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

NCT02081690 | Terminated Phase 3 Results

• 1 other identifier: AC-055-310
• Study Type: interventional
• Target: 160
• Locations: 3 countries
• Sites: 39

Brief Summary

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.

Conditions

Pulmonary Arterial Hypertension

Keywords

PAH-SYMPACT; psychometric instrument

Outcome Measures

Primary Outcomes (4)

• Evaluation of the Reliability and the Construct Validity of the Cardiopulmonary Symptoms Domain of the PAH-SYMPACT

  The Cardiopulmonary Symptoms domain consists of 6 items reported on a 5-point Likert scale (from 0 to 4). The value 0 means "no symptom" and value 4 corresponds to "very severe symptoms".The symptoms part of the PAH-SYMPACT was administered daily over a 7 day period. The recall period of symptom items is the last 24 hours. An average Cardiopulmonary Symptoms domain score is determined based on the daily scores of the 6 items. It was administered two times (daily during 7 days each time) prior to administration of Macitentan (Visit 2, Baseline) and daily during the 7-day period in the treatment period prior to Visit 3 (Week 8) and Visit 4 (Week 16).

  From Screening Visit (Visit 1) to End of Treatment (EOT) Visit (Visit 4, Week 16)

• Evaluation of the Reliability and the Construct Validity of the Cardiovascular Symptoms Domain of the PAH-SYMPACT

  The Cardiovascular Symptoms domain consists of 5 items reported on a 5-point Likert scale (from 0 to 4). The value 0 corresponds to "no symptoms" and value 4 corresponds to "very severe symptoms". The symptoms part of the PAH-SYMPACT was administered daily over a 7 day period. The recall period of symptom items is the last 24 hours. An average Cardiovascular Symptoms domain score is determined based on the daily scores of the 5 items. It was administered two times (daily during 7 days each time) prior to administration of Macitentan (Visit 2, Baseline) and daily during the 7-day period in the treatment period prior to Visit 3 (Week 8) and Visit 4 (Week 16).

  From Screening Visit (Visit 1) to End of Treatment (EOT) Visit (Visit 4, Week 16)

• Evaluation of the Reliability and the Construct Validity of the Physical Impacts Domain of the PAH-SYMPACT

  The Physical Impacts domain consists of 7 items reported on a 5-point Likert scale (from 0 to 4). The value 0 corresponds to "not at all"/"with no difficulty at all" and value 4 corresponds to "very much"/"extremely"/ "not able at all". The impacts part of the PAH-SYMACT was administered on Day 7 of the symptoms part administration. Items in the impact part have a 7 day recall period. An average Physical Impacts domain score is determined based on the 7 items in the domain. It was administered two times prior to administration of Macitentan (Visit 2, Baseline) and during the 7-day period in the treatment period prior to Visit 3 (Week 8) and Visit 4 (Week 16).

  From Screening Visit (Visit 1) to End of Treatment (EOT) Visit (Visit 4, Week 16)

• Evaluation of the Reliability and the Construct Validity of the Cognitive/Emotional Impacts Domain of the PAH-SYMPACT

  The Cognitive/Emotional Impacts domain consists of 4 items reported on a 5-point Likert scale (from 0 to 4). The value 0 corresponds to "not at all"/"with no difficulty at all" and value 4 corresponds to "very much"/"extremely"/ "not able at all". The impacts part of the PAH-SYMACT was administered on Day 7 of the symptoms part administration. Items in the impact part have a 7 day recall period. An average Cognitive/Emotional Impacts domain score is determined based on the 4 items in the domain. It was administered two times prior to administration of Macitentan (Visit 2, Baseline) and during the 7-day period in the treatment period prior to Visit 3 (Week 8) and Visit 4 (Week 16)."

  From Screening Visit (Visit 1) to End of Treatment (EOT) Visit (Visit 4, Week 16)

Study Arms (1)

Macitentan

EXPERIMENTAL

Macitentan tablet, dose of 10 mg, once daily

Drug: Macitentan

Interventions

Macitentan DRUG

Macitentan tablet, dose of 10 mg, once daily

Macitentan

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent prior to initiation of any study-mandated procedure.
• Patients with symptomatic PAH in WHO Functional Class (FC) II or III.
• Patients with PAH belonging to one of the following subgroups of the Dana Point Clinical Classification Group 1:
• Idiopathic, or,
• Heritable, or,
• Drug or toxin induced, or,
• 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.
• Documented hemodynamic diagnosis of PAH by right heart catheterization - performed at any time prior to Screening showing:
• Resting mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg and,
• Resting pulmonary vascular resitance (PVR) \> 240 dyn.s.cm-5 and,
• Pulmonary capillary wede pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) ≤ 15 mmHg.
• minute walk distance (6MWD) ≥ 150 m at Screening.
• Able to fluently speak and read the local language.
• Men or women aged 18-80; women of childbearing potential (as defined below) must:

