Hypertension, Pulmonary, Pulmonary Arterial Hypertension
Conditions
Brief summary
This is a two-part (Phase 2/Phase 3) study of frespaciguat, an inhaled soluble guanylate cyclase stimulator, in participants with pulmonary arterial hypertension (PAH). The first part (Phase 2) will assess three different doses of frespaciguat compared to placebo in a base period of 12 weeks, followed by comparison of three different doses of frespaciguat during an optional 40 month extension period. The treatment dose with the best efficacy and safety profile in the phase 2 cohort base period will be selected for use in the second part (Phase 3) of the study. The primary hypothesis of Phase 2 is that at least one frespaciguat dose is superior to placebo in reducing pulmonary vascular resistance (PVR) from baseline at week 12. The purpose of the second part (Phase 3) of the study is to confirm the efficacy, safety, and tolerability of frespaciguat at the selected dose compared to placebo during a 12 week base period followed by an extension period of up to 5 years. The primary hypothesis of Phase 3 is that frespaciguat is superior to placebo in increasing 6-minute walk distance (6MWD) from baseline at week 12. Due to sponsor's decision this phase/part was not conducted.
Interventions
DRUGFrespaciguat
Frespaciguat (soluble guanylate cyclase stimulator) 380 µg, 100 µg or 32 µg administered as dry powder inhalation
DRUGPlacebo to Frespaciguat
Placebo administered as dry powder inhalation
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
A total of approximately 450 participants will be randomized in this operationally seamless adaptive Phase 2/3 study. Phase 2 of the study will randomize approximately 164 participants into 4 arms, and Phase 3 of the study will randomize approximately 286 participants into 2 arms.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Pulmonary arterial hypertension (PAH) in one of the following groups: * Idiopathic PAH * Heritable PAH * Drug and toxin-induced PAH * PAH associated with connective tissue disease, HIV infection, or congenital heart disease. * Diagnosis of PAH documented by right heart catheterization (RHC). * Eligibility RHC meeting all of the following criteria: * Mean pulmonary artery pressure (mPAP) ≥25 mmHg * Pulmonary vascular resistance (PVR) of ≥3 Wood units * Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) ≤15 mmHg. * World Health Organization functional class (WHO-FC) symptoms between Class II and IV. * Two 6-Minute walk distance (6MWD) measurements between 150 and 500 meters, one at screening and one at randomization. * Stable concomitant background PAH-specific therapy. * Body Mass Index (BMI) between 18.5 kg/m² and 40 kg/m² . * Agree to be abstinent from heterosexual intercourse or use contraception during the intervention period and for at least 14 days after the last dose of study intervention. * Female participants may not be pregnant or breastfeeding.
Exclusion criteria
* Group 2 to 5 pulmonary hypertension. * PAH in one of the following groups: * Long term responders to calcium channel blockers * Overt features of venous/capillary involvement * Evidence of more-than-mild obstructive lung disease. * Evidence of more-than-mild parenchymal lung disease. * Evidence of more-than-mild obstructive sleep apnea (OSA) that is untreated. * Evidence or history of left heart disease, including any of the following: * Left ventricular ejection fraction (LVEF) ≤45% * Moderate or severe left-sided valvular disease (aortic or mitral valve stenosis or regurgitation) * Significant left ventricular diastolic dysfunction on echocardiographic evaluation * Presence of 3 or more of the following risk factors for heart failure with preserved ejection fraction: BMI\>30 kg/m², essential systemic hypertension, diabetes mellitus of any type, or coronary artery disease. * Oxygen saturation measured by pulse oximetry (SpO₂) \<90%, despite supplemental oxygen therapy. * Chronic renal insufficiency (eGFR \<30 mL/min) * Chronic liver disease (i.e., Child-Pugh B or C), portal hypertension, cirrhosis, or significant hepatic laboratory abnormalities. * Current smoker or currently uses electronic cigarettes (vapes). * History of cancer, except: nonmelanomatous skin carcinoma or carcinoma in situ of the cervix or other malignancies which have been successfully treated, with appropriate follow up, and unlikely to recur for the duration of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2 Cohort: Mean Percent Change From Baseline in Pulmonary Vascular Resistance (PVR) at 12 Weeks | At baseline and 12 weeks | PVR was calculated in participants after MK-5475 dosing at baseline and Week 12. PVR is assessed by right heart catheterization (RHC). Based on the variables obtained by right heart catheterization (RHC), the percentage change from baseline PVR was calculated. Per protocol, this outcome measure was assessed only for base period and was not assessed during extension period. |
| Phase 3 Cohort: Mean Change From Baseline in 6-Minute Walk Distance (6MWD) at 12 Weeks | At baseline and 12 weeks | 6MWD is measured by an exercise test known as 6-Minute Walk Test (6MWT) that assesses functional capacity. It measures the distance covered over a time of 6 minutes and is intended to be used as an outcome measure by which to compare changes in excercise capacity. Each participant's 6MWD is to be measured at baseline and at 12 weeks. An increase in the distance walked during the 6MWT indicates improvement in functional exercise capacity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2 Cohort: Mean Change From Baseline in Cardiac Index (CI) at 12 Weeks | At baseline and 12 weeks | The cardiac index (CI) is a hemodynamic measure that represents the cardiac output (CO) of an individual divided by their body surface area (BSA). Cardiac index is assessed by right heart catheterization (RHC). An increase in CI is indicates better right ventricular function and is associated with a reduction of PAH related morbidity and mortality. |
| Phase 2 Cohort: Mean Change From Baseline in Stroke Volume Index (SVI) at 12 Weeks | At baseline and 12 weeks | The stroke volume index represents the amount of blood in mL, per square meter of body surface area, that is mobilized with each heart beat. SVI is assessed by RHC. An increase in SVI indicates better right ventricular function and is associated with a reduction of PAH related morbidity and mortality. |
| Phase 3 Cohort: Mean Change From Baseline in 6-Minute Walk Distance (6MWD) at 24 Weeks | At baseline and 24 weeks | 6MWD is measured by an exercise test known as 6-Minute Walk Test (6MWT) that assesses functional capacity. It measures the distance covered over a time of 6 minutes and is intended to be used as an outcome measure by which to compare changes in exercise capacity. Each participant's 6MWD is to be measured at baseline and at 24 weeks. An increase in the distance walked during the 6MWT indicates improvement in functional exercise capacity. |
| Phase 3 Cohort: Proportion of Participants Whose World Health Organization Functional Class (WHO-FC) is Not Worse at 12 Week Relative to Baseline | At baseline and 12 weeks | The World Health Organization (WHO) classification of functional status is a measure of disease severity, based on a patient's description of their level of functioning and symptoms of disease in relation to their everyday activity. Patients were to be assigned 1 of 4 WHO-FC, dependent on limits of physical activity. As WHO-FC increases from I to IV, limits of physical activity were to increase. |
| Phase 2 Cohort: Mean Change From Baseline in 6-Minute Walk Distance (6MWD) at 12 Weeks | At baseline and 12 weeks | 6MWD is measured by an exercise test known as 6-Minute Walk Test (6MWT) that assesses functional capacity. It measures the distance covered over a time of 6 minutes and is used as an outcome measure by which to compare changes in exercise capacity. Each participant's 6MWD was measured at baseline and at 12 weeks. An increase in the distance walked during the 6MWT indicates improvement in functional exercise capacity. |
| Phase 2 Cohort: Number of Participants Who Discontinued Study Drug Due to an Adverse Event | Up to approximately 2.25 years | An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued treatment due to an AE was assessed. |
| Phase 3 Cohort: Number of Participants Who Experienced an Adverse Event | Up to approximately 2.25 years | An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. |
| Phase 3 Cohort: Number of Participants Who Discontinued Study Drug Due to an AE | Up to approximately 2.25 years | An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued treatment due to an AE was assessed. |
| Phase 2 Cohort: Number of Participants Who Experienced an Adverse Event | Up to approximately 2.25 years | An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. |
| Phase 2 Cohort: Mean Change From Baseline in Mean Right Atrial Pressure (mRAP) at 12 Weeks | At baseline and 12 weeks | mRAP is the blood pressure in the right atrium of the heart. mRAP was assessed by right heart catheterization (RHC).A decrease in mRAP indicates improvement in right ventricular function, reduction of PAH related morbidity. |
Countries
Argentina, Australia, Belgium, Canada, Colombia, France, Germany, Greece, Israel, Italy, Mexico, New Zealand, Poland, Russia, Sweden, Turkey (Türkiye), United Kingdom, United States
Participant flow
Pre-assignment details
The study was planned to be conducted in 2 parts: a Phase 2 dose selection cohort and a Phase 3 confirmatory cohort. Due to sponsor's decision, Phase 3 was not conducted.
Participants by arm
| Arm | Count |
|---|---|
| Base Period: Placebo Participants received placebo via oral inhalation once daily for 12 week base period | 41 |
| Base Period: MK-5475 32 µg Participants received MK-5475 32 µg via oral inhalation once daily for 12 week base period | 42 |
| Base Period: MK-5475 100 µg Participants received MK-5475 100 µg via oral inhalation once daily for 12 week base period | 44 |
| Base Period: MK-5475 380 µg Participants receive MK-5475 380 µg via oral inhalation once daily for 12 week base period | 41 |
| Total | 168 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Base Period | Death | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Base Period | Withdrawal by Subject | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
| Extension Period | Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Extension Period | Death | 0 | 0 | 0 | 0 | 1 | 0 | 2 |
| Extension Period | Pregnancy | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Extension Period | Sponsors Decision | 0 | 0 | 0 | 0 | 41 | 40 | 40 |
| Extension Period | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 5 | 2 |
Baseline characteristics
| Characteristic | Base Period: MK-5475 100 µg | Base Period: Placebo | Base Period: MK-5475 32 µg | Base Period: MK-5475 380 µg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 51.7 Years STANDARD_DEVIATION 14.2 | 52.1 Years STANDARD_DEVIATION 12.7 | 48.1 Years STANDARD_DEVIATION 16.9 | 47.6 Years STANDARD_DEVIATION 15.9 | 49.9 Years STANDARD_DEVIATION 15 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 11 Participants | 14 Participants | 12 Participants | 47 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants | 30 Participants | 27 Participants | 29 Participants | 119 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 3 Participants | 1 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 4 Participants | 4 Participants | 11 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 41 Participants | 32 Participants | 34 Participants | 36 Participants | 143 Participants |
| Sex: Female, Male Female | 32 Participants | 28 Participants | 34 Participants | 30 Participants | 124 Participants |
| Sex: Female, Male Male | 12 Participants | 13 Participants | 8 Participants | 11 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 41 | 0 / 42 | 1 / 44 | 0 / 41 | 1 / 11 | 0 / 9 | 0 / 10 | 0 / 34 | 0 / 37 | 2 / 34 |
| other Total, other adverse events | 18 / 41 | 22 / 42 | 23 / 44 | 21 / 41 | 7 / 11 | 7 / 9 | 8 / 10 | 24 / 34 | 28 / 37 | 28 / 34 |
| serious Total, serious adverse events | 5 / 41 | 4 / 42 | 3 / 44 | 4 / 41 | 3 / 11 | 2 / 9 | 4 / 10 | 5 / 34 | 4 / 37 | 11 / 34 |
Outcome results
Primary
Phase 2 Cohort: Mean Percent Change From Baseline in Pulmonary Vascular Resistance (PVR) at 12 Weeks
PVR was calculated in participants after MK-5475 dosing at baseline and Week 12. PVR is assessed by right heart catheterization (RHC). Based on the variables obtained by right heart catheterization (RHC), the percentage change from baseline PVR was calculated. Per protocol, this outcome measure was assessed only for base period and was not assessed during extension period.
Time frame: At baseline and 12 weeks
Population: All randomized participants who received ≥1 dose of study treatment and had baseline observation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Base Period: Placebo | Phase 2 Cohort: Mean Percent Change From Baseline in Pulmonary Vascular Resistance (PVR) at 12 Weeks | 4.3 Percentage Change | Standard Error 4.45 |
| Base Period: MK-5475 32 µg | Phase 2 Cohort: Mean Percent Change From Baseline in Pulmonary Vascular Resistance (PVR) at 12 Weeks | -4.9 Percentage Change | Standard Error 4.07 |
| Base Period: MK-5475 100 µg | Phase 2 Cohort: Mean Percent Change From Baseline in Pulmonary Vascular Resistance (PVR) at 12 Weeks | -17.6 Percentage Change | Standard Error 4.07 |
| Base Period: MK-5475 380 µg | Phase 2 Cohort: Mean Percent Change From Baseline in Pulmonary Vascular Resistance (PVR) at 12 Weeks | -15.6 Percentage Change | Standard Error 5.39 |
p-value: 0.06895% CI: [-21.3, 2.9]Robust Regression
p-value: <0.00195% CI: [-33.7, -10.3]Robust Regression
p-value: 0.00295% CI: [-33.4, -6.4]Robust Regression
Primary
Phase 3 Cohort: Mean Change From Baseline in 6-Minute Walk Distance (6MWD) at 12 Weeks
6MWD is measured by an exercise test known as 6-Minute Walk Test (6MWT) that assesses functional capacity. It measures the distance covered over a time of 6 minutes and is intended to be used as an outcome measure by which to compare changes in excercise capacity. Each participant's 6MWD is to be measured at baseline and at 12 weeks. An increase in the distance walked during the 6MWT indicates improvement in functional exercise capacity.
Time frame: At baseline and 12 weeks
Population: Phase 3 was not conducted due to the sponsor's decision and thus no data were collected for the outcome measure.
Secondary
Phase 2 Cohort: Mean Change From Baseline in 6-Minute Walk Distance (6MWD) at 12 Weeks
6MWD is measured by an exercise test known as 6-Minute Walk Test (6MWT) that assesses functional capacity. It measures the distance covered over a time of 6 minutes and is used as an outcome measure by which to compare changes in exercise capacity. Each participant's 6MWD was measured at baseline and at 12 weeks. An increase in the distance walked during the 6MWT indicates improvement in functional exercise capacity.
Time frame: At baseline and 12 weeks
Population: All randomized participants in Phase 2 who received ≥1 dose of study treatment and had baseline observation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Base Period: Placebo | Phase 2 Cohort: Mean Change From Baseline in 6-Minute Walk Distance (6MWD) at 12 Weeks | 24.6 Meters | Standard Deviation 66.3 |
| Base Period: MK-5475 32 µg | Phase 2 Cohort: Mean Change From Baseline in 6-Minute Walk Distance (6MWD) at 12 Weeks | 27.4 Meters | Standard Deviation 53.1 |
| Base Period: MK-5475 100 µg | Phase 2 Cohort: Mean Change From Baseline in 6-Minute Walk Distance (6MWD) at 12 Weeks | 10.8 Meters | Standard Deviation 45.6 |
| Base Period: MK-5475 380 µg | Phase 2 Cohort: Mean Change From Baseline in 6-Minute Walk Distance (6MWD) at 12 Weeks | 11.3 Meters | Standard Deviation 38.9 |
Secondary
Phase 2 Cohort: Mean Change From Baseline in Cardiac Index (CI) at 12 Weeks
The cardiac index (CI) is a hemodynamic measure that represents the cardiac output (CO) of an individual divided by their body surface area (BSA). Cardiac index is assessed by right heart catheterization (RHC). An increase in CI is indicates better right ventricular function and is associated with a reduction of PAH related morbidity and mortality.
Time frame: At baseline and 12 weeks
Population: All randomized participants in Phase 2 who received ≥1 dose of study treatment and had baseline observation.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Base Period: Placebo | Phase 2 Cohort: Mean Change From Baseline in Cardiac Index (CI) at 12 Weeks | 0.1 Liter/minutes/meter square (L/min/m^2) |
| Base Period: MK-5475 32 µg | Phase 2 Cohort: Mean Change From Baseline in Cardiac Index (CI) at 12 Weeks | 0.0 Liter/minutes/meter square (L/min/m^2) |
| Base Period: MK-5475 100 µg | Phase 2 Cohort: Mean Change From Baseline in Cardiac Index (CI) at 12 Weeks | 0.2 Liter/minutes/meter square (L/min/m^2) |
| Base Period: MK-5475 380 µg | Phase 2 Cohort: Mean Change From Baseline in Cardiac Index (CI) at 12 Weeks | 0.1 Liter/minutes/meter square (L/min/m^2) |
Secondary
Phase 2 Cohort: Mean Change From Baseline in Mean Right Atrial Pressure (mRAP) at 12 Weeks
mRAP is the blood pressure in the right atrium of the heart. mRAP was assessed by right heart catheterization (RHC).A decrease in mRAP indicates improvement in right ventricular function, reduction of PAH related morbidity.
Time frame: At baseline and 12 weeks
Population: All randomized participants in Phase 2 who received ≥1 dose of study treatment and had baseline observation.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Base Period: Placebo | Phase 2 Cohort: Mean Change From Baseline in Mean Right Atrial Pressure (mRAP) at 12 Weeks | 0.3 Millimeters of Mercury (mmHg) |
| Base Period: MK-5475 32 µg | Phase 2 Cohort: Mean Change From Baseline in Mean Right Atrial Pressure (mRAP) at 12 Weeks | 0.3 Millimeters of Mercury (mmHg) |
| Base Period: MK-5475 100 µg | Phase 2 Cohort: Mean Change From Baseline in Mean Right Atrial Pressure (mRAP) at 12 Weeks | -0.5 Millimeters of Mercury (mmHg) |
| Base Period: MK-5475 380 µg | Phase 2 Cohort: Mean Change From Baseline in Mean Right Atrial Pressure (mRAP) at 12 Weeks | -0.1 Millimeters of Mercury (mmHg) |
Secondary
Phase 2 Cohort: Mean Change From Baseline in Stroke Volume Index (SVI) at 12 Weeks
The stroke volume index represents the amount of blood in mL, per square meter of body surface area, that is mobilized with each heart beat. SVI is assessed by RHC. An increase in SVI indicates better right ventricular function and is associated with a reduction of PAH related morbidity and mortality.
Time frame: At baseline and 12 weeks
Population: All randomized participants in Phase 2 who received ≥1 dose of study treatment and had baseline observation.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Base Period: Placebo | Phase 2 Cohort: Mean Change From Baseline in Stroke Volume Index (SVI) at 12 Weeks | 2.9 mL/beat/m^2 |
| Base Period: MK-5475 32 µg | Phase 2 Cohort: Mean Change From Baseline in Stroke Volume Index (SVI) at 12 Weeks | 0.2 mL/beat/m^2 |
| Base Period: MK-5475 100 µg | Phase 2 Cohort: Mean Change From Baseline in Stroke Volume Index (SVI) at 12 Weeks | 3.2 mL/beat/m^2 |
| Base Period: MK-5475 380 µg | Phase 2 Cohort: Mean Change From Baseline in Stroke Volume Index (SVI) at 12 Weeks | 1.2 mL/beat/m^2 |
Secondary
Phase 2 Cohort: Number of Participants Who Discontinued Study Drug Due to an Adverse Event
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued treatment due to an AE was assessed.
Time frame: Up to approximately 2.25 years
Population: Analysis population consisted of all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Base Period: Placebo | Phase 2 Cohort: Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
| Base Period: MK-5475 32 µg | Phase 2 Cohort: Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 1 Participants |
| Base Period: MK-5475 100 µg | Phase 2 Cohort: Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
| Base Period: MK-5475 380 µg | Phase 2 Cohort: Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
| Extension Period: MK-5475 32 µg | Phase 2 Cohort: Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
| Extension Period: MK-5475 100 µg | Phase 2 Cohort: Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 1 Participants |
| Extension Period: MK-5475 380 μg | Phase 2 Cohort: Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
Secondary
Phase 2 Cohort: Number of Participants Who Experienced an Adverse Event
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Time frame: Up to approximately 2.25 years
Population: Analysis population consisted of all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Base Period: Placebo | Phase 2 Cohort: Number of Participants Who Experienced an Adverse Event | 27 Participants |
| Base Period: MK-5475 32 µg | Phase 2 Cohort: Number of Participants Who Experienced an Adverse Event | 28 Participants |
| Base Period: MK-5475 100 µg | Phase 2 Cohort: Number of Participants Who Experienced an Adverse Event | 28 Participants |
| Base Period: MK-5475 380 µg | Phase 2 Cohort: Number of Participants Who Experienced an Adverse Event | 27 Participants |
| Extension Period: MK-5475 32 µg | Phase 2 Cohort: Number of Participants Who Experienced an Adverse Event | 33 Participants |
| Extension Period: MK-5475 100 µg | Phase 2 Cohort: Number of Participants Who Experienced an Adverse Event | 38 Participants |
| Extension Period: MK-5475 380 μg | Phase 2 Cohort: Number of Participants Who Experienced an Adverse Event | 39 Participants |
Secondary
Phase 3 Cohort: Mean Change From Baseline in 6-Minute Walk Distance (6MWD) at 24 Weeks
6MWD is measured by an exercise test known as 6-Minute Walk Test (6MWT) that assesses functional capacity. It measures the distance covered over a time of 6 minutes and is intended to be used as an outcome measure by which to compare changes in exercise capacity. Each participant's 6MWD is to be measured at baseline and at 24 weeks. An increase in the distance walked during the 6MWT indicates improvement in functional exercise capacity.
Time frame: At baseline and 24 weeks
Population: Phase 3 was not conducted due to the sponsor's decision and thus no data were collected for the outcome measure.
Secondary
Phase 3 Cohort: Number of Participants Who Discontinued Study Drug Due to an AE
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued treatment due to an AE was assessed.
Time frame: Up to approximately 2.25 years
Population: Phase 3 was not conducted due to the sponsor's decision and thus no data were collected for the outcome measure.
Secondary
Phase 3 Cohort: Number of Participants Who Experienced an Adverse Event
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Time frame: Up to approximately 2.25 years
Population: Phase 3 was not conducted due to the sponsor's decision and thus no data were collected for the outcome measure.
Secondary
Phase 3 Cohort: Proportion of Participants Whose World Health Organization Functional Class (WHO-FC) is Not Worse at 12 Week Relative to Baseline
The World Health Organization (WHO) classification of functional status is a measure of disease severity, based on a patient's description of their level of functioning and symptoms of disease in relation to their everyday activity. Patients were to be assigned 1 of 4 WHO-FC, dependent on limits of physical activity. As WHO-FC increases from I to IV, limits of physical activity were to increase.
Time frame: At baseline and 12 weeks
Population: Phase 3 was not conducted due to the sponsor's decision and thus no data were collected for the outcome measure.