Purpose

STUDY OBJECTIVES Primary objective To evaluate the effect of macitentan 10 mg on pulmonary vascular resistance (PVR) as compared to placebo in subjects with pulmonary hypertension (PH) after left ventricular assist device (LVAD) implantation. Secondary objectives To evaluate the effect of macitentan 10 mg as compared to placebo on cardio-pulmonary hemodynamics and disease severity in subjects with PH after LVAD implantation. To evaluate the safety and tolerability of macitentan 10 mg in subjects with PH after LVAD implantation. Exploratory objectives To explore the potential effect of macitentan 10 mg as compared to placebo on right ventricular function in subjects with PH after LVAD implantation. To explore the potential effect of macitentan 10 mg as compared to placebo on selected clinical events in subjects with PH after LVAD implantation. To explore the potential effect of macitentan 10 mg as compared to placebo on renal function as measured by glomerular filtration rate (GFR) in subjects with PH after LVAD implantation.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Written Informed Consent prior to initiation of any study-mandated procedure.
  2. Males or females ≥ 18 years of age.
  3. Surgical implantation of LVAD within 90 days prior to Randomization.
  4. Hemodynamic evidence of PH on Baseline right heart catheterization (RHC) by the thermodilution method. Baseline RHC is defined as the last hemodynamic measurements after LVAD implantation and prior to the first dose of study treatment. PH is defined as:
  5. Mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg and
  6. Pulmonary artery wedge pressure (PAWP) ≤ 18 mmHg and
  7. PVR > 3 Wood units.
  8. Stabilization of the patient for 48 h prior to the Baseline RHC, defined as:
  9. No LVAD pump speed/flow rate changes and
  10. Stable dose of oral diuretics and
  11. No intravenous (i.v.) inotropes or vasopressors and
  12. Patient able to ambulate.
  13. A woman of childbearing potential is eligible only if she has:
  14. A negative serum pregnancy test result during the Screening period (Visit 1) and Randomization (Visit 2) and
  15. Agreement to undertake monthly serum pregnancy tests during the study and up to 30 days after study treatment discontinuation and
  16. Agreement to use one of the methods of contraception / follow the contraception scheme described in Section 4.5 from Screening and up to at least 30 days after study treatment discontinuation.
  17. Patient must be randomized within 14 days of Baseline RHC.

Exclusion Criteria

  1. Documented severe obstructive lung disease defined as: forced expiratory volume in 1 second / forced vital capacity (FEV1/FVC) < 0.7 associated with FEV1 < 50% of predicted value after bronchodilator administration.
  2. Documented moderate to severe restrictive lung disease defined as: total lung capacity < 60% of predicted value.
  3. Documented pulmonary veno-occlusive disease.
  4. Patients undergoing dialysis.
  5. Hemoglobin < 8.5 g/dL at Randomization.
  6. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 × the upper limit of normal (ULN) at Randomization.
  7. Severe hepatic impairment, e.g., Child-Pugh Class C liver disease.
  8. Body weight < 40 kg at Randomization.
  9. Doppler mean blood pressure < 65 mmHg at Randomization.
  10. GFR < 30 mL/min at Randomization.
  11. Pregnant, planning to become pregnant during the study period, or breastfeeding.
  12. Treatment with endothelin receptor antagonists (ERAs), phosphodiesterase-5 (PDE5) inhibitors, i.v., subcutaneous (s.c.), or oral prostanoids, or guanylate cyclase stimulators within 7 days prior to Baseline RHC or study treatment initiation.
  13. Treatment with inhaled prostanoids (e.g., iloprost, epoprostenol) or nitric oxide within 24 h prior to Baseline RHC or study treatment initiation.
  14. Treatment with strong inducers of cytochrome P450 isozyme 3A4 (CYP3A4) within 28 days prior to study treatment initiation (e.g., carbamazepine, rifampicin, rifabutin, phenytoin and St. John's Wort).
  15. Treatment with strong inhibitors of CYP3A4 within 28 days prior to study treatment initiation (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir, saquinavir, boceprevir, telaprevir, iopinavir, fosamprenavir, darunavir, tipranavir, atazanavir, nelfinavir, amprenavir, and idinavir).
  16. Treatment with another investigational drug (planned, or taken) within 28 days prior to study treatment initiation.
  17. Known hypersensitivity to ERAs, or to any of the study treatment excipients.
  18. Any condition that prevents compliance with the protocol or adherence to therapy.
  19. Known concomitant life-threatening disease with a life expectancy < 12 months.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Macitentan 10 mg po
Approximately 78 adult subjects with PH post-LVAD implantation will be randomized (1:1) to receive either macitentan 10 mg, or matching placebo, once daily orally.
  • Drug: Macitentan 10mg
    2 groups, randomized in a 1:1 ratio by an Interactive Voice/Web Randomization System to macitentan 10 mg or placebo
    Other names:
    • Active drug
Placebo Comparator
Placebo sugar pill
Approximately 78 adult subjects with PH post-LVAD implantation will be randomized (1:1) to receive either macitentan 10 mg, or matching placebo, once daily orally.
  • Drug: Placebo sugar pill
    2 groups, randomized in a 1:1 ratio by an Interactive Voice/Web Randomization System to macitentan 10 mg or placebo
    Other names:
    • placebo comparator

Recruiting Locations

#133_Montefiore Medical Center
Bronx, New York 10467
Contact:
Med Info
usmedinfo@actelion.com

More Details

NCT ID
NCT02554903
Status
Recruiting
Sponsor
Actelion

Study Contact

Mona Selej, MD
650-624-6900
mselej@its.jnj.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.