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Pharmacokinetics of Sildenafil in Premature Infants

This study has been completed.
Sponsor:
Collaborators:
Duke University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
The EMMES Corporation
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT01670136
First received: August 17, 2012
Last updated: November 1, 2016
Last verified: November 2016
  Purpose
The purpose of this study is to learn more about the safety and dosing of sildenafil in infants.

Condition Intervention Phase
Persistent Pulmonary Hypertension of the Newborn
Drug: 1 dose of sildenafil
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Pharmacokinetics of Sildenafil in Premature Infants

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Area under the plasma concentration versus time curve 0-24 hours for sildenafil [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Peak plasma concentration of sildenafil [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Clearance of sildenafil [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Volume of distribution at steady state [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Half life of sildenafil [ Time Frame: 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of subjects with adverse events as a measure of safety and tolerability. [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
  • Correlation between serum and dried blood spot samples [ Time Frame: 1-7 days ] [ Designated as safety issue: No ]
  • Evaluate P450 single nucleotide polymorphisms (SNPs) [ Time Frame: 2-7 days ] [ Designated as safety issue: No ]

Enrollment: 34
Study Start Date: February 2013
Study Completion Date: July 2016
Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: sildenafil, standard of care
Infants receiving sildenafil as standard of care
sildenafil administered for study
1 dose of sildenafil administered for study
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.
Other Names:
  • Revatio
  • Viagra

Detailed 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.
  Eligibility

Ages Eligible for Study:   up to 364 Days   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01670136

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35249-7335
United States, Indiana
Riley Hospital
Indianapolis, Indiana, United States, 46202
United States, Kentucky
Kosair Pediatric Research Unit
Louisville, Kentucky, United States, 40202
United States, New York
Albany Medical Center
Albany, New York, United States, 12208
Kings County Hospital Center/SUNY Downstate Medical Center
Brooklyn, New York, United States, 11203
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
Duke University
Durham, North Carolina, United States, 27705
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Duke University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
The EMMES Corporation
Investigators
Principal Investigator: Matthew M Laughon, MD, MPH University of North Carolina
  More Information

Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT01670136     History of Changes
Other Study ID Numbers: 11-1646  HHSN27500014 
Study First Received: August 17, 2012
Last Updated: November 1, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by University of North Carolina, Chapel Hill:
sildenafil
preterm infants
persistent pulmonary hypertension of the newborn

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Persistent Fetal Circulation Syndrome
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Infant, Newborn, Diseases
Sildenafil Citrate
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents

ClinicalTrials.gov processed this record on December 02, 2016