A Phase I Study to Evaluate the Oral Absorption of Nepadutant in Infants

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the gastrointestinal absorption of nepadutant after single dose as oral solution (and the effect of age on its oral absorption) in infants. Oral absorption is evaluated through the drug recovery in urine.

Detailed Description
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This trial aims to evaluate the oral adsorption of nepadutant (0.1 or 0.5 mg/Kg given as one single dose as oral solution) in infants divided in three age strata (from 6 to 24 weeks old). Oral absorption is evaluated by measuring the amount of nepadutant in the urine output collected during the 24 hours after oral administration with special diapers. Safety and tolerability of the drug will be evaluated by monitoring any changes in signs/symptoms at medical examination and vital signs during the fist 4 hours post-dose in the Hospital site and then by the parents at home up to 24 hours and 1 week post nepadutant administration.

Official Title
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Pilot Study to Evaluate the Oral Absorption, Safety, and Tolerability of Nepadutant Administered as Single Oral Doses to Infants With Colic and Other Functional Gastrointestinal Disorders

Conditions
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Infantile Colic, Infantile Functional Gastrointestinal Disorders

Intervention / Treatment
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* Drug: Nepadutant
* Drug: Nepadutant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects will be eligible for inclusion in the study if they meet all of the following criteria: Infants with a history consistent with a diagnosis of colic or other functional gastrointestinal disorders Age >6 weeks and < 24 weeks At least 44 weeks post-conceptual age at enrolment Normal growth Informed consent by parents (one or both) or legal guardian Caregiver available to be trained in collection and storage of used diapers Caregiver available to record feeding episodes and defecations on the diary Exclusion Criteria: Subjects will be excluded from the study if they meet any of the following criteria: Clinical evidence of major cardiovascular, respiratory, renal, hepatic, endocrine, metabolic, gastrointestinal (excluding infantile colic and other functional gastrointestinal disorders, unless associated to symptoms which are likely to interfere with drug absorption, e.g. frequent vomiting), haematological, severe dermatological or neurological pathology or other diseases; Previous major surgery or blood loss Intake of antimuscarinic drugs, simethicone, or dimethicone 24 hours before study treatment administration.

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 24 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Nepadutant 0.1 mg/kg | Drug: Nepadutant<br>* 0.1 mg/Kg as one single oral dose divided in three age strata (from 6 to 24 weeks old)<br>|
| Experimental: 2<br>Nepadutant 0.5 mg/kg | Drug: Nepadutant<br>* 0.5 mg/Kg as one single oral dose divided in three age strata (from 6 to 24 weeks old)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug Concentration Measurement in the Urine Collected by Diapers Along 24 Hours Post Dose and One Week After Dose in All Treated Infants and by Age and Dose Subgroups. | Nepadutant was measured in the 24-h urine collection post both doses (0.1 and 0.5 mg/kg dose), in the age strata 6-<12 and 12-<18 weeks, using urinary collection/extraction from pre-weighed special fiber based diapers. | 24 hours | 
| Drug Concentration Measurement in the Urine Collected by Diapers Along 24 Hours Post Dose and One Week After Dose in All Treated Infants and by Age and Dose Subgroups. | Nepadutant was measured in the 24-h urine collection post both doses (0.1 and 0.5 mg/kg dose), in the age stratum 18-24 weeks, using urinary collection/extraction from pre-weighed special fiber based diapers. | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events After Administration of Single Oral Doses up to 0.5 mg/kg of Nepadutant in Infants. | Number of adverse events (AE) reported by dose and age stratum 6-<12 and 12-<18 weeks. | one week | 
| Number of Adverse Events After Administration of Single Oral Doses up to 0.5 mg/kg of Nepadutant in Infants. | Number of adverse events (AE) reported by dose and age stratum 18-24 weeks. | one week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infantile colic, Abdominal Cramps, Colicky Pain, Functional gastrointestinal disorders