Pulmonary Arterial Hypertension
Conditions
Keywords
PAH
Brief summary
This is a 12-week, international, multicenter, double-blind, three-group, dose-response study to assess the safety and efficacy of BPS-MR in patients with PAH. Eligible patients will have been previously diagnosed with PAH and will be on a stable course of an ERA and/or PDE-5 inhibitor for at least 60 days prior to Baseline. Patients will be randomized to 1 of 3 treatment groups in a 1:1:1 ratio and will be stratified by PAH background therapy (Endothelium Receptor Antagonist (ERA), Phosphodiesterase-5 (PDE-5), and both). The treatment groups consist of one Maximum Tolerated Dose (MTD) and two Fixed Dose (FD) groups. Following randomization, patients will begin taking active drug (60µg) orally twice daily. Patients will visit their investigational site at Week 6 and Week 12 for study evaluations.
Detailed description
This is a 12-week, international, multicenter, double-blind, three-group, dose-response study to assess the safety and efficacy of BPS-MR in patients with PAH. Eligible patients will have been previously diagnosed with PAH and will be on a stable course of an ERA and/or PDE-5 inhibitor for at least 60 days prior to Baseline. A total of approximately 36 patients will be randomized to 1 of 3 treatment groups (12 per group) in a 1:1:1 ratio and will be stratified by PAH background therapy (ERA, PDE-5, and both). The treatment groups consist of one MTD and two FD groups. Following randomization, patients will begin taking active drug (60µg) orally twice daily. Patients will visit their investigational site at Week 6 and Week 12 for study evaluations. Between visits, clinical site personnel will contact patients by phone each week to assess tolerability, provide instructions for a change in dosage, record changes in concomitant medications, and record adverse events. Patients who complete the study will be offered the opportunity to continue taking study medication in a separate open-label continuation protocol. Patients who withdraw early from the study or who otherwise do not elect to enroll into the open-label continuation protocol will be down-titrated off of BPS-MR at the discretion of the Investigator, at a maximum decrement not to exceed one tablet (60µg) b.i.d. per day and a minimum decrement of one tablet (60µg) b.i.d. per week. Patients in the iMTD treatment group will dose escalate weekly by 60µg b.i.d. until they reach the maximum dose of 600µg b.i.d. or they reach an intolerable dose which requires them to down-titrate by 60µg b.i.d. In these instances and at the Investigator's discretion, further attempts at dose escalation may be made. The FD treatment groups will consist of a low dose group receiving 60µg b.i.d. and a high dose group receiving 240µg b.i.d. Patients in the high dose group will dose escalate weekly by 60µg b.i.d. until they reach the fixed dose of 240µg b.i.d. Once patients in these treatment groups have reached their assigned maximum dose of active drug, weekly increases in the number of placebo tablets administered will continue in order to maintain the blind. Patients will be requested to maintain a daily diary of symptoms and study drug administration for evaluation by clinical site personnel. Also, patients will be given the option to contribute blood for pharmacokinetic assessment of BPS/BPS-314d plasma concentrations at the Week 12 visit.
Interventions
60µg Tablets, twice a day for 12 weeks
Sponsors
Lung Biotechnology PBC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. IRB approved written informed consent has been obtained. 2. Male or female, age 18 to 75 years (inclusive). 3. Established diagnosis of pulmonary arterial hypertension that is either idiopathic or familial PAH, collagen vascular disease associated PAH, PAH induced by anorexigens, or PAH associated with repaired congenital systemic-to-pulmonary shunts (repaired ≥5 years). 4. Clinically stable PAH as determined by the Investigator. 5. Able to walk unassisted. 6. Has a complete, unencouraged 6MWT distance of 150 to 450 meters (inclusive) at Screening. 7. Previous (at any time) right heart cardiac catheterization with findings consistent with PAH, specifically mean Pulmonary Arterial Pressure (PAPm) ≥25 mmHg (at rest), Pulmonary Capillary Wedge Pressure (PCWP) (or left ventricular end diastolic pressure) ≤15 mmHg, and Pulmonary Vascular Resistance (PVR) \>3 mmHg/L/min. 8. Previous (at any time) chest radiograph consistent with the diagnosis of PAH. 9. Has been on a stable course of an ERA or/and PDE-5 inhibitor for a minimum of 60 days prior to Baseline. 10. Women of child-bearing potential (defined as less than 1 year post-menopausal or not surgically sterile) must be using an acceptable method of birth control or practicing abstinence. If sexually active, female patients must use a double barrier method of birth control, such as a condom and spermicidal. Patient must have a negative pregnancy test at the Screening and Baseline visits. 11. Willing and able to comply with study requirements and restrictions.
Exclusion criteria
1. Has pulmonary venous hypertension, pulmonary veno-occlusive disease, pulmonary capillary hemangiomatosis, or chronic thromboembolic pulmonary hypertension. 2. Has a history of interstitial lung disease, unless: * Pulmonary Function Testing conducted within 6 months of the Baseline visit demonstrates a Total Lung Capacity ≥ 70 % of predicted. 3. Has a history of obstructive lung disease, unless: * Pulmonary Function Testing conducted within 6 months of the Baseline visit demonstrates a forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio of ≥ 50%. 4. Is pregnant and/or lactating. 5. Changed or discontinued any PAH medication within 60 days prior to the Baseline visit including, but not limited to, an ERA, PDE-5 inhibitor, or calcium channel blocker (with the exception of anticoagulants). 6. Has an ongoing hemorrhagic condition (e.g. upper digestive tract hemorrhage, hemoptysis, etc), or has a pre-existing condition that, in the Investigator's judgment may increase the risk for developing hemorrhage during the study (e.g. hemophilia). Transient hemorrhage (e.g. epistaxis, normal menstrual bleeding, gingival bleeding, hemorrhoidal hemorrhage, etc.) will not preclude enrollment. 7. Has donated blood or plasma, or has lost a volume of blood \>450mL within 6-weeks of the Baseline visit. 8. Has received any investigational medication, device or therapy within 30 days prior to the Baseline visit or is scheduled to receive another investigational drug, device or therapy during the course of the study. 9. Has received any prostanoid therapy at any time. 10. Has any preexisting disease known to cause pulmonary hypertension other than collagen vascular disease. 11. Has any musculoskeletal disease or any other disease that would limit ambulation. 12. Has any form of unrepaired or recently repaired (\< 5 years) congenital systemic-to-pulmonary shunt other than patent foramen ovale. 13. History of pulmonary embolism or deep venous thrombosis. 14. History of ischemic heart disease, including previous myocardial infarction, or symptomatic coronary artery disease, or history of left sided myocardial disease as evidenced by a mean PCWP (or a left ventricular end diastolic pressure) \> 15 mmHg or left ventricular ejection fraction \< 40% as assessed by either multigated angiogram, angiography or echocardiography, or left ventricular shortening fraction \< 22% as assessed by echocardiography. Note that patients in whom abnormal left ventricular function is attributed entirely to impaired left ventricular filling due to the effects of right ventricular overload (i.e. right ventricular hypertrophy and/or dilatation) will not be excluded. 15. Presence of atrial fibrillation (determined from 12-lead ECG at Screening). 16. Any other clinically significant illness that, in the opinion of the Investigator, might put the patient at risk of harm during the study or might adversely affect the interpretation of the study data.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Pulmonary Vascular Resistance at Week 12 | Week 12 | The change in Pulmonary Vascular Resistance (PVR) was evaluated from Baseline to Week 12. PVR is expressed in Wood Units or millimeters of Mercury per Liter per minute (mmHG/L/min) |
| Change From Baseline in Cardiac Output (CO) at Week 12 | Week 12 | The change in Cardiac Output was evaluated from Baseline to Week 12. |
| Change From Baseline in Pulmonary Arterial Pressure at Week 12 | 12 weeks | The change in mean Pulmonary Arterial Pressure (mPAP) was evaluated from Baseline to Week 12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Newly Occurring Clinically Significant ECG Abnormalities | Up to 12 weeks | Clinically significant ECG abnormalities at Baseline only are excluded. |
| Number of Participants With at Least One Post-baseline Clinically Significant Laboratory Value | Up to Week 12 | Post-baseline clinically significant values, as defined by the Investigator, for hematology, serum chemistry, coagulation and urinalysis parameters were summarized. |
| N-Terminal ProB-type Natriuretic Peptide Level at Week 6 and Week 12 | Week 6 and Week 12 | NT-proBNP functions as a strong indicator of prognosis in patients with pulmonary arterial hypertension. |
| Change in Borg Dyspnea Score From Baseline to Week 6 and Week 12 | Baseline, Week 6 and 12 | The modified 0-10 category-ratio Borg scale consists of an 11-point scale rating the maximum level of dyspnea experienced during the 6MWT. Scores range from 0 (for the best condition) and 10 (for the worst condition) with nonlinear spacing of verbal descriptors of severity corresponding to specific numbers. The participant chose the number or the verbal descriptor to reflect presumed ratio properties of sensation or symptom intensity. Only participants with both a measurement at baseline and at the given visit are presented. All efficacy results are descriptive; no statistical analysis was conducted. |
| Change in Six Minute Walk Distance From Baseline to Week 6 and Week 12 | Baseline, Week 6 and 12 | Area used for the Six Minute Walk Test (6MWT) was pre-measured at 30 meters in length. Rest periods were allowed if patient could no longer continue. If patient needed to rest, he/she could stand or sit and then begin again when rested but the clock continued to run. At the end of 6 minutes, the tester called stop while stopping the watch and then measured the distance walked. For purposes of the 6MWT, if patient was assessed at Baseline using oxygen therapy, all future 6MWT were conducted in the same manner. All efficacy results are descriptive; no statistical analysis was conducted. |
| Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 | Week 6 and Week 12 | WHO functional classification for PAH range from Class I (no limitation in physical activity, no dyspnea with normal activity), Class II (slight limitation of physical activity), Class III (marked limitation of physical activity) and Class IV (cannot perform a physical activity without any symptoms, dyspnea at rest). |
Countries
Belgium, Czechia, Germany, Ireland, Romania, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Low Fixed Dose Group (60 ug) Participants in the low dose group received 60 microgram of Beraprost sodium modified release tablets, orally twice daily up to maximum duration of Week 12. | 12 |
| High Fixed Dose Group (240 ug) Participants in the high dose group received starting dose of 60 microgram of Beraprost sodium modified release tablets twice daily which was escalated until they reached the fixed maximum dose of 240 microgram twice daily up to a maximum duration of Week 12 | 12 |
| Maximum Tolerated Dose (MTD) Participants in this group received starting dose of 60 microgram of Beraprost sodium modified release tablets twice daily which was escalated until they reached the fixed maximum dose of 600 microgram twice daily up to a maximum duration of Week 12 or they reached an intolerable dose which required them to down-titrate by 60 microgram twice daily in these instances and at the Investigator's discretion, further attempts at dose escalation may have been made. | 12 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Low Fixed Dose Group (60 ug) | High Fixed Dose Group (240 ug) | Maximum Tolerated Dose (MTD) | Total |
|---|---|---|---|---|
| Age, Continuous | 46.0 years STANDARD_DEVIATION 14.19 | 45.1 years STANDARD_DEVIATION 15.2 | 51.1 years STANDARD_DEVIATION 14.71 | 47.4 years STANDARD_DEVIATION 14.53 |
| Borg Dyspnea Score | 2.71 scores on a scale STANDARD_DEVIATION 1.48 | 3.36 scores on a scale STANDARD_DEVIATION 2.34 | 3.10 scores on a scale STANDARD_DEVIATION 2.27 | 3.05 scores on a scale STANDARD_DEVIATION 2 |
| Cardiac Output (CO) | 4.44 Liters per minute (L/min) STANDARD_DEVIATION 1.12 | 5.53 Liters per minute (L/min) STANDARD_DEVIATION 1.79 | 4.52 Liters per minute (L/min) STANDARD_DEVIATION 1.2 | 4.83 Liters per minute (L/min) STANDARD_DEVIATION 1.45 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 4 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 10 Participants | 8 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Mean Pulmonary Arterial Pressure (mPAP) | 49.58 Millimeters of Mercury (mmHg) STANDARD_DEVIATION 18.72 | 57.91 Millimeters of Mercury (mmHg) STANDARD_DEVIATION 19.03 | 52.40 Millimeters of Mercury (mmHg) STANDARD_DEVIATION 15.54 | 53.21 Millimeters of Mercury (mmHg) STANDARD_DEVIATION 17.73 |
| Pulmonary Vascular Resistance (PVR) | 9.74 Wood Units (mmHg/L/min) STANDARD_DEVIATION 5.35 | 9.39 Wood Units (mmHg/L/min) STANDARD_DEVIATION 4.05 | 10.19 Wood Units (mmHg/L/min) STANDARD_DEVIATION 5.61 | 9.76 Wood Units (mmHg/L/min) STANDARD_DEVIATION 4.89 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 11 Participants | 12 Participants | 35 Participants |
| Sex: Female, Male Female | 10 Participants | 10 Participants | 10 Participants | 30 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 2 Participants | 6 Participants |
| Six Minute Walk Distance | 362.92 meters (m) STANDARD_DEVIATION 51.01 | 388.73 meters (m) STANDARD_DEVIATION 74.21 | 327.70 meters (m) STANDARD_DEVIATION 94.48 | 360.85 meters (m) STANDARD_DEVIATION 75.75 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 12 | 0 / 11 |
| other Total, other adverse events | 13 / 13 | 11 / 12 | 11 / 11 |
| serious Total, serious adverse events | 3 / 13 | 0 / 12 | 1 / 11 |
Outcome results
Primary
Change From Baseline in Cardiac Output (CO) at Week 12
The change in Cardiac Output was evaluated from Baseline to Week 12.
Time frame: Week 12
Population: Randomized participants (actual treatment received) who had completed the study and had received the required protocol processing for the study, i.e., no major protocol deviations (Per-Protocol Population).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Fixed Dose Group (60 ug) | Change From Baseline in Cardiac Output (CO) at Week 12 | 0.16 Liters per minute (L/min) | Standard Deviation 1.17 |
| High Fixed Dose Group (240 ug) | Change From Baseline in Cardiac Output (CO) at Week 12 | 0.07 Liters per minute (L/min) | Standard Deviation 0.84 |
| Maximum Tolerated Dose (MTD) | Change From Baseline in Cardiac Output (CO) at Week 12 | 0.35 Liters per minute (L/min) | Standard Deviation 1.15 |
Primary
Change From Baseline in Pulmonary Arterial Pressure at Week 12
The change in mean Pulmonary Arterial Pressure (mPAP) was evaluated from Baseline to Week 12.
Time frame: 12 weeks
Population: Randomized participants (actual treatment received) who had completed the study and had received the required protocol processing for the study, i.e., no major protocol deviations (Per-Protocol Population).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Fixed Dose Group (60 ug) | Change From Baseline in Pulmonary Arterial Pressure at Week 12 | 0.42 mmHg | Standard Deviation 5.76 |
| High Fixed Dose Group (240 ug) | Change From Baseline in Pulmonary Arterial Pressure at Week 12 | -1.45 mmHg | Standard Deviation 11.96 |
| Maximum Tolerated Dose (MTD) | Change From Baseline in Pulmonary Arterial Pressure at Week 12 | 4.10 mmHg | Standard Deviation 5.15 |
Primary
Change From Baseline in Pulmonary Vascular Resistance at Week 12
The change in Pulmonary Vascular Resistance (PVR) was evaluated from Baseline to Week 12. PVR is expressed in Wood Units or millimeters of Mercury per Liter per minute (mmHG/L/min)
Time frame: Week 12
Population: Randomized participants (actual treatment received) who had completed the study and had received the required protocol processing for the study, i.e., no major protocol deviations (Per-Protocol Population).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Fixed Dose Group (60 ug) | Change From Baseline in Pulmonary Vascular Resistance at Week 12 | 0.37 Wood Units (mmHg/L/min) | Standard Deviation 3.08 |
| High Fixed Dose Group (240 ug) | Change From Baseline in Pulmonary Vascular Resistance at Week 12 | 0.00 Wood Units (mmHg/L/min) | Standard Deviation 1.57 |
| Maximum Tolerated Dose (MTD) | Change From Baseline in Pulmonary Vascular Resistance at Week 12 | 0.13 Wood Units (mmHg/L/min) | Standard Deviation 3.21 |
Secondary
Change in Borg Dyspnea Score From Baseline to Week 6 and Week 12
The modified 0-10 category-ratio Borg scale consists of an 11-point scale rating the maximum level of dyspnea experienced during the 6MWT. Scores range from 0 (for the best condition) and 10 (for the worst condition) with nonlinear spacing of verbal descriptors of severity corresponding to specific numbers. The participant chose the number or the verbal descriptor to reflect presumed ratio properties of sensation or symptom intensity. Only participants with both a measurement at baseline and at the given visit are presented. All efficacy results are descriptive; no statistical analysis was conducted.
Time frame: Baseline, Week 6 and 12
Population: Randomized participants (actual treatment received) who had completed the study and had received the required protocol processing for the study, i.e., no major protocol deviations (Per-Protocol \[PP\] Population).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Fixed Dose Group (60 ug) | Change in Borg Dyspnea Score From Baseline to Week 6 and Week 12 | Week 12 at peak | 0.50 scores on a scale | Standard Deviation 0.81 |
| Low Fixed Dose Group (60 ug) | Change in Borg Dyspnea Score From Baseline to Week 6 and Week 12 | Week 6 | 0.71 scores on a scale | Standard Deviation 1.29 |
| Low Fixed Dose Group (60 ug) | Change in Borg Dyspnea Score From Baseline to Week 6 and Week 12 | Week 12 at trough | 0.45 scores on a scale | Standard Deviation 0.83 |
| High Fixed Dose Group (240 ug) | Change in Borg Dyspnea Score From Baseline to Week 6 and Week 12 | Week 12 at peak | 0.64 scores on a scale | Standard Deviation 2.16 |
| High Fixed Dose Group (240 ug) | Change in Borg Dyspnea Score From Baseline to Week 6 and Week 12 | Week 6 | 0.68 scores on a scale | Standard Deviation 1.65 |
| High Fixed Dose Group (240 ug) | Change in Borg Dyspnea Score From Baseline to Week 6 and Week 12 | Week 12 at trough | 1.11 scores on a scale | Standard Deviation 0.78 |
| Maximum Tolerated Dose (MTD) | Change in Borg Dyspnea Score From Baseline to Week 6 and Week 12 | Week 6 | 0.80 scores on a scale | Standard Deviation 3.13 |
| Maximum Tolerated Dose (MTD) | Change in Borg Dyspnea Score From Baseline to Week 6 and Week 12 | Week 12 at trough | 0.67 scores on a scale | Standard Deviation 3 |
| Maximum Tolerated Dose (MTD) | Change in Borg Dyspnea Score From Baseline to Week 6 and Week 12 | Week 12 at peak | 0.40 scores on a scale | Standard Deviation 2.69 |
Secondary
Change in Six Minute Walk Distance From Baseline to Week 6 and Week 12
Area used for the Six Minute Walk Test (6MWT) was pre-measured at 30 meters in length. Rest periods were allowed if patient could no longer continue. If patient needed to rest, he/she could stand or sit and then begin again when rested but the clock continued to run. At the end of 6 minutes, the tester called stop while stopping the watch and then measured the distance walked. For purposes of the 6MWT, if patient was assessed at Baseline using oxygen therapy, all future 6MWT were conducted in the same manner. All efficacy results are descriptive; no statistical analysis was conducted.
Time frame: Baseline, Week 6 and 12
Population: Randomized participants (actual treatment received) who had completed the study and had received the required protocol processing for the study, i.e., no major protocol deviations (Per-Protocol Population).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Fixed Dose Group (60 ug) | Change in Six Minute Walk Distance From Baseline to Week 6 and Week 12 | Week 12 Peak | 52.82 meters | Standard Deviation 70.53 |
| Low Fixed Dose Group (60 ug) | Change in Six Minute Walk Distance From Baseline to Week 6 and Week 12 | Week 6 Peak | 2.17 meters | Standard Deviation 112.63 |
| Low Fixed Dose Group (60 ug) | Change in Six Minute Walk Distance From Baseline to Week 6 and Week 12 | Week 12 Trough | 44.00 meters | Standard Deviation 50.74 |
| High Fixed Dose Group (240 ug) | Change in Six Minute Walk Distance From Baseline to Week 6 and Week 12 | Week 12 Peak | 42.18 meters | Standard Deviation 83.08 |
| High Fixed Dose Group (240 ug) | Change in Six Minute Walk Distance From Baseline to Week 6 and Week 12 | Week 6 Peak | 29.91 meters | Standard Deviation 46.83 |
| High Fixed Dose Group (240 ug) | Change in Six Minute Walk Distance From Baseline to Week 6 and Week 12 | Week 12 Trough | 47.67 meters | Standard Deviation 92.2 |
| Maximum Tolerated Dose (MTD) | Change in Six Minute Walk Distance From Baseline to Week 6 and Week 12 | Week 6 Peak | 39.90 meters | Standard Deviation 47.59 |
| Maximum Tolerated Dose (MTD) | Change in Six Minute Walk Distance From Baseline to Week 6 and Week 12 | Week 12 Trough | 11.67 meters | Standard Deviation 72.25 |
| Maximum Tolerated Dose (MTD) | Change in Six Minute Walk Distance From Baseline to Week 6 and Week 12 | Week 12 Peak | 47.10 meters | Standard Deviation 48.39 |
Secondary
N-Terminal ProB-type Natriuretic Peptide Level at Week 6 and Week 12
NT-proBNP functions as a strong indicator of prognosis in patients with pulmonary arterial hypertension.
Time frame: Week 6 and Week 12
Population: Randomized participants (actual treatment received) who completed the study and received required protocol processing, ie, no major protocol deviations (PP Population). Overall number of participants analyzed signifies those who were evaluable for the outcome measure; number analyzed signifies those who were evaluable at specified timepoint only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Fixed Dose Group (60 ug) | N-Terminal ProB-type Natriuretic Peptide Level at Week 6 and Week 12 | Week 6 | 6.38 nanograms per Liter (ng/L) | Standard Deviation 1.28 |
| Low Fixed Dose Group (60 ug) | N-Terminal ProB-type Natriuretic Peptide Level at Week 6 and Week 12 | Week 12 | 6.33 nanograms per Liter (ng/L) | Standard Deviation 1.41 |
| High Fixed Dose Group (240 ug) | N-Terminal ProB-type Natriuretic Peptide Level at Week 6 and Week 12 | Week 6 | 5.82 nanograms per Liter (ng/L) | Standard Deviation 0.72 |
| High Fixed Dose Group (240 ug) | N-Terminal ProB-type Natriuretic Peptide Level at Week 6 and Week 12 | Week 12 | 6.06 nanograms per Liter (ng/L) | Standard Deviation 1.08 |
| Maximum Tolerated Dose (MTD) | N-Terminal ProB-type Natriuretic Peptide Level at Week 6 and Week 12 | Week 6 | 6.83 nanograms per Liter (ng/L) | Standard Deviation 1.18 |
| Maximum Tolerated Dose (MTD) | N-Terminal ProB-type Natriuretic Peptide Level at Week 6 and Week 12 | Week 12 | 6.85 nanograms per Liter (ng/L) | Standard Deviation 1.55 |
Secondary
Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12
WHO functional classification for PAH range from Class I (no limitation in physical activity, no dyspnea with normal activity), Class II (slight limitation of physical activity), Class III (marked limitation of physical activity) and Class IV (cannot perform a physical activity without any symptoms, dyspnea at rest).
Time frame: Week 6 and Week 12
Population: Randomized participants (actual treatment received) who had completed the study and had received the required protocol processing for the study, i.e., no major protocol deviations (Per-Protocol Population). Here, number analyzed signifies number of participants evaluable at specified time points only.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Low Fixed Dose Group (60 ug) | Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 | Week 6: Class I | 1 Participants |
| Low Fixed Dose Group (60 ug) | Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 | Week 6: Class II | 6 Participants |
| Low Fixed Dose Group (60 ug) | Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 | Week 6: Class III | 5 Participants |
| Low Fixed Dose Group (60 ug) | Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 | Week 6: Class IV | 0 Participants |
| Low Fixed Dose Group (60 ug) | Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 | Week 12: Class I | 1 Participants |
| Low Fixed Dose Group (60 ug) | Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 | Week 12: Class II | 5 Participants |
| Low Fixed Dose Group (60 ug) | Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 | Week 12: Class III | 6 Participants |
| Low Fixed Dose Group (60 ug) | Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 | Week 12: Class IV | 0 Participants |
| High Fixed Dose Group (240 ug) | Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 | Week 6: Class III | 8 Participants |
| High Fixed Dose Group (240 ug) | Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 | Week 12: Class III | 6 Participants |
| High Fixed Dose Group (240 ug) | Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 | Week 6: Class IV | 0 Participants |
| High Fixed Dose Group (240 ug) | Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 | Week 12: Class I | 1 Participants |
| High Fixed Dose Group (240 ug) | Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 | Week 12: Class II | 4 Participants |
| High Fixed Dose Group (240 ug) | Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 | Week 6: Class I | 0 Participants |
| High Fixed Dose Group (240 ug) | Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 | Week 6: Class II | 3 Participants |
| High Fixed Dose Group (240 ug) | Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 | Week 12: Class IV | 0 Participants |
| Maximum Tolerated Dose (MTD) | Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 | Week 6: Class III | 7 Participants |
| Maximum Tolerated Dose (MTD) | Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 | Week 6: Class II | 3 Participants |
| Maximum Tolerated Dose (MTD) | Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 | Week 6: Class I | 0 Participants |
| Maximum Tolerated Dose (MTD) | Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 | Week 6: Class IV | 0 Participants |
| Maximum Tolerated Dose (MTD) | Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 | Week 12: Class III | 7 Participants |
| Maximum Tolerated Dose (MTD) | Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 | Week 12: Class II | 3 Participants |
| Maximum Tolerated Dose (MTD) | Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 | Week 12: Class I | 0 Participants |
| Maximum Tolerated Dose (MTD) | Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 | Week 12: Class IV | 0 Participants |
Secondary
Number of Participants With at Least One Post-baseline Clinically Significant Laboratory Value
Post-baseline clinically significant values, as defined by the Investigator, for hematology, serum chemistry, coagulation and urinalysis parameters were summarized.
Time frame: Up to Week 12
Population: Randomized participants (per actual treatment received) who received ≥1 dose of study drug (Safety Population). Overall number of participants analyzed signifies those who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Fixed Dose Group (60 ug) | Number of Participants With at Least One Post-baseline Clinically Significant Laboratory Value | 5 participants |
| High Fixed Dose Group (240 ug) | Number of Participants With at Least One Post-baseline Clinically Significant Laboratory Value | 3 participants |
| Maximum Tolerated Dose (MTD) | Number of Participants With at Least One Post-baseline Clinically Significant Laboratory Value | 3 participants |
Secondary
Number of Participants With Newly Occurring Clinically Significant ECG Abnormalities
Clinically significant ECG abnormalities at Baseline only are excluded.
Time frame: Up to 12 weeks
Population: Randomized participants (per actual treatment received) who received ≥1 dose of study drug (Safety Population). Overall number of participants analyzed signifies those who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low Fixed Dose Group (60 ug) | Number of Participants With Newly Occurring Clinically Significant ECG Abnormalities | Right Atrial Abnormality | 0 Participants |
| Low Fixed Dose Group (60 ug) | Number of Participants With Newly Occurring Clinically Significant ECG Abnormalities | Chronic Pulmonary Disease Pattern | 0 Participants |
| Low Fixed Dose Group (60 ug) | Number of Participants With Newly Occurring Clinically Significant ECG Abnormalities | Low QRS Voltage | 0 Participants |
| Low Fixed Dose Group (60 ug) | Number of Participants With Newly Occurring Clinically Significant ECG Abnormalities | Non-Specific ST-T Changes | 0 Participants |
| High Fixed Dose Group (240 ug) | Number of Participants With Newly Occurring Clinically Significant ECG Abnormalities | Non-Specific ST-T Changes | 0 Participants |
| High Fixed Dose Group (240 ug) | Number of Participants With Newly Occurring Clinically Significant ECG Abnormalities | Right Atrial Abnormality | 2 Participants |
| High Fixed Dose Group (240 ug) | Number of Participants With Newly Occurring Clinically Significant ECG Abnormalities | Low QRS Voltage | 0 Participants |
| High Fixed Dose Group (240 ug) | Number of Participants With Newly Occurring Clinically Significant ECG Abnormalities | Chronic Pulmonary Disease Pattern | 1 Participants |
| Maximum Tolerated Dose (MTD) | Number of Participants With Newly Occurring Clinically Significant ECG Abnormalities | Non-Specific ST-T Changes | 1 Participants |
| Maximum Tolerated Dose (MTD) | Number of Participants With Newly Occurring Clinically Significant ECG Abnormalities | Chronic Pulmonary Disease Pattern | 0 Participants |
| Maximum Tolerated Dose (MTD) | Number of Participants With Newly Occurring Clinically Significant ECG Abnormalities | Low QRS Voltage | 1 Participants |
| Maximum Tolerated Dose (MTD) | Number of Participants With Newly Occurring Clinically Significant ECG Abnormalities | Right Atrial Abnormality | 0 Participants |