A Long Term Study to Find Out if Macitentan is an Effective and Safe Treatment for Patients With Heart Failure With Preserved Ejection Fraction and Pulmonary Vascular Disease
Condition: Heart Failure With Preserved Ejection Fraction and Pulmonary Vascular Disease
MeSH terms: Heart Failure; Vascular Diseases
Intervention: macitentan 10 mg
Intervention description: macitentan 10 mg, film-coated tablet, oral use
Intervention MeSH terms: Macitentan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Subjects who remained in main study (SERENADE/AC-055G202, NCT03153111) after randomization and who meet the eligibility criteria described will be eligible to enter this single-arm OL extension study. All enrolled subjects will receive macitentan 10 mg. For this OL extension study no primary efficacy endpoint has been defined and all efficacy endpoints are of exploratory nature. The ones listed below are considered safety endpoints.
Masking: None (Open Label)
Enrollment: 91.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: pulmonary vascular disease; macitentan; heart failure with preserved ejection fraction

Summary:

      The aim of this open-label (OL) extension trial is to study the long-term safety and efficacy
      of macitentan in subjects with heart failure with preserved ejection fraction (HFpEF) and
      pulmonary vascular disease (PVD) beyond the treatment in the double-blind parent SERENADE
      study (AC-055G202, NCT03153111). Furthermore, this OL extension study will give eligible
      subjects of the main study (SERENADE/AC-055G202, NCT03153111) an opportunity to continue or
      start receiving macitentan.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed and dated Informed Consent Form (ICF).

          -  Participant remained in the main study (SERENADE/AC-055G202, NCT03153111) for: a) 52
             weeks after randomization if entered this Open-label (OL) extension study prior to
             protocol Version 4, b) At least 24 weeks after randomization if entering this OL
             extension study under protocol Version 4

          -  A woman of childbearing potential is eligible only if: (1) Negative pre-treatment
             serum pregnancy test; (2) Agreement to undertake monthly pregnancy tests from the
             enrollment visit up to at least 30 days after study treatment discontinuation; and (2)
             Agreement to use reliable contraception from at least 30 days prior to the enrollment
             visit up to at least 30 days after study treatment discontinuation.

        Exclusion Criteria:

          -  Premature discontinuation of study treatment in the main study (SERENADE/AC-055G202,
             NCT03153111) due to an adverse event related to: (1) Edema or fluid retention; (2)
             Worsening of heart failure; (3) Liver aminotransferase elevation; and (4) Study
             treatment, based on investigators' discretion

          -  Liver aminotransferase elevations, at the enrollment visit, fulfilling the following
             criteria: (1) Alanine amino transferase (ALT) / aspartate aminotransferase (AST)
             greater than or equal to (>=) 8 * the upper limit of normal (ULN); (2) ALT/AST >= 3 *
             ULN and associated clinical symptoms of liver injury, for example: nausea, vomiting,
             fever, abdominal pain, jaundice, unusual lethargy or fatigue, flu-like syndrome
             (arthralgia, myalgia, fever); and (3) ALT/AST >= 3 * ULN and associated increase in
             total bilirubin to >= 2 * ULN

          -  Treatment with the following forbidden medications within 1 month prior to the
             enrollment visit: (1) Treatments that may interfere with the assessment of efficacy
             (that is, endothelin receptor antagonists, prostanoids, phosphodiesterase-5
             inhibitors, guanylate cyclase stimulators); (2) Strong cytochrome P-450 3A4 (CYP3A4)
             inducers such as rifabutin, rifampin, rifampicin, rifapentin, carbamazepine,
             phenobarbital, phenytoin, or St. John's wort; (3) Strong CYP3A4 inhibitors such as
             ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, nefazodone,
             ritonavir, and saquinavir or a moderate dual CYP3A4/CYP2C9 inhibitor (for example,
             fluconazole or amiodarone) or co-administration of a combination of moderate CYP3A4
             (for example, ciprofloxacin, cyclosporine, diltiazem, erythromycin, verapamil) and
             moderate CYP2C9 inhibitors (for example, miconazole, piperine), in the 1-month period
             prior to baseline. This will not necessarily apply to participants who are already
             well-managed on such an ongoing combination; and (4) any other investigational
             treatment

          -  Pregnant, planning to be become pregnant or lactating.

          -  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 hypersensitivity to macitentan or drugs of the same class, or any of the study
             drug excipients (for example, soy lecithin, lactose)