Clinical trial NCT01392469: Pharmacokinetic Effects of QTI571 on Sildenafil and Bosentan in Pulmonary Arterial Hypertension Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Arterial Hypertension
Keywords: Pulmonary Arterial Hypertension
Pulmonary Vascular Resistance
Imatinib
Bosentan
Sildenafil
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-07-12
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to investigate the effects of QTI571 (imatinib) on pharmacokinetics of bosentan and sildenafil at steady state when co-administered to participants with pulmonary arterial hypertension.


Eligibility criteria: Inclusion Criteria:

* Participants with Pulmonary arterial hypertension (PAH) in World Health Organization (WHO) Diagnostic Group 1, with pulmonary vascular resistance \> 800 dyne\*sec\*cm\^-5,
* On stable doses of bosentan and sildenafil

Exclusion Criteria:

* Other diagnosis of PAH in World Health Organization (WHO) Diagnostic Group 1 such as congenital large or small unrepaired systemic to pulmonary shunts, portal hypertension, Human Immunodeficiency Virus (HIV) infection, glycogen storage disease, Gaucher's disease, hereditary hemorrhagic teleangiectasia, hemoglobinopathies, myeloproliferative disorders, veno-occlusive pulmonary disease
* Significant lung diseases not related to PAH
* Significant cardiovascular system disorders, hematological system disorders, liver insufficiency
* Significant diseases in other organ system.

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Geometric Mean Ratio of Dose Normalized Area Under the Curve From Time Zero to Tau (AUCtau) for Bosentan Before and After Imatinib Administrations
timeFrame: Day 1: pre-dose, Day 8: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours post-dose, Day 9: pre-dose, Days 22 and 36: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
measure: Geometric Mean Ratio of Dose Normalized AUCtau for Sildenafil Before and After Imatinib Administrations
timeFrame: Day 1: pre-dose, Day 8: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours post-dose, Day 9: pre-dose, Days 22 and 36: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
measure: Geometric Mean Ratio of Dose Normalized Maximum Plasma Concentration (Cmax) for Bosentan Before and After Imatinib Administrations
timeFrame: Day 1: pre-dose, Day 8: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours post-dose, Day 9: pre-dose, Days 22 and 36: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
measure: Geometric Mean Ratio of Dose Normalized Cmax for Sildenafil Before and After Imatinib Administrations
timeFrame: Day 1: pre-dose, Day 8: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours post-dose, Day 9: pre-dose, Days 22 and 36: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
Secondary outcomes:
measure: Number of Participants With At Least One or More Adverse Events (AEs)
timeFrame: From time of first administration of study drug until end of study (up to approximately 18 months)
measure: Dose Normalized Cmax of Imatinib and CGP74588 (Active Metabolite of Imatinib)
timeFrame: Day 1: pre-dose, Day 8: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours post-dose, Day 9: pre-dose, Days 22 and 36: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
measure: Dose Normalized AUCtau of Imatinib and CGP74588 (Active Metabolite of Imatinib)
timeFrame: Day 1: pre-dose, Day 8: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours post-dose, Day 9: pre-dose, Days 22 and 36: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Novartis Investigative Site
state: Florida
city: Weston
country: United States
facility: Novartis Investigative Site
state: Florida
city: Mineola
country: United States
facility: Novartis Investigative Site
state: New York
city: Darlinghurst
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Vilnius
country: Lithuania
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: