Brief Summary
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.
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.
Brief Title
Clinical Study of Macitentan in Patients With Pulmonary Arterial Hypertension to Psychometrically Validate the PAH-SYMPACT Instrument
Categories
Completion Date
Completion Date Type
Actual
Conditions
Pulmonary Arterial Hypertension
Eligibility Criteria
Inclusion Criteria:
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:
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 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•cm-5 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)
2. A women of childbearing potential is eligible only if she meets both criteria below:
* Has a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline and agree to perform monthly urine pregnancy tests, and
* Agrees to use two methods of contraception (one method for patients with a progesterone implant or an intrauterine device or tubal sterilization) from the Screening Visit 1 until one month after study drug discontinuation
Exclusion Criteria:
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. Hemoglobin \< 75% of the lower limit of the normal range at screening
4. Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 3 times the upper limit of normal (ULN) at screening
5. Estimated creatinine clearance \< 30 mL/min at screening
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. Any condition that prevents compliance with the protocol or adherence to therapy
10. 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
11. 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
12. Treatment with riociguat within 3 months prior to Visit 2, or scheduled to receive riociguat during the trial
13. Treatment with strong cytochrome P450 (CYP) 3A4 inducers or inhibitors within 4 weeks prior to Visit 2
14. Recently started (\< 8 weeks prior to Visit 2) or planned cardio-pulmonary rehabilitation program based on exercise
15. Females who are lactating or pregnant (positive Screening or Baseline pregnancy test) or plan to become pregnant during the study
16. Known hypersensitivity to macitentan or its excipients or drugs of the same class
17. Treatment with another investigational drug within 3 months prior to Visit 2
18. 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
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:
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 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•cm-5 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)
2. A women of childbearing potential is eligible only if she meets both criteria below:
* Has a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline and agree to perform monthly urine pregnancy tests, and
* Agrees to use two methods of contraception (one method for patients with a progesterone implant or an intrauterine device or tubal sterilization) from the Screening Visit 1 until one month after study drug discontinuation
Exclusion Criteria:
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. Hemoglobin \< 75% of the lower limit of the normal range at screening
4. Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 3 times the upper limit of normal (ULN) at screening
5. Estimated creatinine clearance \< 30 mL/min at screening
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. Any condition that prevents compliance with the protocol or adherence to therapy
10. 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
11. 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
12. Treatment with riociguat within 3 months prior to Visit 2, or scheduled to receive riociguat during the trial
13. Treatment with strong cytochrome P450 (CYP) 3A4 inducers or inhibitors within 4 weeks prior to Visit 2
14. Recently started (\< 8 weeks prior to Visit 2) or planned cardio-pulmonary rehabilitation program based on exercise
15. Females who are lactating or pregnant (positive Screening or Baseline pregnancy test) or plan to become pregnant during the study
16. Known hypersensitivity to macitentan or its excipients or drugs of the same class
17. Treatment with another investigational drug within 3 months prior to Visit 2
18. 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
Inclusion Criteria
Inclusion Criteria:
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:
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 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•cm-5 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)
2. A women of childbearing potential is eligible only if she meets both criteria below:
* Has a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline and agree to perform monthly urine pregnancy tests, and
* Agrees to use two methods of contraception (one method for patients with a progesterone implant or an intrauterine device or tubal sterilization) from the Screening Visit 1 until one month after study drug discontinuation
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:
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 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•cm-5 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)
2. A women of childbearing potential is eligible only if she meets both criteria below:
* Has a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline and agree to perform monthly urine pregnancy tests, and
* Agrees to use two methods of contraception (one method for patients with a progesterone implant or an intrauterine device or tubal sterilization) from the Screening Visit 1 until one month after study drug discontinuation
Gender
All
Gender Based
false
Keywords
PAH-SYMPACT
Pulmonary Arterial Hypertension
psychometric instrument
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01841762
Org Class
Industry
Org Full Name
Actelion
Org Study Id
AC-055-401
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
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
Primary Outcomes
Outcome Description
Content validity of the PAH-SYMPACT was assessed using item performance, exploratory and confirmatory factor analysis. The final item content and domain structure of PAH-SYMPACT was determined based on these analyses from the Steering Committee (expert clinicians) and findings from the qualitative research done with patients previously.
Outcome Measure
Development and Refinement of the Patient-reported Outcome Measure of Symptoms and Their Impact in PAH (the PAH-SYMPACT)
Outcome Time Frame
From Screening Visit (Day -14) to End of Treatment (EOT) Visit (Visit 4, Week 16)
Outcome Description
The reliability of the PAH-SYMPACT is assessed by test-retest reliability. Intra-class correlation coefficients (ICCs) assess test-retest reliability for the symptom and impact part scores as well as domains. ICCs equal to or greater than 0.70 are considered to demonstrate good test-retest reliability for total and domain scores.
Outcome Measure
Validation of the Patient-reported Outcome Measure of Symptoms and Their Impact in PAH (the PAH-SYMPACT), With Reliability Assessed Via Test-retest Reliability.
Outcome Time Frame
From ePRO period 1 (Days -14 to -8) to ePRO period 2 (Days -7 to -1) in screening period.
Outcome Description
The reliability of the PAH-SYMPACT is assessed by internal consistency reliability. This was determined using Cronbach's alpha-a value on an internal level scale from 0 to 1.0 with higher scores indicating a more-reliable (precise) instrument.
Outcome Measure
Validation of the Patient-reported Outcome Measure of Symptoms and Their Impact in PAH (the PAH-SYMPACT), Assessing Internal Consistency Reliability.
Outcome Time Frame
From ePRO period 1 (Days -14 to -8) to ePRO period 2 (Days -7 to -1) in screening period.
Secondary Outcomes
Outcome Description
Safety events are reported and documented as defined in study protocol.
Outcome Time Frame
From Day 1 (Baseline Visit) to End of Study visit (EoS).
Outcome Measure
Number of Participants With Treatment-emergent Adverse Events, Serious Adverse Events, and Adverse Events Resulting in Patient Study Drug Discontinuation Between Time Periods, BL to End of Study Visit (EoS, Week 16+30 Days for Follow-up Safety Visits)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
James Tauras
Investigator Email
jtauras@montefiore.org
Investigator Phone