Pharmacokinetics of Sildenafil in Premature Infants
This study is currently recruiting participants.
Verified February 2013 by University of North Carolina, Chapel Hill
Sponsor:
University of North Carolina, Chapel Hill
Collaborators:
Duke University
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: February 28, 2013
Last verified: February 2013
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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 ]
| Estimated Enrollment: | 24 |
| Study Start Date: | February 2013 |
| Estimated Study Completion Date: | December 2014 |
| Estimated Primary Completion Date: | February 2014 (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 0.75 mg/kg.
Other Names:
|
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 |
| 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01670136
Contacts
| Contact: Matthew M Laughon, MD, MPH | 919-966-5063 | matt_laughon@med.unc.edu |
| Contact: Jennifer Murphy | 919-668-8795 | Jennifer.murphy@dm.duke.edu |
Locations
| United States, Alabama | |
| University of Alabama at Birmingham | Not yet recruiting |
| Birmingham, Alabama, United States, 35249-7335 | |
| Principal Investigator: Ambalavanan Namasivayam, MD | |
| United States, Indiana | |
| Riley Hospital | Recruiting |
| Indianapolis, Indiana, United States, 46202 | |
| Principal Investigator: Shawn Ahlfeld, MD | |
| United States, Kentucky | |
| Kosair Pediatric Research Unit | Not yet recruiting |
| Louisville, Kentucky, United States, 40202 | |
| Principal Investigator: Dan Stewart, MD | |
| United States, North Carolina | |
| University of North Carolina | Recruiting |
| Chapel Hill, North Carolina, United States, 27599 | |
| Principal Investigator: Sigal Peter-Wohl, MD | |
| Duke University | Not yet recruiting |
| Durham, North Carolina, United States, 27705 | |
| Principal Investigator: C. Michael Cotten, MD | |
| United States, South Carolina | |
| Medical University of South Carolina | Recruiting |
| Charleston, South Carolina, United States, 29425 | |
| Principal Investigator: Andrew Atz, MD | |
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Duke University
The EMMES Corporation
Investigators
| Principal Investigator: | Matthew M Laughon, MD, MPH | University of North Carolina |
More Information
No publications provided
| Responsible Party: | University of North Carolina, Chapel Hill |
| ClinicalTrials.gov Identifier: | NCT01670136 History of Changes |
| Other Study ID Numbers: | 11-1646 |
| Study First Received: | August 17, 2012 |
| Last Updated: | February 28, 2013 |
| Health Authority: | United States: Food and Drug Administration United States: Institutional Review Board |
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 |
Vasodilator Agents Cardiovascular Agents Therapeutic Uses Pharmacologic Actions Phosphodiesterase 5 Inhibitors Phosphodiesterase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on June 18, 2013