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

Phase 2

Terminated

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

Recruitment & 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

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo to nilotinib	Participants were assigned to receive placebo to nilotinib to match 50 mg and 150 mg capsules during 168 days.
Nilotinib	Nilotinib	Participants in cohort 1 were assigned to receive nilotinib 50 mg during 14 days, followed by 150 mg during 14 days, followed by 300 mg during 140 days. Participants in cohort 2 were assigned to receive nilotinib 300 mg during 168 days

Primary Outcome Measures

Name	Time	Method
Change in Pulmonary Vascular Resistance (PVR)	168 days	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.

Secondary Outcome Measures

Name	Time	Method
Change in Six-Minute Walk Distance (6MWD) From Baseline	Baseline, 168 days	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
Total Number of Adverse Events and Serious Adverse Events	168 days	Adverse events were summarized by the number of patients having any adverse event overall and presented in the safety section. Study was prematurely terminated.