Pharmacokinetics of Sildenafil in Premature Infants

Persistent Pulmonary Hypertension of the Newborn Clinical Trial

Official title:

Pharmacokinetics of Sildenafil in Premature Infants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01670136
• Other study ID #: 11-1646
• Secondary ID: HHSN27500014
• Status: Completed
• Phase: Phase 1
• First received: August 17, 2012
• Last updated: November 1, 2016
• Start date: February 2013
• Est. completion date: July 2016

Study information

• Verified date: November 2016
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 364 Days

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Persistent Fetal Circulation Syndrome
• Persistent Pulmonary Hypertension of the Newborn

Intervention

Drug:
• 1 dose of sildenafil
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.

Locations

Country	Name	City	State
United States	Albany Medical Center	Albany	New York
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Kings County Hospital Center/SUNY Downstate Medical Center	Brooklyn	New York
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Duke University	Durham	North Carolina
United States	Riley Hospital	Indianapolis	Indiana
United States	Kosair Pediatric Research Unit	Louisville	Kentucky

Sponsors (4)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	Duke University, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), The EMMES Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	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	Yes
Secondary	Correlation between serum and dried blood spot samples		1-7 days	No
Secondary	Evaluate P450 single nucleotide polymorphisms (SNPs)		2-7 days	No