Tezosentan in Pulmonary Arterial Hypertension

Study Overview
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Brief Summary
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Multicenter, Open-label, Non-comparative, Proof-of-concept, Phase 2a Study to Evaluate the Effect of a Single Infusion of Tezosentan on Pulmonary Vascular Resistance in Patients With Stable, Chronic Pulmonary Arterial Hypertension, Currently Not Treated With Endothelin Receptor Antagonists, Phosphodiesterase-5 Inhibitors or Prostacyclines

Official Title
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Multicenter, Open-label, Non-comparative, Proof-of-concept, Phase 2a Study to Evaluate the Effect of a Single Infusion of Tezosentan on Pulmonary Vascular Resistance in Patients With Stable, Chronic Pulmonary Arterial Hypertension, Currently Not Treated With Endothelin Receptor Antagonists, Phosphodiesterase-5 Inhibitors or Prostacyclines

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Drug: Tezosentan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Male and female patients 18 years of age or older Patients with PAH according to one of the following subgroups of the Venice Classification Group 1: Idiopathic (iPAH), or Familial/heritable (FPAH), or Associated (APAH) with collagen vascular disease Modified NYHA functional class II-III Documented hemodynamic diagnosis of PAH by right heart catheterization at Baseline: Resting mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg and Resting mean PVR ≥ 240 dyn•s•cm-5 and Pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg Exclusion Criteria: Patients with PAH in Venice Classification Groups 2-5, and PAH Group 1 subgroups not covered by inclusion criterion no. 3 Hypotensive patients (systemic systolic blood pressure < 100 mmHg) Patients with body weight < 50 kg (110 lbs) Patients with moderate or severe hepatic impairment (Child-Pugh B and C) Patients with clinically significant chronic renal insufficiency (serum creatinine > 2.5mg/dL / 221µmol/L) Patients who have received any endothelin receptor antagonist (ERA) and/or any phosphodiesterase-5 (PDE-5) inhibitor within 28 days of Baseline Patients who have received prostacyclin (epoprostenol) or prostacyclin analogs (e.g., treprostinil, iloprost) within 28 days of Baseline Patients who have received any investigational drugs within 28 days of Baseline Patients who have received cyclosporine A or tacrolimus within 28 days of Baseline Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with the study Life expectancy less than 12 months Females who are lactating or pregnant or females who are not using a reliable method of birth control (failure rate less than 1% per year) during the study and for at least one month after study drug intake Known hypersensitivity to any of the excipients of the drug formulation Patients with positive response to vasoreactivity test

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tezosentan<br> | Drug: Tezosentan<br>* single infusion of tezosentan 5mg/h over 30 min corresponding to 2.5 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PVR from Baseline to 30 minutes expresses as percent of the Baseline value. |  | 30 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mean right arterial pressure (mRAP) from Baseline to 30 minutes |  | 30 minutes | 
| Change in mPAP from Baseline to 30 min |  | 30 minutes | 
| Change in total pulmonary resistance (TPR) from Baseline to 30 min |  | 30 minutes | 
| Change in PCWP from Baseline to 30 min |  | 30 minutes | 
| Change in cardiac output (CO) from Baseline to 30 min |  | 30 minutes | 
| Change in cardiac index (CI) from Baseline to 30 min |  | 30 minutes |