You may not qualify if:

• 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).
• Known moderate-to-severe restrictive lung disease (i.e., total lung capacity \[TLC\] \< 60% of predicted value).
• Hemoglobin \< 100g/L at Screening.
• Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 3 X upper limit of the normal range (ULN) at Screening.
• Patients undergoing dialysis.
• Systolic blood pressure (SBP) \< 90 mmHg at Screening.
• Body weight \< 40 kg at Screening.
• Known concomitant life-threatening diseases with a life expectancy of \< 12 months.
• Treatment with ERAs within 3 months prior to Visit 2, or scheduled to receive any of these compounds, other than macitentan, during the trial.
• 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.
• Treatment with soluble guanylate cyclase stimulator (riociguat) within 3 months prior to Visit 2, or scheduled to receive riociguat during the trial.
• 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.
• Initiation of diuretics within 1 week prior to the Baseline period.
• Patients on oral diuretics in whom the dose has not been stable for at least 1 week prior to the Baseline period.
• Treatment with cytochrome P4500 (CYP) 3A inducers within 4 weeks prior to Visit 2.

Sponsors & Collaborators

• Actelion: lead

Study Sites (39)

Hôpital de Haut Levêque

Bordeaux, 33604, France

Location

Hôpital Côte de Nacre

Caen, 14033, France

Location

Hôpital Albert Michallon

Grenoble, 38700, France

Location

CHU de Bicêtre

Le Kremlin-Bicêtre, 94270, France

Location

CHRU Lille - Hôpital Cardiologique

Lille, 59037, France

Location

Hôpital Louis Pradel

Lyon, 69677, France

Location

Hôpital Arnaud de Villeneuve

Montpellier, 34295, France

Location

Hôpitaux de Brabois

Nancy, 54511, France

Location

Hôpital Pontchaillou

Rennes, 35033, France

Location

Hôpital Charles Nicolle

Rouen, 76031, France

Location

Hôpital Nord

Saint-Etienne, 42227, France

Location

Hôpital Civil

Strasbourg, 67091, France

Location

Hôpital Larrey

Toulouse, 31059, France

Location

Universita degli Studi di Bari

Bari, 70124, Italy

Location

Ospedale di Venere

Bari, 70131, Italy

Location

Ospedale Sant'Orsola

Bologna, 40138, Italy

Location

A.O.U.C. Careggi

Florence, 50124, Italy

Location

Milan Sacco Hospital

Milan, 20157, Italy

Location

AORN Azienda Ospedaliera dei Colli

Naples, 80131, Italy

Location

Ambulatorio Scompenso Cardiaco e Trapiant

Pavia, 27100, Italy

Location

Istituto di Fisiologia clinica - CNR

Pisa, 56126, Italy

Location

Centro Per La Diagnosi E La Cura Dell'Ipertensione Polmonare

Roma, 00186, Italy

Location

UOC Immunologia Clinica B-PGRM Centro di Riferimento per la Sclerosi Sistemica

Rome, 00161, Italy

Location

Ospedale "S. Maria di Cà Foncello"

Treviso, 31100, Italy

Location

Policlinico G.B. Rossi

Verona, 37134, Italy

Location

Hospital Universitario Insular Gran Canarias

Las Palmas de Gran Canaria, Canary Islands, 35016, Spain

Location

Hospital General de Alicante

Alicante, 03010, Spain

Location

Hospital Val Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic

Barcelona, 08036, Spain

Location

Hospital de Cruces

Bilbao, 48903, Spain

Location

Hospital Reina Sofia

Córdoba, 14004, Spain

Location

Hospital Dr Negrin

Las Palmas de Gran Canaria, 35010, Spain

Location

Hospital 12 Octubre

Madrid, 28041, Spain

Location

Hospital La Paz

Madrid, 28046, Spain

Location

Hospital Carlos Haya

Málaga, 29010, Spain

Location

Hospital Son Espases

Palma de Mallorca, 7010, Spain

Location

Hospital de Valdecilla

Santander, 39008, Spain

Location

Hospital Virgen del Rocio

Seville, 41013, Spain

Location

Hospita General U. Valencia

Valencia, 46014, Spain

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

macitentan

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Clinical Trial Disclosure Manager
• Organization: Actelion Pharmaeuticals Ltd.

clinical-trials-disclosure@actelion.com

Study Officials

• Loïc Perchene

  Actelion

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2014
• First Posted: March 7, 2014
• Study Start: March 1, 2014
• Primary Completion: October 1, 2015
• Study Completion: November 1, 2015
• Last Updated: March 21, 2018
• Results First Posted: February 5, 2018

Record last verified: 2018-02

Locations

IT (12); ES (14); FR (13)