A Phase 2 interventional study of Nepadutant in Colic, sponsored by Menarini Group. Completed at 5 sites in United States. Open to participants aged Up to 6 Months. Per ClinicalTrials.gov, last updated 2023-05-06.
Sponsored by Menarini Group · Phase 2, Interventional, and Treatment
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.
Feeding intolerance is a transient neuro-developmental phenomenon affecting 25% to 40% of infant and toddler, with a peak at 6 weeks of age. Feeding problems include mainly vomiting, slow feeding, refusal to eat and colic.
Current non pharmacological interventions (e.g. message, restriction in maternal diet in breast-feeding infants) and pharmacological treatments (simethicone, antimuscarinic drugs and antiacids) are largely unsatisfactory.
Nepadutant is postulated to have a therapeutic effect in infant colic since it reverts exaggerated intestinal motility and sensitivity induced by different stimuli through the activation of neurokinin-2 receptors, without interferring on the on physiological gastrointestinal transit.
This phase IIa study is designed to test in each participant infant two out of three oral doses of nepadutant in order to measure its blood levels, safety and efficacy with each dose level to be given for 7 concecutive days.
The experimental clinical phase encompasses the following periods:
127 studies on the registry are indexed under Colic; 18 are open to participants now.
This study's enrollment of 27 is below the median of 76 across 110 interventional studies indexed under Colic.
Browse Colic studies →Menarini Group is the lead sponsor of 28 studies on the registry; 1 is open to participants now.
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Clinically significant
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Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days
Drug: Nepadutant
Nepadutant medium dose (0.5mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days
Drug: Nepadutant
Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant medium dose (0.5mg/kg) for additional 7 days
Drug: Nepadutant
Nepadutant oral solution
Also known as: MEN 11420
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: end of first week of treatment (V3) and end of second week of treatment (V4)
Incidence and Severity of AEs_ Number of Adverse Events by Treatment Dose Level
The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.
Time frame: up to 4 weeks
A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04
The population pharmacokinetic analyses is presented. PopPK Clearance estimated with a one compartment model with first order absorption and elimination.
Time frame: 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
PopPK Volume estimated with a one compartment model with first order absorption and elimination. NOTE: for this measure, no inter-individual variability was estimated, therefore the value for each cohort corresponds to the typical value.
Time frame: 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
The population pharmacokinetic analyses is presented. PopPK Ka estimated with a one compartment model with first order absorption and elimination. NOTE: for this measure, no inter-individual variability was estimated, therefore the value for each cohort corresponds to the typical value.
Time frame: 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
The population pharmacokinetic analyses is presented. The PopPK parameter fraction of the dose absorbed (F1) is estimated with a one compartment model with first order absorption and elimination.The results are presented fraction of the absorbed dose with 95% CI of the parameter estimate value
Time frame: 0.5, 1, 2, 3 hours post Single Dose and 24 hours post Repeated Dose
| Milestone | Cohort 3 | Cohort 2 | Cohort 1 |
|---|---|---|---|
| Started | 6 | 15 | 6 |
| Completed | 6 | 15 | 5 |
| Not completed | 0 | 0 | 1 |
| Withdrew: Withdrawal by subject | 0 | 0 | 1 |
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.
| score on a scale | Cohort 3 | Cohort 2 | Cohort 1 |
|---|---|---|---|
| The Absolute Differences of I-GERQ-R Total Score at V3 (End of First Week of Treatment) Respect to the Baseline (V2). | -6.8 ± 9.55 | -7.6 ± 5.5 | -6.8 ± 5.81 |
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.
| Score as sum of units | Cohort 3 | Cohort 2 | Cohort 1 |
|---|---|---|---|
| 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). | -15.2 ± 5.54 | -11.9 ± 6.8 | -8.6 ± 6.66 |
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.
| Score as sum of units | Cohort 3 | Cohort 2 | Cohort 1 |
|---|---|---|---|
| The Absolute Differences of I-GERQ-R Total Score at V5 (Follow-up) Respect to V2 (Baseline). | -7.8 ± 7.6 | -11.1 ± 6.78 | -9.8 ± 7.4 |
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.
| score on a scale | Low Dose Level (0.1mg/kg) | Medium Dose Level 0.5mg/kg |
|---|---|---|
| I-GERQ-R Score Changes vs Baseline (Visit 2) by First Dose Level (0.1mg/kg and 0.5mg/kg). | -6.8 ± 7.31 | -7.6 ± 5.5 |
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.
| Score as sum of units | Medium Dose Level (0.5mg/kg) | High Dose Level 1mg/kg |
|---|---|---|
| I-GERQ-R Score Changes vs Visit 3 by Second Dose Level (0.5mg/kg and 1mg/kg). | -1.4 ± 0.89 | -4.9 ± 4.41 |
The analysis is by treatment - Each infant was treated with two out of three ascending dose (0.1, 0.5 or 1.0 mg/kg), therefore counted in more than one dose level.
| Number of events | High Dose Level (1.0 mg/Kg) | Medium Dose Level (0.5mg/Kg) | Low Dose Level(0.1mg/Kg) |
|---|---|---|---|
| gastrointestinal disorder | 6 | 4 | 3 |
| General disorders and administration site conditio | 1 | 0 | 0 |
| Infections and infestations | 7 | 2 | 1 |
| Injury, poisoning and procedural complications | 1 | 1 | 0 |
| Psychiatric disorders | 0 | 0 | 1 |
| Respiratory, thoracic and medistinal disorders | 3 | 1 | 1 |
| Skin and subcutaneous tissue disorders | 3 | 1 | 3 |
The population pharmacokinetic analyses is presented. PopPK Clearance estimated with a one compartment model with first order absorption and elimination.
| L/h | Cohort1 | Cohort 2 | Cohort 3 |
|---|---|---|---|
| A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04 | 1.24 (0.919 to 1.57) | 1.31 (1.03 to 1.59) | 1.64 (1.39 to 1.89) |
PopPK Volume estimated with a one compartment model with first order absorption and elimination. NOTE: for this measure, no inter-individual variability was estimated, therefore the value for each cohort corresponds to the typical value.
| L | Cohort 1, 2, and 3 |
|---|---|
| A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04 | 22.5 (NA to NA) |
The population pharmacokinetic analyses is presented. PopPK Ka estimated with a one compartment model with first order absorption and elimination. NOTE: for this measure, no inter-individual variability was estimated, therefore the value for each cohort corresponds to the typical value.
| 1/h | Cohort 1, 2 and 3 |
|---|---|
| A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04 | 206 (NA to NA) |
The population pharmacokinetic analyses is presented. The PopPK parameter fraction of the dose absorbed (F1) is estimated with a one compartment model with first order absorption and elimination.The results are presented fraction of the absorbed dose with 95% CI of the parameter estimate value
| fraction of dose absorbed | Cohort 1 | Cohort 2 | Cohort 3 |
|---|---|---|---|
| A Population Pharmacokinetic Analysis to Characterize the Plasma Concentration-time Course for Nepadutant in Infant With Colics From NIC-04 | 0.0275 (0.0199 to 0.0352) | 0.0342 (0.0250 to 0.0433) | 0.0346 (0.0346 to 0.0377) |
Collected over 4 weeks. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| High Dose Level (1.0 mg/Kg) | — | 1/21 (4.8%) | 12/21 (57.1%) |
| Medium Dose Level (0.5mg/Kg) | — | 0/21 (0%) | 2/21 (9.5%) |
| Low Dose Level(0.1mg/Kg) | — | 1/12 (8.3%) | 8/12 (66.7%) |
| Event | High Dose Level (1.0 mg/Kg) | Medium Dose Level (0.5mg/Kg) | Low Dose Level(0.1mg/Kg) |
|---|---|---|---|
| Laryngeal Edema-post intubationRespiratory, thoracic and mediastinal disorders | 0/21 | 0/21 | 1/12 |
| Hospitalisation for investigation for suspected seizuresSurgical and medical procedures | 1/21 | 0/21 | 0/12 |
| Event | High Dose Level (1.0 mg/Kg) | Medium Dose Level (0.5mg/Kg) | Low Dose Level(0.1mg/Kg) |
|---|---|---|---|
| TeethingGastrointestinal disorders | 2/21 | 0/21 | 2/12 |
| ConstipationGastrointestinal disorders | 2/21 | 0/21 | 0/12 |
| DiarrhoeaGastrointestinal disorders | 2/21 | 2/21 | 1/12 |
| Ear infectionInfections and infestations | 2/21 | 0/21 | 0/12 |
| Viral infectionInfections and infestations | 2/21 | 0/21 | 0/12 |
| Dermatitis diaperSkin and subcutaneous tissue disorders | 2/21 | 0/21 | 0/12 |
| CandidiasisInfections and infestations | 0/21 | 0/21 | 1/12 |
| ScreamingPsychiatric disorders | 0/21 | 0/21 | 1/12 |
| Upper respiratory atract congestionRespiratory, thoracic and mediastinal disorders | 0/21 | 0/21 | 1/12 |
| RashSkin and subcutaneous tissue disorders | 0/21 | 0/21 | 1/12 |
Infants with Feeding Intolerance
| Age, Continuous(weeks) | Cohort 3 | Cohort 2 | Cohort 1 | Total |
|---|---|---|---|---|
| Mean | 12.52 ± 4.281 | 13.62 ± 6.468 | 14.27 ± 6.559 | 13.52 ± 5.89 |
| Sex: Female, Male(Participants) | Cohort 3 | Cohort 2 | Cohort 1 | Total |
|---|---|---|---|---|
| Female | 4 | 8 | 2 | 14 |
| Male | 2 | 7 | 4 | 13 |
| Race/Ethnicity, Customized(particpants) | Cohort 3 | Cohort 2 | Cohort 1 | Total |
|---|---|---|---|---|
| Black or African American | 3 | 4 | 1 | 8 |
| White | 3 | 8 | 5 | 16 |
| More than one race | 0 | 3 | 0 | 3 |
| Region of Enrollment(participants) | Cohort 3 | Cohort 2 | Cohort 1 | Total |
|---|---|---|---|---|
| United States | 6 | 15 | 6 | 27 |
| Weight(Kg) | Cohort 3 | Cohort 2 | Cohort 1 | Total |
|---|---|---|---|---|
| Mean | 5.323 ± 0.9085 | 5.623 ± 1.1045 | 5.708 ± 1.764 | 5.576 ± 1.1975 |
| I-GERQ-R total score(Score on a scale) | Cohort 3 | Cohort 2 | Cohort 1 | Total |
|---|---|---|---|---|
| Mean | 24.8 ± 5.4 | 19 ± 6.32 | 21.8 ± 9.91 | 20.8 ± 7.22 |
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Studies of the drug tested here: MEN 11420