Tezosentan in Pulmonary Arterial Hypertension

Condition(s) targeted: Pulmonary Arterial Hypertension

Intervention: Tezosentan (Drug)

Phase: Phase 2

Status: Terminated

Sponsored by: Actelion

Official(s) and/or principal investigator(s):
Elisabet Lindberg, MD, Study Director, Affiliation: Actelion

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: 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

Study design: Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Change in PVR from Baseline to 30 minutes expresses as percent of the Baseline value.

Secondary outcome:

Change in mean right arterial pressure (mRAP) from Baseline to 30 minutes

Change in mPAP from Baseline to 30 min

Change in total pulmonary resistance (TPR) from Baseline to 30 min

Change in PCWP from Baseline to 30 min

Change in cardiac output (CO) from Baseline to 30 min

Change in cardiac index (CI) from Baseline to 30 min

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria: 1. Signed informed consent 2. Male and female patients 18 years of age or older 3. 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

4. Modified NYHA functional class II-III 5. 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: 1. Patients with PAH in Venice Classification Groups 2-5, and PAH Group 1 subgroups not covered by inclusion criterion no. 3 2. Hypotensive patients (systemic systolic blood pressure < 100 mmHg) 3. Patients with body weight < 50 kg (110 lbs) 4. Patients with moderate or severe hepatic impairment (Child-Pugh B and C) 5. Patients with clinically significant chronic renal insufficiency (serum creatinine > 2. 5mg/dL / 221µmol/L) 6. Patients who have received any endothelin receptor antagonist (ERA) and/or any phosphodiesterase-5 (PDE-5) inhibitor within 28 days of Baseline 7. Patients who have received prostacyclin (epoprostenol) or prostacyclin analogs (e. g., treprostinil, iloprost) within 28 days of Baseline 8. Patients who have received any investigational drugs within 28 days of Baseline 9. Patients who have received cyclosporine A or tacrolimus within 28 days of Baseline 10. Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with the study 11. Life expectancy less than 12 months 12. 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 13. Known hypersensitivity to any of the excipients of the drug formulation 14. Patients with positive response to vasoreactivity test

University Hospital of Basel, Clinic of Pneumology, Basel CH - 4031, Switzerland

Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne CH-1011, Switzerland

Hopital Antoine Béclère, Paris, Clamart 92141, France

Washington University School of Medicine, St Louis, Missouri 63110, United States

Baylor College of Medicine, Houston, Texas 77030, United States

Starting date: August 2010
Last updated: July 13, 2012