Tezosentan in Pulmonary Arterial Hypertension

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

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 Overview

• Status: Terminated
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Tezosentan

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Clamart
    • Paris, Clamart, France, 92141
      • Hôpital Antoine Béclère
• Switzerland
  • Basel, Switzerland, CH - 4031
    • University Hospital of Basel, Clinic of Pneumology
  • Lausanne, Switzerland, CH-1011
    • Centre Hospitalier Universitaire Vaudois (CHUV)
• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Tezosentan	Drug: Tezosentan; single infusion of tezosentan 5mg/h over 30 min corresponding to 2.5 mg

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Idorsia Pharmaceuticals Ltd.
• Investigators: Study Director: Elisabet Lindberg, MD, Actelion

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (ACTUAL): November 1, 2010
• Study Completion (ACTUAL): September 1, 2011

Study Registration Dates

• First Submitted: February 25, 2010
• First Submitted That Met QC Criteria: February 26, 2010
• First Posted (ESTIMATE): March 1, 2010

Study Record Updates

• Last Update Posted (ACTUAL): July 9, 2018
• Last Update Submitted That Met QC Criteria: July 6, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Vasodilator Agents; Tezosentan
• Other Study ID Numbers: AC-051-206