E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Indication: Symptomatic Pulmonary Arterial Hypertension
|
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064911 |
E.1.2 | Term | Pulmonary arterial hypertension |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
•To demonstrate that a single dose of iloprost power 15 improves exercise capacity in patients with symptomatic pulmonary arterial hypertension. |
|
E.2.2 | Secondary objectives of the trial |
•To evaluate the effect of a single dose of iloprost power 15 on the Borg dyspnea score. •To evaluate the safety and tolerability of a single dose of iloprost power 15.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Signed informed consent prior to initiation of any study mandated procedure, 2.Male or female >= 18 years of age, 3.Patients with symptomatic idiopathic, familial pulmonary arterial hypertension or pulmonary arterial hypertension associated with HIV or drugs/toxins (APAH) in New York Heart Association (NYHA) functional class II to IV at baseline, 4.6-minute walk distance (6MWD) >= 150 m and <= 450 m at baseline, 5.Pulmonary arterial hypertension (PAH) confirmed by right heart catheterization within 3 years prior to randomization and showing: •Mean pulmonary artery pressure (mPaP) >= 25 mmHg at rest, •Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) < 15 mmHg, •Pulmonary vascular resistance (PVR) at rest > = 240 dyn-sec/cm5. 6.Patients naïve to PAH treatment, or on a stable dose regimen of bosentan, ambrisentan, or sildenafil, monotherapy for at least 4 weeks prior to randomization (no dosage adjustment should have occurred during this period), 7.Women of childbearing potential must use an adequate method of contraception during the study.
|
|
E.4 | Principal exclusion criteria |
1.Pulmonary arterial hypertension related to any condition other than those specified in the inclusion criteria, 2.Pulmonary arterial hypertension associated with significant venous or capillary involvement (PCWP > 15 mmHg), known pulmonary veno-occlusive disease, or pulmonary capillary hemangiomatosis, 3.Moderate to severe obstructive lung disease: forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) < 70% and FEV1 < 65% of predicted value after bronchodilator administration, 4.Moderate to severe restrictive lung disease: total lung capacity (TLC) < 60% of predicted value, 5.Any condition other than PAH, which might affect the patient’s ability to perform a 6-minute walk test (6MWT), 6.Pregnant or breast-feeding women, 7.Systemic hypertension (systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg on repeated measurement), 8.Systolic blood pressure < 95 mmHg, 9.Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C, 10.Chronic renal insufficiency defined by serum creatinine > 2.5 mg/dL (221 μmol/L) or ongoing dialysis, 11.Clinically relevant bleeding disorder or active bleeding, 12.Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3 times the upper limit of normal at screening, 13.HIV seropositive with any of the following: •Active opportunistic infections within 3 months prior to randomization •Changes in antiretroviral regimen within 3 months of randomization •Using inhaled pentamidine 14.For those patients on monotherapy, any contraindication to bosentan, ambrisentan, or sildenafil, according to product label, 15.Treatment with another investigational drug within 30 days prior to randomization, 16.Use of inhaled Iloprost within the last 6 months, 17.Inability to use the inhalation device. 18.Known hypersensitivity to iloprost or any of its excipients. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
6MWD after a single dose of iloprost power 15 or placebo. A mean difference of 12.5 m between iloprost power 15 and placebo is to be detected. Assumptions: •The difference in 6MWD between placebo and iloprost power 15 is normally distributed with standard deviation (SD) 30 m. •The period effect is of relevant size, nevertheless it is not depending on the treatment that is administered first; i.e., no carry-over effect. •Patients do not prematurely discontinue the study due to reasons that might be related to the treatments.
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |