Clinical Study to Evaluate the Safety and Tolerability of Macitentan in Subjects With Combined Pre- and Post-capillary Pulmonary Hypertension (CpcPH) Due to Left Ventricular Dysfunction (MELODY-1)

A Prospective, Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel-group, 12-week Study to Evaluate the Safety and Tolerability of Macitentan in Subjects With Combined Pre- and Post-capillary Pulmonary Hypertension (CpcPH) Due to Left Ventricular Dysfunction

Study to evaluate if macitentan is safe and tolerable enough to be used for treatment of subjects with combined pre- and post-capillary pulmonary hypertension (CpcPH) due to left ventricular dysfunction.

Study Overview

• Status: Completed
• Conditions: Pulmonary Hypertension
• Intervention / Treatment: Drug: Placebo; Drug: Macitentan

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Linz, Austria
    • Krankenhaus der Elisabethinen Linz, 2. Interne Abteilung
  • Vienna, Austria, A-1090
    • Medical University of Vienna and AKH Cardiology
• Belgium
  • Brussels, Belgium, 1070
    • Hôpital Erasme, Cliniques Universitaires de Bruxelles, Cardiologie
  • Leuven, Belgium, 3000
    • University Hospital Gasthuisberg / Interne Geneeskunde - I.G. Pneumologie
• Canada
  • Vancouver, Canada
    • Vancouver General Hospital - The Lung
• Czechia
  • Brno, Czechia
    • FN Brno-Bohunice, I. interní kardiologická klinika
  • Olomouc, Czechia
    • FN Olomouc, 1. Interní klinika - kardiologická
  • Praha, Czechia
    • IKEM (Institut klinické a experimentální medicíny, Institute for Clinical and Experimental Medicine)
  • Praha, Czechia
    • Lékařská fakulta a Všeobecná fakultní nemocnice v Praze, II. Interní klinika kardiologie a angiologie
• France
  • Rouen cedex, France
    • Hôpital Charles Nicolle Service de Cardiologie
• Germany
  • Berlin, Germany
    • DRK Klinken Berlin Kopenick Klinik für Innere Medizin Kardiologie
  • Kiel, Germany
    • Universitätsklinik Schleswig-Holstein Campus Kiel Klinik für Innere Medizin III Kardiologie und Angiologie
  • Köln, Germany
    • Universitätsklinikum Köln Herzzentrum / Klinik III für Innere Medizin (Kardiologie, Pneumologie, Angiologie und Intensivmedizin)
  • Munich, Germany
    • Klinikum der Universität München Medizinische Klinik und Poliklinik 1 - Großhadern Schwerpunkt Pneumologie
• Israel
  • Haifa, Israel, 34362
    • Carmel Medical Center, Pulmonary Unit
  • Jerusalem, Israel, 91120
    • Institute of Pulmonology Hadassah Medical Centre : Ein Karem
  • Rehovot, Israel, 76100
    • Kaplan Medical Centre / Pulmonary Institute and Department of Medicine
  • Tel-Hashomer, Israel, 52621
    • The Chaim Sheba Medical Center / The Institute of Pulmonology, Physiology and Exercise
• Italy
  • Bologna, Italy, 40138
    • A.O. Universitaria Policlinico S. Orsola-Malpighi - Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale - Unità Operativa di Cardiologia
  • Trieste, Italy, 34149
    • Ospedali Riuniti di Trieste
• Spain
  • Barcelona, Spain, 08035
    • Hospital Vall d´Hebron Servicio de Cardiologia
  • Barcelona, Spain, 08036
    • Hospital Clinic Servicio de Cardiologia
  • Cordoba, Spain, 14004
    • Hospital Reina Sofia Servicio de Cardiologia
  • Madrid, Spain, 28041
    • Hospital Universitario 12 Octubre Servicio de Cardiología
• Switzerland
  • Bern, Switzerland
    • Universitätsklinik für Kardiologie Schweizer Herz- und Gefässzentrum Bern
  • Lausanne, Switzerland
    • Centre Hospitalier Universitaire Vaudois Service de Cardiologie
• United States
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Kentuckiana Pulmonary Associates
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University School Of Medicine
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Internal Medicine Cardiology, Pulmonary Hypertension Program
  • Missouri
    • Saint Louis, Missouri, United States
      • Washington University School of Medicine - Center for Advanced Med
  • Ohio
    • Cincinnati, Ohio, United States
      • The Lindner Clinical Trial Center
  • Texas
    • Houston, Texas, United States
      • Houston Methodist Hospital - Heart Failure/Pulm Hypertension

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males and Females >=18 years of age
2. Subjects with combined pre-and post-capillary Pulmonary Hypertension (CpcPH) due to left ventricular dysfunction (subset of WHO groups 2.1 and 2.2)
3. Optimized diuretic therapy

Exclusion Criteria:

1. Types of Pulmonary Hypertension other than WHO groups 2.1 and 2.2 (Nice classification)
2. Administration of PAH-specific therapy (i.e., Endothelin receptor antagonists (ERAs), Prostanoids, Phosphodiesterase 5 (PDE-5) inhibitors, guanylate cyclase stimulators)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Macitentan; oral tablet, 10 mg once daily.	Drug: Macitentan; oral tablet, 10 mg once daily; Other Names: ACT-064992
Placebo Comparator: Placebo; Matching placebo, once daily.	Drug: Placebo; matching placebo; Other Names: matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Experiencing Significant Fluid Retention or Worsening in NYHA Functional Class (FC) up to End-of-treatment	The main endpoint is the number of participants who had at least one of the following: A) significant fluid retention, defined as increase in body weight at any time by ≥ 5% or ≥ 5 kg from baseline due to fluid overload and/or parenteral administration of diuretics. B) Worsening of NYHA functional class from baseline.	From randomization up to End-of-Study (Week 12 + 30 days follow-up) plus 1 calendar day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NT-proBNP at Week 12 Expressed as Percent of Baseline NT-proBNP at Rest		From randomization up to end of treatment period (Week 12)
PVR at Rest at Week 12 Expressed as Percent of Baseline PVR at Rest	Pulmonary vascular resistance (PVR) was assessed at rest by right heart catheterization (RHC).	From randomization up to end of treatment period (Week 12)
Change From Baseline to Week 12 in Mean Pulmonary Arterial Pressure (mPAP)		From randomization up to end of treatment period (Week 12)
Change From Baseline to Week 12 in Mean Right Atrial Pressure (mRAP)		From randomization up to end of treatment period (Week 12)
Change From Baseline to Week 12 in Pulmonary Artery Wedge Pressure (PAWP)		From randomization up to end of treatment period (Week 12)
Change From Baseline to Week 12 in Cardiac Index (CI)		From randomization up to end of treatment period (Week 12)
Change From Baseline to Week 12 in Diastolic Pulmonary Vascular Pressure Gradient (DPG)		From randomization up to end of treatment period (Week 12)

Collaborators and Investigators

• Sponsor: Actelion
• Investigators: Study Chair: Sébastien Roux, PhD, Actelion

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2014
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: February 21, 2014
• First Submitted That Met QC Criteria: February 24, 2014
• First Posted (Estimate): February 25, 2014

Study Record Updates

• Last Update Posted (Actual): May 15, 2019
• Last Update Submitted That Met QC Criteria: April 24, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: pre- and post-capillary pulmonary hypertension; CpcPH
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; Ventricular Dysfunction; Ventricular Dysfunction, Left; Molecular Mechanisms of Pharmacological Action; Endothelin Receptor Antagonists; Endothelin A Receptor Antagonists; Endothelin B Receptor Antagonists; Macitentan
• Other Study ID Numbers: AC-055G201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No