E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pulmonary hypertension in patients with interstitial lung disease. |
|
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of bosentan in treatment of patients with pulmonary hypertension and fibrosing lung disease.
The primary endpoints is a fall from baseline pulmonary vascular resistance (PVR) to week 16 of 20%.
|
|
E.2.2 | Secondary objectives of the trial |
To assess whether bosentan improves exercise capacity, and pulmonary blood flow in patients with pulmonary hypertension and fibrosing lung disease.
The secondary endpoints are changes from baseline to week 16 in the following:
1. right heart catherisation (RHC) parameters: mean pulmonary arterial pressure, right atrial pressure, cardiac index, systemic vascular resistance.
2. Exercise capacity as measured by the 6-minute walk test, and Borg dyspnoea scale
3. Quality of life as measured by the CAMPHOR questionaire
4. Pulmonary blood flow
5. Lung function (DLco% predicted, FVC% predicted, Composite physiological index)
6. WHO functional class
7. Right ventricular mass (cardiac MRI)
8. Brain natriuretic peptide
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients >=18yrs, <80yrs
2. Patients with Idiopathic Pulmonary Fibrosis according to ATS/ERS criteria.
3. Patients with pulmonary hypertension on right heart catheter (mean pulmonary arterial pressure >25mmHg with pulmonary artery occlusion pressure, left atrial pressure or left ventricular end-diastolic pressure <15mmHg).
4. Patients providing written informed consent. |
|
E.4 | Principal exclusion criteria |
1. Patients <18, >80yrs.
2. Patients with unstable disease, or an acute exacerbation of their underlying fibrotic lung disease.
3. Patients with significant other organ co-morbidity including hepatic or renal impairment.
4. Patients with systolic BP < 85mmHg
5. Patients with other conditions that may affect the ability to perform a 6-minute walk test.
6. Patients unable to provide informed consent and comply with the patient protocol.
7. Patients receiving excluded medications (including: epoprostenol, or prostacyclin analogues, phosphodiesterase inhibitors, other endothelin receptor antagonists, drugs with potential interaction with bosentan such as glibenclamide, fluconazole, cyclosporin A, or tacrolimus, and other invesgational agents).
8. Patients with planned surgical intervention during the study period.
9. Pregnant patients or patients of child bearing capacity who are using a reliable contraceptive method.
10. Patients with clinically overt ischaemic heart disease
11. Patients with predominant emphysema on CT scan (greater than interstitial changes)
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary end point is - Fall from baseline PVR (to week 16) of 20%.
|
|
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 | Yes |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Information not present in EudraCT |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |