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

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).

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.