Trial Outcomes & Findings for Effect of ITF2357 on Mucosal Healing in Patients With Moderate-to-severe Active Crohn's Disease (NCT NCT00792740)

NCT ID: NCT00792740

Last Updated: 2023-07-19

Results Overview

The outcome is assessed by endoscopy, in patients with endoscopic and clinical evidence of active moderate-to-severe Crohn's disease not controlled by conventional therapies. The outcome measure defines the rate of patients achieving complete healing in ITT population, i.e disappearance of mucosal ulceration, obtained with ITF2357 treatment.

• Recruitment status: TERMINATED
• Study phase: PHASE1/PHASE2
• Target enrollment: 51 participants
• Primary outcome timeframe: At week 8
• Results posted on: 2023-07-19

Participant Flow

Fifty-one (51) subjects were enrolled in the study, as planned, and 37 of them completed the study as per protocol.

Participant milestones

Measure	Placebo Oral matching placebo capsules, administered bid. Placebo: Placebo will be supplied as matching capsules for oral administration with the same outer appearance of the study drug and with the same dosing scheme (one capsule in the morning and one in the evening)	ITF2357 Oral ITF2357 50 mg bid ITF2357: ITF2357 was administered as hard gelatin capsules for oral administration at the dose strength of 50 mg. Capsules were administered as follow: one capsule in the morning and one in the evening.
Overall Study STARTED	26	25
Overall Study COMPLETED	19	18
Overall Study NOT COMPLETED	7	7

Reasons for withdrawal

Measure	Placebo Oral matching placebo capsules, administered bid. Placebo: Placebo will be supplied as matching capsules for oral administration with the same outer appearance of the study drug and with the same dosing scheme (one capsule in the morning and one in the evening)	ITF2357 Oral ITF2357 50 mg bid ITF2357: ITF2357 was administered as hard gelatin capsules for oral administration at the dose strength of 50 mg. Capsules were administered as follow: one capsule in the morning and one in the evening.
Overall Study Disease Worsening	3	2
Overall Study Personal Reason	1	0
Overall Study Adverse Event	1	3
Overall Study Patient's withdrawal of consent	0	1
Overall Study Termination of the trial by the Sponsor	2	0
Overall Study Other reasons	0	1

Baseline Characteristics

Effect of ITF2357 on Mucosal Healing in Patients With Moderate-to-severe Active Crohn's Disease

Baseline characteristics by cohort

Measure	Placebo n=26 Participants Oral matching placebo capsules, administered bid. Placebo: Placebo will be supplied as matching capsules for oral administration with the same outer appearance of the study drug and with the same dosing scheme (one capsule in the morning and one in the evening)	ITF2357 n=25 Participants Oral ITF2357 50 mg bid ITF2357: ITF2357 was administered as hard gelatin capsules for oral administration at the dose strength of 50 mg. Capsules were administered as follow: one capsule in the morning and one in the evening.	Total n=51 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	26 Participants n=5 Participants	24 Participants n=7 Participants	50 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	14 Participants n=7 Participants	30 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	11 Participants n=7 Participants	21 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	26 Participants n=5 Participants	25 Participants n=7 Participants	51 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: At week 8

Population: ITT: population included all randomized patients who took at least one dose of study treatment.

The outcome is assessed by endoscopy, in patients with endoscopic and clinical evidence of active moderate-to-severe Crohn's disease not controlled by conventional therapies.

The outcome measure defines the rate of patients achieving complete healing in ITT population, i.e disappearance of mucosal ulceration, obtained with ITF2357 treatment.

Outcome measures

Measure	Placebo n=26 Participants Oral matching placebo capsules, administered bid. Placebo: Placebo will be supplied as matching capsules for oral administration with the same outer appearance of the study drug and with the same dosing scheme (one capsule in the morning and one in the evening)	ITF2357 n=25 Participants Oral ITF2357 50 mg bid ITF2357: ITF2357 was administered as hard gelatin capsules for oral administration at the dose strength of 50 mg. Capsules were administered as follow: one capsule in the morning and one in the evening.
Number of Patients Achieving Complete Healing of Mucosal Ulcerations of Ileum and/or Colon	0 Participants	1 Participants

SECONDARY outcome

Timeframe: At Week 8

Population: ITT population included all randomized patients who took at least one dose of study treatment.

