Preliminary Efficacy and Safety Study of Oral Nepadutant in Infant Colic

Study Overview
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Brief Summary
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This phase IIa study is designed as a multi-centre, multinational, randomised, double-blind, placebo controlled study in three parallel groups, with the aim to evaluate the efficacy and safety of Nepadutant given at two oral doses once daily for seven days in comparison to placebo in the treatment of infantile colic.

Detailed Description
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Infant colic is a functional gastrointestinal disorders which affects up to the 30% of the infant population; it is primarily characterised by excessive inconsolable crying starting without any apparent cause and lasting for several hours per day. Current non pharmacological interventions (e.g. message, restriction in maternal diet in breast-feeding infants) and pharmacological treatments (simethicone, antimuscarinic drugs) are largely unsatisfactory. In animal models, Nepadutant reverse the exaggerated intestinal motility and sensitivity, induced by different stimuli, without producing inhibitory effects on these functions at baseline, suggesting that Nepadutant could have a therapeutic effect with no interference on physiological gastrointestinal transit. This phase IIa study is designed to evaluate the efficacy of Nepadutant paediatric oral solution given once daily at two doses in comparison to placebo. The experimental clinical phase encompasses the following periods: Screening period (no study medication) to be done 7 to 4 days prior to randomisation Treatment period, lasting seven days with once daily administration Post treatment period, lasting seven days A safety follow-up visit will be performed approximately 1 month after the first administered dose.

Official Title
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Double-blind, Randomised, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Oral Administration of Nepadutant in Infant Colic

Conditions
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Infantile Colic

Intervention / Treatment
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* Drug: Nepadutant oral solution
* Drug: Nepadutant oral solution
* Drug: Placebo matching Nepadutant oral solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy infants with diagnosis of infant colic according to the following modified Wessel criterion paroxysm of irritability, fussing or crying that start and stop without obvious cause for >3h/day, >3 days/week for one week Age > 4 weeks and < 20 weeks Infants breast-fed mixed fed or formula fed with a stable dietary regimen Normal growth History of no adequate response to conventional treatment alternatives which make the infants in need of medical treatment Willingness to refrain from use of antimuscarinic drugs, simethicone, dimethicone or antiacids during the study period. Exclusion Criteria: Clinical evidence of allergies or other diseases which may cause crying and/or fussiness or may interfere with absorption or clearance of the drug. Suspect of gastroesophageal reflux disease (GERD) Suspect of cow milk allergy.

Ages Eligible for Study
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Minimum Age: 4 Weeks
Maximum Age: 20 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nepadutant Low Dose<br> | Drug: Nepadutant oral solution<br>* Oral administration once daily for 7 days<br>|
| Experimental: Nepadutant High Dose<br> | Drug: Nepadutant oral solution<br>* Oral administration once daily for 7 days<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo matching Nepadutant oral solution<br>* Oral administration once daily for 7 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change of the Mean Daily Crying and Fussing Time for Three Consecutive Days While on Treatment Versus Baseline. | Efficacy assessment to be measured through baby's day diary recorded for three consecutive days while on treatment (i.e. starting from 6 pm on Day 4 and continued for 72 hours) vs baseline (i.e. starting from 6 pm on Day -4 until 1st treatment administration). | Baseline and one week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of 'Responder' Babies at the End of Treatment Period. | Response is defined as a decrease of at least 50% of crying and fussing time during the last 3 days on treatment vs baseline. | baseline and one week | 
| Absolute Change in the Overall Parental Judgment After the First Dose of Treatment Versus Baseline | On a daily basis parents expressed an overall judgement on the study treatment effect based on a 6 rate categorical scale from 0 to 5 (where 0 is for Not at all and 5 is Extremely. The question was How frustrating to you was your baby's crying today?) | 1 day | 
| Absolute Change in the Overall Parental Judgment at the End of Treatment Versus Baseline | On a daily basis parents expressed an overall judgement on the study treatment effect based on a 6 rate categorical scale from 0 to 5 (where 0 is for Not at all and 5 is Extremely. The question was How frustrating to you was your baby's crying today?) | 1 week | 
| Absolute Change in the Overall Parental Judgment After Treatment Discontinuation Versus Baseline | On a daily basis parents expressed an overall judgement on the study treatment effect based on a 6 rate categorical scale from 0 to 5 (where 0 is for Not at all and 5 is Extremely. The question was How frustrating to you was your baby's crying today?) | 10 days | 
| Safety and Tolerability Will be Assessed in Terms of Frequency and Severity of AEs as Well as Frequency of Clinically Significant Changes in Physical Examination and Lab Test. | Safety and tolerability will be assessed for the Safety Population (all patients who received the study drug) in terms of frequency and severity of AEs as well as frequency of clinically significant changes in physical examination and lab test. | up to four weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infantile Colic, tachykinin antagonist, Nepadutant