Clinical trial NCT02081690: A Pulmonary Arterial Hypertension Study With Macitentan to Validate the PAH-SYMPACT™ in France, Italy and Spain
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™
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Pulmonary Arterial Hypertension
Keywords: PAH-SYMPACT
psychometric instrument
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2014-03-07
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Evaluation of the Reliability and the Construct Validity of the Cardiopulmonary Symptoms Domain of the PAH-SYMPACT
timeFrame: From Screening Visit (Visit 1) to End of Treatment (EOT) Visit (Visit 4, Week 16)
measure: Evaluation of the Reliability and the Construct Validity of the Cardiovascular Symptoms Domain of the PAH-SYMPACT
timeFrame: From Screening Visit (Visit 1) to End of Treatment (EOT) Visit (Visit 4, Week 16)
measure: Evaluation of the Reliability and the Construct Validity of the Physical Impacts Domain of the PAH-SYMPACT
timeFrame: From Screening Visit (Visit 1) to End of Treatment (EOT) Visit (Visit 4, Week 16)
measure: Evaluation of the Reliability and the Construct Validity of the Cognitive/Emotional Impacts Domain of the PAH-SYMPACT
timeFrame: From Screening Visit (Visit 1) to End of Treatment (EOT) Visit (Visit 4, Week 16)
Secondary outcomes:
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Hôpital de Haut Levêque
city: Caen
country: France
facility: Hôpital Côte de Nacre
city: Grenoble
country: France
facility: Hôpital Albert Michallon
city: Le Kremlin-Bicêtre
country: France
facility: CHU de Bicêtre
city: Lille
country: France
facility: CHRU Lille - Hôpital Cardiologique
city: Lyon
country: France
facility: Hôpital Louis Pradel
city: Montpellier
country: France
facility: Hôpital Arnaud de Villeneuve
city: Nancy
country: France
facility: Hôpitaux de Brabois
city: Rennes
country: France
facility: Hôpital Pontchaillou
city: Rouen
country: France
facility: Hôpital Charles Nicolle
city: Saint-Etienne
country: France
facility: Hôpital Nord
city: Strasbourg
country: France
facility: Hôpital Civil
city: Toulouse
country: France
facility: Hôpital Larrey
city: Bari
country: Italy
facility: Universita degli Studi di Bari
city: Bari
country: Italy
facility: Ospedale di Venere
city: Bologna
country: Italy
facility: Ospedale Sant'Orsola
city: Firenze
country: Italy
facility: A.O.U.C. Careggi
city: Milan
country: Italy
facility: Milan Sacco Hospital
city: Naples
country: Italy
facility: AORN Azienda Ospedaliera dei Colli
city: Pavia
country: Italy
facility: Ambulatorio Scompenso Cardiaco e Trapiant
city: Pisa
country: Italy
facility: Istituto di Fisiologia clinica - CNR
city: Roma
country: Italy
facility: Centro Per La Diagnosi E La Cura Dell'Ipertensione Polmonare
city: Rome
country: Italy
facility: UOC Immunologia Clinica B-PGRM Centro di Riferimento per la Sclerosi Sistemica
city: Treviso
country: Italy
facility: Ospedale "S. Maria di Cà Foncello"
city: Verona
country: Italy
facility: Policlinico G.B. Rossi
city: Las Palmas de Gran Canaria
country: Spain
facility: Hospital Universitario Insular Gran Canarias
state: Islas Canarias
city: Alicante
country: Spain
facility: Hospital General de Alicante
city: Barcelona
country: Spain
facility: Hospital Val Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic
city: Bilbao
country: Spain
facility: Hospital de Cruces
city: Córdoba
country: Spain
facility: Hospital Reina Sofia
city: Las Palmas de Gran Canaria
country: Spain
facility: Hospital Dr Negrin
city: Madrid
country: Spain
facility: Hospital 12 Octubre
city: Madrid
country: Spain
facility: Hospital La Paz
city: Malaga
country: Spain
facility: Hospital Carlos Haya
city: Palma de Mallorca
country: Spain
facility: Hospital Son Espases
city: Santander
country: Spain
facility: Hospital de Valdecilla
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocio
city: Valencia
country: Spain
facility: Hospita General U. Valencia
Study officials:
affiliation: Actelion
name: Loïc Perchene
role: STUDY_DIRECTOR
References: