Pulmonary Arterial Hypertension
Conditions
Keywords
pulmonary arterial hypertension, inhaled therapy, power disc-15
Brief summary
A Phase IIIb, Multicenter, Open-Label Study of Patients With Pulmonary Arterial Hypertension Treated With Iloprost(Inhalation)Evaluating Safety and Inhalation Times When Converting From Power Disc-6 to Power Disc-15 With the I-neb® Adaptive Aerosol Delivery® System (I-neb® AAD®)
Interventions
DRUGIloprost PD-6
Period 1 (PD-6): study period defined as the 14 days prior to the first dose of study iloprost inhalation with PD-15. Commercial iloprost inhalation solution delivered using the Power Disc-6 with the I-neb® Adaptive Aerosol Delivery (AAD®) system administered 6 to 9 times per day
DRUGIloprost PD-15
Period 2 (PD-15): study period between the administration of the first dose with PD-15 on Day 1 until Day 28 inclusive. Period 3 (PD-15): study period from Day 29 until discontinuation of the PD-15. Commercial iloprost inhalation solution delivered using the Power Disc-15 with the I-neb® Adaptive Aerosol Delivery (AAD®) system administered 6 to 9 times per day
Sponsors
Actelion
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent prior to initiation of any study-mandated procedure. * Male or female patients aged 18-85 years. * Patients with symptomatic pulmonary arterial hypertension in New York Heart Association (NYHA) functional class III or IV at the time of initiation of iloprost inhalation (Ventavis®) therapy using the Power Disc-6 (PD-6). * Patients with the following types of pulmonary arterial hypertension (PAH) belonging to World Health Organization (WHO) Group I: * 1.1: Idiopathic (IPAH) * 1.2: Familial (FPAH) * 1.3: Associated with (APAH) * 1.3.1: Collagen vascular disease * 1.3.2: Congenital systemic-to-pulmonary shunts at least 2 years post surgical repair * 1.3.4: Human immunodeficiency virus (HIV) infection * 1.3.5: Drugs and toxins * PAH confirmed by the most recent right heart catheterization showing: * Mean pulmonary arterial pressure (mPAP)≥ 25 mmHg at rest * Pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg or left ventricular end diastolic pressure (LVEDP) ≤ 15 mmHg. If both PCWP and LVEDP are available then the LVEDP value is retained for inclusion. * Pulmonary vascular resistance (PVR) \> 240 dyn-sec/cm\^5 * Compliant with a treatment regimen of commercial iloprost inhalation (Ventavis® 5 μg) using the I-neb® AAD® equipped with the PD-6 for at least 4 weeks prior to screening. * Pulmonary function tests (PFTs) including forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and total lung capacity (TLC), performed within 6 months of screening. * If taking other medications for PAH, these must have been stable for 60 days prior to baseline. * If taking corticosteroids, these must have been stable for 60 days prior to baseline. * Women of childbearing potential with a negative urine pre-treatment pregnancy test at baseline and who: * consistently and correctly use (from screening and up to 28 days after discontinuation of study drug) a reliable method of contraception with a Pearl index of \< 1%, * are sexually abstinent, or * have a vasectomized partner. A woman is considered to have childbearing potential unless she meets at least one of the following criteria: * Previous bilateral salpingo-oophorectomy or hysterectomy * Premature ovarian failure confirmed by a specialist gynecologist * XY genotype, Turner syndrome, uterine agenesis * Is aged \> 50 years and not treated with any kind of hormone replacement therapy (HRT) for at least 2 years prior to screening, with amenorrhea for at least 24 consecutive months
Exclusion criteria
* PAH belonging to WHO group II-V. * PAH belonging to WHO group I other than that listed in the inclusion criteria, i.e., PAH associated with: * 1.3.3: Portal hypertension * 1.3.6: Other (thyroid disorders, glycogen storage disease, Gaucher disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders, splenectomy) * 1.4: Associated with significant venous or capillary involvement: * 1.4.1: Pulmonary veno-occlusive disease (PVOD) * 1.4.2: Pulmonary capillary hemangiomatosis (PCH). * Receipt of any prostacyclin or prostacyclin analog other than iloprost within 12 weeks before screening. * Anticipation of the need for intravenous prostacyclin use within 28 days of starting the Power Disc-15 (PD-15). * HIV-seropositive with any of the following: * Concomitant active opportunistic infections within 6 months prior to screening * Detectable viral load within 6 months of screening * CD4+ T-cell count \< 200 mm\^3 within 3 months of screening * Changes in antiretroviral regimen within 3 months of screening * Anticipated changes in antiretroviral regimen during study periods 1 or 2 * Using inhaled pentamidine * Systemic hypotension with systolic blood pressure \< 95 mmHg. * Uncontrolled systemic hypertension (systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg on repeated measurement). * History of left-sided heart disease, including any of the following: * hemodynamically significant aortic or mitral valve disease * restrictive or congestive cardiomyopathy * left ventricular ejection fraction \< 40% by multigated radionucleotide angiogram (MUGA), angiography, or echocardiography * coronary artery disease with continuing symptoms of angina pectoris * life-threatening cardiac arrhythmias * Atrial septostomy within 1 year. * History of pulmonary embolism prior to diagnosis of PAH unless it can be documented that chronic thromboembolic pulmonary hypertension (CTEPH) has been specifically excluded (e.g., ventilation/perfusion (VQ) scan, pulmonary angiogram). * Restrictive lung disease: TLC \< 60% of normal predicted value. * Obstructive lung disease: forced expiratory volume/forced vital capacity (FEV1/FVC) \< 0.5 or clinically relevant chronic obstructive lung disease or asthma (including any patient requiring concomitant medication to control symptoms of bronchospasm including as needed (p.r.n.) use). * Clinically relevant bleeding disorder or active bleeding. * Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C or hepatic cirrhosis. * Pregnant or breast-feeding. * Chronic renal insufficiency, as defined by a creatinine of \> 2.5 mg/dL or the requirement for dialysis. * Hemoglobin \< 75% of the lower limit of normal range. * Any condition that prevents compliance with the protocol or adherence to therapy or ability to provide informed consent. * Participation in any other clinical trial, except observational, or receipt of an investigational product within 30 days prior to enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Reporting Treatment-emergent Adverse Events (AEs) | From the first dose to last dose of investigational product, an average of approximately 268 days, plus 48 hours | Number of patients reporting at least one treatment-emergent AE/Serious AE |
| Number of Patients Who Discontinued Iloprost PD-15 Treatment Due to an AE | From the first dose of investigational product to study discontinuation, an average of approximately 268 days | Number of patients reporting at least one treatment-emergent AE/Serious AE leading to discontinuation of study investigational treatment |
| Number of Patients Reporting Treatment-emergent Serious AEs | From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours | Number of patients reporting at least one treatment-emergent serious AEs |
| Systolic Blood Pressure - Iloprost PD-6 (Period 1) | Day 1 | Systolic blood pressure was measured immediately prior to first dosing with Iloprost PD-15 |
| Systolic Blood Pressure - Iloprost PD-15 (Period 2) | Day 28 | Systolic blood pressure was measured on Day 28 of treatment with Iloprost PD-15 |
| Systolic Blood Pressure - Iloprost PD-15 (Period 3) | an average of approximately 268 days | Systolic blood pressure was measured at the end of study visit |
| Change in Systolic Blood Pressure - (Period 1 to Period 2) | Day 1 and Day 28 | Systolic blood pressure was measured on Day 1 prior to treatment with Iloprost PD-15 (Period 1) and Day 28 of treatment with Iloprost PD-15 (Period 2) |
| Change in Systolic Blood Pressure - (Period 1 to Period 3) | Day 1 and End of study visit, an average of approximately 268 days | Systolic blood pressure was measured on Day 1 prior to treatment with Iloprost PD-15 (Period 1) and at the end of treatment with Iloprost PD-15 (Period 3) |
| Diastolic Blood Pressure - Iloprost PD-6 (Period 1) | Day 1 | Diastolic blood pressure was measured immediately prior to first dosing with Iloprost PD-15 |
| Diastolic Blood Pressure - Iloprost PD-15 (Period 2) | Day 28 | Diastolic blood pressure was measured on Day 28 of treatment with Iloprost PD-15 |
| Diastolic Blood Pressure - Iloprost PD-15 (Period 3) | an average of approximately 268 days | Diastolic blood pressure was measured at the end of study visit |
| Change in Diastolic Blood Pressure - (Period 1 to Period 2) | Day 1 and Day 28 | Diastolic blood pressure was measured on Day 1 prior to treatment with Iloprost PD-15 (Period 1) and Day 28 of treatment with Iloprost PD-15 (Period 2) |
| Change in Diastolic Blood Pressure - (Period 1 to Period 3) | Day 1 and End of study visit, an average of approximately 268 days | Diastolic blood pressure was measured on Day 1 prior to treatment with Iloprost PD-15 (Period 1) and at the end of treatment with Iloprost PD-15 (Period 3) |
| Heart Rate - Iloprost PD-6 (Period 1) | Day 1 | Heart rate was measured immediately prior to first dosing with Iloprost PD-15 |
| Heart Rate - Iloprost PD-15 (Period 2) | Day 28 | Heart rate was measured on Day 28 of treatment with Iloprost PD-15 |
| Heart Rate - Iloprost PD-15 (Period 3) | an average of approximately 268 days | Heart rate was measured at the end of study visit |
| Change in Heart Rate - (Period 1 to Period 2) | Day 1 and Day 28 | Heart rate was measured on Day 1 prior to treatment with Iloprost PD-15 (Period 1) and Day 28 of treatment with Iloprost PD-15 (Period 2) |
| Change in Heart Rate - (Period 1 to Period 3) | Day 1 and End of study visit, an average of approximately 268 days | Heart rate was measured on Day 1 prior to treatment with Iloprost PD-15 (Period 1) and at the end of treatment with Iloprost PD-15 (Period 3) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| NYHA Functional Class - Iloprost PD-15 (Period 3, End of Study Visit)) | average of approximately 268 days | Disease severity was assessed by NYHA classification of PAH criteria: Class I: no limitation of physical activity (PA). Ordinary PA: no undue dyspnea/fatigue, chest pain, near syncope. Class II: slight limitation of PA. Comfortable at rest. Ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class III: marked limitation of PA. Comfortable at rest. Less than ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class IV: inability to carry out PA without symptoms. Right heart failure. Dyspnea/fatigue may even have been present at rest. Discomfort increased by any PA. |
| Number of Patients With Improved, no Change, or Worsening of NYHA Functional Class - (Period 1, Prior to First Dose With Iloprost PD-15 to Period 2, Day 28) | average approximately 28 days | Disease severity was assessed by NYHA classification of PAH criteria: Class I: no limitation of physical activity (PA). Ordinary PA: no undue dyspnea/fatigue, chest pain, near syncope. Class II: slight limitation of PA. Comfortable at rest. Ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class III: marked limitation of PA. Comfortable at rest. Less than ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class IV: inability to carry out PA without symptoms. Right heart failure. Dyspnea/fatigue may even have been present at rest. Discomfort increased by any PA. |
| Number of Patients With Improved, no Change, or Worsening of NYHA Functional Class - (Period 1, Prior to First Dose With Iloprost PD-15 to Period 3, End of Study Visit) | average approximately 268 days | Disease severity was assessed by NYHA classification of PAH criteria: Class I: no limitation of physical activity (PA). Ordinary PA: no undue dyspnea/fatigue, chest pain, near syncope. Class II: slight limitation of PA. Comfortable at rest. Ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class III: marked limitation of PA. Comfortable at rest. Less than ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class IV: inability to carry out PA without symptoms. Right heart failure. Dyspnea/fatigue may even have been present at rest. Discomfort increased by any PA. |
| Patient Global Self Assessment - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15) | average of approximately 28 days | The Patient Global Self Assessment is a 7-point scale that was presented to patients prior to conducting visit-specific study procedures. Patients were asked to compare their current PAH status to their status in the past by selecting one of the following options: markedly better; moderately better; mildly better; no change; mildly worse; moderately worse; or markedly worse. On Day 1 prior to their first dose of iloprost with PD-15 (Baseline), patients were asked to compare their PAH status to that during Screening (if the Screening and Baseline visits were conducted on the same day, then patients were asked to compare their PAH status to that in the past 2 weeks). On Day 28 and at the end of study (EOS) visit, patients were asked to compare their PAH status to that of the previous visit. |
| Average Inhalation Time - Iloprost PD-6 (Period 1) | average of approximately 28 days | The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used. |
| Patient Global Self Assessment - Iloprost PD-15 (Period 3, End of Study Visit)) | average of approximately 268 days | The Patient Global Self Assessment is a 7-point scale that was presented to patients prior to conducting visit-specific study procedures. Patients were asked to compare their current PAH status to their status in the past by selecting one of the following options: markedly better; moderately better; mildly better; no change; mildly worse; moderately worse; or markedly worse. On Day 1 prior to their first dose of iloprost with PD-15 (Baseline), patients were asked to compare their PAH status to that during Screening (if the Screening and Baseline visits were conducted on the same day, then patients were asked to compare their PAH status to that in the past 2 weeks). On Day 28 and at the EOS visit, patients were asked to compare their PAH status to that of the previous visit. |
| Number of Patients With Improved, no Change, or Worse Patient Global Self Assessment - Change From Previous Visit to Period 2, Day 28 | average of approximately 28 days | The Patient Global Self Assessment is a 7-point scale that was presented to patients prior to conducting visit-specific study procedures. Patients were asked to compare their current PAH status to their status in the past by selecting one of the following options: markedly better; moderately better; mildly better; no change; mildly worse; moderately worse; or markedly worse. On Day 1 prior to their first dose of iloprost with PD-15 (Baseline), patients were asked to compare their PAH status to that during Screening (if the Screening and Baseline visits were conducted on the same day, then patients were asked to compare their PAH status to that in the past 2 weeks). On Day 28 and at the EOS visit, patients were asked to compare their PAH status to that of the previous visit. |
| Number of Patients With Improved, no Change, or Worse Patient Global Self Assessment - Change From Previous Visit to Period 3, End of Study Visit | average of approximately 268 days | The Patient Global Self Assessment is a 7-point scale that was presented to patients prior to conducting visit-specific study procedures. Patients were asked to compare their current PAH status to their status in the past by selecting one of the following options: markedly better; moderately better; mildly better; no change; mildly worse; moderately worse; or markedly worse. On Day 1 prior to their first dose of iloprost with PD-15 (Baseline), patients were asked to compare their PAH status to that during Screening (if the Screening and Baseline visits were conducted on the same day, then patients were asked to compare their PAH status to that in the past 2 weeks). On Day 28 and at the EOS visit, patients were asked to compare their PAH status to that of the previous visit. |
| Patient Global Self Assessment - Iloprost PD-15 (Period 2, Day 28) | average of approximately 28 days | The Patient Global Self Assessment is a 7-point scale that was presented to patients prior to conducting visit-specific study procedures. Patients were asked to compare their current PAH status to their status in the past by selecting one of the following options: markedly better; moderately better; mildly better; no change; mildly worse; moderately worse; or markedly worse. On Day 1 prior to their first dose of iloprost with PD-15 (Baseline), patients were asked to compare their PAH status to that during Screening (if the Screening and Baseline visits were conducted on the same day, then patients were asked to compare their PAH status to that in the past 2 weeks). On Day 28 and at the EOS visit, patients were asked to compare their PAH status to that of the previous visit. |
| Average Inhalation Time - Iloprost PD-15 (Period 2) | average of approximately 28 days | The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used. |
| Average Inhalation Time - Iloprost PD-15 (Period 3) | average of approximately 240 days | The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used. |
| Change in Average Inhalation Time - (Period 1 to Period 2) | average approximately 56 days | The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used. |
| Percentage of Complete Doses Delivered - Iloprost PD-6 (Period 1) | average of approximately 28 days | The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used. |
| Average Number of Days of Dosing - Iloprost PD-6 (Period 1) | average of approximately 28 days | The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used. |
| Average Number of Days of Dosing - Iloprost PD-15 (Period 2) | average of approximately 28 days | The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used. |
| Average Number of Days of Dosing - Iloprost PD-15 (Period 3) | average of approximately 240 days | The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used. |
| Change in Average Number of Days of Dosing - (Period 1 to Period 2) | average approximately 56 days | The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used. |
| Average Number of Daily Doses - Iloprost PD-6 (Period 1) | average of approximately 28 days | The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used. |
| Average Number of Daily Doses - Iloprost PD-15 (Period 2) | average of approximately 28 days | The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used. |
| Average Number of Daily Doses - Iloprost PD-15 (Period 3) | average of approximately 240 days | The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used. |
| Change in Average Number of Daily Doses - (Period 1 to Period 2) | average approximately 56 days | The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used. |
| Percentage of Complete Doses Delivered - Iloprost PD-15 (Period 2) | average of approximately 28 days | The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used. |
| Percentage of Complete Doses Delivered - Iloprost PD-15 (Period 3) | average of approximately 240 days | The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used. |
| Change in Percentage of Complete Doses Delivered - (Period 1 to Period 2) | average approximately 56 days | The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used. |
| New York Health Association (NYHA) Functional Class - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15) | average of approximately 28 days | Disease severity was assessed by NYHA classification of PAH criteria: Class I: no limitation of physical activity (PA). Ordinary PA: no undue dyspnea/fatigue, chest pain, near syncope. Class II: slight limitation of PA. Comfortable at rest. Ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class III: marked limitation of PA. Comfortable at rest. Less than ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class IV: inability to carry out PA without symptoms. Right heart failure. Dyspnea/fatigue may even have been present at rest. Discomfort increased by any PA. |
| NYHA Functional Class - Iloprost PD-15 (Period 2, Day 28) | average of approximately 28 days | Disease severity was assessed by NYHA classification of PAH criteria: Class I: no limitation of physical activity (PA). Ordinary PA: no undue dyspnea/fatigue, chest pain, near syncope. Class II: slight limitation of PA. Comfortable at rest. Ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class III: marked limitation of PA. Comfortable at rest. Less than ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class IV: inability to carry out PA without symptoms. Right heart failure. Dyspnea/fatigue may even have been present at rest. Discomfort increased by any PA. |
Countries
United States
Participant flow
Recruitment details
Patients were enrolled at 22 U.S. centers
Pre-assignment details
Adults with pulmonary arterial hypertension (PAH) who were using Ventavis (Iloprost) Inhalation Solution Delivered by I-Neb Utilizing Power Disc-6 (PD-6) were enrolled
Participants by arm
| Arm | Count |
|---|---|
| Iloprost iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-6 (PD-6) and Power Disc-15 (PD-15). | 63 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 12 |
| Overall Study | Inhaled medication other than iloprost | 4 |
| Overall Study | Investigator's judgement | 5 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Non-compliance | 1 |
| Overall Study | Other | 3 |
| Overall Study | Withdrawal of consent | 3 |
Baseline characteristics
| Characteristic | Iloprost |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 28 Participants |
| Age, Categorical Between 18 and 65 years | 35 Participants |
| Age Continuous | 59.9 years STANDARD_DEVIATION 12.91 |
| Region of Enrollment United States | 63 participants |
| Sex: Female, Male Female | 58 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 50 / 63 |
| serious Total, serious adverse events | 18 / 63 |
Outcome results
Primary
Change in Diastolic Blood Pressure - (Period 1 to Period 2)
Diastolic blood pressure was measured on Day 1 prior to treatment with Iloprost PD-15 (Period 1) and Day 28 of treatment with Iloprost PD-15 (Period 2)
Time frame: Day 1 and Day 28
Population: Safety population - missing data were not imputed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Change in Diastolic Blood Pressure - (Period 1 to Period 2) | -0.5 mmHg | Standard Deviation 9.66 |
Primary
Change in Diastolic Blood Pressure - (Period 1 to Period 3)
Diastolic blood pressure was measured on Day 1 prior to treatment with Iloprost PD-15 (Period 1) and at the end of treatment with Iloprost PD-15 (Period 3)
Time frame: Day 1 and End of study visit, an average of approximately 268 days
Population: Safety population - missing data were not imputed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Change in Diastolic Blood Pressure - (Period 1 to Period 3) | -2.3 mmHg | Standard Deviation 10.64 |
Primary
Change in Heart Rate - (Period 1 to Period 2)
Heart rate was measured on Day 1 prior to treatment with Iloprost PD-15 (Period 1) and Day 28 of treatment with Iloprost PD-15 (Period 2)
Time frame: Day 1 and Day 28
Population: Safety population - missing data were not imputed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Change in Heart Rate - (Period 1 to Period 2) | 0.3 beats per minute | Standard Deviation 12.24 |
Primary
Change in Heart Rate - (Period 1 to Period 3)
Heart rate was measured on Day 1 prior to treatment with Iloprost PD-15 (Period 1) and at the end of treatment with Iloprost PD-15 (Period 3)
Time frame: Day 1 and End of study visit, an average of approximately 268 days
Population: Safety population - missing data were not imputed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Change in Heart Rate - (Period 1 to Period 3) | 2.6 beats per minute | Standard Deviation 13.89 |
Primary
Change in Systolic Blood Pressure - (Period 1 to Period 2)
Systolic blood pressure was measured on Day 1 prior to treatment with Iloprost PD-15 (Period 1) and Day 28 of treatment with Iloprost PD-15 (Period 2)
Time frame: Day 1 and Day 28
Population: Safety population - missing data were not imputed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Change in Systolic Blood Pressure - (Period 1 to Period 2) | -1.9 mmHg | Standard Deviation 13.07 |
Primary
Change in Systolic Blood Pressure - (Period 1 to Period 3)
Systolic blood pressure was measured on Day 1 prior to treatment with Iloprost PD-15 (Period 1) and at the end of treatment with Iloprost PD-15 (Period 3)
Time frame: Day 1 and End of study visit, an average of approximately 268 days
Population: Safety population - missing data were not imputed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Change in Systolic Blood Pressure - (Period 1 to Period 3) | 0.8 mmHg | Standard Deviation 17.82 |
Primary
Diastolic Blood Pressure - Iloprost PD-15 (Period 2)
Diastolic blood pressure was measured on Day 28 of treatment with Iloprost PD-15
Time frame: Day 28
Population: Safety population - missing data were not imputed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Diastolic Blood Pressure - Iloprost PD-15 (Period 2) | 67.0 mmHg | Standard Deviation 8.86 |
Primary
Diastolic Blood Pressure - Iloprost PD-15 (Period 3)
Diastolic blood pressure was measured at the end of study visit
Time frame: an average of approximately 268 days
Population: Safety population - missing data were not imputed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Diastolic Blood Pressure - Iloprost PD-15 (Period 3) | 65.6 mmHg | Standard Deviation 9.5 |
Primary
Diastolic Blood Pressure - Iloprost PD-6 (Period 1)
Diastolic blood pressure was measured immediately prior to first dosing with Iloprost PD-15
Time frame: Day 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Diastolic Blood Pressure - Iloprost PD-6 (Period 1) | 67.6 mmHg | Standard Deviation 10.57 |
Primary
Heart Rate - Iloprost PD-15 (Period 2)
Heart rate was measured on Day 28 of treatment with Iloprost PD-15
Time frame: Day 28
Population: Safety population - missing data were not imputed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Heart Rate - Iloprost PD-15 (Period 2) | 74.2 beats per minute | Standard Deviation 11.76 |
Primary
Heart Rate - Iloprost PD-15 (Period 3)
Heart rate was measured at the end of study visit
Time frame: an average of approximately 268 days
Population: Safety population - missing data were not imputed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Heart Rate - Iloprost PD-15 (Period 3) | 75.6 beats per minute | Standard Deviation 13.66 |
Primary
Heart Rate - Iloprost PD-6 (Period 1)
Heart rate was measured immediately prior to first dosing with Iloprost PD-15
Time frame: Day 1
Population: Safety population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Heart Rate - Iloprost PD-6 (Period 1) | 73.8 beats per minute | Standard Deviation 11.67 |
Primary
Number of Patients Reporting Treatment-emergent Adverse Events (AEs)
Number of patients reporting at least one treatment-emergent AE/Serious AE
Time frame: From the first dose to last dose of investigational product, an average of approximately 268 days, plus 48 hours
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Iloprost | Number of Patients Reporting Treatment-emergent Adverse Events (AEs) | 53 participants |
Primary
Number of Patients Reporting Treatment-emergent Serious AEs
Number of patients reporting at least one treatment-emergent serious AEs
Time frame: From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Iloprost | Number of Patients Reporting Treatment-emergent Serious AEs | 18 participants |
Primary
Number of Patients Who Discontinued Iloprost PD-15 Treatment Due to an AE
Number of patients reporting at least one treatment-emergent AE/Serious AE leading to discontinuation of study investigational treatment
Time frame: From the first dose of investigational product to study discontinuation, an average of approximately 268 days
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Iloprost | Number of Patients Who Discontinued Iloprost PD-15 Treatment Due to an AE | 8 participants |
Primary
Systolic Blood Pressure - Iloprost PD-15 (Period 2)
Systolic blood pressure was measured on Day 28 of treatment with Iloprost PD-15
Time frame: Day 28
Population: Safety population - missing data were not imputed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Systolic Blood Pressure - Iloprost PD-15 (Period 2) | 116.2 mmHg | Standard Deviation 14.71 |
Primary
Systolic Blood Pressure - Iloprost PD-15 (Period 3)
Systolic blood pressure was measured at the end of study visit
Time frame: an average of approximately 268 days
Population: Safety population - missing data were not imputed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Systolic Blood Pressure - Iloprost PD-15 (Period 3) | 119.0 mmHg | Standard Deviation 17.47 |
Primary
Systolic Blood Pressure - Iloprost PD-6 (Period 1)
Systolic blood pressure was measured immediately prior to first dosing with Iloprost PD-15
Time frame: Day 1
Population: Safety population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Systolic Blood Pressure - Iloprost PD-6 (Period 1) | 117.7 mmHg | Standard Deviation 15.61 |
Secondary
Average Inhalation Time - Iloprost PD-15 (Period 2)
The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.
Time frame: average of approximately 28 days
Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Average Inhalation Time - Iloprost PD-15 (Period 2) | 7.7 minutes | Standard Deviation 4.01 |
Secondary
Average Inhalation Time - Iloprost PD-15 (Period 3)
The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.
Time frame: average of approximately 240 days
Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Average Inhalation Time - Iloprost PD-15 (Period 3) | 8.4 minutes | Standard Deviation 4.3 |
Secondary
Average Inhalation Time - Iloprost PD-6 (Period 1)
The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.
Time frame: average of approximately 28 days
Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Average Inhalation Time - Iloprost PD-6 (Period 1) | 13.9 minutes | Standard Deviation 5.83 |
Secondary
Average Number of Daily Doses - Iloprost PD-15 (Period 2)
The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.
Time frame: average of approximately 28 days
Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Average Number of Daily Doses - Iloprost PD-15 (Period 2) | 5.6 doses per day | Standard Deviation 1.14 |
Secondary
Average Number of Daily Doses - Iloprost PD-15 (Period 3)
The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.
Time frame: average of approximately 240 days
Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Average Number of Daily Doses - Iloprost PD-15 (Period 3) | 4.7 doses per day | Standard Deviation 1.69 |
Secondary
Average Number of Daily Doses - Iloprost PD-6 (Period 1)
The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.
Time frame: average of approximately 28 days
Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Average Number of Daily Doses - Iloprost PD-6 (Period 1) | 5.1 doses per day | Standard Deviation 1.48 |
Secondary
Average Number of Days of Dosing - Iloprost PD-15 (Period 2)
The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.
Time frame: average of approximately 28 days
Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Average Number of Days of Dosing - Iloprost PD-15 (Period 2) | 27.4 days | Standard Deviation 2.66 |
Secondary
Average Number of Days of Dosing - Iloprost PD-15 (Period 3)
The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.
Time frame: average of approximately 240 days
Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Average Number of Days of Dosing - Iloprost PD-15 (Period 3) | 240 days | Standard Deviation 139.03 |
Secondary
Average Number of Days of Dosing - Iloprost PD-6 (Period 1)
The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.
Time frame: average of approximately 28 days
Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Average Number of Days of Dosing - Iloprost PD-6 (Period 1) | 27.6 days | Standard Deviation 1.11 |
Secondary
Change in Average Inhalation Time - (Period 1 to Period 2)
The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.
Time frame: average approximately 56 days
Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Change in Average Inhalation Time - (Period 1 to Period 2) | -6.1 minutes | Standard Deviation 2.92 |
Comparison: Comparison of the change in average inhalation times from Period I (PD-6) to Period II (PD-15)p-value: <0.00195% CI: [-6.9, -5.4]t-test, 2 sided
Secondary
Change in Average Number of Daily Doses - (Period 1 to Period 2)
The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.
Time frame: average approximately 56 days
Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Change in Average Number of Daily Doses - (Period 1 to Period 2) | 0.5 doses per day | Standard Deviation 1 |
Comparison: Comparison of the change in average number of daily doses from Period I (PD-6) to Period II (PD-15)p-value: <0.00195% CI: [0.2, 0.7]t-test, 2 sided
Secondary
Change in Average Number of Days of Dosing - (Period 1 to Period 2)
The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.
Time frame: average approximately 56 days
Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Change in Average Number of Days of Dosing - (Period 1 to Period 2) | -0.2 days | Standard Deviation 2.93 |
Comparison: Comparison of the change in average number of days of dosing from Period I (PD-6) to Period II (PD-15)p-value: 0.5995% CI: [-1, 0.6]t-test, 2 sided
Secondary
Change in Percentage of Complete Doses Delivered - (Period 1 to Period 2)
The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.
Time frame: average approximately 56 days
Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Change in Percentage of Complete Doses Delivered - (Period 1 to Period 2) | 11.0 percentage of complete doses | Standard Deviation 17.23 |
Comparison: Comparison of the change in percentage of complete doses delivered from Period I (PD-6) to Period II (PD-15)p-value: <0.000195% CI: [6.5, 15.6]t-test, 2 sided
Secondary
New York Health Association (NYHA) Functional Class - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15)
Disease severity was assessed by NYHA classification of PAH criteria: Class I: no limitation of physical activity (PA). Ordinary PA: no undue dyspnea/fatigue, chest pain, near syncope. Class II: slight limitation of PA. Comfortable at rest. Ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class III: marked limitation of PA. Comfortable at rest. Less than ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class IV: inability to carry out PA without symptoms. Right heart failure. Dyspnea/fatigue may even have been present at rest. Discomfort increased by any PA.
Time frame: average of approximately 28 days
Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Iloprost | New York Health Association (NYHA) Functional Class - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15) | Class IV | 4 participants |
| Iloprost | New York Health Association (NYHA) Functional Class - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15) | Class I | 3 participants |
| Iloprost | New York Health Association (NYHA) Functional Class - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15) | Class II | 17 participants |
| Iloprost | New York Health Association (NYHA) Functional Class - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15) | Class III | 34 participants |
Secondary
Number of Patients With Improved, no Change, or Worsening of NYHA Functional Class - (Period 1, Prior to First Dose With Iloprost PD-15 to Period 2, Day 28)
Disease severity was assessed by NYHA classification of PAH criteria: Class I: no limitation of physical activity (PA). Ordinary PA: no undue dyspnea/fatigue, chest pain, near syncope. Class II: slight limitation of PA. Comfortable at rest. Ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class III: marked limitation of PA. Comfortable at rest. Less than ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class IV: inability to carry out PA without symptoms. Right heart failure. Dyspnea/fatigue may even have been present at rest. Discomfort increased by any PA.
Time frame: average approximately 28 days
Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Iloprost | Number of Patients With Improved, no Change, or Worsening of NYHA Functional Class - (Period 1, Prior to First Dose With Iloprost PD-15 to Period 2, Day 28) | Improved | 4 participants |
| Iloprost | Number of Patients With Improved, no Change, or Worsening of NYHA Functional Class - (Period 1, Prior to First Dose With Iloprost PD-15 to Period 2, Day 28) | No change | 50 participants |
| Iloprost | Number of Patients With Improved, no Change, or Worsening of NYHA Functional Class - (Period 1, Prior to First Dose With Iloprost PD-15 to Period 2, Day 28) | Worse | 1 participants |
Secondary
Number of Patients With Improved, no Change, or Worsening of NYHA Functional Class - (Period 1, Prior to First Dose With Iloprost PD-15 to Period 3, End of Study Visit)
Disease severity was assessed by NYHA classification of PAH criteria: Class I: no limitation of physical activity (PA). Ordinary PA: no undue dyspnea/fatigue, chest pain, near syncope. Class II: slight limitation of PA. Comfortable at rest. Ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class III: marked limitation of PA. Comfortable at rest. Less than ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class IV: inability to carry out PA without symptoms. Right heart failure. Dyspnea/fatigue may even have been present at rest. Discomfort increased by any PA.
Time frame: average approximately 268 days
Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Iloprost | Number of Patients With Improved, no Change, or Worsening of NYHA Functional Class - (Period 1, Prior to First Dose With Iloprost PD-15 to Period 3, End of Study Visit) | Improved | 7 participants |
| Iloprost | Number of Patients With Improved, no Change, or Worsening of NYHA Functional Class - (Period 1, Prior to First Dose With Iloprost PD-15 to Period 3, End of Study Visit) | No change | 37 participants |
| Iloprost | Number of Patients With Improved, no Change, or Worsening of NYHA Functional Class - (Period 1, Prior to First Dose With Iloprost PD-15 to Period 3, End of Study Visit) | Worse | 4 participants |
Secondary
Number of Patients With Improved, no Change, or Worse Patient Global Self Assessment - Change From Previous Visit to Period 2, Day 28
The Patient Global Self Assessment is a 7-point scale that was presented to patients prior to conducting visit-specific study procedures. Patients were asked to compare their current PAH status to their status in the past by selecting one of the following options: markedly better; moderately better; mildly better; no change; mildly worse; moderately worse; or markedly worse. On Day 1 prior to their first dose of iloprost with PD-15 (Baseline), patients were asked to compare their PAH status to that during Screening (if the Screening and Baseline visits were conducted on the same day, then patients were asked to compare their PAH status to that in the past 2 weeks). On Day 28 and at the EOS visit, patients were asked to compare their PAH status to that of the previous visit.
Time frame: average of approximately 28 days
Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Iloprost | Number of Patients With Improved, no Change, or Worse Patient Global Self Assessment - Change From Previous Visit to Period 2, Day 28 | Improved | 34 participants |
| Iloprost | Number of Patients With Improved, no Change, or Worse Patient Global Self Assessment - Change From Previous Visit to Period 2, Day 28 | No change | 21 participants |
| Iloprost | Number of Patients With Improved, no Change, or Worse Patient Global Self Assessment - Change From Previous Visit to Period 2, Day 28 | Worse | 1 participants |
Secondary
Number of Patients With Improved, no Change, or Worse Patient Global Self Assessment - Change From Previous Visit to Period 3, End of Study Visit
The Patient Global Self Assessment is a 7-point scale that was presented to patients prior to conducting visit-specific study procedures. Patients were asked to compare their current PAH status to their status in the past by selecting one of the following options: markedly better; moderately better; mildly better; no change; mildly worse; moderately worse; or markedly worse. On Day 1 prior to their first dose of iloprost with PD-15 (Baseline), patients were asked to compare their PAH status to that during Screening (if the Screening and Baseline visits were conducted on the same day, then patients were asked to compare their PAH status to that in the past 2 weeks). On Day 28 and at the EOS visit, patients were asked to compare their PAH status to that of the previous visit.
Time frame: average of approximately 268 days
Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Iloprost | Number of Patients With Improved, no Change, or Worse Patient Global Self Assessment - Change From Previous Visit to Period 3, End of Study Visit | Improved | 27 participants |
| Iloprost | Number of Patients With Improved, no Change, or Worse Patient Global Self Assessment - Change From Previous Visit to Period 3, End of Study Visit | No change | 17 participants |
| Iloprost | Number of Patients With Improved, no Change, or Worse Patient Global Self Assessment - Change From Previous Visit to Period 3, End of Study Visit | Worse | 6 participants |
Secondary
NYHA Functional Class - Iloprost PD-15 (Period 2, Day 28)
Disease severity was assessed by NYHA classification of PAH criteria: Class I: no limitation of physical activity (PA). Ordinary PA: no undue dyspnea/fatigue, chest pain, near syncope. Class II: slight limitation of PA. Comfortable at rest. Ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class III: marked limitation of PA. Comfortable at rest. Less than ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class IV: inability to carry out PA without symptoms. Right heart failure. Dyspnea/fatigue may even have been present at rest. Discomfort increased by any PA.
Time frame: average of approximately 28 days
Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Iloprost | NYHA Functional Class - Iloprost PD-15 (Period 2, Day 28) | Class I | 3 participants |
| Iloprost | NYHA Functional Class - Iloprost PD-15 (Period 2, Day 28) | Class II | 17 participants |
| Iloprost | NYHA Functional Class - Iloprost PD-15 (Period 2, Day 28) | Class III | 33 participants |
| Iloprost | NYHA Functional Class - Iloprost PD-15 (Period 2, Day 28) | Class IV | 2 participants |
Secondary
NYHA Functional Class - Iloprost PD-15 (Period 3, End of Study Visit))
Disease severity was assessed by NYHA classification of PAH criteria: Class I: no limitation of physical activity (PA). Ordinary PA: no undue dyspnea/fatigue, chest pain, near syncope. Class II: slight limitation of PA. Comfortable at rest. Ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class III: marked limitation of PA. Comfortable at rest. Less than ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class IV: inability to carry out PA without symptoms. Right heart failure. Dyspnea/fatigue may even have been present at rest. Discomfort increased by any PA.
Time frame: average of approximately 268 days
Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Iloprost | NYHA Functional Class - Iloprost PD-15 (Period 3, End of Study Visit)) | Class II | 20 participants |
| Iloprost | NYHA Functional Class - Iloprost PD-15 (Period 3, End of Study Visit)) | Class I | 3 participants |
| Iloprost | NYHA Functional Class - Iloprost PD-15 (Period 3, End of Study Visit)) | Class III | 19 participants |
| Iloprost | NYHA Functional Class - Iloprost PD-15 (Period 3, End of Study Visit)) | Class IV | 6 participants |
Secondary
Patient Global Self Assessment - Iloprost PD-15 (Period 2, Day 28)
The Patient Global Self Assessment is a 7-point scale that was presented to patients prior to conducting visit-specific study procedures. Patients were asked to compare their current PAH status to their status in the past by selecting one of the following options: markedly better; moderately better; mildly better; no change; mildly worse; moderately worse; or markedly worse. On Day 1 prior to their first dose of iloprost with PD-15 (Baseline), patients were asked to compare their PAH status to that during Screening (if the Screening and Baseline visits were conducted on the same day, then patients were asked to compare their PAH status to that in the past 2 weeks). On Day 28 and at the EOS visit, patients were asked to compare their PAH status to that of the previous visit.
Time frame: average of approximately 28 days
Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Iloprost | Patient Global Self Assessment - Iloprost PD-15 (Period 2, Day 28) | Markedly better | 7 participants |
| Iloprost | Patient Global Self Assessment - Iloprost PD-15 (Period 2, Day 28) | Moderately better | 15 participants |
| Iloprost | Patient Global Self Assessment - Iloprost PD-15 (Period 2, Day 28) | Mildly better | 12 participants |
| Iloprost | Patient Global Self Assessment - Iloprost PD-15 (Period 2, Day 28) | No change | 21 participants |
| Iloprost | Patient Global Self Assessment - Iloprost PD-15 (Period 2, Day 28) | Mildly worse | 0 participants |
| Iloprost | Patient Global Self Assessment - Iloprost PD-15 (Period 2, Day 28) | Moderately worse | 1 participants |
| Iloprost | Patient Global Self Assessment - Iloprost PD-15 (Period 2, Day 28) | Markedly worse | 0 participants |
Secondary
Patient Global Self Assessment - Iloprost PD-15 (Period 3, End of Study Visit))
The Patient Global Self Assessment is a 7-point scale that was presented to patients prior to conducting visit-specific study procedures. Patients were asked to compare their current PAH status to their status in the past by selecting one of the following options: markedly better; moderately better; mildly better; no change; mildly worse; moderately worse; or markedly worse. On Day 1 prior to their first dose of iloprost with PD-15 (Baseline), patients were asked to compare their PAH status to that during Screening (if the Screening and Baseline visits were conducted on the same day, then patients were asked to compare their PAH status to that in the past 2 weeks). On Day 28 and at the EOS visit, patients were asked to compare their PAH status to that of the previous visit.
Time frame: average of approximately 268 days
Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Iloprost | Patient Global Self Assessment - Iloprost PD-15 (Period 3, End of Study Visit)) | Markedly better | 6 participants |
| Iloprost | Patient Global Self Assessment - Iloprost PD-15 (Period 3, End of Study Visit)) | Moderately better | 10 participants |
| Iloprost | Patient Global Self Assessment - Iloprost PD-15 (Period 3, End of Study Visit)) | Mildly better | 11 participants |
| Iloprost | Patient Global Self Assessment - Iloprost PD-15 (Period 3, End of Study Visit)) | No change | 17 participants |
| Iloprost | Patient Global Self Assessment - Iloprost PD-15 (Period 3, End of Study Visit)) | Mildly worse | 4 participants |
| Iloprost | Patient Global Self Assessment - Iloprost PD-15 (Period 3, End of Study Visit)) | Moderately worse | 1 participants |
| Iloprost | Patient Global Self Assessment - Iloprost PD-15 (Period 3, End of Study Visit)) | Markedly worse | 1 participants |
Secondary
Patient Global Self Assessment - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15)
The Patient Global Self Assessment is a 7-point scale that was presented to patients prior to conducting visit-specific study procedures. Patients were asked to compare their current PAH status to their status in the past by selecting one of the following options: markedly better; moderately better; mildly better; no change; mildly worse; moderately worse; or markedly worse. On Day 1 prior to their first dose of iloprost with PD-15 (Baseline), patients were asked to compare their PAH status to that during Screening (if the Screening and Baseline visits were conducted on the same day, then patients were asked to compare their PAH status to that in the past 2 weeks). On Day 28 and at the end of study (EOS) visit, patients were asked to compare their PAH status to that of the previous visit.
Time frame: average of approximately 28 days
Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Iloprost | Patient Global Self Assessment - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15) | Markedly better | 8 participants |
| Iloprost | Patient Global Self Assessment - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15) | Moderately better | 8 participants |
| Iloprost | Patient Global Self Assessment - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15) | Mildly better | 9 participants |
| Iloprost | Patient Global Self Assessment - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15) | No change | 31 participants |
| Iloprost | Patient Global Self Assessment - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15) | Mildly worse | 2 participants |
| Iloprost | Patient Global Self Assessment - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15) | Moderately worse | 0 participants |
| Iloprost | Patient Global Self Assessment - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15) | Markedly worse | 0 participants |
Secondary
Percentage of Complete Doses Delivered - Iloprost PD-15 (Period 2)
The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.
Time frame: average of approximately 28 days
Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Percentage of Complete Doses Delivered - Iloprost PD-15 (Period 2) | 95.4 percentage of complete doses | Standard Deviation 14.75 |
Secondary
Percentage of Complete Doses Delivered - Iloprost PD-15 (Period 3)
The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.
Time frame: average of approximately 240 days
Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Percentage of Complete Doses Delivered - Iloprost PD-15 (Period 3) | 94.2 percentage of complete doses | Standard Deviation 12.02 |
Secondary
Percentage of Complete Doses Delivered - Iloprost PD-6 (Period 1)
The time and date of inhalation, inhalation time (minutes), and dose completion status (\<12.5%, ≥12.5 to \<100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.
Time frame: average of approximately 28 days
Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Iloprost | Percentage of Complete Doses Delivered - Iloprost PD-6 (Period 1) | 84.3 percentage of complete doses | Standard Deviation 23.42 |