Participants	5.7 Scores on a scale STANDARD_DEVIATION 0.5 • n=7 Participants	5.7 Scores on a scale STANDARD_DEVIATION 0.6 • n=5 Participants	5.7 Scores on a scale STANDARD_DEVIATION 0.6 • n=4 Participants	5.7 Scores on a scale STANDARD_DEVIATION 0.6 • n=21 Participants
IBS-Symptom Severity Scale score	343.4 Scores on a scale STANDARD_DEVIATION 68.8 • n=5 Participants	333.3 Scores on a scale STANDARD_DEVIATION 78.3 • n=7 Participants	332.6 Scores on a scale STANDARD_DEVIATION 74.3 • n=5 Participants	335.7 Scores on a scale STANDARD_DEVIATION 69.4 • n=4 Participants	336.3 Scores on a scale STANDARD_DEVIATION 72.7 • n=21 Participants
European Quality of Life Questionnaire 5D (EQ-5D) QoL VAS	54.5 Scores on a scale STANDARD_DEVIATION 22.9 • n=5 Participants	55.5 Scores on a scale STANDARD_DEVIATION 21.9 • n=7 Participants	58.1 Scores on a scale STANDARD_DEVIATION 22.9 • n=5 Participants	55.3 Scores on a scale STANDARD_DEVIATION 22.3 • n=4 Participants	55.8 Scores on a scale STANDARD_DEVIATION 22.5 • n=21 Participants

PRIMARY outcome

Timeframe: Eight weeks

Population: Intention-to-Treat (559)

Outcome measures

Outcome measures
Measure	Ibodutant 1 mg n=140 Participants oral tablet, once daily	Ibodutant 3 mg n=138 Participants oral tablet, once daily	Ibodutant 10 mg n=139 Participants oral tablet, once daily	Placebo n=142 Participants oral tablet, once daily
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); Intention-to-treat (ITT). Responders according to the 75% rule/"Yes"	45 participants	46 participants	55 participants	39 participants
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); Intention-to-treat (ITT). Responders according to the 75% rule/"No"	95 participants	92 participants	84 participants	103 participants

SECONDARY outcome

Timeframe: Eight weeks

Population: Intention-to-Treat (559)

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)

Outcome measures

Outcome measures
Measure	Ibodutant 1 mg n=140 Participants oral tablet, once daily	Ibodutant 3 mg n=138 Participants oral tablet, once daily	Ibodutant 10 mg n=139 Participants oral tablet, once daily	Placebo n=142 Participants oral tablet, once daily
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 4 Weeks With Satisfactory Relief During 8 Weeks of Treatment (50% Rule) in the ITT Population Responders according to the 50% rule/"Yes"	72 participants	61 participants	74 participants	55 participants
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 4 Weeks With Satisfactory Relief During 8 Weeks of Treatment (50% Rule) in the ITT Population Responders according to the 50% rule/"No"	68 participants	77 participants	65 participants	87 participants

SECONDARY outcome

Timeframe: Eight weeks

Population: Intention-to-treat; i.e. all ITT patients who provided EQ-5D data at Visit 2 (start of treatment) and Visit 4 (end of treatment).

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.

Outcome measures

Outcome measures
Measure	Ibodutant 1 mg n=131 Participants oral tablet, once daily	Ibodutant 3 mg n=133 Participants oral tablet, once daily	Ibodutant 10 mg n=133 Participants oral tablet, once daily	Placebo n=131 Participants oral tablet, once daily
Quality of Life Changes (Using EuroQoL EQ-5D Questionnaire) Baseline (randomisation)	56.4 units on a scale Standard Deviation 20.6	58.2 units on a scale Standard Deviation 22.0	57.2 units on a scale Standard Deviation 22.0	58.7 units on a scale Standard Deviation 21.5
Quality of Life Changes (Using EuroQoL EQ-5D Questionnaire) Visit 4	71.3 units on a scale Standard Deviation 17.2	72.1 units on a scale Standard Deviation 18.7	66.7 units on a scale Standard Deviation 20.7	72.2 units on a scale Standard Deviation 17.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Eight weeks

Population: Intention-to-Treat in the female population (333)

Outcome measures

Outcome measures
Measure	Ibodutant 1 mg n=89 Participants oral tablet, once daily	Ibodutant 3 mg n=87 Participants oral tablet, once daily	Ibodutant 10 mg n=79 Participants oral tablet, once daily	Placebo n=78 Participants oral tablet, once daily
Subgroup Analysis: Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort According to the 75% Rule in the Female ITT Population Responders according to 75% rule/"No"	57 participants	52 participants	42 participants	59 participants
Subgroup Analysis: Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort According to the 75% Rule in the Female ITT Population Responders according to 75% rule/"Yes"	32 participants	35 participants	37 participants	19 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Eight weeks

Population: Intention-to-Treat in the male population (226)

Outcome measures

Outcome measures
Measure	Ibodutant 1 mg n=51 Participants oral tablet, once daily	Ibodutant 3 mg n=51 Participants oral tablet, once daily	Ibodutant 10 mg n=60 Participants oral tablet, once daily	Placebo n=64 Participants oral tablet, once daily
Subgroup Analysis: Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort According to the 75% Rule in the Male ITT Population Responders according to the 75% rule/"Yes"	13 participants	11 participants	18 participants	20 participants
Subgroup Analysis: Response for Relief of Overall IBS Symptoms and of Abdominal Pain/Discomfort According to the 75% Rule in the Male ITT Population Responders according to the 75% rule/"No"	38 participants	40 participants	42 participants	44 participants

Adverse Events

Ibodutant 1 mg

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Ibodutant 3 mg

Serious events: 1 serious events

Other events: 19 other events

Deaths: 0 deaths

Ibodutant 10 mg

Serious events: 1 serious events

Other events: 29 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ibodutant 1 mg n=141 participants at risk oral tablet, once daily	Ibodutant 3 mg n=142 participants at risk oral tablet, once daily	Ibodutant 10 mg n=139 participants at risk oral tablet, once daily	Placebo n=143 participants at risk oral tablet, once daily
Eye disorders Mydriasis	0.00% 0/141 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	0.00% 0/142 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	0.00% 0/139 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	0.70% 1/143 • Number of events 1 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).
Metabolism and nutrition disorders Diabetes Mellitus type II	0.00% 0/141 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	0.00% 0/142 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	0.72% 1/139 • Number of events 1 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	0.00% 0/143 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).
Infections and infestations Acute Appendicitis	0.00% 0/141 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	0.70% 1/142 • Number of events 1 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	0.00% 0/139 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	0.00% 0/143 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).
Gastrointestinal disorders Worsened Abdominal Pain	0.00% 0/141 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	0.00% 0/142 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	0.00% 0/139 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	0.70% 1/143 • Number of events 1 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterus Myomatosus	0.00% 0/141 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	0.00% 0/142 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	0.00% 0/139 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	0.70% 1/143 • Number of events 1 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).

Other adverse events

Other adverse events
Measure	Ibodutant 1 mg n=141 participants at risk oral tablet, once daily	Ibodutant 3 mg n=142 participants at risk oral tablet, once daily	Ibodutant 10 mg n=139 participants at risk oral tablet, once daily	Placebo n=143 participants at risk oral tablet, once daily
Gastrointestinal disorders Abdominal pain	0.71% 1/141 • Number of events 1 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	1.4% 2/142 • Number of events 2 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	0.00% 0/139 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	2.1% 3/143 • Number of events 4 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).
Gastrointestinal disorders Nausea	0.71% 1/141 • Number of events 1 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	2.8% 4/142 • Number of events 4 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	3.6% 5/139 • Number of events 5 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	2.1% 3/143 • Number of events 3 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).
Infections and infestations Gastroenteritis	0.00% 0/141 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	1.4% 2/142 • Number of events 2 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	2.2% 3/139 • Number of events 3 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	0.00% 0/143 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).
Infections and infestations Influenza	0.00% 0/141 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	1.4% 2/142 • Number of events 2 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	2.2% 3/139 • Number of events 3 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	3.5% 5/143 • Number of events 5 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).
Infections and infestations Nasopharyngitis	3.5% 5/141 • Number of events 6 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	2.8% 4/142 • Number of events 4 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	3.6% 5/139 • Number of events 5 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	2.1% 3/143 • Number of events 3 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).
Infections and infestations Upper Respiratory Tract Infection	0.00% 0/141 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	0.00% 0/142 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	2.2% 3/139 • Number of events 3 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	0.70% 1/143 • Number of events 1 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).
Investigations Blood Creatine Phosphokinase Increased	2.1% 3/141 • Number of events 3 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	0.00% 0/142 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	0.72% 1/139 • Number of events 1 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	0.70% 1/143 • Number of events 1 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).
Nervous system disorders Dizziness	2.1% 3/141 • Number of events 3 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	1.4% 2/142 • Number of events 2 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	0.72% 1/139 • Number of events 1 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	0.00% 0/143 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).
Nervous system disorders Headache	5.0% 7/141 • Number of events 7 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	2.1% 3/142 • Number of events 3 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	5.8% 8/139 • Number of events 11 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).	2.8% 4/143 • Number of events 4 • 8 weeks for Treatment Emergent Signs and Symptoms (TESS) 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).

Additional Information

Angela Capriati MD PhD, Corporate Director of Clinical Research

Menarini Ricerche S.p.A.

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 PI will allow Sponsor at least 60 days time to review and comment upon the publication manuscript. No publication of PI is permitted before the overall publication of the multicentre study made by the Sponsor (or its designee), unless said overall publication is not made within 18 months from the completion of the Final Study Report.
Publication restrictions are in place

Restriction type: OTHER