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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02081690
• Date of registration: 05/03/2014
• Prospective Registration: No
• Primary sponsor: Actelion
• Public title: A Pulmonary Arterial Hypertension Study With Macitentan to Validate the PAH-SYMPACT™ in France, Italy and Spain ORCHESTRA
• Scientific 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™
• Date of first enrolment: March 1, 2014
• Target sample size: 160
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02081690
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

France, Italy, Spain

Contacts

• Name: Loïc Perchene
• Affiliation: Actelion

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Pulmonary Arterial Hypertension

Intervention(s)

Drug: Macitentan

Primary Outcome(s)

Evaluation of the Reliability and the Construct Validity of the Cardiopulmonary Symptoms Domain of the PAH-SYMPACT [Time Frame: 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 [Time Frame: 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 [Time Frame: 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 [Time Frame: From Screening Visit (Visit 1) to End of Treatment (EOT) Visit (Visit 4, Week 16)]

Secondary ID(s)

AC-055-310

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 05/02/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02081690