Preliminary Efficacy and Safety Study of Oral Nepadutant in Infant Colic (no-cry)

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

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.

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.

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).

Response is defined as a decrease of at least 50% of crying and fussing time during the last 3 days on treatment vs 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?")

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?")

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?")

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.

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.