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.

Study Overview

• Status: Completed
• Conditions: Infantile Colic
• Intervention / Treatment: Drug: Nepadutant oral solution; Drug: Placebo matching Nepadutant oral solution

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 115
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • München, Germany, 80337
    • Dr. von Haunersches Kinderspital Ludwig Maximilians Universität München
• Poland
  • Lublin, Poland, 20-093
    • Klinika Patologii Noworodkow, Niemowlat I Kardiologii, Dzieciecy Szpital Kliniczny
• Russian Federation
  • Moscow, Russian Federation, 117997
    • Federal Scientific Clinical Center of Children Hematology, Oncology and Immunology
  • Moscow, Russian Federation, 119331
    • Moscow State Healthcare Institution Municipal Pediatric health center № 10
  • Moscow, Russian Federation, 119991
    • Moscow State Medical University
  • Moscow, Russian Federation, 123317
    • Federal Scientific Clinical Center of Children Hematology, Oncology and Immunology
  • St. Petersburg, Russian Federation, 194100
    • St. Petersburg State Pediatric Medical Academy
  • St. Petersburg, Russian Federation, 199191
    • St. Petersburg State Institution of Healthcare Municipal Pediatric health center № 35
• Sweden
  • Umeå, Sweden, SE-901 85
    • Pediatrics Department of Clinical sciences Umeå university

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 weeks to 4 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo matching Nepadutant oral solution; Oral administration once daily for 7 days
Experimental: Nepadutant High Dose	Drug: Nepadutant oral solution; Oral administration once daily for 7 days
Experimental: Nepadutant Low Dose	Drug: Nepadutant oral solution; Oral administration once daily for 7 days

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Menarini Group
• Investigators: Study Chair: Sibylle Koletzko, MD, Dr. v. Haunersches Kinderspital Ludwig Maximilians University D- 80337 München, Germany

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: December 9, 2010
• First Submitted That Met QC Criteria: December 9, 2010
• First Posted (Estimate): December 10, 2010

Study Record Updates

• Last Update Posted (Estimate): June 10, 2015
• Last Update Submitted That Met QC Criteria: May 26, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Infantile Colic; Nepadutant; tachykinin antagonist
• Additional Relevant MeSH Terms: Infant, Newborn, Diseases; Colic; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Pharmaceutical Solutions; MEN 11420
• Other Study ID Numbers: NIC-03