E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
pulmonary arterial hypertension |
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MedDRA Classification |
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 safety and tolerability of oral STI571 compared with placebo in patients with pulmonary arterial hypertension. • To evaluate efficacy of oral STI571 as measured by improvement in 6-minute walk test.
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E.2.2 | Secondary objectives of the trial |
•To evaluate the efficacy of oral STI571 as measured by improvement Borg dyspoena scale, clinical status (WHO/NYHA class and dyspoena score), and changes in pulmonary haemodynamic parameters (including mean pulmonary arterial pressure, cardiac output and pulmonary vascular resistance) time to clinical worsening, changes in plasma biomarker levels. •To collect and monitor safety data of imatinib, provided as open label medication to patients with pulmonary arterial hypertension (PAH) who were enrolled in the six month randomized, placebo controlled STI571E2203 study. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Male and female patients equal to or greater than 18 years of age. 2. Diagnosis of pulmonary arterial hypertension (PAH) according to the Venice classification system (2003), of either primary (idiopathic), familial or secondary to systemic sclerosis (excluding those with marked pulmonary fibrosis). 3. Female patients of child bearing potential must be using a double-barrier contraception, i.e. intra-uterine device plus condom, or spermicidal gel plus condom or oral contraceptive plus condom up to completion of the Study Completion visit. 4. Able to communicate well with the investigator, to understand and comply with the requirements of the study. Understand and sign the written informed consent. 5. Subjects who are presently receiving imatinib following participation in the randomized STI571E2203 Study or subjects who will complete participation in the six month randomized STI571E2203 Study. |
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E.4 | Principal exclusion criteria |
1. Any subject who did not participate in the STI571E2203 Study. 2. Any subject who experienced syncope, pre syncope or new arrhythmias while participating in the STI571E2203. 3. Donation or loss of 400 ml or more of blood within 8 weeks prior to participation in the extension study. 4. Any subject who has developed any of the following exclusion criteria during participation in the STI571E2203 Study (subjects who are already receiving compassionate use imatinib, but have developed any of the following will be considered on a case by case basis). - Chronic thromboembolic pulmonary hypertension. - Treatment with catecholamines (e.g. adrenalin > 500 ng/kg x min, noradrenalin > 500 ng/kg x min, dopamine > 5 ng/kg x min). - Acute heart failure or chronic left sided heart failure. - Severe (systemic) arterial hypertension (> 200 mmHg (systolic) or > 120 mmHg (diastolic). - Congenital or acquired valvular or myocardial disease. - Deficiencies of blood coagulation (i.e. based on relevant changes in coagulation parameters), inherited or acquired blood coagulation disorders e.g. defects in factor VIII (Haemophilia A, v. Willebarnd syndrome), factor XII, factor XIII;decreased generation of coagulation factors due to acute or chronic liver diseases, deficient coagulation due to auto-antibodies against coagulation factors such as in lupus anticoagulant. - Disseminated intravascular coagulation (DIC). - Deficient thrombocyte function, thrombocytopenia < 40000/µl. - Evidence of major bleeding or intracranial hemorrhage. - History of latent bleeding risk such as diabetic retinopathy, history of gastrointestinal bleeding (due to gastric or duodenal ulcers), or colitis ulcerosa. - Moderate hepatic insufficiency Transaminase levels >= 4 fold the upper limit of normal or a bilirubin >= 2 fold the upper limit of normal. Elevated transaminase level should be carefully monitored because of known liver toxicity of STI571. - Renal insufficiency (serum creatinine > 200 µmol/l). - Previous therapeutic radiation of lungs or mediastinum. - History of elevated intracranial pressure (ICP >= 20 mmHg). - Pregnancy, breast feeding. - Patients whose underlying disease is not likely to permit them to survive the study. - Sickle cell anemia. - History of drug or alcohol abuse within the 12 months prior to dosing. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy analysis, will be on the difference between six minute walk tests at Week 24 between the two treatment groups, appropriate statistical testing will be performed on an intention to treat basis. A secondary analysis on the per protocol population will also be performed. Further analysis will be performed on all other secondary variables, where the mean and confidence interval for each variable will be listed and appropriate statistical comparisons made.
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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 | Information not present in EudraCT |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.1.6 | Cross over | No |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
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 | Yes |
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
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Last visit of last subject |
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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 | |
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 |