Infantile Colic, Infantile Functional Gastrointestinal Disorders
Conditions
Keywords
Infantile colic, Abdominal Cramps, Colicky Pain, Functional gastrointestinal disorders
Brief summary
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.
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.
Interventions
DRUGNepadutant
0.1 mg/Kg as one single oral dose divided in three age strata (from 6 to 24 weeks old)
Sponsors
Menarini Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Weeks to 24 Weeks
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 24 hours | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events After Administration of Single Oral Doses up to 0.5 mg/kg of Nepadutant in Infants. | one week | Number of adverse events (AE) reported by dose and age stratum 6-\<12 and 12-\<18 weeks. |
Countries
United States
Participant flow
Recruitment details
The recruitment period extended from March 2008 to May 2009 at three Hospital Clinics
Pre-assignment details
Twenty out of the 21 enrolled infants were treated with study medication (1 infant did not attend the clinic after screening). NOTE: although the goal was to enroll 24 subjects, slow subject enrollment and expired drug restricted enrollment to 20 subjects
Participants by arm
| Arm | Count |
|---|---|
| Nepadutant 0.1 mg/kg Nepadutant 0.1 mg/kg | 12 |
| Nepadutant 0.5 mg/kg Nepadutant 0.5 mg/kg | 8 |
| Total | 20 |
Baseline characteristics
| Characteristic | Nepadutant 0.1 mg/kg | Total | Nepadutant 0.5 mg/kg |
|---|---|---|---|
| Age, Customized Age Group 12 to <18 weeks | 4 participants | 9 participants | 5 participants |
| Age, Customized Age Group 18 to 24 weeks | 4 participants | 4 participants | 0 participants |
| Age, Customized Age Group 6 to <12 weeks | 4 participants | 7 participants | 3 participants |
| Region of Enrollment United States | 12 participants | 20 participants | 8 participants |
| Sex: Female, Male Female | 6 Participants | 11 Participants | 5 Participants |
| Sex: Female, Male Male | 6 Participants | 9 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 12 | 2 / 8 |
| serious Total, serious adverse events | 0 / 12 | 0 / 8 |
Outcome results
Primary
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.
Time frame: 24 hours
Population: Urinary drug concentration was analysed by dose and age stratum of the infants (18-24 weeks of age). Imputation technique was adopted for urine samples highly contaminated by faeces.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nepadutant 0.1 mg/kg | 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. | 1127 ng | Standard Deviation 1032 |
Primary
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.
Time frame: 24 hours
Population: Urinary drug concentration was analysed by dose and age stratum of the infants (6-\<12 and 12- \<18 weeks of age). Imputation technique was adopted for urine samples highly contaminated by faeces.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nepadutant 0.1 mg/kg | 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. | 6- <12 week old | 5041 ng | Standard Deviation 7081 |
| Nepadutant 0.1 mg/kg | 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. | 12- < 18 week old | 2095 ng | Standard Deviation 1151 |
| Nepadutant 0.5 mg/kg | 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. | 6- <12 week old | 6474 ng | Standard Deviation 2463 |
| Nepadutant 0.5 mg/kg | 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. | 12- < 18 week old | 3727 ng | Standard Deviation 2845 |
Secondary
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.
Time frame: one week
Population: Number of adverse events by dose and age stratum (18-24 weeks of age) are reported by system organ class and preferred term.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nepadutant 0.1 mg/kg | Number of Adverse Events After Administration of Single Oral Doses up to 0.5 mg/kg of Nepadutant in Infants. | 3 Adverse Events |
Secondary
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.
Time frame: one week
Population: Number of adverse events by dose and age strata (6-\<12 and 12- \<18 weeks of age) are reported by system organ class and preferred term.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nepadutant 0.1 mg/kg | Number of Adverse Events After Administration of Single Oral Doses up to 0.5 mg/kg of Nepadutant in Infants. | 6- <12 week old | 0 Adverse Events |
| Nepadutant 0.1 mg/kg | Number of Adverse Events After Administration of Single Oral Doses up to 0.5 mg/kg of Nepadutant in Infants. | 12- < 18 week old | 1 Adverse Events |
| Nepadutant 0.5 mg/kg | Number of Adverse Events After Administration of Single Oral Doses up to 0.5 mg/kg of Nepadutant in Infants. | 12- < 18 week old | 1 Adverse Events |
| Nepadutant 0.5 mg/kg | Number of Adverse Events After Administration of Single Oral Doses up to 0.5 mg/kg of Nepadutant in Infants. | 6- <12 week old | 3 Adverse Events |