Double-blind, randomised, placebo-controlled, parallel group pilot study to evaluate the efficacy and safety of oral administration of Nepadutant in infant colic babies not responder to conventional treatments

INTERVENTION: Product Name: Nepadutant Pharmaceutical Form: Oral solution INN or Proposed INN: nepadutant CAS Number: 183747‐35‐5 Concentration unit: µg/ml microgram(s)/millilitre Concentration type: equal Concentration number: 400‐ Pharmaceutical form of the placebo: Oral solution Route of administration of the placebo: Oral use Product Name: Nepadutant Pharmaceutical Form: Oral solution INN or Proposed INN: nepadutant CAS Number: 183747‐35‐5 Concentration unit: µl/ml microlitre(s)/millilitre Concentration type: equal Concentration number: 2000‐ Pharmaceutical form of the placebo: Oral solution Route of administration of the placebo: Oral use CONDITION: Infant colic ; MedDRA version: 9.1 Level: LLT Classification code 10061247 PRIMARY OUTCOME: Main Objective: This study is designed to evaluate the efficacy of Nepadutant paediatric oral solution given once daily at two doses in comparison to placebo. Primary end point(s): Aabsolute change of the mean daily crying and fussing combined time as recorded on the “baby’s day” diary for three consecutive days while on treatment (i.e. starting from 6 pm on Day 4 and continued for 72 hours) versus baseline (i.e. starting from 6 pm on Day ‐4 until 1st treatment administration). Secondary Objective: • To assess the duration of treatment effect after end of treatment. •To assess the safety and tolerability after 7 day repeated doses. •To select the dose to be tested in the subsequent Phase II/III clinical development. •To evaluate the pharmacokinetics of Nepadutant in infants. INCLUSION CRITERIA: 1. 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”, and confirmed by Crying Patterns Questionnaire. NOTE: At randomisation, eligibility of patient has to be confirmed also by at least 2 days with at least 3h/day overall crying and fussing time recorded on “baby’s day” diary during the 3 day period from Day ‐4 to Day ‐1. 2. History of no adequate response to more than one conventional pharmacological or non‐pharmacological treatment alternatives, such as simethicone, probiotics, herbal tea, behaviour interventions, which make the infants in need of medical treatment. 3. Age = 6 weeks and < 4 months with a post‐conceptual age (PCA) > 44 weeks at the enrolment. 4. Infants exclusively breast‐fed. 5. Normal growth (body weight, length, and head circumference > ‐2 SD or 5th percentile, a