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

NCT ID: NCT02081690

Last Updated: 2018-03-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-01
• Study Completion Date: 2015-11-01

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Macitentan

Macitentan tablet, dose of 10 mg, once daily

Group Type: EXPERIMENTAL

Macitentan

Intervention Type: DRUG

Macitentan tablet, dose of 10 mg, once daily

Interventions

Macitentan

Macitentan tablet, dose of 10 mg, once daily

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Actelion

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Loïc Perchene

Role: STUDY_DIRECTOR

Actelion

Locations

Hôpital de Haut Levêque

Bordeaux, , France

Hôpital Côte de Nacre

Caen, , France

Hôpital Albert Michallon

Grenoble, , France

CHU de Bicêtre

Le Kremlin-Bicêtre, , France

CHRU Lille - Hôpital Cardiologique

Lille, , France

Hôpital Louis Pradel

Lyon, , France

Hôpital Arnaud de Villeneuve

Montpellier, , France

Hôpitaux de Brabois

Nancy, , France

Hôpital Pontchaillou

Rennes, , France

Hôpital Charles Nicolle

Rouen, , France

Hôpital Nord

Saint-Etienne, , France

Hôpital Civil

Strasbourg, , France

Hôpital Larrey

Toulouse, , France

Universita degli Studi di Bari

Bari, , Italy

Ospedale di Venere

Bari, , Italy

Ospedale Sant'Orsola

Bologna, , Italy

A.O.U.C. Careggi

Florence, , Italy

Milan Sacco Hospital

Milan, , Italy

AORN Azienda Ospedaliera dei Colli

Naples, , Italy

Ambulatorio Scompenso Cardiaco e Trapiant

Pavia, , Italy

Istituto di Fisiologia clinica - CNR

Pisa, , Italy

Centro Per La Diagnosi E La Cura Dell'Ipertensione Polmonare

Roma, , Italy

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

Rome, , Italy

Ospedale "S. Maria di Cà Foncello"

Treviso, , Italy

Policlinico G.B. Rossi

Verona, , Italy

Hospital Universitario Insular Gran Canarias

Las Palmas de Gran Canaria, Canary Islands, Spain

Hospital General de Alicante

Alicante, , Spain

Hospital Val Hebron

Barcelona, , Spain

Hospital Clinic

Barcelona, , Spain

Hospital de Cruces

Bilbao, , Spain

Hospital Reina Sofia

Córdoba, , Spain

Hospital Dr Negrin

Las Palmas de Gran Canaria, , Spain

Hospital 12 Octubre

Madrid, , Spain

Hospital La Paz

Madrid, , Spain

Hospital Carlos Haya

Málaga, , Spain

Hospital Son Espases

Palma de Mallorca, , Spain

Hospital de Valdecilla

Santander, , Spain

Hospital Virgen del Rocio

Seville, , Spain

Hospita General U. Valencia

Valencia, , Spain

Countries

France; Italy; Spain

Other Identifiers

AC-055-310

Identifier Type: -

Identifier Source: org_study_id