A Multicenter, Open Label, Ascending 7 Day-Repeated Dose Study to Investigate Efficacy, Safety and Pharmacokinetics of Nepadutant In Infants With Feeding Intolerance
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 27
- 试验地点
- 5
- 主要终点
- The Absolute Differences of I-GERQ-R Total Score at V3 (End of First Week of Treatment) Respect to the Baseline (V2).
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 6 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Cohort 3
Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days
干预措施: Nepadutant (Drug)
Cohort 2
Nepadutant medium dose (0.5mg/kg) for 7 days followed by Nepadutant high dose (1mg/kg) for additional 7 days
干预措施: Nepadutant (Drug)
Cohort 1
Nepadutant low dose (0.1mg/kg) for 7 days followed by Nepadutant medium dose (0.5mg/kg) for additional 7 days
干预措施: Nepadutant (Drug)
结局指标
主要结局
The Absolute Differences of I-GERQ-R Total Score at V3 (End of First Week of Treatment) Respect to the Baseline (V2).
时间窗: Baseline (V2) and end of first week of treatment (V3)
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.
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).
时间窗: V3 (end of 1st week of treatment) and V4 (end of 2nd 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.
The Absolute Differences of I-GERQ-R Total Score at V5 (Follow-up) Respect to V2 (Baseline).
时间窗: Baseline (V2) and follow up 2 weeks after the last administered dose (V5)
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.
I-GERQ-R Score Changes vs Baseline (Visit 2) by First Dose Level (0.1mg/kg and 0.5mg/kg).
时间窗: Baseline (V2) and end of 1st week of treatment(V3)
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.
I-GERQ-R Score Changes vs Visit 3 by Second Dose Level (0.5mg/kg and 1mg/kg).
时间窗: end of first week of treatment (V3) and end of second week of treatment (V4)
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.
次要结局
- 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)