A non-randomized, multiple dose, three treatment period, open-label, single sequence, single group study to evaluate the pharmacokinetic effect of two doses of QTI571 (imatinib) on the co-administered drugs sildenafil and bosentan in pulmonary arterial hypertension (PAH) patients. - ND

OVARTIS FARMA0 sites24 target enrollmentFebruary 7, 2011

ConditionsPulmonary arterial hypertension (PAH)MedDRA version: 9.1Level: LLTClassification code 10064911

DrugsGLIVEC REVATIO TRACLEER

Overview

Phase: Not Applicable
Intervention: Not specified
Conditions: Pulmonary arterial hypertension (PAH)
Sponsor: OVARTIS FARMA
Enrollment: 24
Status: Active, not recruiting
Last Updated: 13 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

February 7, 2011

End Date

TBD

Last Updated

13 years ago

Study Type

Interventional clinical trial of medicinal product

Sex

All

Investigators

Sponsor

OVARTIS FARMA

Eligibility 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

•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 LVEF\<45%),hypoxia (WHO Diagnostic Group III),chronic pulmonary thromboembolic disease(WHO Diagnostic Group IV) or other miscellaneous causes(WHO Diagnostic Class V).7\.Significant lung disease not related to PAH such as parasitic diseases affecting lungs, congenital abnormalities of the lungs,thorax or diaphragm or bronchial asthma associated with chronic hypoxia that may contribute to severity of PAH, diagnosis of pulmonary artery or vein stenosis, a diagnosis of chronic pulmonary thromboembolic disease(WHO Diagnostic Group IV).8\.Patients with systemic sclerosis may participate only if a pulmonary function test result within the last 6 months is available at screening visit, that shows a total lung capacity of \>70% 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 \< 50 x 103/µL, neutropenia with WBC \< 0\.5 of the lower limit of normal range, or hemoglobin \< 10 g/dL 10\.Cardiovascular disorders (for more details, see the protocol).11\.With deficiencies of blood coagulation, inherited or acquired blood coagulation disorders (for more details, see the protocol).12\.With evidence of major bleeding or intracranial hemorrhage and a history of latent bleeding risk such as diabetic retinopathy,gastrointestinal bleeding due to gastric or duodenal ulcers, or colitis ulcerosa.13\. With a history of elevated intracranial pressure.14\. With a history of moderate or greater hepatic insufficiency or transaminase levels \> 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