Pharmacokinetics of Sildenafil in Premature Infants

Study Overview
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Brief Summary
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The purpose of this study is to learn more about the safety and dosing of sildenafil in infants.

Detailed Description
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Pharmacokinetics and safety of sildenafil will be studied in preterm infants who are receiving sildenafil per standard of care or 1 dose prescribed for the study.

Official Title
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Pharmacokinetics of Sildenafil in Premature Infants

Conditions
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Persistent Pulmonary Hypertension of the Newborn

Intervention / Treatment
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* Drug: 1 dose of sildenafil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cohort 1: Gestational age 28 weeks or less receiving sildenafil as standard of care < 365 postnatal days Cohort 2: Gestational age 28 weeks or less 7-28 postnatal days of age Mechanical ventilation or nasal continuous positive airway pressure (NCPAP) or high-flow nasal cannula Intravenous line in place Exclusion Criteria: Cohort 1: Any condition that would make the participant, in the opinion of the investigator, unsuitable for the study Cohort 2: Previous exposure to sildenafil within 7 days prior to enrollment Any condition that would make the participant, in the opinion of the investigator, unsuitable for the study History of allergic reactions to sildenafil AST > ULN or ALT > 3x ULN Currently on a vasopressor for hypotension Known sickle cell disease

Ages Eligible for Study
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Maximum Age: 364 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: sildenafil, standard of care<br>Infants receiving sildenafil as standard of care | |
| Other: sildenafil administered for study<br>1 dose of sildenafil administered for study | Drug: 1 dose of sildenafil<br>* A single IV dose of sildenafil will be administered over 90 minutes with no greater than a 15-minute flush. Final dose to be determined based on at least the first 4 participants enrolled in Cohort 1; final dose expected to be a single dose between 0.25 and 0.5 mg/kg.<br>* Other names: Viagra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve 0-24 hours for sildenafil |  | IV study dose 0-15 min,1-2,3-4,12-14,24-30,48-56hr after flush.Clinical care: IV <0.5hr before dose <15 min & 3-4hr after flush <0.5hr before next dose. Enteral <0.5hr before dose, 1-2 & 3-4hr after dose, <0.5hr before next dose. 22-26hr after last dose | 
| Peak plasma concentration of sildenafil |  | IV study dose 0-15 min,1-2,3-4,12-14,24-30,48-56hr after flush.Clinical care: IV <0.5hr before dose <15 min & 3-4hr after flush <0.5hr before next dose. Enteral <0.5hr before dose, 1-2 & 3-4hr after dose, <0.5hr before next dose. 22-26hr after last dose | 
| Clearance of sildenafil |  | IV study dose 0-15 min,1-2,3-4,12-14,24-30,48-56hr after flush.Clinical care: IV <0.5hr before dose <15 min & 3-4hr after flush <0.5hr before next dose. Enteral <0.5hr before dose, 1-2 & 3-4hr after dose, <0.5hr before next dose. 22-26hr after last dose | 
| Volume of distribution at steady state |  | IV study dose 0-15 min,1-2,3-4,12-14,24-30,48-56hr after flush.Clinical care: IV <0.5hr before dose <15 min & 3-4hr after flush <0.5hr before next dose. Enteral <0.5hr before dose, 1-2 & 3-4hr after dose, <0.5hr before next dose. 22-26hr after last dose | 
| Half life of sildenafil |  | IV study dose 0-15 min,1-2,3-4,12-14,24-30,48-56hr after flush.Clinical care: IV <0.5hr before dose <15 min & 3-4hr after flush <0.5hr before next dose. Enteral <0.5hr before dose, 1-2 & 3-4hr after dose, <0.5hr before next dose. 22-26hr after last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events as a measure of safety and tolerability. |  | From the time of the first dose to 3 days after the last dose; serious adverse events will be collected from the first dose of sildenafil to 7 days after the last dose of sildenafil | 
| Correlation between serum and dried blood spot samples |  | 1-7 days | 
| Evaluate P450 single nucleotide polymorphisms (SNPs) |  | 2-7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sildenafil, preterm infants, persistent pulmonary hypertension of the newborn