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
Phoenix/Scottsdale, Ariz., Jacksonville, Fla., Rochester, Minn.
Trial status: Open for Enrollment
Why is this study being done?
SYMPHONY is prospective, multi-center, open-label, single-arm, Phase 3b psychometric validation study of the PAH-SYMPACT, a new quality of life questionnaire for patients with pulmonary arterial hypertension. Patients will be in the study for 5 1/2 months, 4 months of which they will receive macitentan, 10 mg, once daily.
The primary objectives are to demonstrate the final content validity of the PAH SYMPACT instrument, to demonstrate the psychometric characteristics of reliability and construct validity of the PAH-SYMPACT instrument, and to demonstrate the ability of the PAH SYMPACT instrument to detect change. The secondary objective is to assess the safety of macitentan in patients with pulmonary arterial hypertension. The exploratory objective is to explore the effects of macitentan on PAH symptoms and their impact (as measured by the PAH-SYMPACT) in patients with pulmonary arterial hypertension.
Who is eligible to participate?
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 - performed at any time prior to Screening showing:
1. Resting mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg and
2. Resting pulmonary vascular resistance (PVR) > 240 dyn•s•cmx5 and
3. Pulmonary capillary wedge 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 English
7. For patients on phosphodiesterase type-5 inhibitors (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.
1. A woman is considered to be of childbearing potential unless she:
- Has not yet entered puberty, or
- Does not have a uterus, or
- Has gone through menopause (has not had a period for at least 12 months for natural reasons, or who has had their ovaries removed)
A women of childbearing potential must:
Have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline and agree to perform monthly urine pregnancy tests, and Agree to use one of the protocol-specified birth control options from the Screening Visit 1 until one month after study drug discontinuation
1. Moderate to severe obstructive lung disease: forced expiratory volume in one second (FEV1) / forced vital capacity < 70% and FEV1 < 65% of predicted value after bronchodilator administration
2. Moderate to severe restrictive lung disease: total lung capacity < 60% of predicted value
3. Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C
4. Hemoglobin < 75% of the lower limit of the normal range at screening
5. Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3 x the upper limit of normal (ULN) at screening
6. Estimated creatinine clearance < 30 mL/min at screening
7. Systolic blood pressure (SBP) < 90 mmHg at screening
8. Body weight < 40 kg at screening
9. Known concomitant life-threatening diseases with a life expectancy of < 12 months
10. Any condition that prevents compliance with the protocol or adherence to therapy
11. Treatment with endothelin receptor antagonists (ERAs) within 3 months prior to Visit 2, or scheduled to receive any of these compounds, other than macitentan, during the trial
12. 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
13. Treatment with riociguat within 3 months prior to Visit 2, or scheduled to receive riociguat during the trial
14. Treatment with cytochrome P450 (CYP) 3A inducers within 4 weeks prior to Visit 2
15. Recently started (< 8 weeks prior to Visit 2) or planned cardiopulmonary rehabilitation program based on exercise
16. Females who are lactating or pregnant (positive Screening or Baseline pregnancy test) or plan to become pregnant during the study
17. Known hypersensitivity to macitentan or its excipients or drugs of the same class
18. Treatment with another investigational drug within 3 months prior to Visit 2
19. 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