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

A Multicenter, Open Label, Ascending 7 Day-Repeated Dose Study to Investigate Efficacy, Safety and Pharmacokinetics of Nepadutant In Infants With Feeding Intolerance

The present pilot study is aimed to obtain preliminary data on the effect of three ascending oral dose levels of nepadutant on the relief of symptoms associated with feeding intolerance. In addition, the assessment of drug exposure (PK assessment) will provide additional information on the dose-effect relationship, thus supporting the dose selection and dosing schedule in the future studies.

Feeding intolerance is a transient neuro-developmental phenomenon affecting 25% to 40% of infant and toddler, with a peak at 6 weeks of age. Feeding problems include mainly vomiting, slow feeding, refusal to eat and colic.

Current non pharmacological interventions (e.g. message, restriction in maternal diet in breast-feeding infants) and pharmacological treatments (simethicone, antimuscarinic drugs and antiacids) are largely unsatisfactory.

Nepadutant is postulated to have a therapeutic effect in infant colic since it reverts exaggerated intestinal motility and sensitivity induced by different stimuli through the activation of neurokinin-2 receptors, without interferring on the on physiological gastrointestinal transit.

This phase IIa study is designed to test in each participant infant two out of three oral doses of nepadutant in order to measure its blood levels, safety and efficacy with each dose level to be given for 7 concecutive days.

The experimental clinical phase encompasses the following periods:

• Screening period (no study medication), lasting approximately 7 days prior to randomization
• Treatment period, lasting fourteen days (7 days fore each dose)with once daily administration
• A safety follow-up visit, approximately four weeks after start of treatment.

Inclusion Criteria:

• Infants with a clinical diagnosis of feeding intolerance.
• Age ≤ 6 months at the enrolment.
• Normal growth.
• Infants who can refrain from use of erythromycin, metoclopramide, antihistaminic drug, proton pump inhibitors (PPIs), antacids, antimuscarinic drugs, simethicone and dimethicone from 1 week prior randomization until end of study.

Exclusion Criteria:

• Any clinically relevant event (excluding those relevant to the condition under study) which has occurred within one week prior to randomization.
• Any pharmacological treatment starting within one week prior to randomization.
• Infants for whom a change in the diet (i.e. weaning) has been performed within one week prior to randomization or is planned during the study period.