Efficacy, Safety, Tolerability and Pharmacokinetics (PK) of Nilotinib (AMN107) in Pulmonary Arterial Hypertension (PAH)

Pulmonary Arterial Hypertension Clinical Trial

Official title:

A 24 Week, Randomized, Double Blind, Multicenter, Placebocontrolled Efficacy, Safety, Tolerability and PK Trial of Nilotinib (Tasigna®, AMN107) in Pulmonary Arterial Hypertension (PAH)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01179737
• Other study ID #: CAMN107X2201
• Secondary ID: 2010-019883-36
• Status: Terminated
• Phase: Phase 2
• First received: August 3, 2010
• Last updated: April 14, 2014
• Start date: July 2010
• Est. completion date: January 2013

Study information

• Verified date: April 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaKorea: Korea FDAGermany: Ministry of HealthSwitzerland: SwissmedicSingapore: Health Sciences AuthorityItaly: The Italian Medicines AgencyHungary: Institutional Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The purpose of this trial was to establish the safety, tolerability and PK of nilotinib in this population and to test the hypothesis that 6 months treatment with nilotinib will significantly reduce pulmonary artery resistance.

Description:

The purpose of this trial was to establish the safety, tolerability and PK of nilotinib in this population and to test the hypothesis that 6 months

Other known NCT identifiers

• NCT01531270

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 23
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• World Health Organization (WHO) Functional Class II or III

• 6MWD = 150 m and = 450 m at screening

• Current diagnosis of PAH according to Dana Point 2008 Meeting

• Inadequate clinical response on one or more class(es) of PAH drug

• Stabilization of pulmonary hypertension medications for = 2 months on approved therapeutic dose of at least one PAH drug and still symptomatic with WHO functional Class II or III performance.

Exclusion Criteria:

• Women of child-bearing potential not practicing birth control

• In treatment with chronic nitric oxide therapy

• Pre-existing lung disease

• Use of drugs prolonging the QT interval or strong CYP3A4 inhibitors

• Long QT syndrome or QTc > 450 ms males; > 470 ms females.

• WHO Class IV

• Pulmonary capillary wedge pressure > 15 mm Hg

• Other diagnosis of PAH in WHO Diagnostic Group 1

• PAH associated with: venous hypertension (WHO Diagnostic Group II), hypoxia (WHO Diagnostic Group III), chronic pulmonary thromboembolic disease (WHO Diagnostic Group IV) or other miscellaneous causes (WHO Diagnostic Class V, which includes sarcoidosis, histiocytosis X, lymphangiomatosis, compression of pulmonary vessels)

• Thrombocytopenia < 50 x109/L (50 x 103/µL)

• Uncontrolled systemic arterial hypertension, systolic > 160 mm Hg or diastolic >90 mm Hg

• Any advanced, severe, or unstable disease of any type that may interfere with the primary and secondary endpoint evaluations.

Other protocol-defined inclusion/exclusion criteria may apply

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Nilotinib
Nilotinib capsules for oral administration at 50 mg, 150 mg twice a day and 300 mg (2 capsules of 150 mg) twice a day.
• Placebo to nilotinib
Placebo to nilotinib capsules for oral administration to match 50 mg, 150 mg and 300 mg capsules twice a day

Locations

Country	Name	City	State
Canada	Novartis Investigative Site	Calgary	Alberta
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Marburg
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Switzerland	Novartis Investigative Site	Zurich
United States	Novartis Investigative Site	Ann Arbor	Michigan
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Chapel Hill	North Carolina
United States	Novartis Investigative Site	Cleveland	Ohio
United States	Novartis Investigative Site	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Korea, Republic of,  Singapore,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Pulmonary Vascular Resistance (PVR)	Change in pulmonary vascular resistance is measured via right heart catheter assessment according to local hospital procedures. It assesses several prognostic hemodynamic variables in pulmonary hypertension, including Pulmonary Vascular Resistance (PVR). Study was prematurely terminated and not powered for efficacy.	168 days	No
Secondary	Change in Six-Minute Walk Distance (6MWD) From Baseline	During standardized walk course participants are connected to a portable pulse oximeter via a finger probe and instructed to walk at a comfortable speed for as far as they could manage in 6 minutes. Study was prematurely terminated and efficacy data were not analyzed or summarized	Baseline, 168 days	No
Secondary	Total Number of Adverse Events and Serious Adverse Events	Adverse events were summarized by the number of patients having any adverse event overall and presented in the safety section. Study was prematurely terminated.	168 days	Yes