Pharmacokinetic Effects of QTI571 on Sildenafil and Bosentan in Pulmonary Arterial Hypertension Participants

Novartis

Status and phase: Completed; Phase 3

Conditions: Pulmonary Arterial Hypertension

Treatments: Drug: Imatinib; Drug: Bosentan; Drug: Sildenafil

Study type: Interventional

Funder types: Industry

Identifiers

NCT01392469

2010-021344-17 (EudraCT Number)

CQTI571A2102

Details and patient eligibility

About

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.

Enrollment: 21 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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21 participants in 1 patient group

Imatinib + Bosentan + Sildenafil

Experimental group

Description:

Participants received treatment with bosentan 125 milligrams (mg) twice daily and sildenafil thrice daily for 8 days in treatment period 1. Participants were on the same sildenafil dose level (20, 40, 50 or 60 mg) they had been at study entry which was well tolerated in conjunction with bosentan. Following treatment period 1, the participants received concomitant treatment of oral imatinib 200 mg daily, bosentan 125 mg twice daily and sildenafil thrice daily for 14 days in treatment period 2. Following treatment period 2, the participants received concomitant treatment of oral imatinib 400 mg daily, bosentan 125 mg twice daily and sildenafil thrice daily for 14 days in treatment period 3.

Treatment:

Drug: Sildenafil

Drug: Bosentan

Drug: Imatinib