PK, Safety and Preliminary Efficacy Study of Montelukast in Critically Ill Infants With Developing Bronchopulmonary Dysplasia

Официальное название

Pharmacokinetics, Safety and Preliminary Efficacy Study of Montelukast in Critically Ill Infants With Developing Bronchopulmonary Dysplasia

Обзор

The purpose of the study is to learn how safe montelukast may be in premature infants at significant risk for Bronchopulmonary Dysplasia (BPD) and to determine how much and how quickly montelukast moves from the stomach into the bloodstream, and how quickly it is removed from the bloodstream. Data supporting the prospect of montelukast benefit involved 6 previous studies involving 206 preterm infants. The dosing ranged from 0.5 to 2.5 mg/kg/day, which aligns with the proposed initial dose of 0.75 mg/kg/day. Though each previous study had a small population, collectively they reveal montelukast as a promising drug in populations of preterm infants developing BPD and for individual preterm infants who are "developing BPD." Thus, researchers expect clinical benefit for preterm infants in this study. Despite the benefit-to-risk ratio presented by these previous studies, the optimal dose remains to be determined; thus, this study design and PK analysis will start with the lowest dose that is likely to provide direct benefit to participants.

Подробное описание

Multi-center, Prospective, Randomized, Double-masked, Placebo-Controlled Trial Participants (n=28) will be enrolled into a randomized, double-blinded, placebo-controlled trial of once daily montelukast (0.75 mg/kg/day) or placebo (1:1 allotment) for 7 days in critically ill premature infants with developing BPD.

The overall aim is to characterize the pharmacokinetics (PK), short- and long-term adverse events (safety), and respiratory support changes (preliminary efficacy) with montelukast following once daily dosing for 7 days.

Primary: Characterize the PK of montelukast in critically ill premature infants with developing bronchopulmonary dysplasia (BPD).

Secondary: Describe the acute safety profile of montelukast and 2-year developmental progress in critically ill premature infants with developing BPD.

Tertiary: Determine preliminary efficacy of montelukast in critically ill premature infants with developing BPD.

Inpatient participation: Will vary based on gestational age and age at randomization; Up to approximately 60 days (7 days of study drug plus 30 days of post-drug safety monitoring or to 36 weeks postmenstrual age, whichever is longer).

Outpatient participation: Medical and neurodevelopmental follow-up assessments at 6, 12, 18 and 24 months old.

Вмешательства

• Препарат montelukast 4 mg granule
  Montelukast sodium (4 mg oral granules) dissolved into 5mL of breast milk/formula yielding a solution concentration of 0.8mg/mL. Dosed once daily by weight, montelukast (0.75 mg/kg/day) or placebo .
• Препарат Placebo
  Plain breast milk or formula

Первичные конечные точки

• Apparent clearance (CL/F) of montelukast [Срок оценки: From enrollment to 14 days post first dose.]

Вторичные конечные точки (12)

• Volume of distribution [Срок оценки: From first dose of study drug though 7 days post last dose.]
• Half-life [Срок оценки: From first dose of study drug though 7 days post last dose.]
• Area Under Curve (AUC) [Срок оценки: From first dose of study drug though 7 days post last dose.]
• Maximum Concentration (Cmax) [Срок оценки: From first dose of study drug though 7 days post last dose.]
• Death- Safety [Срок оценки: From 30 days post treatment or 36 weeks PMA, whichever is longer; through 24 months of follow-up.]
• Serious Adverse Events [Срок оценки: At or before 30 days post treatment or 36 weeks PMA, whichever is longer.]
• Total Neuropsychiatric Adverse Events (NPAE) [Срок оценки: From first dose to 30 days post treatment or 36-weeks PMA, whichever is longer.]
• Neonatal Infections [Срок оценки: From first dose till at or before 30 days post treatment or 36 weeks PMA, whichever is longer.]
• Neurodevelopmental outcomes (Bayley-4) [Срок оценки: From first dose through 24 months of age.]
• Neurodevelopmental outcomes (Ages and Stages Questionnaires (ASQ)) [Срок оценки: 6 months, 12 months, 18 months, and 24 months]
• Neurodevelopmental outcomes (Child Behavior Checklist (CBCL) [Срок оценки: 18 months, 24 months]
• Oxygen saturation index (OSI) [Срок оценки: From randomization baseline to day 7 of treatment.]

Критерии участия

Критерии включения

• Documented informed consent from parent or guardian, prior to study activities
• Receiving mechanical ventilation \[high frequency or conventional\] and requiring supplemental oxygen (FiO2 ≥ 30%) at time of randomization
• <28 weeks' gestational age and <1000 g bodyweight at birth
• 7 to 28 (inclusive) days postnatal age at the time of first study drug dose
• Able to tolerate 5 mL of enteral volume

Критерии исключения

• Previous enrollment and dosing in the current PRISM study (NICHD-2023-MON01)
• Previous exposure to montelukast within 7 days prior to randomization
• Known allergy to montelukast
• PI deems infant - prior to enrollment - is not expected to survive
• Has a disease complication that would preclude safe participation of the participant
• Increased respiratory support due to intercurrent illness (e.g., sepsis, necrotizing enterocolitis, etc.). Infants should be excluded from the study until after resolution of the acute event
• Congenital lung and diaphragmatic malformations

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 5 центров

• Arkansas Children's Hospital — Little Rock
• University of Massachusetts — Amherst
• University Medical Center of Southern Nevada — Las Vegas
• University of North Carolina (UNC) — Chapel Hill
• East Carolina University — Greenville

Идентификаторы

NCT: NCT07101640 · Pro00114044 · R01HD113201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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