CDEIS (Crohn's Disease Endoscopic Index of Severity) is an index for determining the severity of Crohn's disease with endoscopic localization to ileum and colon; A patient was defined 'fully endoscopic remissed' whether the CDEIS score at week 8 was equal or lower than three points

CDEIS score considers 4 parameters, each one evaluated in 5 pre-defined segments of the colon.

The score can be calculated even in case of incomplete investigations, as the results of the individual segments are divided by the number of segments investigated.

Score Scale:

< 3 remission; 3 - 8 mild endoscopic activity; 9 - 12 moderate endoscopic activity; > 12 severe endoscopic activity.

The higher the score, the worse is patient's situation.

Outcome measures

Measure	Placebo n=26 Participants Oral matching placebo capsules, administered bid. Placebo: Placebo will be supplied as matching capsules for oral administration with the same outer appearance of the study drug and with the same dosing scheme (one capsule in the morning and one in the evening)	ITF2357 n=25 Participants Oral ITF2357 50 mg bid ITF2357: ITF2357 was administered as hard gelatin capsules for oral administration at the dose strength of 50 mg. Capsules were administered as follow: one capsule in the morning and one in the evening.
Number of Patients Achieving Full Endoscopic Remission ( Based on CDEIS Score)	2 Participants	1 Participants

SECONDARY outcome

Timeframe: At week 8

Population: ITT population included all randomized patients who took at least one dose of study treatment.

CDEIS (Crohn's Disease Endoscopic Index of Severity) is an index for determining the severity of Crohn's disease with endoscopic localization to ileum and colon; A patient was defined 'endoscopic remissed' whether the CDEIS score at week 8 was equal or lower than six points.

CDEIS score considers 4 parameters, each one evaluated in 5 pre-defined segments of the colon ).

The score can be calculated even in case of incomplete investigations, as the results of the individual segments are divided by the number of segments investigated.

The higher the score, the worse is patient's situation.

Score Scale:

< 3 remission; 3 - 8 mild endoscopic activity; 9 - 12 moderate endoscopic activity; > 12 severe endoscopic activity.

A patient was defined 'endoscopic remissed' whether the CDEIS score at week 8 was equal or lower than six points.

Outcome measures

Measure	Placebo n=26 Participants Oral matching placebo capsules, administered bid. Placebo: Placebo will be supplied as matching capsules for oral administration with the same outer appearance of the study drug and with the same dosing scheme (one capsule in the morning and one in the evening)	ITF2357 n=25 Participants Oral ITF2357 50 mg bid ITF2357: ITF2357 was administered as hard gelatin capsules for oral administration at the dose strength of 50 mg. Capsules were administered as follow: one capsule in the morning and one in the evening.
Number of Patients Achieving Endoscopic Remission (Based on CDEIS Score)	3 Participants	5 Participants

SECONDARY outcome

Timeframe: At week 8

Population: ITT population included all randomized patients who took at least one dose of study treatment.

CDEIS (Crohn's Disease Endoscopic Index of Severity) is an index for determining the severity of Crohn's disease with endoscopic localization to ileum and colon;

A patient was considered in 'endoscopic response' whether the change in CDEIS score at week 8 versus baseline was equal or greater than 4.5 points.

CDEIS score considers 4 parameters, each one evaluated in 5 pre-defined segments of the colon ).

The score can be calculated even in case of incomplete investigations, as the results of the individual segments are divided by the number of segments investigated.

The higher the score, the worse is patient's situation

Score Scale:

< 3 remission; 3 - 8 mild endoscopic activity; 9 - 12 moderate endoscopic activity; > 12 severe endoscopic activity.

A patient was considered in 'endoscopic response' whether the change in CDEIS score at week 8 versus baseline was equal or greater than 4.5 points.

Outcome measures

Measure	Placebo n=26 Participants Oral matching placebo capsules, administered bid. Placebo: Placebo will be supplied as matching capsules for oral administration with the same outer appearance of the study drug and with the same dosing scheme (one capsule in the morning and one in the evening)	ITF2357 n=25 Participants Oral ITF2357 50 mg bid ITF2357: ITF2357 was administered as hard gelatin capsules for oral administration at the dose strength of 50 mg. Capsules were administered as follow: one capsule in the morning and one in the evening.
Number of Patients Achieving Endoscopic Response (Based on CDEIS Score)	6 Participants	7 Participants

SECONDARY outcome

Timeframe: From Baseline to week 8

Population: ITT population included all randomized patients who took at least one dose of study treatment.

CDEIS is an index to determ the endoscopic severity of Crohn's disease. Its score considers 4 parameters, each one evaluated in 5 pre-defined segments of the colon (ileum, ascending colon, transverse colon, descending colon and sigmoid loop, and rectum). These 4 parameters are: Deep ulcerations (12 if present, 0 if absent = total 1); Superficial ulcerations (6 if present, 0 if absent = total 2); Surface involved by disease (mm/10 on VAS = = total 3); Surface involved by ulcerations (mm/10 on VAS = total 4).

Sum of Totals 1+2+3+4 =Total A Number of segments visualized in part or entirely (from 1 to 5)= n Total A/n =Total B if ulcerated stenosis in any segment, add 3 =Total C If non-ulcerated stenosis in any segment, add 3= Total D Total B+C+D=CDEIS grand score (min=0; max=NA)

Decoding score < 3 remission; 3 - 8 mild endoscopic activity; 9 - 12 moderate endoscopic activity; > 12 severe endoscopic activity.

The higher the score, the worse is patient's status.

Outcome measures

Measure	Placebo n=26 Participants Oral matching placebo capsules, administered bid. Placebo: Placebo will be supplied as matching capsules for oral administration with the same outer appearance of the study drug and with the same dosing scheme (one capsule in the morning and one in the evening)	ITF2357 n=25 Participants Oral ITF2357 50 mg bid ITF2357: ITF2357 was administered as hard gelatin capsules for oral administration at the dose strength of 50 mg. Capsules were administered as follow: one capsule in the morning and one in the evening.
The Mean Changes of Crohn's Disease Endoscopic Index of Severity (CDEIS) From Baseline to Week 8	-2.5 score on a scale Standard Deviation 5.6	-2.4 score on a scale Standard Deviation 4.2

SECONDARY outcome

Timeframe: From Baseline to week 8

Population: ITT population included all randomized patients who took at least one dose of study treatment.

SES-CD is another index to determ the endoscopic severity of Crohn's disease. Its score considers 4 parameters, each one evaluated in 5 pre-defined segments of the colon (ileum, ascending colon, transverse colon, descending colon and sigmoid loop, and rectum). These 4 parameters are:

ulcers? 0: no; 1: aphthous (0.1-0.5 cm); 2: large (0.5-2 cm); 3: very large (>2 cm); Surface involved by inflammation 0: 0%

1: <50% 2: 50-75% 3: >75% Surface involved by ulcerations 0: 0%

1. <10%

2. 10-30%

3. >30% Stenosis?

0: No

1. Single, can be passed

2. Multiple, can be passed

3. Cannot be passed The scores for each individual segment are added together as a sum score (min=0; max=60) The higher the score, the worse the outcome.

Decoding score 0 - 2 remission 3 - 6 mild endoscopic activity 7 - 15 moderate endoscopic activity > 15 severe endoscopic activity

Outcome measures

Measure	Placebo n=26 Participants Oral matching placebo capsules, administered bid. Placebo: Placebo will be supplied as matching capsules for oral administration with the same outer appearance of the study drug and with the same dosing scheme (one capsule in the morning and one in the evening)	ITF2357 n=25 Participants Oral ITF2357 50 mg bid ITF2357: ITF2357 was administered as hard gelatin capsules for oral administration at the dose strength of 50 mg. Capsules were administered as follow: one capsule in the morning and one in the evening.
The Mean Changes of Simple Endoscopic Score for Crohn Disease (SES-CD) From Baseline to Week 8	-2.6 score on a scale Standard Deviation 4.5	-2.0 score on a scale Standard Deviation 4.0

SECONDARY outcome

Timeframe: Weeks 4 and 8, and follow-up at 1 month

Population: ITT population included all randomized patients who took at least one dose of study treatment.

CDAI (Crohn's Disease Activity Index): frequently used to assess disease severity. It gives a score ranging from 0 to over 600, based on a diary of symptoms kept by the patient for 7 days, and other measurements such as the patient's weight and haematocrit.

The higher the score, the worse is patient's situation A patient is defined 'remissed' whether the CDAI score is lower than 150 points.

A patient is defined 'responder' whether the change in CDAI score versus baseline is greater to 100 points

Outcome measures

Measure	Placebo n=26 Participants Oral matching placebo capsules, administered bid. Placebo: Placebo will be supplied as matching capsules for oral administration with the same outer appearance of the study drug and with the same dosing scheme (one capsule in the morning and one in the evening)	ITF2357 n=25 Participants Oral ITF2357 50 mg bid ITF2357: ITF2357 was administered as hard gelatin capsules for oral administration at the dose strength of 50 mg. Capsules were administered as follow: one capsule in the morning and one in the evening.
The Mean Changes of CDAI Score From Baseline to Week 4-8-follow up At week 4	-85.3 score on a scale Standard Deviation 95.9	-32.7 score on a scale Standard Deviation 84.5
The Mean Changes of CDAI Score From Baseline to Week 4-8-follow up At week 8	-119 score on a scale Standard Deviation 96.5	-54.7 score on a scale Standard Deviation 94.3
The Mean Changes of CDAI Score From Baseline to Week 4-8-follow up At follow-up 1 month	-106 score on a scale Standard Deviation 91.6	-83.8 score on a scale Standard Deviation 82.0

SECONDARY outcome

Timeframe: Weeks 4 and 8, and follow-up at 1 month

Population: ITT population included all randomized patients who took at least one dose of study treatment.

"Remission" is defined as the disappearance of signs and symptoms of the disease.

CDAI (Crohn's Disease Activity Index): frequently used to assess disease severity. It gives a score ranging from 0 to over 600, based on a diary of symptoms kept by the patient for 7 days, and other measurements such as the patient's weight and haematocrit.

The higher the score, the worse is patient's situation A patient is defined 'remissed' whether the CDAI score is lower than 150 points.

A patient is defined 'responder' whether the change in CDAI score versus baseline is greater to 100 points

Outcome measures

Measure	Placebo n=26 Participants Oral matching placebo capsules, administered bid. Placebo: Placebo will be supplied as matching capsules for oral administration with the same outer appearance of the study drug and with the same dosing scheme (one capsule in the morning and one in the evening)	ITF2357 n=25 Participants Oral ITF2357 50 mg bid ITF2357: ITF2357 was administered as hard gelatin capsules for oral administration at the dose strength of 50 mg. Capsules were administered as follow: one capsule in the morning and one in the evening.
Number of Patients Achieving Remission (Based on CDAI Score) At week 4	10 Participants	4 Participants
Number of Patients Achieving Remission (Based on CDAI Score) At week 8	14 Participants	7 Participants
Number of Patients Achieving Remission (Based on CDAI Score) At follow-up after one month	11 Participants	9 Participants

SECONDARY outcome

Timeframe: Weeks 4 and 8, and follow-up at 1 month

Population: ITT population included all randomized patients who took at least one dose of study treatment.

"Response" is defined as the reaction to a stimulus or to a treatment, especially in a favorable way.

CDAI (Crohn's Disease Activity Index): frequently used to assess disease severity. It gives a score ranging from 0 to over 600, based on a diary of symptoms kept by the patient for 7 days, and other measurements such as the patient's weight and haematocrit.

The higher the score, the worse is patient's situation. A patient is defined 'remissed' whether the CDAI score is lower than 150 points.

A patient is defined 'responder' whether the change in CDAI score versus baseline is greater to 100 points

Outcome measures

Measure	Placebo n=26 Participants Oral matching placebo capsules, administered bid. Placebo: Placebo will be supplied as matching capsules for oral administration with the same outer appearance of the study drug and with the same dosing scheme (one capsule in the morning and one in the evening)	ITF2357 n=25 Participants Oral ITF2357 50 mg bid ITF2357: ITF2357 was administered as hard gelatin capsules for oral administration at the dose strength of 50 mg. Capsules were administered as follow: one capsule in the morning and one in the evening.
Number of Patients Achieving Response (Based on CDAI Score) At week 4	11 Participants	6 Participants
Number of Patients Achieving Response (Based on CDAI Score) At week 8	14 Participants	8 Participants
Number of Patients Achieving Response (Based on CDAI Score) At follow up, after one month	14 Participants	11 Participants

SECONDARY outcome

Timeframe: At Pre-Treatment period (Week 0); At treatment period (Week 1, Week 2, Week 4, week 6, Week 8); At Follow-up period (1month)

Population: ITT population includes all randomized patients who took at least one dose of study treatment.

Treatment-related adverse events are adverse events (AE) which occurs during an interventional study and which are surely related to study treatment dosing.

Outcome measures

Measure	Placebo n=26 Participants Oral matching placebo capsules, administered bid. Placebo: Placebo will be supplied as matching capsules for oral administration with the same outer appearance of the study drug and with the same dosing scheme (one capsule in the morning and one in the evening)	ITF2357 n=25 Participants Oral ITF2357 50 mg bid ITF2357: ITF2357 was administered as hard gelatin capsules for oral administration at the dose strength of 50 mg. Capsules were administered as follow: one capsule in the morning and one in the evening.
Number of Patients With at Least One Related Adverse Event to Study Treatment	13 Participants	12 Participants

SECONDARY outcome

Timeframe: Pre-dose, week 2, week 4, week 6

Population: Per Protocol Population (PP) - all randomized patients who received at least one dose of study medication without major protocol deviations

Individual plasma levels of ITF2357 (before morning dose) after repeated oral administration of ITF2357 (50mg b.i.d.) in patients with Crohn's disease were assessed.

Outcome measures

Measure	Placebo n=21 Participants Oral matching placebo capsules, administered bid. Placebo: Placebo will be supplied as matching capsules for oral administration with the same outer appearance of the study drug and with the same dosing scheme (one capsule in the morning and one in the evening)	ITF2357 Oral ITF2357 50 mg bid ITF2357: ITF2357 was administered as hard gelatin capsules for oral administration at the dose strength of 50 mg. Capsules were administered as follow: one capsule in the morning and one in the evening.
Plasma Levels of ITF2357 Before Morning Dose of ITF2357 Pre-dose	0.00 ng/mL Standard Deviation 0.00	—
Plasma Levels of ITF2357 Before Morning Dose of ITF2357 Week 2	16.87 ng/mL Standard Deviation 6.09	—
Plasma Levels of ITF2357 Before Morning Dose of ITF2357 Week 4	16.97 ng/mL Standard Deviation 11.54	—
Plasma Levels of ITF2357 Before Morning Dose of ITF2357 Week 6	14.50 ng/mL Standard Deviation 6.78	—

SECONDARY outcome

Timeframe: Pre-dose, week 2, week 4, week 6

Population: Per Protocol Population (PP) - all randomized patients who received at least one dose of study medication without major protocol deviations

Individual plasma levels of metabolite ITF2374 (before morning dose) after repeated oral administration of ITF2357 (50mg b.i.d.) in patients with Crohn's disease were assessed.

Outcome measures

Measure	Placebo n=21 Participants Oral matching placebo capsules, administered bid. Placebo: Placebo will be supplied as matching capsules for oral administration with the same outer appearance of the study drug and with the same dosing scheme (one capsule in the morning and one in the evening)	ITF2357 Oral ITF2357 50 mg bid ITF2357: ITF2357 was administered as hard gelatin capsules for oral administration at the dose strength of 50 mg. Capsules were administered as follow: one capsule in the morning and one in the evening.
Plasma Levels of Metabolite ITF2374 Before Morning Dose of ITF2357. Pre-dose	0.00 ng/mL Standard Deviation 0.00	—
Plasma Levels of Metabolite ITF2374 Before Morning Dose of ITF2357. Week 2	15.09 ng/mL Standard Deviation 6.92	—
Plasma Levels of Metabolite ITF2374 Before Morning Dose of ITF2357. Week 4	12.93 ng/mL Standard Deviation 7.36	—
Plasma Levels of Metabolite ITF2374 Before Morning Dose of ITF2357. Week 6	13.24 ng/mL Standard Deviation 8.16	—

SECONDARY outcome

Timeframe: Pre dose, week 2, week 4, week 6.

Population: Per Protocol Population (PP) - all randomized patients who received at least one dose of study medication without major protocol deviations

Individual plasma levels of Metabolite ITF2375 (before morning dose) after repeated oral administration of ITF2357 (50mg b.i.d.) in patients with Crohn's disease were assessed.

Outcome measures

Measure	Placebo n=21 Participants Oral matching placebo capsules, administered bid. Placebo: Placebo will be supplied as matching capsules for oral administration with the same outer appearance of the study drug and with the same dosing scheme (one capsule in the morning and one in the evening)	ITF2357 Oral ITF2357 50 mg bid ITF2357: ITF2357 was administered as hard gelatin capsules for oral administration at the dose strength of 50 mg. Capsules were administered as follow: one capsule in the morning and one in the evening.
Plasma Levels of Metabolite ITF2375 Before Morning Dose of ITF2357. pre-dose	0.00 ng/mL Standard Deviation 0.00	—
Plasma Levels of Metabolite ITF2375 Before Morning Dose of ITF2357. week 2	121.23 ng/mL Standard Deviation 88.83	—
Plasma Levels of Metabolite ITF2375 Before Morning Dose of ITF2357. week 4	112.80 ng/mL Standard Deviation 109.74	—
Plasma Levels of Metabolite ITF2375 Before Morning Dose of ITF2357. week 6	101.36 ng/mL Standard Deviation 76.32	—

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 17 other events

Deaths: 0 deaths

ITF2357

Serious events: 3 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=26 participants at risk Oral matching placebo capsules, administered bid. Placebo: Placebo will be supplied as matching capsules for oral administration with the same outer appearance of the study drug and with the same dosing scheme (one capsule in the morning and one in the evening)	ITF2357 n=25 participants at risk Oral ITF2357 50 mg bid ITF2357: ITF2357 was administered as hard gelatin capsules for oral administration at the dose strength of 50 mg. Capsules were administered as follow: one capsule in the morning and one in the evening.
Gastrointestinal disorders Crohn's Disease	3.8% 1/26 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	12.0% 3/25 • Number of events 3 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Musculoskeletal and connective tissue disorders Back Pain	3.8% 1/26 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	0.00% 0/25 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)

Other adverse events

Measure	Placebo n=26 participants at risk Oral matching placebo capsules, administered bid. Placebo: Placebo will be supplied as matching capsules for oral administration with the same outer appearance of the study drug and with the same dosing scheme (one capsule in the morning and one in the evening)	ITF2357 n=25 participants at risk Oral ITF2357 50 mg bid ITF2357: ITF2357 was administered as hard gelatin capsules for oral administration at the dose strength of 50 mg. Capsules were administered as follow: one capsule in the morning and one in the evening.
Cardiac disorders Sinus Bradycardia	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Gastrointestinal disorders Vomiting	3.8% 1/26 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	24.0% 6/25 • Number of events 7 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Gastrointestinal disorders Abdominal pain	15.4% 4/26 • Number of events 5 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	20.0% 5/25 • Number of events 5 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Gastrointestinal disorders Crohn's disease	11.5% 3/26 • Number of events 3 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	16.0% 4/25 • Number of events 4 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Gastrointestinal disorders Abdominal pain upper	3.8% 1/26 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	12.0% 3/25 • Number of events 3 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Gastrointestinal disorders Dyspepsia	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	12.0% 3/25 • Number of events 5 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Gastrointestinal disorders Nausea	3.8% 1/26 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	12.0% 3/25 • Number of events 6 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Gastrointestinal disorders Diarrhoea	3.8% 1/26 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Gastrointestinal disorders Haemorrhoids	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Gastrointestinal disorders Perianal Erythema	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Gastrointestinal disorders Abdominal Tenderness	3.8% 1/26 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	0.00% 0/25 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Gastrointestinal disorders Anal Abscess	3.8% 1/26 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	0.00% 0/25 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Gastrointestinal disorders Faeces Discoloured	3.8% 1/26 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	0.00% 0/25 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Gastrointestinal disorders Gingival Bleeding	3.8% 1/26 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	0.00% 0/25 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Gastrointestinal disorders Pruritus Ani	3.8% 1/26 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	0.00% 0/25 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
General disorders Pyrexia	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	12.0% 3/25 • Number of events 3 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
General disorders Chest Pain	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	8.0% 2/25 • Number of events 2 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
General disorders Chills	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
General disorders Fatigue	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
General disorders Oedema	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Infections and infestations Urinary tract infection	3.8% 1/26 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	8.0% 2/25 • Number of events 2 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Infections and infestations Bronchopneumonia	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Infections and infestations Influenza	11.5% 3/26 • Number of events 3 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Infections and infestations Laryngitis	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Infections and infestations Nasopharyngitis	11.5% 3/26 • Number of events 3 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 2 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Infections and infestations Bronchitis	11.5% 3/26 • Number of events 3 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	0.00% 0/25 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Infections and infestations Cystitis	3.8% 1/26 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	0.00% 0/25 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Infections and infestations Gastroenteritis Rotavirus	3.8% 1/26 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	0.00% 0/25 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Infections and infestations Gastroenteritis Viral	3.8% 1/26 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	0.00% 0/25 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Infections and infestations Sinusitis	3.8% 1/26 • Number of events 2 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	0.00% 0/25 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Investigations Blood Magnesium decreased	3.8% 1/26 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	8.0% 2/25 • Number of events 2 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Investigations Electrocardiogram QT prolonged	3.8% 1/26 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Investigations Platelet count decreased	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Investigations Red blood cell count decreased	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Investigations White blood cell count decreased	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Investigations C-reactive protein increased	7.7% 2/26 • Number of events 2 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	0.00% 0/25 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Investigations Haemoglobin decreased	3.8% 1/26 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	0.00% 0/25 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Investigations pH Urine increased	3.8% 1/26 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	0.00% 0/25 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Investigations Red blood cell sedimentation rate increased	3.8% 1/26 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	0.00% 0/25 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Investigations Sputum Abnormal	3.8% 1/26 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	0.00% 0/25 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Metabolism and nutrition disorders Dehydration	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	12.0% 3/25 • Number of events 4 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	12.0% 3/25 • Number of events 4 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Metabolism and nutrition disorders Decreased Appetite	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Musculoskeletal and connective tissue disorders Arthralgia	7.7% 2/26 • Number of events 2 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	12.0% 3/25 • Number of events 3 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Musculoskeletal and connective tissue disorders Ankylosing Spondylitis	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Musculoskeletal and connective tissue disorders Back Pain	3.8% 1/26 • Number of events 2 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Musculoskeletal and connective tissue disorders Joint Swelling	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 2 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Musculoskeletal and connective tissue disorders Groin Pain	3.8% 1/26 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	0.00% 0/25 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Nervous system disorders Headache	3.8% 1/26 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	12.0% 3/25 • Number of events 3 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Nervous system disorders Paraesthesia	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 2 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Nervous system disorders Tremor	3.8% 1/26 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	0.00% 0/25 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Psychiatric disorders Delirium	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Psychiatric disorders Nervousness	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Renal and urinary disorders Micturition Disorder	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Renal and urinary disorders Bacteriuria	3.8% 1/26 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	0.00% 0/25 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Reproductive system and breast disorders Dysmenorrhoea	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Respiratory, thoracic and mediastinal disorders Cough	3.8% 1/26 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	0.00% 0/25 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	3.8% 1/26 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	0.00% 0/25 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Skin and subcutaneous tissue disorders Erythema nodosum	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Skin and subcutaneous tissue disorders Pruritus	7.7% 2/26 • Number of events 2 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Skin and subcutaneous tissue disorders Rash	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Vascular disorders Hot flush	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Vascular disorders Intermittent claudication	0.00% 0/26 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	4.0% 1/25 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)
Vascular disorders Systolic Hypertension	3.8% 1/26 • Number of events 1 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)	0.00% 0/25 • Adverse event data were collected from Week 0 up to week 8 and during follow up period (which lasts for one month)

Additional Information

Tiziano Oldoni, MD

Italfarmaco SpA

Phone: +39 0264432540

Email: t.oldoni@italfarmaco.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place