Trial Outcomes & Findings for Preliminary Efficacy, Safety and Pharmacokinetics Study of Nepadutant in Infant With Feeding Intolerance (NCT NCT01532518)

NCT ID: NCT01532518

Last Updated: 2023-05-06

Results Overview

Results obtained at V2 serve as baseline values for the assessment of effects at V3 (i.e. end of first week of treatment). Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R ), with a minimum-maximum score of 0-42 (minimum for diagnosis \>15). The higher values reflect worse outcome. The questionnaire comprised 12 items as questions quantifying aspects of regurgitation (3 questions), crying (3 questions), feeding refusal (2 questions), apnea/cyanosis (2 questions), hiccups and arching. Questions with 4 possible options have a score ranging from 0 to 3; questions with 5 possible options have a score ranging from 0 to 4. The scores of each item are summed, so the total score is presented.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 27 participants
• Primary outcome timeframe: Baseline (V2) and end of first week of treatment (V3)
• Results posted on: 2023-05-06

Participant Flow

Participant milestones

Measure	Cohort 3 Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution	Cohort 2 Nepadutant medium dose (0.5mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution	Cohort 1 Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant medium dose (0.5mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution
Overall Study STARTED	6	15	6
Overall Study COMPLETED	6	15	5
Overall Study NOT COMPLETED	0	0	1

Reasons for withdrawal

Measure	Cohort 3 Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution	Cohort 2 Nepadutant medium dose (0.5mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution	Cohort 1 Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant medium dose (0.5mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution
Overall Study Withdrawal by Subject	0	0	1

Baseline Characteristics

Preliminary Efficacy, Safety and Pharmacokinetics Study of Nepadutant in Infant With Feeding Intolerance

Baseline characteristics by cohort

Measure	Cohort 3 n=6 Participants Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution	Cohort 2 n=15 Participants Nepadutant medium dose (0.5mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution	Cohort 1 n=6 Participants Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant medium dose (0.5mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution	Total n=27 Participants Total of all reporting groups
Age, Continuous	12.52 weeks STANDARD_DEVIATION 4.281 • n=5 Participants	13.62 weeks STANDARD_DEVIATION 6.468 • n=7 Participants	14.27 weeks STANDARD_DEVIATION 6.559 • n=5 Participants	13.52 weeks STANDARD_DEVIATION 5.89 • n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	8 Participants n=7 Participants	2 Participants n=5 Participants	14 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	7 Participants n=7 Participants	4 Participants n=5 Participants	13 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	3 particpants n=5 Participants	4 particpants n=7 Participants	1 particpants n=5 Participants	8 particpants n=4 Participants
Race/Ethnicity, Customized White	3 particpants n=5 Participants	8 particpants n=7 Participants	5 particpants n=5 Participants	16 particpants n=4 Participants
Race/Ethnicity, Customized More than one race	0 particpants n=5 Participants	3 particpants n=7 Participants	0 particpants n=5 Participants	3 particpants n=4 Participants
Region of Enrollment United States	6 participants n=5 Participants	15 participants n=7 Participants	6 participants n=5 Participants	27 participants n=4 Participants
Weight	5.323 Kg STANDARD_DEVIATION 0.9085 • n=5 Participants	5.623 Kg STANDARD_DEVIATION 1.1045 • n=7 Participants	5.708 Kg STANDARD_DEVIATION 1.764 • n=5 Participants	5.576 Kg STANDARD_DEVIATION 1.1975 • n=4 Participants
I-GERQ-R total score	24.8 Score on a scale STANDARD_DEVIATION 5.4 • n=5 Participants	19 Score on a scale STANDARD_DEVIATION 6.32 • n=7 Participants	21.8 Score on a scale STANDARD_DEVIATION 9.91 • n=5 Participants	20.8 Score on a scale STANDARD_DEVIATION 7.22 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline (V2) and end of first week of treatment (V3)

Population: Infants with feeding intolerance who received at least 1 dose of nepadutant. In the 3rd cohort 1 subject didn't report I-GERQ-R score at randomization. In the 1rst cohort 1 patient early terminated after V2.

Results obtained at V2 serve as baseline values for the assessment of effects at V3 (i.e. end of first week of treatment).

Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R ), with a minimum-maximum score of 0-42 (minimum for diagnosis >15). The higher values reflect worse outcome. The questionnaire comprised 12 items as questions quantifying aspects of regurgitation (3 questions), crying (3 questions), feeding refusal (2 questions), apnea/cyanosis (2 questions), hiccups and arching. Questions with 4 possible options have a score ranging from 0 to 3; questions with 5 possible options have a score ranging from 0 to 4.

The scores of each item are summed, so the total score is presented.

Outcome measures

Measure	Cohort 3 n=5 Participants Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution	Cohort 2 n=15 Participants Nepadutant medium dose (0.5mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution	Cohort 1 n=5 Participants Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant medium dose (0.5mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution
The Absolute Differences of I-GERQ-R Total Score at V3 (End of First Week of Treatment) Respect to the Baseline (V2).	-6.8 score on a scale Standard Deviation 9.55	-7.6 score on a scale Standard Deviation 5.5	-6.8 score on a scale Standard Deviation 5.81

PRIMARY outcome

Timeframe: V3 (end of 1st week of treatment) and V4 (end of 2nd week of treatment)

Population: Infants with feeding intolerance who received at least 1 dose of nepadutant. In the 3rd cohort 1 subject didn't report I-GERQ-R score at randomization. In the 1rst cohort 1 patient early terminated after V2.

The results obtained at V3 are used as baseline for the second week treatment period (V4).

Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R ), with a minimum-maximum score of 0-42 (minimum for diagnosis >15). The higher values reflect worse outcome. The questionnaire comprised 12 items as questions quantifying aspects of regurgitation (3 questions), crying (3 questions), feeding refusal (2 questions), apnea/cyanosis (2 questions), hiccups and arching. Questions with 4 possible options have a score ranging from 0 to 3; questions with 5 possible options have a score ranging from 0 to 4.

The scores of each item are summed, so the total score is presented.

Outcome measures

Measure	Cohort 3 n=5 Participants Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution	Cohort 2 n=15 Participants Nepadutant medium dose (0.5mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution	Cohort 1 n=5 Participants Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant medium dose (0.5mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution
The Absolute Differences of I-GERQ-R Total Score at V4 (End of 2nd Week of Treatment) Respect to V3 (End of 1st Week of Treatment).	-15.2 Score as sum of units Standard Deviation 5.54	-11.9 Score as sum of units Standard Deviation 6.8	-8.6 Score as sum of units Standard Deviation 6.66

PRIMARY outcome

Timeframe: Baseline (V2) and follow up 2 weeks after the last administered dose (V5)

Population: Infants with feeding intolerance who received at least 1 dose of nepadutant. In the 3rd cohort 1 subject didn't report I-GERQ-R score at randomization. In the 1rst cohort 1 patient early terminated after V2.

Results obtained at V2 serve as baseline values for follow-up assessment 2 weeks after the last administered dose (V5) Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R ), with a minimum-maximum score of 0-42 (minimum for diagnosis >15). The higher values reflect worse outcome. The questionnaire comprised 12 items as questions quantifying aspects of regurgitation (3 questions), crying (3 questions), feeding refusal (2 questions), apnea/cyanosis (2 questions), hiccups and arching. Questions with 4 possible options have a score ranging from 0 to 3; questions with 5 possible options have a score ranging from 0 to 4.

The scores of each item are summed, so the total score is presented.

Outcome measures

Measure	Cohort 3 n=5 Participants Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution	Cohort 2 n=15 Participants Nepadutant medium dose (0.5mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution	Cohort 1 n=5 Participants Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant medium dose (0.5mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution
The Absolute Differences of I-GERQ-R Total Score at V5 (Follow-up) Respect to V2 (Baseline).	-7.8 Score as sum of units Standard Deviation 7.6	-11.1 Score as sum of units Standard Deviation 6.78	-9.8 Score as sum of units Standard Deviation 7.4

PRIMARY outcome

Timeframe: Baseline (V2) and end of 1st week of treatment(V3)

Population: Subjects with feeding intolerance who received at least 1 dose of nepadutant (first dose level 0.1mg/kg and 0.5 mg/kg). One subject in the 3rd cohort didn't report I-GERQ-R score at V2.

