Pharmacokinetic Study of Sub-q and IV Treprostinil in Kids With Pulmonary Arterial Hypertension (PAH)

NCT ID: NCT02318186

Last Updated: 2017-10-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

51 participants

Study Classification

OBSERVATIONAL

Study Start Date

2013-10-31

Study Completion Date

2017-08-01

Brief Summary

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Abstract

This is a multi-center, open-label pharmacokinetic (PK) study examining the relationship between the steady-state plasma concentration and dose of treprostinil delivered intravenously or subcutaneously in children with pulmonary arterial hypertension (PAH). Subjects will be divided into 5 cohorts by age. A blood sample will be obtained from each subject at steady state. Additional blood samples will be obtained from a small subset of subjects with a 15% increase or with at least a 15ng/kg/min increase in dose from steady state. Samples will be sent to a pharmacokinetic laboratory for analysis. Linear regression analysis will be used to determine the relationship between the steady state plasma concentration and drug dose. A power model will be used to assess dose proportionality.

Detailed Description

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Background Information and Rationale

Treprostinil has not been adequately studied to determine its safety and efficacy in children ≤ 16 years old. However, the drug's use and tolerance in children with PAH has been demonstrated in studies with small sample sizes.

Although the pharmacokinetic relationship of treprostinil has been established in adult patients with PAH, the relationship between the steady-state plasma concentration and dose for children requires further investigation because of physiologic differences, such as the maturity of enzyme systems and drug clearance mechanisms, between children and adults. The subjects in this study will be divided into cohorts by age to address the physiologic changes that occur throughout childhood.

Currently, no data exists demonstrating the relationship between the steady-state plasma concentration and dose for children treated with intravenously or subcutaneously delivered treprostinil. Understanding the pharmacokinetics of treprostinil among different age cohorts in children will provide the data to make an informed recommendation for dosing based on age (and possibly weight).

Conditions

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Pulmonary Arterial Hypertension

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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0 months - 1 year

No interventions assigned to this group

11-16 years

No interventions assigned to this group

7-11 years

No interventions assigned to this group

4-6 years

No interventions assigned to this group

1-3 years

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

1. Patients must be on continuous intravenous or subcutaneous treprostinil for the treatment of pulmonary arterial hypertension, defined as mean pulmonary artery pressure \>25mmHg at rest with a PVRi \> 3 Wood units.
2. Patients must be between the ages of 0 to 16 years at the time of study enrollment.
3. Written informed consent and assent, when applicable, must be completed.

Exclusion Criteria

1. Patients with severe liver or renal diseases.
2. Female patients who may be pregnant or breastfeeding
3. Written informed consent and assent not completed due to patient and/or parent or legal guardian unwilling to participate.
4. Patients on concomitant use of a CYP2C inhibitor or inducer.
Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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United Therapeutics

INDUSTRY

Sponsor Role collaborator

Seattle Children's Hospital

OTHER

Sponsor Role collaborator

University of Colorado, Denver

OTHER

Sponsor Role collaborator

Children's Hospital of Philadelphia

OTHER

Sponsor Role collaborator

Jeffrey A. Feinstein

OTHER

Sponsor Role lead

Responsible Party

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Jeffrey A. Feinstein

Director, Vera Moulton Wall Center for Pulmonary Vascular Disease

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Jeffrey Feinstein, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

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Lucille Packard Children's Hospital

Palo Alto, California, United States

Site Status

Countries

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United States

References

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Ivy DD, Claussen L, Doran A. Transition of stable pediatric patients with pulmonary arterial hypertension from intravenous epoprostenol to intravenous treprostinil. Am J Cardiol. 2007 Mar 1;99(5):696-8. doi: 10.1016/j.amjcard.2006.09.119. Epub 2007 Jan 10.

Reference Type BACKGROUND
PMID: 17317374 (View on PubMed)

Levy M, Celermajer DS, Bourges-Petit E, Del Cerro MJ, Bajolle F, Bonnet D. Add-on therapy with subcutaneous treprostinil for refractory pediatric pulmonary hypertension. J Pediatr. 2011 Apr;158(4):584-8. doi: 10.1016/j.jpeds.2010.09.025. Epub 2010 Oct 30.

Reference Type BACKGROUND
PMID: 21035821 (View on PubMed)

McSwain CS, Benza R, Shapiro S, Hill N, Schilz R, Elliott CG, Zwicke DL, Oudiz RJ, Staszewski JP, Arneson CP, Wade M, Zaccardelli D, McLaughlin V. Dose proportionality of treprostinil sodium administered by continuous subcutaneous and intravenous infusion. J Clin Pharmacol. 2008 Jan;48(1):19-25. doi: 10.1177/0091270007309708.

Reference Type BACKGROUND
PMID: 18094217 (View on PubMed)

Other Identifiers

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UT PK Treprostinil

Identifier Type: -

Identifier Source: org_study_id