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Safety and Tolerability of Transitioning from Parenteral Treprostinil to Oral Treprostinil in Patients with Pulmonary Arterial Hypertension

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Conference: 2014 International PHA Conference and Scientific Sessions

Release Date: 06.22.2014

Presentation Type: Abstracts

File Download: 2014 Conference Abstract - Meredith Howell

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Treprostinil (TRE) diolamine is an oral, sustained release prostacyclin tablet being developed for the treatment of pulmonary arterial hypertension (PAH). Patients currently using parenteral TRE may consider transitioning to oral TRE if this becomes an option.

Rationale: Treprostinil (TRE) diolamine is an oral, sustained release prostacyclin tablet being developed for the treatment of pulmonary arterial hypertension (PAH). Patients currently using parenteral TRE may consider transitioning to oral TRE if this becomes an option.

Aim: The aim of this study is to investigate the tolerability, safety, pharmacokinetics and logistics for transitioning patients from parenteral TRE to oral TRE.

Methods: This is an ongoing, open-label, multi-center study for subjects with well-compensated PAH being managed with treprostinil (25-150 ng/kg/min) plus an oral PAH-specific therapy. To prioritize safety, subjects must have WHO FC I/II symptoms and cardiac index ≥ 2.2 L/m/m2.  Key assessments include 6MWD, hemodynamics, WHO FC, and pharmacokinetics. 

Results: The study is ongoing with 27 subjects enrolled. Baseline demographics included a median age of 50 years (18-80) and median 6MWD of 457 meters (279-641); most patients were idiopathic or heritable PAH (n=19). The median treprostinil dose at baseline was 54 ng/kg/min (25-124.5) with 25 patients receiving SC. Seven patients were receiving ERA & PDE5-I, seventeen PDE5-I, and three ERA therapy. The majority of patients were transitioned to oral TRE within four days as inpatients. Ten patients were transitioned from parenteral treprostinil to oral TRE twice daily and seventeen patients to oral TRE three times daily. At the end of the transition phase, the median total daily dose of oral TRE was 24.0 mg. Nine patients have reached Week 24 assessments (longest post-transition follow-up of 76 weeks), seventeen patients are ongoing, and one patient with scleroderma did not tolerate oral TRE (after transition) and returned to parenteral treprostinil. Interim data were available on the first nine patients to reach Week 24. Median 6MWD at Week 24 was 453 meters (354-641) with no worsening of WHO FC. Pharmacokinetic analyses confirmed that 1 mg TID ~ 5 ng/kg/min in terms of treprostinil exposure (AUC) for a typical 70kg patient.

Conclusions: Stable, carefully-selected PAH patients receiving parenteral treprostinil can be safely transitioned to oral TRE twice or three times daily under close medical observation without a significant decline in exercise capacity or worsening functional classification. Quality of life, treatment satisfaction, and more complete pharmacokinetic data analyses are ongoing.

Type: Clinical Sciences

Funded by United Therapeutics Corporation