Epoprostenol for Injection in Pulmonary Arterial Hypertension (EPITOME-1)

November 29, 2012 updated by: Actelion

A Phase IV, Open-label, Randomized, Multicenter Study of the Safety, Tolerability,and Pharmacokinetics of ACT- 385781A Compared to Flolan® in Injectable Prostanoid Treatment-naïve Patients With Pulmonary Arterial Hypertension (PAH)

This is a prospective, multi-center, open-label, randomized, Phase IV exploratory study comparing safety, tolerability, pharmacokinetics, and effectiveness of ACT-385781A and Flolan (epoprostenol sodium) in patients with pulmonary arterial hypertension who are naïve to injectable prostanoid treatment and in need of such treatment. Approximately 30 patients from 8 U.S. clinical sites will be randomized to receive either ACT-385781A or Flolan (2:1 respectively) for 28 days of treatment.

Study Overview

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • California
      • La Jolla, California, United States, 92037
        • University of California - San Diego
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado - Denver
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt Medical Center
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male or female subjects aged 18-65 years
  2. Patients with the following types of pulmonary arterial hypertension (PAH) belonging to WHO Group I:

    • Idiopathic (IPAH)
    • Heritable (HPAH)
    • Associated (APAH) with

      • Connective tissue diseases
      • Drugs and toxins
  3. Patients with PAH in modified NYHA functional class III or IV at the time of enrollment in need of injectable epoprostenol.
  4. Patients must be injectable prostanoid treatment-naïve and either

    • newly diagnosed and not yet treated with specific PAH therapies or
    • currently treated with existing background PAH therapy with one or more of the following medications for 90 days prior to enrollment and on a stable dose for 30 days prior to enrollment:

      • Bosentan
      • Ambrisentan
      • Sildenafil
      • Tadalafil
  5. Women of childbearing potential must use a reliable method of contraception.

Exclusion Criteria:

  1. Patients with respiratory and/or cardiovascular distress in need of emergency care including i.v. epoprostenol administration or any vasopressive i.v. drugs
  2. Known pulmonary veno-occlusive disease (PVOD)
  3. Current use of i.v. inotropic agents
  4. Tachycardia with heart rate > 120 beats/min
  5. Pulmonary arterial hypertension related to any condition other than those specified in the inclusion criteria
  6. Known hypersensitivity to the formulations of ACT-385781A or any of its excipients, and Flolan or any of its excipients
  7. Use of inhaled iloprost or treprostinil during the week prior to screening
  8. Cerebrovascular events (e.g., transient ischemic attack or stroke) within 6 months of screening
  9. History of myocardial infarction
  10. History of left-sided heart disease, including any of the following:

    • hemodynamically significant aortic or mitral valve disease
    • restrictive or congestive cardiomyopathy
    • left ventricular ejection fraction < 40% by multigated radionucleotide angiogram(MUGA),angiography, or echocardiography
    • unstable angina pectoris
    • life-threatening cardiac arrhythmias
  11. Chronic bleeding disorder
  12. Infection(s) within the past month that in the mind of the investigator would contraindicate the use of epoprostenol
  13. Pregnancy or breast-feeding
  14. Participation in another clinical trial, except observational (noninterventional), or receipt of an investigational product within 30 days prior to randomization
  15. Any known factor or disease that might interfere with treatment compliance, study conduct or interpretation of the results such as drug or alcohol dependence or psychiatric disease
  16. Known concomitant life-threatening disease other than PAH with a life expectancy < 12 months

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 1
ACT-385781A (Actelion Epoprostenol)
per Prescribing Information
Active Comparator: 2
Flolan®
Per Prescribing Information

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose Normalized Pharmacokinetics of 6,15-diketo-13,14-dihydro-Prostacyclin F1alpha at 2 ng/kg/Min
Time Frame: Day 1
The plasma concentration for the epoprostenol metabolite 6,15-diketo-13,14-dihydro-Prostacyclin F1alpha was measured at 2 ng/kg/min just prior to the next up-titration. Dose-normalized concentrations are used to summarize the results.
Day 1
Dose Normalized Pharmacokinetics of 6,15-diketo-13,14-dihydro-Prostacyclin F1alpha at 4 ng/kg/Min
Time Frame: Day 1
The plasma concentration for the epoprostenol metabolite 6,15-diketo-13,14-dihydro-Prostacyclin F1alpha was measured at 4 ng/kg/min just prior to the next up-titration. Dose-normalized concentrations are used to summarize the results.
Day 1
Dose Normalized Pharmacokinetics of 6-keto-Prostacyclin F1alpha at 2 ng/kg/Min
Time Frame: Day 1
The plasma concentration for the epoprostenol metabolite 6-keto-Prostacyclin F1alpha was measured at 2 ng/kg/min just prior to the next up-titration. Dose-normalized concentrations are used to summarize the results.
Day 1
Dose Normalized Pharmacokinetics of 6-keto-Prostacyclin F1alpha at 4 ng/kg/Min
Time Frame: Day 1
The plasma concentration for the epoprostenol metabolite 6-keto-Prostacyclin F1alpha was measured at 4 ng/kg/min just prior to the next up-titration. Dose-normalized concentrations are used to summarize the results.
Day 1
Six-minute Walk Distance (6MWD) - Baseline and Day 28
Time Frame: Baseline and 28 days (+3 days)
The 6-minute walk test (6MWT) was to be performed prior to initiating study treatment either during the screening visit or on Day 1 prior to drug initiation, and Day 28 (End of treatment (EOT)). This assessment is a non-encouraged test that measures the distance walked for a duration of 6 minutes. The 6MWD was recorded in the Case Report Form (CRF).
Baseline and 28 days (+3 days)
Patients With New York Heart Association (NYHA) Functional Class Change (Improved or Worsened) From Baseline to Day 28
Time Frame: From baseline to 28 days (+3 days)
Disease severity was assessed by NYHA classification of PAH criteria: Class I: no limitation of physical activity (PA). Ordinary PA: no undue dyspnea/fatigue, chest pain, near syncope. Class II: slight limitation of PA. Comfortable at rest. Ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class III: marked limitation of PA. Comfortable at rest. Less than ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class IV: inability to carry out PA without symptoms. Right heart failure. Dyspnea/fatigue may even have been present at rest. Discomfort increased by any PA.
From baseline to 28 days (+3 days)
Percentage Central Venous Blood Oxygen Saturation (ScVO2) - Baseline and Day 28
Time Frame: Baseline and 28 days
Central venous blood oxygen saturation assessment was performed only in specific centers. Measurements for ScVO2 were performed during the inpatient hospitalization period on Day 1 (prior to drug initiation) and on Day 28 (EOT). Samples for ScVO2 were obtained by aspirating blood from the indwelling central venous catheter. After the sample had been drawn, the catheter was primed with study drug in order to refill the lumen to avoid interruption in treatment and sudden decompensation.
Baseline and 28 days
Blood Pressure - Baseline and Day 28
Time Frame: Baseline and 28 days
Blood pressure (systolic and diastolic) were measured indirectly using an automatic oscillometric device, on the same arm for each measurement. The Blood Pressure was assessed at baseline and at Day 28 (End of Study Treatment visit).
Baseline and 28 days
Heart Rate - Baseline and Day 28
Time Frame: Baseline and 28 days
Heart rate was measured indirectly using an automatic oscillometric device, on the same arm for each measurement. The Heart Rate was assessed at Baseline and at Day 28 (End of Study Treatment visit).
Baseline and 28 days
Body Weight - Baseline and Day 28
Time Frame: Baseline and 28 days
Body weight was measured both at baseline and day 28.
Baseline and 28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Study Director: Wade Benton, PharmD, Actelion

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2010

Primary Completion (Actual)

May 1, 2011

Study Completion (Actual)

July 1, 2011

Study Registration Dates

First Submitted

April 15, 2010

First Submitted That Met QC Criteria

April 15, 2010

First Posted (Estimate)

April 16, 2010

Study Record Updates

Last Update Posted (Estimate)

December 3, 2012

Last Update Submitted That Met QC Criteria

November 29, 2012

Last Verified

November 1, 2012

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Pulmonary Arterial Hypertension

Clinical Trials on ACT-385781A (Actelion Epoprostenol)

3
Subscribe