Preliminary Efficacy, Safety and Pharmacokinetics Study of Nepadutant in Infant With Feeding Intolerance

NCT01532518 | Completed Phase 2 Results

• 1 other identifier: NIC-04
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 5

Brief Summary

The present pilot study is aimed to obtain preliminary data on the effect of three ascending oral dose levels of nepadutant on the relief of symptoms associated with feeding intolerance. In addition, the assessment of drug exposure (PK assessment) will provide additional information on the dose-effect relationship, thus supporting the dose selection and dosing schedule in the future studies.

Conditions

Colic

Keywords

Feeding intolerance; Infant; tachykinin antagonist; Infant colic; Nepadutant

Outcome Measures

Primary Outcomes (5)

• The Absolute Differences of I-GERQ-R Total Score at V3 (End of First Week of Treatment) Respect to the Baseline (V2).

  Results obtained at V2 serve as baseline values for the assessment of effects at V3 (i.e. end of first week of treatment). Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R ), with a minimum-maximum score of 0-42 (minimum for diagnosis \>15). The higher values reflect worse outcome. The questionnaire comprised 12 items as questions quantifying aspects of regurgitation (3 questions), crying (3 questions), feeding refusal (2 questions), apnea/cyanosis (2 questions), hiccups and arching. Questions with 4 possible options have a score ranging from 0 to 3; questions with 5 possible options have a score ranging from 0 to 4. The scores of each item are summed, so the total score is presented.

  Baseline (V2) and end of first week of treatment (V3)

• The Absolute Differences of I-GERQ-R Total Score at V4 (End of 2nd Week of Treatment) Respect to V3 (End of 1st Week of Treatment).

  The results obtained at V3 are used as baseline for the second week treatment period (V4). Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R ), with a minimum-maximum score of 0-42 (minimum for diagnosis \>15). The higher values reflect worse outcome. The questionnaire comprised 12 items as questions quantifying aspects of regurgitation (3 questions), crying (3 questions), feeding refusal (2 questions), apnea/cyanosis (2 questions), hiccups and arching. Questions with 4 possible options have a score ranging from 0 to 3; questions with 5 possible options have a score ranging from 0 to 4. The scores of each item are summed, so the total score is presented.

  V3 (end of 1st week of treatment) and V4 (end of 2nd week of treatment)

• The Absolute Differences of I-GERQ-R Total Score at V5 (Follow-up) Respect to V2 (Baseline).

  Results obtained at V2 serve as baseline values for follow-up assessment 2 weeks after the last administered dose (V5) Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R ), with a minimum-maximum score of 0-42 (minimum for diagnosis \>15). The higher values reflect worse outcome. The questionnaire comprised 12 items as questions quantifying aspects of regurgitation (3 questions), crying (3 questions), feeding refusal (2 questions), apnea/cyanosis (2 questions), hiccups and arching. Questions with 4 possible options have a score ranging from 0 to 3; questions with 5 possible options have a score ranging from 0 to 4. The scores of each item are summed, so the total score is presented.

  Baseline (V2) and follow up 2 weeks after the last administered dose (V5)

• I-GERQ-R Score Changes vs Baseline (Visit 2) by First Dose Level (0.1mg/kg and 0.5mg/kg).

  Change in Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R) Score. Assessing the I-GERQ-R score changes vs baseline (Visit 2) by first dose level (0.1mg/kg and 0.5mg/kg). Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R ), with a minimum-maximum score of 0-42 (minimum for diagnosis \>15). The higher values reflect worse outcome. The questionnaire comprised 12 items as questions quantifying aspects of regurgitation (3 questions), crying (3 questions), feeding refusal (2 questions), apnea/cyanosis (2 questions), hiccups and arching. Questions with 4 possible options have a score ranging from 0 to 3; questions with 5 possible options have a score ranging from 0 to 4. The scores of each item are summed, so the total score is presented.

  Baseline (V2) and end of 1st week of treatment(V3)

• I-GERQ-R Score Changes vs Visit 3 by Second Dose Level (0.5mg/kg and 1mg/kg).

  Change in Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R) Score. Assessing the I-GERQ-R score changes vs Visit 3 by second dose level (0.5mg/kg and 1mg/kg). Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R ), with a minimum-maximum score of 0-42 (minimum for diagnosis \>15). The higher values reflect worse outcome. The questionnaire comprised 12 items as questions quantifying aspects of regurgitation (3 questions), crying (3 questions), feeding refusal (2 questions), apnea/cyanosis (2 questions), hiccups and arching. Questions with 4 possible options have a score ranging from 0 to 3; questions with 5 possible options have a score ranging from 0 to 4. The scores of each item are summed, so the total score is presented.

  end of first week of treatment (V3) and end of second week of treatment (V4)

Secondary Outcomes (5)

• Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level

  up to 4 weeks

• A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04

  0.5, 1, 2, 3 hours post Single Dose and 24 hours post Repeated Dose

• A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04

  0.5, 1, 2, 3 hours post Single Dose and 24 hours post Repeated Dose

• A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04

  0.5, 1, 2, 3 hours post Single Dose and 24 hours post Repeated Dose

• A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04

  0.5, 1, 2, 3 hours post Single Dose and 24 hours post Repeated Dose

Study Arms (3)

Cohort 3

EXPERIMENTAL

Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days

Drug: Nepadutant

Cohort 2

EXPERIMENTAL

Nepadutant medium dose (0.5mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days

Drug: Nepadutant

Cohort 1

EXPERIMENTAL

Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant medium dose (0.5mg/kg) for additional 7 days

Drug: Nepadutant

Interventions

Nepadutant DRUG

Nepadutant oral solution

Also known as: MEN 11420

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: Up to 6 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Infants with a clinical diagnosis of feeding intolerance.
• Age ≤ 6 months at the enrolment.
• Normal growth.
• Infants who can refrain from use of erythromycin, metoclopramide, antihistaminic drug, proton pump inhibitors (PPIs), antacids, antimuscarinic drugs, simethicone and dimethicone from 1 week prior randomization until end of study.

You may not qualify if:

• Any clinically relevant event (excluding those relevant to the condition under study) which has occurred within one week prior to randomization.
• Any pharmacological treatment starting within one week prior to randomization.
• Infants for whom a change in the diet (i.e. weaning) has been performed within one week prior to randomization or is planned during the study period.

Sponsors & Collaborators

• Menarini Group: lead

Study Sites (5)

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Children's Center for Digestive Healthcare

Atlanta, Georgia, 30342, United States

Location

Kosair Charities Pediatric Clinical Research Unit / University of Louisville

Louisville, Kentucky, 40202, United States

Location

SUNY Downstate Medical Center

Albany, New York, 12207, United States

Location

The University of Toledo College of Medicine\The Toledo Children's Hospital

Toledo, Ohio, 43606, United States

Location

MeSH Terms

Conditions

Colic

Interventions

MEN 11420

Condition Hierarchy (Ancestors)

Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Limitations and Caveats

Study performed in a small number of subjects.

Results Point of Contact

• Title: Dr. Angela Capriati
• Organization: Menarini Ricerche

acapriati@menarini-ricerche.it

+39 05556809990

Study Officials

• Jeffrey L Blumer, MD, PhD

  The University of Toledo Medical Center 3000 Arlington Avenue, Toledo OH 43614 USA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2012
• First Posted: February 14, 2012
• Study Start: August 1, 2011
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: May 6, 2023
• Results First Posted: May 6, 2023

Record last verified: 2022-08

Locations

US (5)