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

Novartis

Status and phase: Terminated; Phase 2

Conditions: Pulmonary Arterial Hypertension

Treatments: Drug: Placebo to nilotinib; Drug: Nilotinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT01179737

2010-019883-36 (EudraCT Number)

CAMN107X2201

Details and patient eligibility

About

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.

Full 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

Enrollment: 23 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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23 participants in 2 patient groups, including a placebo group

Nilotinib

Experimental group

Description:

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

Treatment:

Drug: Nilotinib

Placebo

Placebo Comparator group

Description:

Participants were assigned to receive placebo to nilotinib to match 50 mg and 150 mg capsules during 168 days.

Treatment:

Drug: Placebo to nilotinib