Change in Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R) Score. Assessing the I-GERQ-R score changes vs baseline (Visit 2) by first dose level (0.1mg/kg and 0.5mg/kg). Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R ), with a minimum-maximum score of 0-42 (minimum for diagnosis >15). The higher values reflect worse outcome. The questionnaire comprised 12 items as questions quantifying aspects of regurgitation (3 questions), crying (3 questions), feeding refusal (2 questions), apnea/cyanosis (2 questions), hiccups and arching. Questions with 4 possible options have a score ranging from 0 to 3; questions with 5 possible options have a score ranging from 0 to 4.

The scores of each item are summed, so the total score is presented.

Outcome measures

Measure	Cohort 3 n=10 Participants Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution	Cohort 2 n=15 Participants Nepadutant medium dose (0.5mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution	Cohort 1 Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant medium dose (0.5mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution
I-GERQ-R Score Changes vs Baseline (Visit 2) by First Dose Level (0.1mg/kg and 0.5mg/kg).	-6.8 score on a scale Standard Deviation 7.31	-7.6 score on a scale Standard Deviation 5.5	—

PRIMARY outcome

Timeframe: end of first week of treatment (V3) and end of second week of treatment (V4)

Population: Subjects with feeding intolerance who received at least 1 dose of nepadutant (second dose level 0.5mg/kg and 1 mg/kg) 1 subject in the first cohort early terminated after V2

Change in Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R) Score. Assessing the I-GERQ-R score changes vs Visit 3 by second dose level (0.5mg/kg and 1mg/kg).

Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R ), with a minimum-maximum score of 0-42 (minimum for diagnosis >15). The higher values reflect worse outcome. The questionnaire comprised 12 items as questions quantifying aspects of regurgitation (3 questions), crying (3 questions), feeding refusal (2 questions), apnea/cyanosis (2 questions), hiccups and arching. Questions with 4 possible options have a score ranging from 0 to 3; questions with 5 possible options have a score ranging from 0 to 4.

The scores of each item are summed, so the total score is presented.

Outcome measures

Measure	Cohort 3 n=5 Participants Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution	Cohort 2 n=21 Participants Nepadutant medium dose (0.5mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution	Cohort 1 Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant medium dose (0.5mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution
I-GERQ-R Score Changes vs Visit 3 by Second Dose Level (0.5mg/kg and 1mg/kg).	-1.4 Score as sum of units Standard Deviation 0.89	-4.9 Score as sum of units Standard Deviation 4.41	—

SECONDARY outcome

Timeframe: up to 4 weeks

Population: All subjects who received at least one administration of study treatment including dose tolerability test (safety population)

The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.

Outcome measures

Measure	Cohort 3 n=21 Participants Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution	Cohort 2 n=21 Participants Nepadutant medium dose (0.5mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution	Cohort 1 n=12 Participants Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant medium dose (0.5mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution
Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level gastrointestinal disorder	6 Number of events	4 Number of events	3 Number of events
Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level General disorders and administration site conditio	1 Number of events	0 Number of events	0 Number of events
Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level Infections and infestations	7 Number of events	2 Number of events	1 Number of events
Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level Injury, poisoning and procedural complications	1 Number of events	1 Number of events	0 Number of events
Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level Psychiatric disorders	0 Number of events	0 Number of events	1 Number of events
Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level Respiratory, thoracic and medistinal disorders	3 Number of events	1 Number of events	1 Number of events
Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level Skin and subcutaneous tissue disorders	3 Number of events	1 Number of events	3 Number of events

SECONDARY outcome

Timeframe: 0.5, 1, 2, 3 hours post Single Dose and 24 hours post Repeated Dose

Population: At visit 2, samples from 12 subjects in 0.1 mg/kg and from 15 subjects in 0.5 mg/kg. At visit 3\*, 4\*: samples from 15 subjects in 0.1 - 0.5 mg/kg cohort, from 5 in 0.5 - 1 mg/kg cohort and from 6 in 0.1 - 1 mg/kg cohort. \*N=26 instead of 27 as one patient early terminated the study

The population pharmacokinetic analyses is presented. PopPK Clearance estimated with a one compartment model with first order absorption and elimination.

Outcome measures

Measure	Cohort 3 n=6 Participants Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution	Cohort 2 n=15 Participants Nepadutant medium dose (0.5mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution	Cohort 1 n=6 Participants Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant medium dose (0.5mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution
A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04	1.24 L/h Interval 0.919 to 1.57	1.31 L/h Interval 1.03 to 1.59	1.64 L/h Interval 1.39 to 1.89

SECONDARY outcome

Timeframe: 0.5, 1, 2, 3 hours post Single Dose and 24 hours post Repeated Dose

Population: At visit 2, samples from 6 subjects in Cohort 1 at 0.1mg/kg; 6 subjects in Cohort 3 at 0,1 mg/kg; 15 subjects in Cohort 2 at 0.5 mg/kg. At visit 3\*, 4\*: samples from 5 subjects in Cohort 1 (0.1 - 0.5 mg/kg), 15 subjects in Cohort 2 (0.5 - 1 mg/kg) and 6 subjects in Cohort 3 (0.1 - 1 mg/kg).

PopPK Volume estimated with a one compartment model with first order absorption and elimination. NOTE: for this measure, no inter-individual variability was estimated, therefore the value for each cohort corresponds to the typical value.

Outcome measures

Measure	Cohort 3 n=27 Participants Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution	Cohort 2 Nepadutant medium dose (0.5mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution	Cohort 1 Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant medium dose (0.5mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution
A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04	22.5 L no inter-individual variability was estimated, the value for all cohorts corresponds to the typical value.	—	—

SECONDARY outcome

Timeframe: 0.5, 1, 2, 3 hours post Single Dose and 24 hours post Repeated Dose

Population: At visit 2, samples from 6 subjects in Cohort 1 at 0.1mg/kg; 6 subjects in Cohort 3 at 0,1 mg/kg; 15 subjects in Cohort 2 at 0.5 mg/kg. At visit 3\*, 4\*: samples from 5 subjects in Cohort 1 (0.1 - 0.5 mg/kg), 15 subjects in Cohort 2 (0.5 - 1 mg/kg) and 6 subjects in Cohort 3 (0.1 - 1 mg/kg).

The population pharmacokinetic analyses is presented. PopPK Ka estimated with a one compartment model with first order absorption and elimination. NOTE: for this measure, no inter-individual variability was estimated, therefore the value for each cohort corresponds to the typical value.

Outcome measures

Measure	Cohort 3 n=27 Participants Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution	Cohort 2 Nepadutant medium dose (0.5mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution	Cohort 1 Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant medium dose (0.5mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution
A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04	206 1/h no inter-individual variability was estimated, therefore the value for each cohort corresponds to the typical value.	—	—

SECONDARY outcome

Timeframe: 0.5, 1, 2, 3 hours post Single Dose and 24 hours post Repeated Dose

Population: At visit 2, samples from 6 subjects in Cohort 1 at 0.1mg/kg; 6 subjects in Cohort 3 at 0,1 mg/kg; 15 subjects in Cohort 2 at 0.5 mg/kg. At visit 3\*, 4\*: samples from 5 subjects in Cohort 1 (0.1 - 0.5 mg/kg), 15 subjects in Cohort 2 (0.5 - 1 mg/kg) and 6 subjects in Cohort 3 (0.1 - 1 mg/kg).

The population pharmacokinetic analyses is presented. The PopPK parameter fraction of the dose absorbed (F1) is estimated with a one compartment model with first order absorption and elimination.The results are presented fraction of the absorbed dose with 95% CI of the parameter estimate value

Outcome measures

Measure	Cohort 3 n=6 Participants Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution	Cohort 2 n=15 Participants Nepadutant medium dose (0.5mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution	Cohort 1 n=6 Participants Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant medium dose (0.5mg/kg) for additional 7 days Nepadutant: Nepadutant oral solution
A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04	0.0275 fraction of dose absorbed Interval 0.0199 to 0.0352	0.0342 fraction of dose absorbed Interval 0.025 to 0.0433	0.0346 fraction of dose absorbed Interval 0.0346 to 0.0377

Adverse Events

High Dose Level (1.0 mg/Kg)

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Medium Dose Level (0.5mg/Kg)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Low Dose Level(0.1mg/Kg)

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Measure	High Dose Level (1.0 mg/Kg) n=21 participants at risk Subjects who received at least 1 dose of nepadutant 1.0mg/kg (Subjects who took Nepadutant 1.0 mg/dl for the additional 7 days - coming from Nepadutant 0.1 mg/kg and 0.5 mg/kg) Nepadutant: Nepadutant oral solution	Medium Dose Level (0.5mg/Kg) n=21 participants at risk Subjects who received at least 1 dose of nepadutant 0.5 mg/kg (subjects who took Nepadutant 0.5 mg/dl for the first 7 days AND subjects who took Nepadutant 0.5 mg/dl for the additional 7 days - coming from Neapdutant 0.1 mg/kg) Nepadutant: Nepadutant oral solution	Low Dose Level(0.1mg/Kg) n=12 participants at risk Subjects who received at least 1 dose of nepadutant 0.1 mg/kg (subjects who took Nepadutant 0.1mg/dl for the first 7 days) Nepadutant: Nepadutant oral solution
Surgical and medical procedures Hospitalisation for investigation for suspected seizures	4.8% 1/21 • Number of events 1 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.	0.00% 0/21 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.	0.00% 0/12 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.
Respiratory, thoracic and mediastinal disorders Laryngeal Edema-post intubation	0.00% 0/21 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.	0.00% 0/21 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.	8.3% 1/12 • Number of events 1 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.

Other adverse events

Measure	High Dose Level (1.0 mg/Kg) n=21 participants at risk Subjects who received at least 1 dose of nepadutant 1.0mg/kg (Subjects who took Nepadutant 1.0 mg/dl for the additional 7 days - coming from Nepadutant 0.1 mg/kg and 0.5 mg/kg) Nepadutant: Nepadutant oral solution	Medium Dose Level (0.5mg/Kg) n=21 participants at risk Subjects who received at least 1 dose of nepadutant 0.5 mg/kg (subjects who took Nepadutant 0.5 mg/dl for the first 7 days AND subjects who took Nepadutant 0.5 mg/dl for the additional 7 days - coming from Neapdutant 0.1 mg/kg) Nepadutant: Nepadutant oral solution	Low Dose Level(0.1mg/Kg) n=12 participants at risk Subjects who received at least 1 dose of nepadutant 0.1 mg/kg (subjects who took Nepadutant 0.1mg/dl for the first 7 days) Nepadutant: Nepadutant oral solution
Gastrointestinal disorders Constipation	9.5% 2/21 • Number of events 2 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.	0.00% 0/21 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.	0.00% 0/12 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.
Gastrointestinal disorders Diarrhoea	9.5% 2/21 • Number of events 2 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.	9.5% 2/21 • Number of events 2 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.	8.3% 1/12 • Number of events 1 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.
Gastrointestinal disorders Teething	9.5% 2/21 • Number of events 2 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.	0.00% 0/21 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.	16.7% 2/12 • Number of events 2 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.
Infections and infestations Ear infection	9.5% 2/21 • Number of events 2 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.	0.00% 0/21 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.	0.00% 0/12 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.
Infections and infestations Viral infection	9.5% 2/21 • Number of events 2 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.	0.00% 0/21 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.	0.00% 0/12 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.
Skin and subcutaneous tissue disorders Dermatitis diaper	9.5% 2/21 • Number of events 2 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.	0.00% 0/21 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.	0.00% 0/12 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.
Infections and infestations Candidiasis	0.00% 0/21 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.	0.00% 0/21 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.	8.3% 1/12 • Number of events 1 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.
Psychiatric disorders Screaming	0.00% 0/21 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.	0.00% 0/21 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.	8.3% 1/12 • Number of events 1 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.
Respiratory, thoracic and mediastinal disorders Upper respiratory atract congestion	0.00% 0/21 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.	0.00% 0/21 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.	8.3% 1/12 • Number of events 1 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.
Skin and subcutaneous tissue disorders Rash	0.00% 0/21 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.	0.00% 0/21 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.	8.3% 1/12 • Number of events 1 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.
Skin and subcutaneous tissue disorders Seborrhoic dermatitis	0.00% 0/21 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.	0.00% 0/21 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.	8.3% 1/12 • Number of events 1 • 4 weeks Analysed for the Safety Population (all patients who received the study drug) The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.

Additional Information

Dr. Angela Capriati

Menarini Ricerche

Phone: +39 05556809990

Email: acapriati@menarini-ricerche.it

Results disclosure agreements

• Principal investigator is a sponsor employee Principal Investigators are NOT employed by the organization sponsoring the study. There IS an agreement between the Principal Investigator and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. The results of the study cannot 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