Extension of the Psychometric Validation Study ORCHESTRA in Patients With PAH

An Extension of AC-055-310, 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™

Prospective, multi-center, open-label, single-arm, Phase 3b extension study of macitentan in patients with PAH.

To assess the long-term safety of macitentan in patients with pulmonary arterial hypertension (PAH) beyond treatment in the AC-055-310 study.

Study Overview

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

Detailed Description

To assess the long-term safety of macitentan in patients with pulmonary arterial hypertension (PAH) beyond treatment in the AC-055-310 study.

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Bron Cedex, France, 69677
    • Hôpital Louis Pradel
  • Caen, France, 14033
    • Hopital Cote de Nacre
  • Grenoble, France, 38700
    • Hopital Albert Michallon
  • Le Kremlin-Bicêtre, France, 94270
    • CHU de Bicêtre
  • Lille, France, 59037
    • CHRU Lille - Hôpital Cardiologique
  • Montpellier, France, 34295
    • Hôpital Arnaud de Villeneuve
  • Nancy, France, 54511
    • Hôpitaux de Brabois
  • Pessac, France, 33604
    • Hopital de Haut Levêque
  • Rennes, France, 35033
    • Hôpital Pontchaillou
  • Rouen, France, 76031
    • Hôpital Charles Nicolle
  • Saint-Etienne, France, 42227
    • Hopital Nord
  • Strasbourg, France, 67091
    • Hôpital CIVIL
  • Toulouse, France, 31059
    • Hôpital Larrey
• Italy
  • Bologna, Italy, 40138
    • Ospedale Sant'Orsola
  • Firenze, Italy, 50124
    • A.O.U.C. Careggi
  • Rome, Italy, 00161
    • UOC Immunologia Clinica B-PGRM Centro di Riferimento per la Sclerosi Sistemica
  • Rome, Italy, 00186
    • Centro Per La Diagnosi E La Cura Dell'Ipertensione Polmonare
  • Verona, Italy, 37134
    • Policlinico G.B. Rossi
• Spain
  • Alicante, Spain, 03010
    • Hospital General de Alicante
  • Barcelona, Spain, 08036
    • Hospital Clínic
  • Barcelona, Spain, 08035
    • Hospital Val Hebron
  • Bilbao, Spain, 48903
    • Hospital de Cruces
  • Córdoba, Spain, 14004
    • Hospital Reina Sofía
  • Las Palmas de Gran Canaria, Spain, 35010
    • Hospital Dr Negrin
  • Las Palmas de Gran Canaria, Spain, 35016
    • Hospital Universitario Insular Gran Canarias
  • Madrid, Spain, 28046
    • Hospital La Paz
  • Madrid, Spain, 28041
    • Hospital 12 Octubre
  • Malaga, Spain, 29010
    • Hospital Carlos Haya
  • Palma de Mallorca, Spain, 7010
    • Hospital Son Espases
  • Santander, Spain, 39008
    • Hospital de Valdecilla
  • Sevilla, Spain, 41013
    • Hospital Virgen Del Rocio
  • Valencia, Spain, 46014
    • Hospita General U. Valencia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed informed consent prior to any study-mandated procedure.
2. Patients with PAH who completed the ORCHESTRA study (AC-055-310) as scheduled

3. Women of childbearing potential (as defined below) must:

   • Have a negative serum pregnancy test at Visit 1 (i.e., Visit 4 of study AC 055 310) and agree to perform monthly serum pregnancy tests.

   • Agree to use two reliable methods of contraception in parallel, from 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 one 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. Patients who prematurely discontinued study drug in study AC-055-310.
2. Females who are lactating or pregnant (positive Visit 1 pregnancy test) or plan to become pregnant during the study.
3. AST and/or ALT more than 3 X ULN.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Macitentan; 10 mg once daily	Drug: Macitentan; 10 mg once daily; Other Names: ACT-064992

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the long-term safety of macitentan in patients with pulmonary arterial hypertension (PAH) beyond treatment in the AC-055-310 study.	Treatment-emergent adverse events (AEs); AEs leading to premature discontinuation of study drug; Treatment-emergent serious adverse events (SAEs); Proportion of patients with treatment-emergent ALT and/or AST abnormality (> 3, > 5, and > 8 x ULN) associated or not with total bilirubin > 2 x ULN.; Proportion of patients with treatment-emergent hemoglobin abnormality (≦ 100 g/L, and ≦ 80 g/L)	Baseline to end of treatment visit (around 6 months on average)

Collaborators and Investigators

• Sponsor: Actelion
• Investigators: Study Director: Loïc Perchenet, Actelion

Publications and helpful links

Helpful Links

• Extension of the psychometric validation study ORCHESTRA in patients with PAH

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2014
• Primary Completion (Actual): September 19, 2018
• Study Completion (Actual): September 19, 2018

Study Registration Dates

• First Submitted: April 8, 2014
• First Submitted That Met QC Criteria: April 10, 2014
• First Posted (Estimate): April 14, 2014

Study Record Updates

• Last Update Posted (Actual): September 20, 2019
• Last Update Submitted That Met QC Criteria: September 19, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: PAH; pulmonary arterial hypertension; PAH-SYMPACT; psychometric instrument
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Molecular Mechanisms of Pharmacological Action; Endothelin Receptor Antagonists; Endothelin A Receptor Antagonists; Endothelin B Receptor Antagonists; Macitentan
• Other Study ID Numbers: AC-055-311