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

• Register: ClinicalTrials.gov
• Last refreshed on: 28 June 2021
• Main ID: NCT01392469
• Date of registration: 10/05/2011
• Prospective Registration: No
• Primary sponsor: Novartis Pharmaceuticals
• Public title: Pharmacokinetic Effects of QTI571 on Sildenafil and Bosentan in Pulmonary Arterial Hypertension Participants
• Scientific 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
• Date of first enrolment: April 20, 2011
• Target sample size: 21
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01392469
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Australia, Belgium, Germany, Italy, Lithuania, Romania, Turkey, United Kingdom, United States

Contacts

• Name: Novartis Pharmaceuticals
• Affiliation: Novartis Pharmaceuticals

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Pulmonary Arterial Hypertension

Intervention(s)

Drug: Bosentan

Drug: Imatinib

Drug: Sildenafil

Primary Outcome(s)

Geometric Mean Ratio of Dose Normalized Maximum Plasma Concentration (Cmax) for Bosentan Before and After Imatinib Administrations [Time Frame: 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]

Geometric Mean Ratio of Dose Normalized Area Under the Curve From Time Zero to Tau (AUCtau) for Bosentan Before and After Imatinib Administrations [Time Frame: 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]

Geometric Mean Ratio of Dose Normalized AUCtau for Sildenafil Before and After Imatinib Administrations [Time Frame: 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]

Geometric Mean Ratio of Dose Normalized Cmax for Sildenafil Before and After Imatinib Administrations [Time Frame: 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 Outcome(s)

Number of Participants With At Least One or More Adverse Events (AEs) [Time Frame: From time of first administration of study drug until end of study (up to approximately 18 months)]

Dose Normalized Cmax of Imatinib and CGP74588 (Active Metabolite of Imatinib) [Time Frame: 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]

Dose Normalized AUCtau of Imatinib and CGP74588 (Active Metabolite of Imatinib) [Time Frame: 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 ID(s)

2010-021344-17

CQTI571A2102

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 21/06/2021
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01392469