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 (PD-6) to Power Disc-15 (PD-15) With the I-neb® AAD®
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 63
- 试验地点
- 36
- 主要终点
- Number of Patients Reporting Treatment-emergent Adverse Events (AEs)
研究概览
简要总结
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®)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Iloprost
The study enrolled patients who were already using iloprost with PD-6 without any safety or tolerability concerns, thereby facilitating a direct comparison of the PD-15 to the PD-6.
The single-arm design allowed each patient to serve as his/her own control
干预措施: Iloprost PD-6 (Drug)
Iloprost
The study enrolled patients who were already using iloprost with PD-6 without any safety or tolerability concerns, thereby facilitating a direct comparison of the PD-15 to the PD-6.
The single-arm design allowed each patient to serve as his/her own control
干预措施: Iloprost PD-15 (Drug)
结局指标
主要结局
Number of Patients Reporting Treatment-emergent Adverse Events (AEs)
时间窗: 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
时间窗: 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
时间窗: 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)
时间窗: Day 1
Systolic blood pressure was measured immediately prior to first dosing with Iloprost PD-15
Systolic Blood Pressure - Iloprost PD-15 (Period 2)
时间窗: Day 28
Systolic blood pressure was measured on Day 28 of treatment with Iloprost PD-15
Systolic Blood Pressure - Iloprost PD-15 (Period 3)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: Day 1
Diastolic blood pressure was measured immediately prior to first dosing with Iloprost PD-15
Diastolic Blood Pressure - Iloprost PD-15 (Period 2)
时间窗: Day 28
Diastolic blood pressure was measured on Day 28 of treatment with Iloprost PD-15
Diastolic Blood Pressure - Iloprost PD-15 (Period 3)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: Day 1
Heart rate was measured immediately prior to first dosing with Iloprost PD-15
Heart Rate - Iloprost PD-15 (Period 2)
时间窗: Day 28
Heart rate was measured on Day 28 of treatment with Iloprost PD-15
Heart Rate - Iloprost PD-15 (Period 3)
时间窗: 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)
时间窗: 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)
时间窗: 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)
次要结局
- Average Inhalation Time - Iloprost PD-6 (Period 1)(average of approximately 28 days)
- Average Inhalation Time - Iloprost PD-15 (Period 2)(average of approximately 28 days)
- Average Inhalation Time - Iloprost PD-15 (Period 3)(average of approximately 240 days)
- Change in Average Inhalation Time - (Period 1 to Period 2)(average approximately 56 days)
- Average Number of Days of Dosing - Iloprost PD-6 (Period 1)(average of approximately 28 days)
- Average Number of Days of Dosing - Iloprost PD-15 (Period 2)(average of approximately 28 days)
- Average Number of Days of Dosing - Iloprost PD-15 (Period 3)(average of approximately 240 days)
- Change in Average Number of Days of Dosing - (Period 1 to Period 2)(average approximately 56 days)
- Average Number of Daily Doses - Iloprost PD-6 (Period 1)(average of approximately 28 days)
- Average Number of Daily Doses - Iloprost PD-15 (Period 2)(average of approximately 28 days)
- Average Number of Daily Doses - Iloprost PD-15 (Period 3)(average of approximately 240 days)
- Change in Average Number of Daily Doses - (Period 1 to Period 2)(average approximately 56 days)
- Percentage of Complete Doses Delivered - Iloprost PD-6 (Period 1)(average of approximately 28 days)
- Percentage of Complete Doses Delivered - Iloprost PD-15 (Period 2)(average of approximately 28 days)
- Percentage of Complete Doses Delivered - Iloprost PD-15 (Period 3)(average of approximately 240 days)
- Change in Percentage of Complete Doses Delivered - (Period 1 to Period 2)(average approximately 56 days)
- 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)
- NYHA Functional Class - Iloprost PD-15 (Period 2, Day 28)(average of approximately 28 days)
- NYHA Functional Class - Iloprost PD-15 (Period 3, End of Study Visit))(average of approximately 268 days)
- 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)
- 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)
- Patient Global Self Assessment - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15)(average of approximately 28 days)
- Patient Global Self Assessment - Iloprost PD-15 (Period 2, Day 28)(average of approximately 28 days)
- Patient Global Self Assessment - Iloprost PD-15 (Period 3, End of Study Visit))(average of approximately 268 days)
- 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)
- 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)