E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pulmonary arterial hypertension (PAH) patients who have a PVR≥800 dynes.sec.cm-5 despite treatment with two or more specific PAH therapies |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064911 |
E.1.2 | Term | Pulmonary arterial hypertension |
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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 evaluate the long-term safety and tolerability of QTI571 |
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E.2.2 | Secondary objectives of the trial |
• Continue to evaluate the long-term efficacy of QTI571 as measured by the change in 6MWD from baseline. • Continue to assess time to clinical worsening (TTCW) endpoints including all cause mortality, hospitalization for worsening PAH for at least overnight (established by external adjudication committee), worsening of WHO functional class, or a drop in 6MWD by 15% both as a composite endpoint and by individual time to clinical worsening events. • To assess the impact of QTI571 on medical resource utilisation
Exploratory objectives: • To explore the long-term efficacy of QTI571 in any patients that are not able to tolerate 400mg QD by measurement of 6MWD and TTCW. • Compare the change from baseline in 6MWD and TTCW from time to entrance into extension study between patients treated with imatinib and placebo during the core study CQTI571A2301. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent must be obtained, from the patient or a legal guardian, before any assessment is performed. 2. Patients who participated in CQTI571A2301 clinical trial and completed the week 24 visit of the study protocol including all Study Completion assessments. 3. Patients who withdrew from the CQTI571A2301 study prematurely for reasons not related to study drug or not related to a safety issue, but performed all Study Completion assessments. (These patients will be eligible to enter the extension study 24 weeks after initial dosing in the core study CQTI571A2301). |
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E.4 | Principal exclusion criteria |
1. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant UNLESS they are using two birth control methods. The two methods can be a double barrier method or a barrier method plus a hormonal method. Adequate barrier methods of contraception include: diaphragm, condom (by the partner), intrauterine device (copper or hormonal), or sponge with spermicide. Hormonal contraceptives include any marketed contraceptive agent that includes an estrogen and/or a progestational agent 2. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL) 3. Patients with a pulmonary capillary wedge pressure > 15 mm Hg at time of Study Completion Assessments in core protocol CQTI571A2301. If pulmonary capillary wedge pressure is not attainable, then a left atrial pressure measurement may be used in its place. [In France, left atrial pressure measurement may not be used in place of pulmonary capillary wedge pressure.] 4. Patients with LVEF < 45% 5. Patients with thrombocytopenia, platelet count < 50 x109/L(50 x 103/μL) 6. Patients with uncontrolled systemic arterial hypertension, systolic > 160 mm Hg or diastolic >90 mm Hg 7. Patients with a QTcF > 450 ms for males and > 470 ms for females in the absence of right bundle branch block (based on Visit 1 ECG if required to be performed). 8. Male subjects must be using two acceptable methods of contraception, (e.g a condom or occlusive cap plus spermicide) for the entire duration of the study, up to the Study Completion visit, and refrain from fathering a child in the three months following the last study drug administration. Periodic abstinence and withdrawal are not acceptable methods of contraception. 9. [(France only) Patients for whom a lung transplant is indicated in the next 6 months.]
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E.5 End points |
E.5.1 | Primary end point(s) |
• Safety will be monitored by standard safety laboratories, ECG, echocardiogram, adverse event reporting. |
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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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 29 |
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 |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |