Phase 4
Completed N=30
Epoprostenol for Injection in Pulmonary Arterial Hypertension
Source: ClinicalTrials.gov NCT01105091 ↗Enrolled (actual)
30
Serious AEs
26.7%
Results posted
Aug 2012
Primary outcomePrimary: Dose Normalized Pharmacokinetics of 6,15-diketo-13,14-dihydro-Prostacyclin F1alpha at 2 ng/kg/Min — 98.0; 83.1 (pg/ml)/(ng/kg/min)
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Dose Normalized Pharmacokinetics of 6,15-diketo-13,14-dihydro-Prostacyclin F1alpha at 2 ng/kg/Min |
98.0; 83.1 | — |
| PRIMARY Dose Normalized Pharmacokinetics of 6,15-diketo-13,14-dihydro-Prostacyclin F1alpha at 4 ng/kg/Min |
90.9; 59.6 | — |
| PRIMARY Dose Normalized Pharmacokinetics of 6-keto-Prostacyclin F1alpha at 2 ng/kg/Min |
85.5; 109.2 | — |
| PRIMARY Dose Normalized Pharmacokinetics of 6-keto-Prostacyclin F1alpha at 4 ng/kg/Min |
93.1; 95.0 | — |
| PRIMARY Six-minute Walk Distance (6MWD) - Baseline and Day 28 |
339.0; 302.5; 288.0; 323.5 | — |
| PRIMARY Patients With New York Heart Association (NYHA) Functional Class Change (Improved or Worsened) From Baseline to Day 28 |
6; 3; 0; 0 | — |
| PRIMARY Percentage Central Venous Blood Oxygen Saturation (ScVO2) - Baseline and Day 28 |
63.0; 61.5; 58.0; 56.0 | — |
| PRIMARY Blood Pressure - Baseline and Day 28 |
106.5; 106.5; 117.5; 116.0; 62.0; 68.0 | — |
| PRIMARY Heart Rate - Baseline and Day 28 |
83.0; 77.5; 85.0; 88.0 | — |
| PRIMARY Body Weight - Baseline and Day 28 |
74.1; 74.2; 73.6; 73.3 | — |
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT01105091). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.