Clinical trial NCT01105091: Epoprostenol for Injection in Pulmonary Arterial Hypertension
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pulmonary Arterial Hypertension
Keywords: Pulmonary Arterial Hypertension
PAH
EPITOME-1
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2010-04-16
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Dose Normalized Pharmacokinetics of 6,15-diketo-13,14-dihydro-Prostacyclin F1alpha at 2 ng/kg/Min
timeFrame: Day 1
measure: Dose Normalized Pharmacokinetics of 6,15-diketo-13,14-dihydro-Prostacyclin F1alpha at 4 ng/kg/Min
timeFrame: Day 1
measure: Dose Normalized Pharmacokinetics of 6-keto-Prostacyclin F1alpha at 2 ng/kg/Min
timeFrame: Day 1
measure: Dose Normalized Pharmacokinetics of 6-keto-Prostacyclin F1alpha at 4 ng/kg/Min
timeFrame: Day 1
measure: Six-minute Walk Distance (6MWD) - Baseline and Day 28
timeFrame: Baseline and 28 days (+3 days)
measure: Patients With New York Heart Association (NYHA) Functional Class Change (Improved or Worsened) From Baseline to Day 28
timeFrame: From baseline to 28 days (+3 days)
measure: Percentage Central Venous Blood Oxygen Saturation (ScVO2) - Baseline and Day 28
timeFrame: Baseline and 28 days
measure: Blood Pressure - Baseline and Day 28
timeFrame: Baseline and 28 days
measure: Heart Rate - Baseline and Day 28
timeFrame: Baseline and 28 days
measure: Body Weight - Baseline and Day 28
timeFrame: Baseline and 28 days
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Actelion
name: Wade Benton, PharmD
role: STUDY_DIRECTOR
References: