Epoprostenol for Injection in Pulmonary Arterial Hypertension

NCT01105091 | Completed Phase 4 Results

• 1 other identifier: AC-066A401
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Pulmonary Arterial Hypertension

Keywords

Pulmonary Arterial Hypertension; PAH; EPITOME-1

Outcome Measures

Primary Outcomes (10)

• Dose Normalized Pharmacokinetics of 6,15-diketo-13,14-dihydro-Prostacyclin F1alpha at 2 ng/kg/Min

  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

  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

  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

  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

  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

  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

  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

  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

  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

  Body weight was measured both at baseline and day 28.

  Baseline and 28 days

Study Arms (2)

1

ACTIVE COMPARATOR

ACT-385781A (Actelion Epoprostenol)

Drug: ACT-385781A (Actelion Epoprostenol)

2

ACTIVE COMPARATOR

Flolan®

Drug: Flolan®

Interventions

ACT-385781A (Actelion Epoprostenol) DRUG

per Prescribing Information

1

Flolan® DRUG

Per Prescribing Information

2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Actelion: lead

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

Epoprostenol

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Prostaglandins I; Prostaglandins; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Autacoids; Inflammation Mediators; Biological Factors

Limitations and Caveats

The EPITOME-1 study is an open label study without a primary endpoint. The sample size was determined based on feasibility and not a power calculation.

Results Point of Contact

• Title: Wade Benton, PharmD, Director of Medical Affairs
• Organization: Actelion Pharmaceuticals, US

wade.benton@actelion.com

650-808-6562

Study Officials

• Wade Benton, PharmD

  Actelion

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2010
• First Posted: April 16, 2010
• Study Start: March 1, 2010
• Primary Completion: May 1, 2011
• Study Completion: July 1, 2011
• Last Updated: February 4, 2025
• Results First Posted: August 23, 2012

Record last verified: 2025-01