Pharmacokinetic Study of Sub-q and IV Treprostinil in Kids With Pulmonary Arterial Hypertension (PAH) (PKRemodulin)
Multi-center, Open-label Pharmacokinetic Study of Subcutaneously and Intravenously Administered Treprostinil in Children With Pulmonary Arterial Hypertension (PAH)
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.
Panoramica dello studio
Stato
Condizioni
Descrizione dettagliata
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).
Tipo di studio
Iscrizione (Effettivo)
Contatti e Sedi
Luoghi di studio
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California
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Palo Alto, California, Stati Uniti, 94304
- Lucille Packard Children's Hospital
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Metodo di campionamento
Popolazione di studio
Descrizione
Inclusion Criteria:
- 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.
- Patients must be between the ages of 0 to 16 years at the time of study enrollment.
- Written informed consent and assent, when applicable, must be completed.
Exclusion Criteria:
- Patients with severe liver or renal diseases.
- Female patients who may be pregnant or breastfeeding
- Written informed consent and assent not completed due to patient and/or parent or legal guardian unwilling to participate.
- Patients on concomitant use of a CYP2C inhibitor or inducer.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
Coorti e interventi
Gruppo / Coorte |
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0 months - 1 year
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11-16 years
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7-11 years
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4-6 years
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1-3 years
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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To determine the relationship between steady-state plasma concentration and dose of treprostinil within each age cohort and among age cohorts.
Lasso di tempo: at least 48 hours after most-recent titration
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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.
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at least 48 hours after most-recent titration
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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To correlate PK level of treprostinil with the presence or absence of side effects
Lasso di tempo: At time of blood draw
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A survey of side effects (GI, neurological, cardiac, respiratory, skin) will be administered at time of blood draw.
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At time of blood draw
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Collaboratori e investigatori
Pubblicazioni e link utili
Pubblicazioni generali
- 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.
- 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.
- 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.
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Inizio studio
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- UT PK Treprostinil
Piano per i dati dei singoli partecipanti (IPD)
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Descrizione del piano IPD
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