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

NCT07101640 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: Pro00114044R01HD113201
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Bronchopulmonary Dysplasia (BPD); Premature Births; Critical Illness

Keywords

PK; Pharmacokinetics; bronchopulmonary dysplasia; montelukast

Outcome Measures

Primary Outcomes (1)

• Apparent clearance (CL/F) of montelukast

  The elimination of montelukast divided by the concentration of montelukast.

  From enrollment to 14 days post first dose.

Secondary Outcomes (12)

• Volume of distribution

  From first dose of study drug though 7 days post last dose.

• Half-life

  From first dose of study drug though 7 days post last dose.

• Area Under Curve (AUC)

  From first dose of study drug though 7 days post last dose.

• Maximum Concentration (Cmax)

  From first dose of study drug though 7 days post last dose.

• Death- Safety

  From 30 days post treatment or 36 weeks PMA, whichever is longer; through 24 months of follow-up.

Other Outcomes (6)

• Delirium Assessment

  From Enrollment until at 36 weeks PMA who remain hospitalized.

• Clinical Bronchopulmonary Dysplasia (BPD)

  From first dose through 36 Week PMA.

• Time on supplemental oxygen

  From the time of randomization until 30 days post last dose or 36 week PMA, whichever is longer.

Study Arms (2)

Montelukast Sodium

EXPERIMENTAL

Once daily montelukast dosed at 0.75 mg/kg/day, maximum dose 4mg. 4mg of montelukast mixed in 5mlL breast milk/formula for a concentration of 0.8mg/mL.

Drug: montelukast 4 mg granule

Placebo

PLACEBO COMPARATOR

Plain breast milk or formula

Drug: Placebo

Interventions

montelukast 4 mg granule DRUG

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 .

Also known as: montelukast sodium

Montelukast Sodium

Placebo DRUG

Plain breast milk or formula

Placebo

Eligibility Criteria

• Age: Up to 28 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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
• to 28 (inclusive) days postnatal age at the time of first study drug dose
• Able to tolerate 5 mL of enteral volume

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• University of North Carolina, Chapel Hill: collaborator
• University Medical Center of Southern Nevada: collaborator
• East Carolina University: collaborator
• University of Massachusetts, Worcester: collaborator
• Arkansas Children's Hospital Research Institute: collaborator

Study Sites (4)

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

RECRUITING

University Medical Center of Southern Nevada

Las Vegas, Nevada, 89102, United States

RECRUITING

University of North Carolina (UNC)

Chapel Hill, North Carolina, 27599, United States

RECRUITING

East Carolina University

Greenville, North Carolina, 27858, United States

RECRUITING

MeSH Terms

Conditions

Bronchopulmonary Dysplasia; Premature Birth; Critical Illness

Interventions

montelukast

Condition Hierarchy (Ancestors)

Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2025
• First Posted: August 3, 2025
• Study Start: February 23, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): May 31, 2028
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)