Clinical trial NCT01532518: Preliminary Efficacy, Safety and Pharmacokinetics Study of Nepadutant in Infant With Feeding Intolerance
Official title: A Multicenter, Open Label, Ascending 7 Day-Repeated Dose Study to Investigate Efficacy, Safety and Pharmacokinetics of Nepadutant In Infants With Feeding Intolerance
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colic
Keywords: Feeding intolerance
Infant
tachykinin antagonist
Infant colic
Nepadutant
Lead sponsor: Menarini Group
Sponsor class: INDUSTRY
First posted: 2012-02-14
Enrollment: 27
Sex: ALL
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: The Absolute Differences of I-GERQ-R Total Score at V3 (End of First Week of Treatment) Respect to the Baseline (V2).
timeFrame: Baseline (V2) and end of first week of treatment (V3)
measure: 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).
timeFrame: V3 (end of 1st week of treatment) and V4 (end of 2nd week of treatment)
measure: The Absolute Differences of I-GERQ-R Total Score at V5 (Follow-up) Respect to V2 (Baseline).
timeFrame: Baseline (V2) and follow up 2 weeks after the last administered dose (V5)
measure: I-GERQ-R Score Changes vs Baseline (Visit 2) by First Dose Level (0.1mg/kg and 0.5mg/kg).
timeFrame: Baseline (V2) and end of 1st week of treatment(V3)
measure: I-GERQ-R Score Changes vs Visit 3 by Second Dose Level (0.5mg/kg and 1mg/kg).
timeFrame: end of first week of treatment (V3) and end of second week of treatment (V4)
Secondary outcomes:
measure: Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level
timeFrame: up to 4 weeks
measure: A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04
timeFrame: 0.5, 1, 2, 3 hours post Single Dose and 24 hours post Repeated Dose
measure: A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04
timeFrame: 0.5, 1, 2, 3 hours post Single Dose and 24 hours post Repeated Dose
measure: A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04
timeFrame: 0.5, 1, 2, 3 hours post Single Dose and 24 hours post Repeated Dose
measure: A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04
timeFrame: 0.5, 1, 2, 3 hours post Single Dose and 24 hours post Repeated Dose
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Atlanta
country: United States
facility: Children's Center for Digestive Healthcare
state: Georgia
city: Louisville
country: United States
facility: Kosair Charities Pediatric Clinical Research Unit / University of Louisville
state: Kentucky
city: Albany
country: United States
facility: SUNY Downstate Medical Center
state: New York
city: Toledo
country: United States
facility: The University of Toledo College of Medicine\The Toledo Children's Hospital
state: Ohio
Study officials:
affiliation: The University of Toledo Medical Center 3000 Arlington Avenue, Toledo OH 43614 USA
name: Jeffrey L Blumer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: