A multi-center, open-label, single-arm, Phase 3b study of macitentan in patients with Pulmonary Arterial Hypertension to psychometrically validate the PAH-SYMPACT instrument

Study ID
STU 042013-072

Cancer Related
No

Healthy Volunteers
No

Study Sites

  • UT Southwestern University Hospital—St. Paul

Contact
Megha Sharma
214-645-6489
megha.sharma@utsouthwestern.edu

Principal Investigator
Kelly Chin

Summary

This is a prospective, multi-center, open-label, single-arm, Phase 3b study of macitentan in patients with PaH. This study is designed to psychometrically validate the PaH-SYMPaCT instrument. approximately 275 patients will receive macitentan for the study period of 4 months. The study is planned to be conducted in approximately 75 centers in the united States.
The study includes four consecutive periods of study participation:

Screening period: Days-28 to-15
The Screening period includes the Screening Visit (Visit 1).

Baseline period: From Days -14 to -1
The Baseline period includes:
o Two 7-day periods (ePRo Periods 1, 2) in which the PaH-SYMPaCT
symptom part will be completed (Days-14 to-8 and Days-7 to Day-1);
the PaH-SYMPaCT impact part will be completed on Days-8 and -1.

Treatment period: From Baseline Visit (Day 1, Visit 2) to end of Treatment
(eoT) Visit at Week 16 (Day 112+3 days, Visit 4) or premature treatment
discontinuation,

The Treatment period includes:
o Visit 2, which must occur within 3 days of ePRo Period 2 completion.
o a visit at Week 8 (Day 56+3, Visit 3)
o PaH-SYMPaCT completion period beginning 7 days prior to Week 8
visit (ePRo Period 3)
o a visit at Week 16 (Day 112+3, Visit 4)
o PaH-SYMPaCT completion period beginning 7 days prior to Week 16
visit (ePRo Period 4)

The purpose of the study is to complete content validation and to psychometrically validate the PaH-SYMPaCT in patients with PaH. in addition, the following endpoints will be assessed:
aes leading to premature discontinuation of study drug;
* Treatment-emergent serious adverse events (Saes);
* Change from Baseline to Week 16 in vital signs; i.e., supine SBP, DBP, and HR;
* Treatment-emergent marked laboratory abnormalities;
* Treatment-emergent eCG abnormalities.

Change from Baseline (ePRo Period 2) to Week 8 (ePRo Period 3) and change from Baseline (ePRo Period 2) to Week 16 (ePRo Period 4) in PaH-SYMPaCT symptom and impact part scores, and respective domain scores, if applicable.

Participant Eligibility

1.Signed informed consent prior to initiation of any study-mandated procedure
2. Patients with symptomatic PAH in World Health Organization (WHO) Functional
Class (FC) II to IV
3. Patients with PAH belonging to one of the following subgroups of the Dana Point
Clinical Classification Group 1:
a. Idiopathic, or
b. Heritable, or
c. Drug or toxin induced, or
d. Associated with one of the following:
i. Connective tissue disease
ii. Congenital heart disease with simple systemic-to-pulmonary shunt at
least one year after surgical repair
iii. HIV infection
4. Documented hemodynamic diagnosis of PAH by right heart catheterization x
performed at any time prior to Screening showing:
a. Resting mPAP >= 25 mmHg and
b. Resting PVR > 240 dyn
* s
* cm - 5 and
c. 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 English
7. For patients on PDE5i, inhaled prostacyclin analogues, or calcium channel blockers,
stable doses for at least 3 months prior to Visit 2
8. For patients on oral diuretics, stable doses for at least 4 weeks prior to Visit 2
9. Men or women aged 18 or older
a. A woman is considered to be of childbearing potential unless she meets at
least one of the following criteria:
i. Previous bilateral salpingo-oophorectomy or hysterectomy
ii. Premature ovarian failure confirmed by a specialist
iii. Pre-pubescence, XY genotype, Turner syndrome, uterine agenesis
iv. Postmenopausal, defined as 12 consecutive months with no menses
without an alternative medical cause (International Conference on
Harmonisation [ICH] M3 definition)
b. A woman of childbearing potential is eligible only if she meets criterion (i)
and criteria (ii) or (iii) below:
i. Has a negative serum pregnancy test at the Screening Visit and a
negative urine pregnancy test at Visit 2 and agrees to perform monthly
urine pregnancy tests
ii. Agrees to use the following methods of contraception from the Screening Visit 1
until one month after study drug discontinuation
1. Of the two contraceptive methods, one must be from Group 1,
and one must be from Group 2, defined as follows:
a. Group 1: Oral, implantable, transdermal or injectable
hormonal contraceptives, intrauterines devices, female
sterilization (tubal ligation), or partner[Single Quote]s sterilization
(vasectomy). If a hormonal contraceptive is chosen
from this group, it must be taken for at least one month
prior to Visit 2
b. Group 2: Female or male condoms, diaphragm or
cervical cap, in combination with a spermicide
2. Sexual abstinence, rhythm methods or contraception by the
partner alone are not considered as acceptable methods of
contraception for this study
iii. Adheres to true abstinence from intercourse with a male partner when
this is in line with the preferred lifestyle of the patient (homosexual
women and women in religious order x e.g., nuns)