A Phase I Study to Evaluate the Oral Absorption of Nepadutant in Infants

Pilot Study to Evaluate the Oral Absorption, Safety, and Tolerability of Nepadutant Administered as Single Oral Doses to Infants With Colic and Other Functional Gastrointestinal Disorders

The purpose of the study is to evaluate the gastrointestinal absorption of nepadutant after single dose as oral solution (and the effect of age on its oral absorption) in infants. Oral absorption is evaluated through the drug recovery in urine.

Study Overview

• Status: Completed
• Conditions: Infantile Colic; Infantile Functional Gastrointestinal Disorders
• Intervention / Treatment: Drug: Nepadutant; Drug: Nepadutant

Detailed Description

This trial aims to evaluate the oral adsorption of nepadutant (0.1 or 0.5 mg/Kg given as one single dose as oral solution) in infants divided in three age strata (from 6 to 24 weeks old). Oral absorption is evaluated by measuring the amount of nepadutant in the urine output collected during the 24 hours after oral administration with special diapers.

Safety and tolerability of the drug will be evaluated by monitoring any changes in signs/symptoms at medical examination and vital signs during the fist 4 hours post-dose in the Hospital site and then by the parents at home up to 24 hours and 1 week post nepadutant administration.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Kosair Charities Pediatric Clinical Rsearch Unit University of Louisville
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Rainbow Babies and Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 5 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Subjects will be eligible for inclusion in the study if they meet all of the following criteria:

• Infants with a history consistent with a diagnosis of colic or other functional gastrointestinal disorders
• Age >6 weeks and < 24 weeks
• At least 44 weeks post-conceptual age at enrolment
• Normal growth
• Informed consent by parents (one or both) or legal guardian
• Caregiver available to be trained in collection and storage of used diapers
• Caregiver available to record feeding episodes and defecations on the diary

Exclusion Criteria:

Subjects will be excluded from the study if they meet any of the following criteria:

• Clinical evidence of major cardiovascular, respiratory, renal, hepatic, endocrine, metabolic, gastrointestinal (excluding infantile colic and other functional gastrointestinal disorders, unless associated to symptoms which are likely to interfere with drug absorption, e.g. frequent vomiting), haematological, severe dermatological or neurological pathology or other diseases;
• Previous major surgery or blood loss
• Intake of antimuscarinic drugs, simethicone, or dimethicone 24 hours before study treatment administration.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Nepadutant 0.1 mg/kg	Drug: Nepadutant; 0.1 mg/Kg as one single oral dose divided in three age strata (from 6 to 24 weeks old); Drug: Nepadutant; 0.5 mg/Kg as one single oral dose divided in three age strata (from 6 to 24 weeks old)
Experimental: 2; Nepadutant 0.5 mg/kg	Drug: Nepadutant; 0.1 mg/Kg as one single oral dose divided in three age strata (from 6 to 24 weeks old); Drug: Nepadutant; 0.5 mg/Kg as one single oral dose divided in three age strata (from 6 to 24 weeks old)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drug Concentration Measurement in the Urine Collected by Diapers Along 24 Hours Post Dose and One Week After Dose in All Treated Infants and by Age and Dose Subgroups.	Nepadutant was measured in the 24-h urine collection post both doses (0.1 and 0.5 mg/kg dose), in the age strata 6-<12 and 12-<18 weeks, using urinary collection/extraction from pre-weighed special fiber based diapers.	24 hours
Drug Concentration Measurement in the Urine Collected by Diapers Along 24 Hours Post Dose and One Week After Dose in All Treated Infants and by Age and Dose Subgroups.	Nepadutant was measured in the 24-h urine collection post both doses (0.1 and 0.5 mg/kg dose), in the age stratum 18-24 weeks, using urinary collection/extraction from pre-weighed special fiber based diapers.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events After Administration of Single Oral Doses up to 0.5 mg/kg of Nepadutant in Infants.	Number of adverse events (AE) reported by dose and age stratum 6-<12 and 12-<18 weeks.	one week
Number of Adverse Events After Administration of Single Oral Doses up to 0.5 mg/kg of Nepadutant in Infants.	Number of adverse events (AE) reported by dose and age stratum 18-24 weeks.	one week

Collaborators and Investigators

• Sponsor: Menarini Group
• Investigators: Study Chair: Jeffrey L Blumer, MD, PHD, Rainbow Babies and Children's Hospital

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): May 1, 2009

Study Registration Dates

• First Submitted: April 3, 2008
• First Submitted That Met QC Criteria: April 3, 2008
• First Posted (Estimate): April 9, 2008

Study Record Updates

• Last Update Posted (Estimate): October 17, 2011
• Last Update Submitted That Met QC Criteria: October 11, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: Functional gastrointestinal disorders; Infantile colic; Abdominal Cramps; Colicky Pain
• Additional Relevant MeSH Terms: Infant, Newborn, Diseases; Gastrointestinal Diseases; Digestive System Diseases; Colic; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; MEN 11420
• Other Study ID Numbers: NIC 02; Oral absorption; of Nepadutant in Infants