Clinical trial NCT01179737: Efficacy, Safety, Tolerability and Pharmacokinetics (PK) of Nilotinib (AMN107) in Pulmonary Arterial Hypertension (PAH)
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pulmonary Arterial Hypertension
Keywords: Pulmonary Arterial Hypertension
Nilotinib
6MWD
Pulmonary Hypertension
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-08-11
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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

Eligibility criteria: 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

Primary outcomes:
measure: Change in Pulmonary Vascular Resistance (PVR)
timeFrame: 168 days
Secondary outcomes:
measure: Change in Six-Minute Walk Distance (6MWD) From Baseline
timeFrame: Baseline, 168 days
measure: Total Number of Adverse Events and Serious Adverse Events
timeFrame: 168 days
Other outcomes:
Locations:
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Chapel Hill
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Cleveland
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Nashville
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Calgary
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Marburg
country: Germany
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Zurich
country: Switzerland
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: