Table 2.
Overview of treprostinil pivotal and clinical pharmacokinetics studies
| Section | Route(s) of administration | Population | Sample size | Study design |
|---|---|---|---|---|
| Remodulin® (treprostinil sodium) | ||||
| Pivotal trial | SC | PAH patients | 470 | 12-week, double-blind, placebo-controlled, multicenter trial in recently diagnosed patients receiving no prior background therapy (e.g., endothelin receptor antagonists, epoprostenol) (mean dose 9.3 ng/kg/min) |
| 2.1.1 | IV/SC | Healthy volunteers | 51 | Randomized, open-label, 2-period crossover bioequivalence PK |
| 2.1.2 | SC | Healthy volunteers | 14 | Single-center, open-label, non-randomized, long-term, dose-escalation PK |
| 2.1.3 | IV/SC | PAH patients | 49 | Multicenter, open-label, multiple-cohort PK |
| Tyvaso® (treprostinil sodium) | ||||
| Pivotal trial | Inhaled | PAH patients | 235 | 12-week, randomized, double-blind, placebo-controlled multicenter trial in clinically stable patients, mostly NYHA class III, receiving background therapy with either bosentan (70 %) or sildenafil (30 %) for at least 3 months prior to study initiation (mean dose 50 µg qid) |
| 2.2.1 | Healthy volunteers | 18 | Open-label, randomized, three-period crossover, absolute bioavailability | |
| 2.2.2 | Healthy volunteers | 40 | Double-blind, randomized, placebo-controlled, single-dose, dose-escalation, maximum tolerated dose PK | |
| 2.2.3 | PAH patients | 17 | Multicenter, prospective, open-label safety evaluation and PK substudy | |
| Orenitram® (treprostinil diolamine) | ||||
| Pivotal trial | Oral | PAH patients | 349 | 12-week, double-blind, placebo-controlled, multicenter trial in recently diagnosed patients receiving no prior background therapy (e.g., endothelin receptor antagonists, phosphodiesterase type 5 inhibitor) (mean dose 3.4 mg bid) |
| 2.3.1 | Healthy volunteers | 10 | Open-label, 3-cohort, randomized, 2-period, crossover safety and PK | |
| 2.3.1 | Healthy volunteers | 32 | Open-label, randomized, single-dose, 4-period, crossover safety and PK | |
| 2.3.1 | Healthy volunteers | 36 | Randomized, double-blind, placebo-controlled, parallel-group, dose-escalating safety and PK | |
| 2.3.2 | Healthy volunteers | 26 | Single-center, randomized, 2-period, crossover, drug interaction study: acetaminophen | |
| Healthy volunteers | 15 | Single-center, single-blind, vehicle-controlled, 2-period crossover drug interaction study: warfarin | ||
| Healthy volunteers | 22 | Single-center, open-label, 3-period, 3-sequence crossover, drug interaction study: Tracleer® | ||
| Healthy volunteers | 17 | Single-center, open-label, 3-period, 3-sequence crossover, drug interaction study: Revatio® | ||
| Healthy volunteers | 20 | Single-center, open-label, single-sequence, drug interaction study: rifampin | ||
| Healthy volunteers | 40 | Single-center, open-label, single-sequence, drug interaction study: fluconazole | ||
| Healthy volunteers | 40 | Single-center, open-label, 2-cohort, 2-sequence, 2-period, crossover, drug interaction study: gemfibrozil | ||
| Healthy volunteers | 30 | Open-label, single-sequence, crossover, drug interaction study: esomeprazole | ||
| 2.3.3 | Hepatic dysfunction and healthy volunteers | 30 | Open-label, 3-cohort, safety and PK in patients with varying degrees of hepatic dysfunction compared with healthy volunteers | |
| 2.3.3 | Renal dysfunction and healthy volunteers | 16 | Open-label safety and PK study pre- and post-dialysis compared with healthy volunteers | |
| 2.3.4 | PAH patients | 70 | Multi-center, open-label, long-term PK substudy | |
| 2.3.5 | Healthy volunteers | 19 | 9-Day, open-label, single-center, single-group, repeat tid dosing study | |
| PAH patients | 13 | Single-center, pharmacokinetic and tolerability study comparing bid with tid dosing | ||
| 2.3.6 | PAH patients | 33 | Multi-center, open-label, 24-week, safety and tolerability study of subjects transitioning from continuous IV/SC Remodulin® infusion to oral treprostinil | |
bid twice daily, IV intravenous, NYHA New York Heart Association, PAH pulmonary arterial hypertension, PK pharmacokinetic, qid four times daily, SC subcutaneous, tid three times daily