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

This study has been terminated.
(Slow recruitment)
Sponsor:
Information provided by (Responsible Party):
Actelion
ClinicalTrials.gov Identifier:
NCT02081690
First received: March 5, 2014
Last updated: February 26, 2016
Last verified: February 2016
  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
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).


Enrollment: 160
Study Start Date: March 2014
Study Completion Date: November 2015
Primary Completion Date: October 2015 (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   (Adult, Senior)
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
Bordeaux, France, 33604
Hôpital Côte de Nacre
Caen, France, 14033
Hôpital Albert Michallon
Grenoble, France, 38700
CHU de Bicêtre
Le Kremlin-Bicêtre, France, 94270
CHRU Lille - Hôpital Cardiologique
Lille, France, 59037
Hôpital Louis Pradel
Lyon, France, 69677
Hôpital Arnaud de Villeneuve
Montpellier, France, 34295
Hôpitaux de Brabois
Nancy, France, 54511
Hôpital Pontchaillou
Rennes, France, 35033
Hôpital Charles Nicolle
Rouen, France, 76031
Hôpital Nord
Saint-Etienne, France, 42227
Hôpital Civil
Strasbourg, France, 67091
Hôpital Larrey
Toulouse, France, 31059
Italy
Universita degli Studi di Bari
Bari, Italy, 70124
Ospedale di Venere
Bari, Italy, 70131
Ospedale Sant'Orsola
Bologna, Italy, 40138
A.O.U.C. Careggi
Firenze, Italy, 50124
Milan Sacco Hospital
Milan, Italy, 20157
AORN Azienda Ospedaliera dei Colli
Naples, Italy, 80131
Ambulatorio Scompenso Cardiaco e Trapiant
Pavia, Italy, 27100
Istituto di Fisiologia clinica - CNR
Pisa, Italy, 56126
Centro Per La Diagnosi E La Cura Dell'Ipertensione Polmonare
Roma, Italy, 00186
UOC Immunologia Clinica B-PGRM Centro di Riferimento per la Sclerosi Sistemica
Rome, Italy, 00161
Ospedale "S. Maria di Cà Foncello"
Treviso, Italy, 31100
Policlinico G.B. Rossi
Verona, Italy, 37134
Spain
Hospital Universitario Insular Gran Canarias
Las Palmas de Gran Canaria, Islas Canarias, Spain, 35016
Hospital General de Alicante
Alicante, Spain, 03010
Hospital Val Hebron
Barcelona, Spain, 08035
Hospital Clinic
Barcelona, Spain, 08036
Hospital de Cruces
Bilbao, Spain, 48903
Hospital Reina Sofia
Córdoba, Spain, 14004
Hospital Dr Negrin
Las Palmas de Gran Canaria, Spain, 35010
Hospital 12 Octubre
Madrid, Spain, 28041
Hospital La Paz
Madrid, Spain, 28046
Hospital Carlos Haya
Malaga, Spain, 29010
Hospital Son Espases
Palma de Mallorca, Spain, 7010
Hospital de Valdecilla
Santander, Spain, 39008
Hospital Virgen del Rocio
Sevilla, Spain, 41013
Hospita General U. Valencia
Valencia, Spain, 46014
Sponsors and Collaborators
Actelion
Investigators
Study Director: Loïc Perchene Actelion
  More Information

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: February 26, 2016
Health Authority: Spain: Comité Ético de Investigación Clínica
France: Conseil National de l'Ordre des Médecins
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Italy: Ethics Committee
Italy: The Italian Medicines Agency
Spain: Agencia Española de Medicamentos y Productos Sanitarios
France: Committee for the Protection of Personnes

Keywords provided by Actelion:
PAH-SYMPACT
psychometric instrument

Additional relevant MeSH terms:
Familial Primary Pulmonary Hypertension
Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases
Macitentan
Endothelin A Receptor Antagonists
Endothelin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Endothelin B Receptor Antagonists

ClinicalTrials.gov processed this record on August 29, 2016