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

• ClinicalTrials.gov Identifier: NCT01258153
• Recruitment Status: Completed
• First Posted: December 10, 2010
• Results First Posted: June 10, 2015
• Last Update Posted: June 10, 2015
• Sponsor: Menarini Group
• Information provided by (Responsible Party): Menarini Group

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Infantile Colic	Drug: Nepadutant oral solution; Drug: Placebo matching Nepadutant oral solution	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 115 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Double-blind, Randomised, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Oral Administration of Nepadutant in Infant Colic
• Study Start Date: November 2010
• Actual Primary Completion Date: December 2013
• Actual Study Completion Date: March 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Absolute Change of the Mean Daily Crying and Fussing Time for Three Consecutive Days While on Treatment Versus Baseline. [ Time Frame: Baseline and one week ]
   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).

Secondary Outcome Measures :

1. Percentage of 'Responder' Babies at the End of Treatment Period. [ Time Frame: baseline and one week ]
   Response is defined as a decrease of at least 50% of crying and fussing time during the last 3 days on treatment vs baseline.
2. Absolute Change in the Overall Parental Judgment After the First Dose of Treatment Versus Baseline [ Time Frame: 1 day ]

   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?")

3. Absolute Change in the Overall Parental Judgment at the End of Treatment Versus Baseline [ Time Frame: 1 week ]

   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?")

4. Absolute Change in the Overall Parental Judgment After Treatment Discontinuation Versus Baseline [ Time Frame: 10 days ]

   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?")

5. 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. [ Time Frame: up to four weeks ]
   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.

Eligibility Criteria

• Ages Eligible for Study: up to 20 Weeks (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Germany

Dr. von Haunersches Kinderspital Ludwig Maximilians Universität München

München, Germany, 80337

Poland

Klinika Patologii Noworodkow, Niemowlat I Kardiologii, Dzieciecy Szpital Kliniczny

Lublin, Poland, 20-093

Russian Federation

Federal Scientific Clinical Center of Children Hematology, Oncology and Immunology

Moscow, Russian Federation, 117997

Moscow State Healthcare Institution Municipal Pediatric health center № 10

Moscow, Russian Federation, 119331

Moscow State Medical University

Moscow, Russian Federation, 119991

Federal Scientific Clinical Center of Children Hematology, Oncology and Immunology

Moscow, Russian Federation, 123317

St. Petersburg State Pediatric Medical Academy

St. Petersburg, Russian Federation, 194100

St. Petersburg State Institution of Healthcare Municipal Pediatric health center № 35

St. Petersburg, Russian Federation, 199191

Sweden

Pediatrics Department of Clinical sciences Umeå university

Umeå, Sweden, SE-901 85

Sponsors and Collaborators

Menarini Group

Investigators

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

More Information

• Responsible Party: Menarini Group
• ClinicalTrials.gov Identifier: NCT01258153
• Other Study ID Numbers: NIC-03
• First Posted: December 10, 2010
• Results First Posted: June 10, 2015
• Last Update Posted: June 10, 2015
• Last Verified: May 2015

Keywords provided by Menarini Group:

Infantile Colic; tachykinin antagonist; Nepadutant

Additional relevant MeSH terms:

Colic; Infant, Newborn, Diseases; Pharmaceutical Solutions; MEN 11420; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents