A Pulmonary Arterial Hypertension Study With Macitentan to Validate the PAH-SYMPACT™ in France, Italy and Spain (ORCHESTRA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Actelion
Sponsor:
Information provided by (Responsible Party):
Actelion
ClinicalTrials.gov Identifier:
NCT02081690
First received: March 5, 2014
Last updated: August 7, 2014
Last verified: August 2014
  Purpose

Prospective, multi-center, open-label, single-arm, Phase 3b psychometric validation study.

Primary objectives: To evaluate the psychometric characteristics of reliability and construct validity of the French, Italian and Spanish versions of the PAH-SYMPACT™.

To evaluate the ability of the French, Italian and Spanish versions of the PAH SYMPACT™ to detect change.

Secondary objective: To assess the safety of macitentan in patients with pulmonary arterial hypertension (PAH).

Exploratory objective: To explore the effects of macitentan on PAH symptoms and their impact (as measured by the PAH-SYMPACT™) in patients with PAH in France, Italy and Spain.


Condition Intervention Phase
Pulmonary Arterial Hypertension (PAH)
Drug: Macitentan
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-center, Open-label, Single-arm, Phase 3b Study of Macitentan in Patients With Pulmonary Arterial Hypertension to Psychometrically Validate the French, Italian and Spanish Versions of the PAH-SYMPACT™

Resource links provided by NLM:


Further study details as provided by Actelion:

Primary Outcome Measures:
  • Psychometric validation of the French, Italian and Spanish versions of the PAH-SYMPACT™ patient-reported outcome tool [ Time Frame: From Screening Visit (Visit 1) to End of Treatment (EOT) Visit (Visit 4, Week 16) ] [ Designated as safety issue: Yes ]
    Evaluation of the psychometric characteristics of reliability and construct validity of the PAH-SYMPACT, and the ability of the PAH-SYMPACT to detect change.

  • Change in the PAH-SYMPACT symptom and impact scores [ Time Frame: From Baseline Visit (Visit 2, Day 1) to Week 8 and from Baseline Visit to Week 16 ] [ Designated as safety issue: No ]
    Change in the PAH-SYMPACT symptom and impact scores assessed by the PAH-SYMPACT questionnaire.


Secondary Outcome Measures:
  • Assessment of the safety of macitentan [ Time Frame: From Screening Visit (Visit 1) to End of Treatment (EOT) Visit (Visit 4, Week 16) ] [ Designated as safety issue: Yes ]
    Frequency of treatment-emergent adverse events (AEs); AEs leading to premature discontinuation of study drug; treatment emergent serious adverse events (SAEs); change from Baseline to Week 16 in vital signs; treatment-emergent liver aminotransferase abnormalities (>3, >5, and >8 X upper limit of normal) associated or not with total bilirubin >2 X upper limit of normal; treatment-emergent hemoglobin abnormality (≦100 g/L and ≦80 g/L).


Estimated Enrollment: 160
Study Start Date: March 2014
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Macitentan
Macitentan tablet, dose of 10 mg, once daily
Drug: Macitentan
Macitentan tablet, dose of 10 mg, once daily

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed informed consent prior to initiation of any study-mandated procedure.
  2. Patients with symptomatic PAH in WHO Functional Class (FC) II or III.
  3. Patients with PAH belonging to one of the following subgroups of the Dana Point Clinical Classification Group 1:

    1. Idiopathic, or,
    2. Heritable, or,
    3. Drug or toxin induced, or,
    4. Associated with one of the following:

    i. Connective tissue disease, ii. Congenital heart disease with simple systemic-to-pulmonary shunt at least 1 year after surgical repair, iii. HIV infection.

  4. Documented hemodynamic diagnosis of PAH by right heart catheterization - performed at any time prior to Screening showing:

    1. Resting mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg and,
    2. Resting pulmonary vascular resitance (PVR) > 240 dyn.s.cm-5 and,
    3. Pulmonary capillary wede pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) ≤ 15 mmHg.
  5. 6-minute walk distance (6MWD) ≥ 150 m at Screening.
  6. Able to fluently speak and read the local language.
  7. Men or women aged 18-80; women of childbearing potential (as defined below) must:

    1. Have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline and agree to perform monthly serum pregnancy tests, and,
    2. Agree to use two reliable methods of contraception in parallel, from Screening Visit 1 until 1 month after study drug discontinuation (see details below).

      • A female is considered to have childbearing potential unless she meets at least one of the following criteria:

        • Previous bilateral salpingo and/or oophorectomy, or hysterectomy.
        • Premature ovarian failure confirmed by a specialist.
        • Pre-pubescence, XY genotype, Turner syndrome, uterine agenesis.
        • Postmenopausal, defined as 12 consecutive months with no menses without an alternative medical cause.
      • Of the two contraceptive methods that must be used, one must be from Group 1, and one must be from Group 2, defined as follows:

        • Group 1: Oral, implantable, transdermal or injectable hormonal contraceptives, intrauterine devices, female sterilization (tubal ligation or non surgical sterilization, e.g., permanent contraception with Essure procedure), or partner's sterilization (vasectomy). If a hormonal contraceptive is chosen from this group, it must be taken for at least 1 month prior to enrollment. Alternatively, if the Essure procedure is chosen as a contraceptive method, a hysterosalpingogram must have been performed to confirm correct location of the microinserts and tubal occlusion (as per manufacturer's recommendations).
        • Group 2: Female or male condoms, diaphragm or cervical cap, any of them in combination with a spermicide.
      • Sexual abstinence, rhythm methods, or contraception by the partner alone are not considered as acceptable methods of contraception for this study.

Exclusion Criteria:

  1. Known moderate-to-severe obstructive lung disease (i.e., forced expiratory volume in one second [FEV1] < 80 % of predicted, with FEV1 / forced vital capacity [FVC] < 70%) or known significant chronic lung disease diagnosed by chest imaging (e.g., interstitial lung disease, emphysema).
  2. Known moderate-to-severe restrictive lung disease (i.e., total lung capacity [TLC] < 60% of predicted value).
  3. Hemoglobin < 100g/L at Screening.
  4. Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3 X upper limit of the normal range (ULN) at Screening.
  5. Patients undergoing dialysis.
  6. Systolic blood pressure (SBP) < 90 mmHg at Screening.
  7. Body weight < 40 kg at Screening.
  8. Known concomitant life-threatening diseases with a life expectancy of < 12 months.
  9. Treatment with ERAs within 3 months prior to Visit 2, or scheduled to receive any of these compounds, other than macitentan, during the trial.
  10. Treatment with intravenous or subcutaneous prostacyclin or prostacyclin analogs within 3 months prior to Visit 2, or scheduled to receive any of these compounds during the trial.
  11. Treatment with soluble guanylate cyclase stimulator (riociguat) within 3 months prior to Visit 2, or scheduled to receive riociguat during the trial.
  12. Patients who changed the dose of or discontinued phosphodiesterase type-5 inhibitor (PDE5i), inhaled prostacyclin analogues, or calcium channel blockers within 3 months prior to Visit 2.
  13. Initiation of diuretics within 1 week prior to the Baseline period.
  14. Patients on oral diuretics in whom the dose has not been stable for at least 1 week prior to the Baseline period.
  15. Treatment with cytochrome P4500 (CYP) 3A inducers within 4 weeks prior to Visit 2.
  16. Recently started (< 8 weeks prior to Visit 2) or planned cardio-pulmonary rehabilitation program based on exercise.
  17. Females who are lactating or pregnant (positive Screening or Baseline pregnancy test) or plan to become pregnant during the study.
  18. Known hypersensitivity to macitentan or its excipients or drugs of the same class.
  19. Treatment with another investigational drug within 3 months prior to Visit 2.
  20. 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02081690

Locations
France
Hôpital de Haut Levêque Recruiting
Bordeaux, France, 33604
Contact: Claire Dromer    33557656189    claire.dromer@chu-bordeaux.fr   
Hôpital Côte de Nacre Recruiting
Caen, France, 14033
Contact: Emmanuel Bergot    33 2 31064677    bergot-e@chu-caen.fr   
Hôpital Albert Michallon Recruiting
Grenoble, France, 38700
Contact: Christophe Pison    +33-4-76765834    cpison@chu-grenoble.fr   
CHU de Bicêtre Recruiting
Le Kremlin-Bicêtre, France, 94270
Contact: Laurent Savale    33145217991    laurent.savale@gmail.com   
CHRU Lille - Hôpital Cardiologique Recruiting
Lille, France, 59037
Contact: Pascal DeGroote    +33 3 20 44 57 21    pascal.degroote@chru-lille.fr   
Hôpital Louis Pradel Recruiting
Lyon, France, 69677
Contact: Vincent Cottin    33472357072    vincent.cottin@chu-lyon.fr   
Hôpital Arnaud de Villeneuve Recruiting
Montpellier, France, 34295
Contact: Arnaud Bourdin    +33 4 67 33 60 91    arnaud01009157@gmail.com   
Hôpitaux de Brabois Recruiting
Nancy, France, 54511
Contact: Jean-Francois Chabot    +33-3-83154021    f.chabot@chu-nancy.fr   
Hôpital Pontchaillou Recruiting
Rennes, France, 35033
Contact: Céline Chabanne    +33-2-99282519    celine.chabanne@chu-rennes.fr   
Hôpital Charles Nicolle Recruiting
Rouen, France, 76031
Contact: Fabrice Bauer    +33-2-32888232    fabrice.bauer@chu-rouen.fr   
Hôpital Nord Recruiting
Saint-Etienne, France, 42227
Contact: Laurent Bertoletti    +33-4-77127770    laurent.bertoletti@gmail.com   
Hôpital Civil Recruiting
Strasbourg, France, 67091
Contact: Matthieu Canuet    33 3 6955 0645    matthieu.canuet@chru-strasbourg.fr   
Hôpital Larrey Recruiting
Toulouse, France, 31059
Contact: Grégoire Prévot    335677717 09    prevot.g@chu-toulouse.fr   
Italy
Ospedale Sant'Orsola Recruiting
Bologna, Italy, 40138
Contact: Nazzareno Galiè    +39 0516363536    nazzareno.galie@unibo.it   
A.O.U.C. Careggi Recruiting
Firenze, Italy, 50124
Contact: Chiara Arcangeli    +39-347-6290100    chiarcangeli@yahoo.it   
Ambulatorio Scompenso Cardiaco e Trapiant Recruiting
Pavia, Italy, 27100
Contact: Stefano Ghio    +39-0382-503460    s.ghio@smatteo.pv.it   
Istituto di Fisiologia clinica - CNR Recruiting
Pisa, Italy, 56126
Contact: Carlo Marini    050 315 2143    marini@ifc.cnr.it   
Centro Per La Diagnosi E La Cura Dell'Ipertensione Polmonare Enrolling by invitation
Roma, Italy, 00186
UOC Immunologia Clinica B-PGRM Centro di Riferimento per la Sclerosi Sistemica Recruiting
Rome, Italy, 00161
Contact: Simonetta Pisarri    39-6-49972075    simonetta.pisarri@uniroma1.it   
Policlinico G.B. Rossi Recruiting
Verona, Italy, 37134
Contact: Claudio Lunardi    +39-0458-124759    claudio.lunardi@univr.it   
Spain
Hospital Universitario Insular Gran Canarias Recruiting
Las Palmas de Gran Canaria, Islas Canarias, Spain, 35016
Contact: Francisco Javier Guerra Ramos    34654451489    fcojavguerra@hotmail.com   
Hospital General de Alicante Recruiting
Alicante, Spain, 03010
Contact: Gil Carbonell    34618840520    jgc01a@saludalia.com   
Hospital Val Hebron Recruiting
Barcelona, Spain, 08035
Contact: Manuel Lopez Meseguer    34932746000; Ext: 6208    manuelop@vhebron.net   
Hospital Clinic Recruiting
Barcelona, Spain, 08036
Contact: Joan Albert Barbera Mir    34932275747    jbarbera@clinic.ub.es   
Hospital de Cruces Recruiting
Bilbao, Spain, 48903
Contact: Victoria Egurbide Astobiza    34946006348    mvictoria.egurbidearberas@osakidetza.net   
Hospital Reina Sofia Recruiting
Córdoba, Spain, 14004
Contact: Francisco Santos Luna    34957010411    fsantos1957@hotmail.com   
Hospital 12 Octubre Recruiting
Madrid, Spain, 28041
Contact: Pilar Escribano Subias    34913908669    pilar.escribano@telefonica.net   
Hospital La Paz Recruiting
Madrid, Spain, 28046
Contact: Juan Jose Rios Blanco    34630064677    juanjo.rios@gmail.com   
Hospital Carlos Haya Recruiting
Malaga, Spain, 29010
Contact: Enrique de Ramón    34630373364    ederamongm2@gmail.com   
Hospital Son Espases Recruiting
Palma de Mallorca, Spain, 7010
Contact: Ernest Sala Llinas    34871 206507 ext 76507    Ernest.sala@ssib.es   
Hospital de Valdecilla Recruiting
Santander, Spain, 39008
Contact: Jose Manuel Cifrian Martinez    34696 859 471    jmcifrian@humv.es   
Hospital Virgen del Rocio Recruiting
Sevilla, Spain, 41013
Contact: Remedios Otero Candelera    34955013172    rotero@separ.es   
Hospita General U. Valencia Recruiting
Valencia, Spain, 46014
Contact: Gustavo Juan Samper    34961972230    Gustavo.Juan@uv.es   
Sponsors and Collaborators
Actelion
  More Information

No publications provided

Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT02081690     History of Changes
Other Study ID Numbers: AC-055-310
Study First Received: March 5, 2014
Last Updated: August 7, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
France: Committee for the Protection of Personnes
France: Conseil National de l'Ordre des Médecins
Italy: Ethics Committee
Italy: The Italian Medicines Agency
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Spain: Comité Ético de Investigación Clínica

Additional relevant MeSH terms:
Hypertension, Pulmonary
Hypertension
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on August 27, 2014