- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01105091
Epoprostenol for Injection in Pulmonary Arterial Hypertension (EPITOME-1)
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)
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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California
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La Jolla, California, United States, 92037
- University of California - San Diego
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Colorado
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Aurora, Colorado, United States, 80045
- University of Colorado - Denver
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North Carolina
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Durham, North Carolina, United States, 27710
- Duke University Medical Center
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- University of Pennsylvania
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Tennessee
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Nashville, Tennessee, United States, 37232
- Vanderbilt Medical Center
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Texas
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Dallas, Texas, United States, 75390
- University of Texas Southwestern Medical Center
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Houston, Texas, United States, 77030
- Baylor College of Medicine
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Male or female subjects aged 18-65 years
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
- Patients with PAH in modified NYHA functional class III or IV at the time of enrollment in need of injectable epoprostenol.
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
- Women of childbearing potential must use a reliable method of contraception.
Exclusion Criteria:
- Patients with respiratory and/or cardiovascular distress in need of emergency care including i.v. epoprostenol administration or any vasopressive i.v. drugs
- Known pulmonary veno-occlusive disease (PVOD)
- Current use of i.v. inotropic agents
- Tachycardia with heart rate > 120 beats/min
- Pulmonary arterial hypertension related to any condition other than those specified in the inclusion criteria
- Known hypersensitivity to the formulations of ACT-385781A or any of its excipients, and Flolan or any of its excipients
- Use of inhaled iloprost or treprostinil during the week prior to screening
- Cerebrovascular events (e.g., transient ischemic attack or stroke) within 6 months of screening
- History of myocardial infarction
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
- Chronic bleeding disorder
- Infection(s) within the past month that in the mind of the investigator would contraindicate the use of epoprostenol
- Pregnancy or breast-feeding
- Participation in another clinical trial, except observational (noninterventional), or receipt of an investigational product within 30 days prior to randomization
- 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
- Known concomitant life-threatening disease other than PAH with a life expectancy < 12 months
Study Plan
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)
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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
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Blood Pressure - Baseline and Day 28
Time Frame: Baseline and 28 days
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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
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Body Weight - Baseline and Day 28
Time Frame: Baseline and 28 days
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Body weight was measured both at baseline and day 28.
|
Baseline and 28 days
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Wade Benton, PharmD, Actelion
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- AC-066A401
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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.
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