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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Actelion
ClinicalTrials.gov Identifier:
NCT01105091
First received: April 15, 2010
Last updated: November 29, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Pulmonary Arterial Hypertension
Drug: ACT-385781A (Actelion Epoprostenol)
Drug: Flolan®
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Actelion:

Primary Outcome Measures:
  • Dose Normalized Pharmacokinetics of 6,15-diketo-13,14-dihydro-Prostacyclin F1alpha at 2 ng/kg/Min [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    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.

  • Dose Normalized Pharmacokinetics of 6,15-diketo-13,14-dihydro-Prostacyclin F1alpha at 4 ng/kg/Min [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    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.

  • Dose Normalized Pharmacokinetics of 6-keto-Prostacyclin F1alpha at 2 ng/kg/Min [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    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.

  • Dose Normalized Pharmacokinetics of 6-keto-Prostacyclin F1alpha at 4 ng/kg/Min [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    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.

  • Six-minute Walk Distance (6MWD) - Baseline and Day 28 [ Time Frame: Baseline and 28 days (+3 days) ] [ Designated as safety issue: No ]
    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).

  • 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) ] [ Designated as safety issue: No ]
    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.

  • Percentage Central Venous Blood Oxygen Saturation (ScVO2) - Baseline and Day 28 [ Time Frame: Baseline and 28 days ] [ Designated as safety issue: No ]
    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.

  • Blood Pressure - Baseline and Day 28 [ Time Frame: Baseline and 28 days ] [ Designated as safety issue: Yes ]
    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).

  • Heart Rate - Baseline and Day 28 [ Time Frame: Baseline and 28 days ] [ Designated as safety issue: Yes ]
    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).

  • Body Weight - Baseline and Day 28 [ Time Frame: Baseline and 28 days ] [ Designated as safety issue: No ]
    Body weight was measured both at baseline and day 28.


Enrollment: 30
Study Start Date: March 2010
Study Completion Date: July 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
ACT-385781A (Actelion Epoprostenol)
Drug: ACT-385781A (Actelion Epoprostenol)
per Prescribing Information
Active Comparator: 2
Flolan®
Drug: Flolan®
Per Prescribing Information

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01105091

Locations
United States, California
University of California - San Diego
La Jolla, California, United States, 92037
United States, Colorado
University of Colorado - Denver
Aurora, Colorado, United States, 80045
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Vanderbilt Medical Center
Nashville, Tennessee, United States, 37232
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
Baylor College of Medicine
Houston, Texas, United States, 77030
Sponsors and Collaborators
Actelion
Investigators
Study Director: Wade Benton, PharmD Actelion
  More Information

No publications provided

Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT01105091     History of Changes
Other Study ID Numbers: AC-066A401
Study First Received: April 15, 2010
Results First Received: July 20, 2012
Last Updated: November 29, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Actelion:
Pulmonary Arterial Hypertension
PAH
EPITOME-1

Additional relevant MeSH terms:
Hypertension, Pulmonary
Hypertension
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Cardiovascular Diseases
Epoprostenol
Tezosentan
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Vasodilator Agents

ClinicalTrials.gov processed this record on July 26, 2014