Pulmonary Arterial HypertensionPhase 4EPITOME-1NCT01105091

Epoprostenol for Injection in Pulmonary Arterial Hypertension

A Phase 4 study testing ACT-385781A (Actelion Epoprostenol) and Flolan® in people with Pulmonary Arterial Hypertension, run by Actelion.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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… Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Pulmonary Arterial Hypertension
What is being tested?: ACT-385781A (Actelion Epoprostenol) and Flolan®
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 30 participants
Where: No sites listed yet
Study dates: Mar 2010to Jul 2011
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Show all 16Show fewer

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.

Who cannot join

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

Show all 21Show fewer

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

About this study

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)

Conditions: Pulmonary Arterial Hypertension
Being tested: ACT-385781A (Actelion Epoprostenol), Flolan®
Keywords: Pulmonary Arterial Hypertension, PAH, EPITOME-1
Medical subject headings: Pulmonary Arterial Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ACT-385781A (Actelion Epoprostenol)Drug
per Prescribing Information
Flolan®Drug
Per Prescribing Information

Study groups in NCT01105091
Study group	Role	What they receive
1	Active comparator	ACT-385781A (Actelion Epoprostenol) Receives: Drug: ACT-385781A (Actelion Epoprostenol)
2	Active comparator	Flolan® Receives: Drug: Flolan®

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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).
Measured: Baseline and 28 days
Body Weight - Baseline and Day 28
Body weight was measured both at baseline and day 28.
Measured: Baseline and 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2010Jul 2011

First posted16 Apr 2010 (estimated)
Study startMar 2010
Primary completionMay 2011
Study completionJul 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 30 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01105091
Sponsor's protocol ID: AC-066A401
Acronym: EPITOME-1
Status last verified: Jan 2025
First submitted: 15 Apr 2010
Last updated: 4 Feb 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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All Pulmonary Arterial Hypertension trials

Study at a glance

From the registry record, last updated by the sponsor on 4 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT01105091
Acronym / sponsor ID: EPITOME-1 / AC-066A401
Conditions: Pulmonary Arterial Hypertension
Keywords: Pulmonary Arterial Hypertension, PAH, EPITOME-1
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 30 participants (actual)
Lead sponsor: ActelionIndustry (pharma, biotech, devices)
Study start: Mar 2010
Primary completion: May 2011 (actual)
Study completion: Jul 2011 (actual)
First posted: 16 Apr 2010 (estimated)
Results: Posted 23 Aug 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
1	Active comparator	Drug: ACT-385781A (Actelion Epoprostenol)ACT-385781A (Actelion Epoprostenol)
2	Active comparator	Drug: Flolan®Flolan®

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (16 listed)

Male or female subjects aged 18-65 years
Patients with the following types of pulmonary arterial hypertension (PAH) belonging to WHO Group I:
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
Women of childbearing potential must use a reliable method of contraception.

Key exclusion criteria (21 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ACT-385781A (Actelion Epoprostenol)per Prescribing Information	Drug	1
Flolan®Per Prescribing Information	Drug	2

Primary outcome

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.
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.
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.
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.
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).
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.
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.
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).
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).
Body Weight - Baseline and Day 28
Time frame: Baseline and 28 days
Body weight was measured both at baseline and day 28.

Results and safety

Results posted to the registry on 23 Aug 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
ACT-385781A (Epoprostenol for Injection)	20	18
Flolan® (Epoprostenol Sodium) for Injection	10	10

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

Time frame: Day 1. Median (Full Range). Unit: (pg/ml)/(ng/kg/min)

Measure	ACT-385781A (Epoprostenol for Injection) n = 15	Flolan® (Epoprostenol Sodium) for Injection n = 6
Value	98.0 (12.5 to 416.5)	83.1 (36.0 to 158.5)

Population analysed: A per-protocol analysis set that included all patients in the treated set who did not violate the protocol in a way that might affect the evaluation of the effect of the study drug(s) on the pharmacokinetic endpoints.

Primary outcome: Dose Normalized Pharmacokinetics of 6,15-diketo-13,14-dihydro-Prostacyclin F1alpha at 4 ng/kg/Min

Time frame: Day 1. Median (Full Range). Unit: (pg/ml)/(ng/kg/min)

Measure	ACT-385781A (Epoprostenol for Injection) n = 10	Flolan® (Epoprostenol Sodium) for Injection n = 6
Value	90.9 (29.3 to 195.0)	59.6 (24.9 to 170.5)

Primary outcome: Dose Normalized Pharmacokinetics of 6-keto-Prostacyclin F1alpha at 2 ng/kg/Min

Time frame: Day 1. Median (Full Range). Unit: (pg/ml)/(ng/kg/min)

Measure	ACT-385781A (Epoprostenol for Injection) n = 15	Flolan® (Epoprostenol Sodium) for Injection n = 6
Value	85.5 (12.5 to 374.5)	109.2 (38.4 to 152.0)

Primary outcome: Dose Normalized Pharmacokinetics of 6-keto-Prostacyclin F1alpha at 4 ng/kg/Min

Time frame: Day 1. Median (Full Range). Unit: (pg/ml)/(ng/kg/min)

Measure	ACT-385781A (Epoprostenol for Injection) n = 10	Flolan® (Epoprostenol Sodium) for Injection n = 6
Value	93.1 (29.8 to 457.5)	95.0 (33.3 to 201.0)

Adverse events

Time frame: Screening to day 28 for treatment-emergent (TE) adverse events (AEs) during dosing inpatient hospitalization and during outpatient period up to day 28 (EOT). TE serious AEs (SAEs) up to 30 days post study drug.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
ACT-385781A (Epoprostenol for Injection)	6 of 20 (30%)	20 of 20 (100%)	Not reported
Flolan® (Epoprostenol Sodium) for Injection	2 of 10 (20%)	10 of 10 (100%)	Not reported

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Wade Benton, PharmD study director

Actelion

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing ACT-385781A (Actelion Epoprostenol) and Flolan® in people with Pulmonary Arterial Hypertension, run by Actelion.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Aug 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Normalized Pharmacokinetics of 6,15-diketo-13,14-dihydro-Prostacyclin F1alpha at 2 ng/kg/Min (time frame: Day 1). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01105091.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2025.