Clinical trial NCT01077297: Tezosentan in Pulmonary Arterial Hypertension
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pulmonary Arterial Hypertension
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2010-03-01
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility 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

Primary outcomes:
measure: Change in PVR from Baseline to 30 minutes expresses as percent of the Baseline value.
timeFrame: 30 minutes
Secondary outcomes:
measure: Change in mean right arterial pressure (mRAP) from Baseline to 30 minutes
timeFrame: 30 minutes
measure: Change in mPAP from Baseline to 30 min
timeFrame: 30 minutes
measure: Change in total pulmonary resistance (TPR) from Baseline to 30 min
timeFrame: 30 minutes
measure: Change in PCWP from Baseline to 30 min
timeFrame: 30 minutes
measure: Change in cardiac output (CO) from Baseline to 30 min
timeFrame: 30 minutes
measure: Change in cardiac index (CI) from Baseline to 30 min
timeFrame: 30 minutes
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Paris
country: France
facility: Hopital Antoine Béclère
state: Clamart
city: Basel
country: Switzerland
facility: University Hospital of Basel, Clinic of Pneumology
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois (CHUV)
Study officials:
affiliation: Actelion
name: Elisabet Lindberg, MD
role: STUDY_DIRECTOR
References: