Tezosentan in Pulmonary Arterial Hypertension

Phase 2

Terminated

Brief Summary: 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

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Tezosentan	Tezosentan	-

Primary Outcome Measures

Name	Time	Method
Change in PVR from Baseline to 30 minutes expresses as percent of the Baseline value.	30 minutes

Secondary Outcome Measures

Name	Time	Method
Change in total pulmonary resistance (TPR) from Baseline to 30 min	30 minutes
Change in cardiac output (CO) from Baseline to 30 min	30 minutes
Change in PCWP from Baseline to 30 min	30 minutes
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 cardiac index (CI) from Baseline to 30 min	30 minutes

Locations (5): Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Baylor College of Medicine
🇺🇸
Houston, Texas, United States
Hopital Antoine Béclère
🇫🇷
Paris, Clamart, France
University Hospital of Basel, Clinic of Pneumology
🇨🇭
Basel, Switzerland
Centre Hospitalier Universitaire Vaudois (CHUV)
🇨🇭
Lausanne, Switzerland