Pulmonary arterial hypertension (PAH) MedDRA version: 9.1 Level: LLT Classification code 10064911
Conditions
Interventions
Trade Name: GLIVEC
Pharmaceutical Form: Tablet
INN or Proposed INN: IMATINIB MESYLATE
CAS Number: 220127-57-1
Current Sponsor code: QTI571
Concentration unit: mg milligram(s)
Concentration type: equa
Sponsors
NOVARTIS FARMA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Male or female patients aged 18 years or older. 2.A current diagnosis of Pulmonary Arterial Hypertension (PAH) according to the Dana Point 2008 Meeting: WHO Diagnostic Group I, idiopathic or heritable (familial or sporadic) PAH, PAH associated with collagen vascular disease including systemic sclerosis, rheumatoid arthritis, mixed connective tissue diseases, and overlap syndrome. PAH following one year post repair of congenital heart defect (ASD, VSD or PDA), or PAH associated with diet therapies or other drugs. 3.A PVR>800 dynes.sec.cm-5 as assessed by right heart catheterization (RHC) at screening or within 6 months preceding screening, despite treatment with two specific PAH therapies such as endothelin receptor antagonists, phosphodiesterase 5 inhibitor or prostacyclin analogues. 4.WHO Functional Class II-III. 5.Ability to provide written informed consent. 6.Patients must be on a stable dose of bosentan (125 mg b.i.d) and a stable dose of sildenafil(as prescribed by their physician) for at least 4 weeks prior to randomization, and are expected to remain on these doses throughout the duration of the study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant UNLESS they use two birth control methods.2. Pregnant or nursing (lactating) women 3.Have previously received treatment with QTI571 (imatinib).4.Have shown intolerance to sildenafil or bosentan.5. With other diagnosis of PAH in WHO Diagnostic Group 1.6.With a diagnosis of PAH associated with: venous hypertension(WHO Diagnostic Group II, including LVEF70% of predicted,or if the TLC=70% of the predicted,a chest CT (within last 6 months)must be available that shows minimal lung parenchyma involvement.9. Significant hematological disorders including: thrombocyte dysfunction, thrombocytopenia with platelet 3 times the upper limit of normal or bilirubin > 2 times ULN. 15. With a history of renal insufficiency (serum creatinine > 200 µmol/L or 2.6 mg/dL).16.Previous therapeutic radiation of lungs or mediastinum.17.With a history of sickle cell anemia.18.With an advanced, severe, or unstable disease of any type that may interfere with the primary and secondary endpoint evaluations.19.With a history of immunodeficiency diseases, including HIV,a history of Hepatitis B or C.20. Alcohol or drug abuse within last 6 months before screening visit.21.With a known hypersensitivity to QTI571 (imatinib) or drugs similar to the study drug.22.With absolute contraindications to sildenafil (concomitant use of organic nitrates,hypersensitivity ractions to sildenafil, intake of other PDE-5 inhibitors).23.With absolute contraindications to bosentan (pregnancy, concomitant intake of cyclosporine A or glyburide, hypersensitivity reactions).24.Body weight below 40 kg.25.Need for concomitant treatment with the compounds known to be strong inhibitors or inducers of CYP3A, CYP2C9.26.Having used other investigational drugs at the time of enrollment, or within 30 days or 5 elimination half-lives of the drug at enrollment, whichever is longer.27. Fertile males UNLESS the subject agrees to comply with two highly effective contraceptive methods comprising a barrier method for the entire duration of the study, up to the Study Comple
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the effect of two dose levels of QTI571 on the pharmacokinetics of the coadministered drugs sildenafil and bosentan at steady-state in patients with pulmonary arterial hypertension.;Secondary Objective: - To evaluate the safety and tolerability of QTI571 and the co-administered drugs sildenafil and bosentan at pharmacokinetic steady state in patients with pulmonary arterial hypertension - To evaluate the pharmacokinetics of QTI571 and its active metabolite at steady-state in patients with pulmonary arterial hypertension;Primary end point(s): Pharmacokinetics analysis | — |
Countries
Italy
Outcome results
None listed